CHAPTER 3 - Hemostasis, Surgical Bleeding, and Transfusion Seymour I. Sc !

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BIOLOGY OF HEMOSTASIS Hemostasis is a complex process that prevents or terminates blood loss rom a disr!pted intravasc!lar space" provides a ibrin net#or$ or tiss!e repair" and" !ltimatel%" removes the ibrin #hen it is no lon&er needed 'Fi&( )*+,( Endothelial cells !nctionall% act to prevent clottin&( The% inter ere #ith platelet recr!itment b% inactivatin& adenosine diphosphate 'A-.,( The% provide an environment in #hich thrombin is also inactivated b% complexin& #ith antithrombin III( Endothelial cells release thrombomod!lin" #hich do#n* mod!lates the coa&!lation process( Fo!r ma/or ph%siolo&ic events participate" both in se0!ence and interdependentl%" in the hemostatic process( 1asc!lar constriction" platelet pl!& ormation" ibrin ormation" and ibrinol%sis occ!r in that &eneral order" b!t the prod!cts o each o these o!r processes are interrelated in s!ch a #a% that there is a contin!!m and m!ltiple rein orcements 'Fi&( )*2,( 1asc!lar 3onstriction 1asoconstriction is the initial vasc!lar response to in/!r%" even at the capillar% level( It is dependent !pon local contraction o smooth m!scle that has a re lex response to vario!s stim!li( The initial vasc!lar constriction occ!rs be ore an% platelet adherence at the site o in/!r%( Adherence o endothelial cells to ad/acent endothelial cells ma% be s! icient to ca!se cessation o blood loss rom the intravasc!lar space( 1asoconstriction is s!bse0!entl% lin$ed to platelet pl!& and ibrin ormation( Thromboxane A 2 'T4A 2," #hich res!lts rom the release o arachidonic acid rom platelet membranes d!rin& a&&re&ation" is a po#er !l vasoconstrictor( B% contrast" prostac%clin" #hich is also secreted d!rin& the platelet release reaction" is a potent vasodilator( Serotonin" 5*h%drox%tr%ptamine '5*HT," released d!rin& platelet a&&re&ation" is another vasoconstrictor" b!t it has been sho#n that #hen platelets have been depleted o serotonin in vivo" constriction is not inhibited( Brad%$inin and ibrinopeptides in the coa&!lation schema are also capable o contractin& smooth m!scle( Some patients #ith mild bleedin& disorders and a prolon&ed bleedin& time have" as their onl% abnormalit%" capillar% loops that ail to constrict in response to in/!r%( A lateral incision in a small arter% ma% remain open beca!se o ph%sical orces" #hereas complete transection o a similarl% si6ed vessel contracts to the extent that bleedin& ma% cease spontaneo!sl%( The vasc!lar response actor sho!ld also incl!de the contrib!tion o press!re provided b% s!rro!ndin& tiss!es( Bleedin& rom a small ven!le r!pt!red b% tra!ma" in the thi&h o an athlete" ma% be ne&li&ible beca!se o the compressive e ect o s!rro!ndin& m!scle( In the same individ!al" bleedin& rom a similar vessel in the nasal m!cosa ma% be si&ni icant( 7hen there is lo# perivasc!lar press!re" as seen in patients #ith m!scle atroph% accompan%in& a&in&" in patients on prolon&ed steroid therap%" and in patients #ith the Ehlers*-anlos s%ndrome" bleedin& tends to be more persistent( 1asc!lar abnormalities" s!ch as hereditar% hemorrha&ic telan&iectasia" ma% predispose the patient to bleedin& rom the involved re&ion(

.latelet F!nction .latelets are 2*mm diameter ra&ments o me&a$ar%oc%tes and n!mber 288"888 to 988"888:mm) in circ!latin& blood #ith a li e span o ; to < da%s( The% pla% an inte&ral role in hemostasis alon& t#o path#a%s( .latelets" #hich normall% do not adhere to each other or to the normal vessel #all" orm a pl!& that stops bleedin& #hen vasc!lar disr!ption occ!rs( In/!r% to the intima exposes s!bendothelial colla&en to #hich platelets adhere #ithin +5 s o the tra!matic event( This re0!ires von 7illebrand actor 'v7F," a protein that is lac$in& in patients #ith von 7illebrand=s disease( The platelets then expand and develop pse!dopodal processes and also initiate a release reaction that recr!its other platelets rom the circ!latin& blood( As a conse0!ence" a loose platelet a&&re&ate orms" sealin& the disr!pted blood vessel( The a&&re&ation !p to this point is reversible and is not associated #ith secretion( This process is $no#n as primar% hemostasis( The administration o heparin does not inter ere #ith this reaction" #hich is #h% hemostasis can occ!r in the heparini6ed patient( A-. and serotonin are principal mediators in this process o adhesion and a&&re&ation( 1ario!s prosta&landins have opposin& activities( Arachidonic acid" released rom platelet membranes" is converted b% c%cloox%&enase to prosta&landin G2 '.GG2, and .GH2" #hich in t!rn are converted to T4A 2" a potent platelet a&&re&ator and vasoconstrictor( B% contrast" .GI2 'prostac%clin, and .GE2 inhibit a&&re&ation and act as vasodilators( A-." released rom dama&ed tiss!es and platelets" pl!s platelet actor 9 and trace thrombin on the platelet s!r ace in the ace o 3a2 > and M&2 >" stim!late a platelet release reaction b% #hich the content o the platelet and its &ran!les is dischar&ed( Fibrino&en is re0!ired or this process( Thrombin pla%s a central role in this process b% stim!latin& platelet de&ran!lation and activatin& the &eneration o thromboxane A2( -!rin& this process" platelet actor 9"b* thrombo&lob!lin" platelet*derived &ro#th actor" A-." serotonin" and calci!m are introd!ced into the plasma( The release reaction res!lts in compaction o the platelets and the ormation o an ?amorpho!s@ pl!&" #hich is no lon&er reversible( This process is inhibited b% c%clic adenosine monophosphate 'cAM.,( As a conse0!ence o the release reaction" platelet actor ) is made available and contrib!tes phospholipid to several sta&es o the coa&!lation cascade( The lipoprotein s!r ace provided b% platelets catal%6es reactions that are involved in the conversion o prothrombin ' actor II, into thrombin 'Fi&( )* ),( .latelet actor ) is involved in the reaction b% #hich activated actor I4 'I4a," actor 1III" and calci!m activate actor 4( It is also involved in the reaction b% #hich actor 4a" actor 1" and 3a2 > activate actor II( .latelets ma% also pla% a role in the initial activation o actors 4I and 4II( .latelet actor 9 and b*thrombo&lob!lin are also made available d!rin& the release reaction" and the% ma% inhibit the activit% o heparin and modi % ibrin ormation( The platelets also pla% a role in the ibrinol%tic process b% releasin& an inhibitor o plasmino&en activation( 3oa&!lation 3oa&!lation is the process b% #hich prothrombin is converted into the proteol%tic en6%me thrombin" #hich in t!rn cleaves the ibrino&en molec!le to orm insol!ble ibrin in order to stabili6e and add to the platelet pl!&( 3oa&!lation consists o a series o 6%mo&en activation sta&es in #hich circ!latin& proen6%mes are converted in

se0!ence to activated proteases 'Fi&( )*9,( The traditional concept o the clottin& s%stem evolved rom test t!be anal%sis and ollo#s t#o path#a%sA the intrinsic path#a% involves components normall% present in blood" and the extrinsic path#a% is initiated b% the tiss!e lipoprotein 'Fi&( )*5,( In the intrinsic path#a% actor 4II is activated b% bindin& to s!bendothelial colla&en( .re$alli$rein and hi&h* molec!lar* #ei&ht $inino&en ampli % this contact phase( Activated actor 4II '4IIa, proteol%ticall% cleaves actor 4I and also pre$alli$rein to orm actor 4Ia and $alli$rein( In the presence o 3a2 >" actor 4Ia activates actor I4 'I4a,( This in t!rn complexes #ith actor 1III" #hich can be activated to a more potent orm b% thrombin" and" in the presence o 3a2 > and the phospholipid platelet actor )" activates actor 4( In the extrinsic path#a%" the tiss!e phospholipid" thromboplastin" reacts #ith actor 1II and 3a2 > to activate actor 4( Activated actor 4 '4a," prod!ced b% the t#o path#a%s" proteol%ses prothrombin ' actor II, to orm thrombin( The e ects o thrombin are limited to the area o endothelial disr!ption b% several processes( Thrombin activates the ibrin stabili6in& actor '4III, and cleaves ibrinopeptides A and B rom ibrino&en ' actor I, to orm ibrin" a monomer that is cross*lin$ed #ith actor 4IIIa" to orm a stable clot 'Fi&( )* B,( The escape o thrombin into the circ!lation is prevented rom complexin& #ith antithrombin locall% b% the bindin& o the thrombin to thrombomod!lin on the endotheli!m" creatin& a complex that cannot cleave ibrino&en and also activatin& protein 3" #hich in t!rn inactivates actors 1 and 1III( Additionall%" circ!latin& thrombin is inactivated b% plasma protease inhibitors( This process is accelerated b% actor 1" tiss!e lipoproteins" platelet s!r ace phospholipids" and 3a2 >( All the coa&!lation actors except thromboplastin" 3a2 >" and most o actor 1III are s%nthesi6ed in the liver( Factors II" 1II" I4" and 4 re0!ire vitamin C or their prod!ction 'Table )*+,( Fibrinol%sis Fibrinol%sis is a nat!ral process directed at maintainin& the patenc% o blood vessels b% l%sis o ibrin deposits( Also involved in the maintenance o vasc!lar patenc% is circ!latin& antithrombin III 'ATIII, #hich ne!trali6es the action o thrombin and other proteases in the coa&!lation cascade( Fibrinol%sis is initiated at the same time as the clottin& mechanism !nder the in l!ence o circ!latin& $inases" tiss!e activators" and $alli$rein that are present in man% or&ans" incl!din& veno!s endotheli!m( Fibrinol%sis is dependent on the en6%me plasmin" #hich is derived rom a prec!rsor plasma protein 'plasmino&en, 'Fi&( )*;,( .lasmino&en levels are $no#n to rise as a conse0!ence o exercise" veno!s occl!sion" and anoxia( .lasmino&en activation is also initiated b% the activation o actor 4II( The plasmino&en is pre erentiall% absorbed on ibrin deposits( The en6%me plasmin l%ses ibrin and acts on other coa&!lant proteins as #ell" incl!din& ibrino&en" actor 1" and actor 1III( The smaller ra&ments o pol%peptide prod!cts o ibrin that are prod!ced inter ere #ith normal platelet a&&re&ationD the lar&er ra&ments are incorporated into the clot in lie! o normal ibrin monomers and res!lt in an !nstable clot( H!man blood also contains an antiplasmin that inhibits plasmino&en activation" and platelets are believed to possess anti ibrinol%tic activit%(

C#$%E$ITA& HE'#STATIC (E)ECTS

Inheritance The modes o inheritance o hemostatic disorders" #ith onl% rare exceptions" are o three t%pesA '+, a!tosomal dominant" '2, a!tosomal recessive" and '), sex*lin$ed recessive( The most common hemostatic disorder transmitted b% the a!tosomal dominant mode is von 7illebrand=s disease( Hereditar% hemorrha&ic telan&iectasia and actor 4I de icienc% also appear to be transmitted in this ashion( Occasionall%" in a pedi&ree #ith an a!tosomal dominant &ene" an apparentl% normal person ma% transmit disease to his or her child( The parent clearl% carried the &ene" #hich clinicall% expressed no de ect( In inherited hemostatic disorders" the di erence in clinical expression bet#een dominant and recessive &enes is a &raded one rather than an ?all* or*none@ phenomenon( The hetero6%&o!s individ!al #ith an a!tosomal recessive trait ma% have a meas!rable de icienc% o the actor &overned b% that &ene" b!t no clinical disease( In order to demonstrate clinical expression o disease" the individ!al m!st be homo6%&o!s( This appears to be the case" or example" in actor 4 de icienc%( Other hemostatic disorders probabl% inherited in this mode are de iciencies in actor 1" actor 1II" and actor I( Sex*lin$ed recessive inheritance &overns tr!e hemophilia ' actor 1III de icienc%, and actor I4 de icienc% '3hristmas disease,( The &enes or these diseases are recessive in expression and are carried on the emale '4, chromosome( 7hen paired #ith the normal 4 chromosome 'the emale carrier state," clinical disease is not present( 7hen the a ected 4 chromosome is paired #ith the normal male 'Y, chromosome" clinical disease is expressed( Platelet (eficiencies Hereditar% 0!antitative disorders incl!de disorders o platelet prod!ction 'hereditar% thromboc%topenia, and platelet destr!ction '7is$ott*Aldrich s%ndrome,( The most common con&enital platelet de icienc% is the abnormalit% seen in von 7illebrand=s disease" in #hich the von 7illebrand actor 'v7F, is missin&D v7F has been sho#n to be re0!ired or platelet adhesion to s!bendothelial colla&en 'see section belo#,( Also" platelets rom patients #ith von 7illebrand=s disease" !nli$e those o normal patients" ail to a&&re&ate in vitro #ith the addition o ristocetin( Another inherited disorder a ectin& platelets is the rare Bernard*So!lier s%ndrome( .atients #ith Bernard*So!lier s%ndrome have normal levels o v7F" and the addition o v7F does not a ect a&&re&ation o platelets in the presence o ristocetin( In Bernard*So!lier s%ndrome" the platelet membrane receptor or v7F" a portion o the &l%coprotein I complex" is missin&( Glan6mann=s thrombasthenia is a rare con&enital disorder in #hich platelets ail to a&&re&ate in the presence o A-. and mediation o actors involved in clot retention is impaired( .atients #ith con&enital a ibrino&enemia also have impairment o platelet a&&re&ation beca!se ibrino&en is re0!ired or this process to occ!r( .atients #ith con&enital a ibrino&enemia have dist!rbed platelet !nction" mani ested b% a prolon&ed bleedin& time correctable b% ibrino&en administration(

3on&enital disorders o platelet secretion incl!de stora&e pool disease" in #hich the platelets lac$ the stora&e capabilit% o A-. re0!ired or a&&re&ation( The Hermans$%* .!dla$ s%ndrome 'oc!loc!taneo!s albinism" ceroidli$e deposits in macropha&es" and bleedin& diathesis, is classi ied in this cate&or%( 3on&enital primar% release de ects have also been described and are responsible or prolon&ed bleedin& time( Congenital (efects of Coagulation )actors Factor 1III -e icienc% '3lassical Hemophilia, 3lassical hemophilia 'hemophilia A, is a disease o males( The ail!re to s%nthesi6e actor 1III in normal proportions is inherited as a sex*lin$ed recessive trait( Spontaneo!s m!tations acco!nt or almost 28 percent o cases( The incidence o the disease is approximatel% +A+8"888 to +A+5"888 pop!lation" and the clinical mani estations can be extremel% variable( 3linical Mani estations 3haracteristicall%" the severit% o clinical mani estations is related to the de&ree o de icienc% o actor 1III( Spontaneo!s bleedin& and severe complications are the r!le #hen virt!all% no actor 1III can be detected in the plasma( 7hen plasma actor 1III concentrations are in the ran&e o 5 percent o normal" the patient ma% have no spontaneo!s bleedin& %et ma% bleed severel% #ith tra!ma or s!r&ical treatment( .atients #ith levels &reater than 5 percent o normal '&reater than 8(85 !nits:mL, are considered mild hemophiliacs( .atients #hose actor 1III levels all bet#een + and 5 percent o normal are considered moderatel% severe hemophiliacs( T%picall%" members o the same pedi&ree #ith tr!e hemophilia have approximatel% the same de&ree o clinical mani estations( 7hile the severel% a ected patient ma% bleed d!rin& earl% in anc%" si&ni icant bleedin& t%picall% is noted irst #hen the child is a toddler( At that time" in addition to the classic bleedin& into /oints" epistaxis and hemat!ria ma% be noted( Bleedin& that is li e*threatenin& ma% ollo# in/!r% to the ton&!e or lin&!al ren!l!m( Tracheal compression and retrophar%n&eal bleedin& ma% ollo# tonsillar in ection( Intracranial bleedin&" associated #ith tra!ma in hal the cases" acco!nts or 25 percent o deaths( 1asc!lar and ne!ral compromise ma% occ!r in relation to press!re secondar% to bleedin& into a so t*tiss!e closed space( Talipes e0!in!s contract!re de ormit% ma% be seen in severel% hemophilic patients secondar% to bleedin& into the cal ( 1ol$mann=s contract!re o the orearm and lexion contract!res o the $nees and elbo#s are also disablin& se0!elae o deep so t*tiss!e bleedin&( Hemarthrosis is the most characteristic orthopaedic problem( Bleedin& into the /oint ma% ca!se e# s%mptoms !ntil distention o the /oint caps!le occ!rs( A lar&e hemarthrosis &enerall% is mani ested b% a tender" s#ollen" #arm" and pain !l /oint( M!scle spasm and pain aro!nd the /oint arise rom involvement o periartic!lar str!ct!res( These si&ns ma% mimic in ection( The same orthopaedic problems are noted in association #ith severe actor I4 de icienc% '3hristmas disease,( Eetroperitoneal bleedin& ma% ollo# li tin& o a heav% ob/ect or stren!o!s exercise( Si&ns o posterior peritoneal irritation and spasm o the iliopsoas s!&&est the dia&nosis( H%povolemic shoc$ ma% occ!r" since the amo!nt o blood loss that can ta$e place in this settin& is enormo!s( The clinical mani estations o intram!ral intestinal hematoma are na!sea and vomitin&" cramp% abdominal pain" and si&ns o

peritoneal irritation that mimic those o appendicitis( Fever and le!$oc%tosis ma% be noted( Eadio&raphs o the abdomen ma% ail to reveal an% abnormalit% or ma% displa% a modest amo!nt o ile!s( Fpper &astrointestinal examination ma% demonstrate a !ni orm thic$enin& o m!cosal olds that has been described as a ?pic$et ence@ or ?stac$ o coins@ appearance 'Fi&( )*G,( Intram!ral hematomas o the intestine occ!r in other hemostatic disorders and there ore sho!ld be considered #hen an% patient #ith a hemostatic problem presents #ith indin&s s!&&estin& an ac!te intraabdominal process( Treatment Eeplacement Therap% The plasma concentration o actor 1III necessar% or maintenance o hemostatic inte&rit% is normall% 0!ite small( .atients #ith as little as 2 to ) percent o actor 1III activit% !s!all% do not bleed spontaneo!sl%( Once serio!s bleedin& be&ins" ho#ever" a m!ch hi&her level o actor 1III activit%" probabl% approachin& )8 percent" is necessar% to achieve hemostasis( The hal *li e o actor 1III is G to +2 h( A ter administration o a &iven dose o actor 1III" approximatel% one*hal o the initial posttrans !sion activit% disappears rom the plasma in 9 h( This earl% disappearance is tho!&ht to be d!e in lar&e part to di !sion rom the intravasc!lar space( The period o e0!ilibration ma% extend or as lon& as G h" at #hich time onl% abo!t one* 0!arter o the initial level remains in the circ!latin& blood( From that time on" the slope o disappearance is less steep( T#ent%* o!r ho!rs a ter a &iven dose" no more than ; to G percent o administered actor 1III activit% remains #ithin the circ!lation( One !nit o actor 1III activit% is considered that amo!nt present in + mL o normal plasma( Act!all%" resh ro6en plasma contains 8(B8 !nit:mL( Theoreticall%" in a patient #ith 8 percent activit%" to achieve an initial posttrans !sion level o B8 percent o normal" !sin& resh plasma" a vol!me o plasma e0!al to B8 percent o the patient=s estimated plasma vol!me #o!ld have to be administered( Table )*2 sho#s approximate levels o actor 1III re0!ired or hemostasis in di erent disorders( The minim!m hemostatic level o actor 1III or mild hemorrha&es is )8 percentD or /oint and m!scle bleedin& and ma/or hemorrha&es" it is 58 percent( For ma/or s!r&er% and li e*threatenin& bleedin&" levels o G8 to +88 percent sho!ld be reached preoperativel% and maintained above )8 percent or 2 #ee$s( Eememberin& the loss rom the circ!lation" one*hal the initial dose #o!ld need to be s!pplied ever% +2 h( The !se o resh plasma in s!ch circ!mstances #o!ld re0!ire a vol!me that is excessive( Factor 1III concentrates are available that circ!mvent this problem( 3r%oprecipitate concentrates o actor 1III can be re&arded as containin& <(B !nits:mL( The amo!nt o material to be &iven can be comp!ted rom the orm!la .atient=s #ei&ht '$&, H desired rise o actor 1III 'I avera&e normal, : Total !nits o actor 1III in dose J E #here E is a actor that is airl% constant or an% &iven t%pe o material and represents the rise o actor 1III obtained in the patient=s plasma or ever% !nit o trans !sed actor 1III per $ilo&ram o the patient=s bod% #ei&ht( Hal that amo!nt is s!bse0!entl% administered ever% 9 to B h to maintain a sa e level(

A variet% o actor 1III concentrates are available( Ee&ardless o the preparation emplo%ed" contin!ed laborator% assessment o circ!latin& actor 1III level is an important element in the control o these patients( 7et* ro6en cr%oprecipitate is pre erred or replacement in patients #ith mild hemophilia since the ris$ o hepatitis is less than it is #ith actor 1III concentrates( The latter are pre erred or ma/or replacement problems( In mild hemophilia A and in mild von 7illebrand=s disease" --A1. '+*desamino* G*d*ar&inine vasopressin," a s%nthetic derivative o vasopressin" has been !sed to e ect a dose*dependent increase o all actor 1III activities and to e ect release o plasmino&en activator( --A1. red!ces blood loss associated #ith ma/or s!r&ical proced!res b% 98 percent( .atients !nder&oin& orthopaedic or ne!ros!r&ical proced!res sho!ld also receive a ibrinol%tic inhibitor( A ter ma/or s!r&ical treatment o the hemophiliac" trans !sion replacement o actor 1III sho!ld be contin!ed or at least +8 da%s( 7o!nds sho!ld be #ell healed and all drains removed be ore termination o therap%( I s!t!res remain" trans !sion sho!ld be reinstit!ted be ore the% are removed( Man% recent reports doc!ment the sa et% o ma/or s!r&ical proced!res in hemophilic patients receivin& replacement therap%( B!t in one lar&e series the incidence o postoperative hemorrha&e did not improve over a +B*%ear period despite a three old increase in dosa&e o actor 1III" s!&&estin& that circ!latin& actor 1III levels are not the sole determinant o bleedin& in these patients( The vir!ses o homolo&o!s ser!m hepatitis and HI1 have been transmitted b% vario!s plasma concentrates( Other complications o replacement therap% incl!de the appearance o inhibitors o actor 1III" #hich ma% arise in the hemophiliacs #ho have had trans !sion( These inhibitors have been characteri6ed as antibodies o the &G variet%( The% tend to diminish in several #ee$s i !rther trans !sion is not emplo%ed( Laborator% search or these actors sho!ld be carried o!t in ever% hemophilic patient #ho is considered a candidate or elective s!r&ical treatment" as their presence complicates trans !sion mana&ement( .aradoxical bleedin& ma% occ!r in patients trans !sed to an appropriate actor 1III level as a res!lt o the development o abnormal platelet !nction( Ad/!nctive Mana&ement Treatment o so t tiss!e bleedin& is directed at the prevention o air#a% obstr!ction and vasc!lar and ne!ral dama&e( These are accomplished best b% the administration o s! icient actor 1III( Bed rest and cold pac$s can be o some assistance( In &eneral" res!lts o asciotom% to relieve press!re have varied rom disappointin& to disastro!s( The occasional development o lar&e c%sts has res!lted in s! icient de ormit% and disabilit% to re0!ire amp!tation( The primar% treatment o hemophilic hemarthrosis is directed at maintainin& !ll ran&e o motion and minimal destr!ction o the cartila&e( Aspiration o blood rom the hemophilic /oint is not !ni orml% endorsed" and #hen re&arded as necessar% it sho!ld be considered a ma/or s!r&ical event( Elevation o actor 1III level b% trans !sion is necessar%( The proced!re sho!ld be carried o!t in the operatin& room !nder strict sterile preca!tions( In most instances aspiration is not re0!ired" and the combination o actor 1III replacement and local cold pac$in& proves s! icient( .h%siotherap% pla%s a critical role and sho!ld consist o active exercises" since the patient is !nli$el% to move the extremit% to a point #here bleedin& #ill rec!r( .assive exercises o ten

res!lt in rec!rrence o bleedin&( The reader is re erred to the revie# b% 3!rtiss or details o orthopaedic mana&ement( The mana&ement o intram!ral intestinal hematoma and retroperitoneal bleedin& is based on appropriate trans !sion therap% and avoidance o s!r&ical treatment( Even #hen a relativel% minor proced!re" s!ch as tracheostom%" is per ormed" the plasma level o actor 1III sho!ld be raised above 25 to )8 percent( Since dental h%&iene !s!all% is poor in hemophilic patients" dental and oral s!r&ical treatment re0!entl% are necessar%( Factor I4 -e icienc% '3hristmas -isease, Factor I4 de icienc% clinicall% is indistin&!ishable rom actor 1III de icienc% and also has an 4*lin$ed recessive mode o inheritance( These t#o entities #ere considered a sin&le disease !ntil +<52" #hen their !ni0!e de iciencies #ere doc!mented( Factor I4 de icienc% acco!nts or 28 percent o hemophiliacs( Li$e classical hemophilia 'hemophilia A," 3hristmas disease 'hemophilia B," can occ!r in severe" moderate" or mild orms accordin& to the level o actor I4 activit% in the plasma( One*hal o a licted patients have the severe orm" #hich has a actor I4 level o less than + percent( .atients have a prolon&ed partial thromboplastin time '.TT,( Treatment Most patients #ith severe actor I4 de icienc% re0!ire s!bstit!tion therap% on a re&!lar basis( All patients re0!ire s!bstit!tion therap% #henever minor or ma/or s!r&er% is per ormed( Therap% is &enerall% based on the administration o resh ro6en plasma or" rarel%" actor I4 concentrates( Initiall% the rate o disappearance o actor I4 rom the circ!lation is more rapid than that o actor 1IIID s!bse0!entl% actor I4" #ith a hal *li e o +G to 98 h" has a slo#er disappearance rate( -!rin& severe hemorrha&e" treatment sho!ld be directed at achievin& plasma actor I4 levels o 28 to 58 percent o normal or the irst ) to 5 da%s" and then maintainin& the plasma level at +8 to 28 percent o normal or approximatel% +8 da%s( The !s!al dail% dose is )8 to 58 !nits:$& o bod% #ei&ht" ollo#ed b% 28 !nits:$& o bod% #ei&ht:29 h( 7hen an operation is re0!ired" the plasma level o approximatel% 58 to ;8 percent o normal sho!ld be achieved( -!rin& the operation and the irst postoperative da%" B8 !nits:$& o bod% #ei&ht:29 h is recommended" ollo#ed b% )8 to 98 !nits:$& ever% 29 h or the next 2 to ) da%s" and 28 !nits:$& ever% 29 h or ) to 9 da%s( In all instances" the levels sho!ld be monitored b% laborator% determinations( The development o antibodies a&ainst actor I4 represents a serio!s complication that is di ic!lt to deal #ith( This occ!rs in abo!t +8 percent o patients #ith 3hristmas disease( These patients are mana&ed b% #ithholdin& all in !sion therap% #ith blood or plasma( Hi&h doses o actor I4 concentrates combined #ith c%clophosphamide have been e ective( von 7illebrand=s -isease von 7illebrand=s disease occ!rs as commonl% as tr!e hemophilia( The increasin& reco&nition o this disease is related to more reliable actor 1III assa%s( This hereditar% disorder o hemostasis is !s!all% transmitted as an a!tosomal dominant trait" b!t recessive inheritance ma% occ!r( The disease is characteri6ed b% a dimin!tion o the level o actor 1IIIA3 'procoa&!lant, activit% that corrects the clottin& abnormalit% in hemophilia A plasma( The red!ction o actor 1IIIA3 activit% !s!all% is not as &reat as that seen in classical hemophilia( Also !nli$e classical

hemophilia" in #hich actor 1IIIA3 activit% remains constant" in the patient #ith von 7illebrand=s disease" variation in the level o circ!latin& actor 1IIIA3 activit% ma% be noted( 3haracteristicall%" these patients also have a prolon&ed bleedin& time" b!t this is less constant than the actor 1IIIA3 red!ction( A &iven patient ma% have an abnormal bleedin& time on one occasion and a normal bleedin& time on another( The level o actor 1III*related anti&en ' actor 1IIIAA&, is disproportionatel% lo#er than that o actor 1IIIA3" and ristocetin ails to ca!se platelet a&&re&ation in abo!t ;8 percent o patients #ith the disease( The vast ma/orit% o patients have a prolon&ed activated partial thromboplastin time 'a.TT,( 3linical Mani estations The mani estations o bleedin& !s!all% are mild and o ten are overloo$ed !ntil tra!ma or the stress o s!r&ical treatment ma$es them apparent( A care !l clinical histor% is there ore o &reat importance in these patients( Spontaneo!s mani estations o ten are limited to bleedin& into the s$in or mild m!co!s membrane bleedin&( Epistaxis and menorrha&ia have been relativel% common in the a!thor=s experience( Serio!s bleedin& a ter dental extractions and tonsillectom% also are not !ncommon( Fatal bleedin& rom the &astrointestinal tract has been described( Treatment Treatment is directed at correctin& the bleedin& time and actor 1III EAv7F 'the von 7illebrand actor,( Onl% cr%oprecipitate is reliabl% e ective( L%ophili6ed concentrates o actor 1IIIA3 lac$ the re0!ired actor 1III EAv7F( Ke#er actor 1III concentrates have a !ll complement o v7F( Bleedin& time is corrected #ith cr%oprecipitate +8 to 98 !nits:$& o bod% #ei&ht:+2 h( Eeplacement therap% sho!ld be be&!n + da% be ore a s!r&ical proced!re( Aspirin m!st be avoided or +8 da%s be ore an elective operation( -!ration o treatment sho!ld be the same as that described or the patient #ith classical hemophilia( Intraveno!s hi&h*dose &*&lob!lin has been !sed s!ccess !ll% to treat an ac0!ired t%pe o von 7illebrand=s disease associated #ith m%eloproli erative disorders" le!$emias" and l%mphomas( An analo&!e o the antidi!retic hormone vasopressin" --A1. 'desmopressin acetate," administered intraveno!sl% temporaril% ' or + to 2 h, increases v7FAA&" ristocetin co actor" and 1IIIA3 and shortens the bleedin& time( -esmopressin ma% ind!ce thromboc%topenia and release tiss!e plasmino&en activator( Rare (eficiencies of Coagulation )actors Factor 4I 'plasma thromboplastin antecedent L.TA M, de icienc% 'Eosenthal=s s%ndrome, is a mild disorder occ!rrin& mainl% in patients o Ne#ish ancestr%( .atients ma% !nder&o ma/or proced!res #itho!t si&ni icant bleedin&( Fresh ro6en plasma is therape!tic( Factor 1 'proaccelerin, de icienc% 'parahemophilia, is rareD si&ni icant bleedin& !s!all% occ!rs in homo6%&otes( Excessive bleedin& is characteristicall% associated #ith actor levels lo#er than + percent o normal( Administration o resh ro6en plasma to raise the level to 25 percent o normal is s! icient( Factor 1II 'proconvertin, de icienc% also is associated #ith excessive operative bleedin& in homo6%&o!s patients( Administration o ban$ed plasma to raise the actor level above +8 percent o normal provides ade0!ate hemostasis( Factor 4 'St!art*.ro#er, de icienc% is associated #ith am%loidosis and #ith amilial carotid bod% t!mors( Fro6en or normal plasma is therape!tic(

Factor II (prothrombin) deficiencyA * Eare and * 3an be corrected #ith plasma in !sion levels &reater than )8I o normal( VII deficiency: Altho!&h the prothrombin time '.T, #ill reveal actor 1II de icienc%" it cannot be !sed as a &!ide to therap% beca!se it remains abnormal #hen ade0!ate levels o actor 1II are achieved( Patients with factor VII deficiency have normal PTT and thrombin time (TT). Speci ic assa%s can de ine an% o these de iciencies( 1itamin C therap% is ine ective in raisin& levels o actors II" 1" 1II" 4" and 4I( 7hen the trans !sion pro&rams o!tlined earlier or de icienc% o the prothrombin &ro!p o actors ' actors II" 1" 1II" and 4, are emplo%ed" the one*sta&e prothrombin time does not ret!rn to normal( Eather" a one*sta&e .T sli&htl% less than t#ice the control val!e is achieved( This is s! icient to res!lt in normal hemostasis( O the o!r ?prothrombin@ actors" onl% actor 1 m!st be provided as resh or reshl% ro6en plasma( Stored plasma is e0!all% e ective as therap% or actors II" 1II" and 4( In erited )i*rinogen A*normalities Incl!ded in this cate&or% are patients #ith con&enital a ibrino&enemia" h%po ibrino&enemia" and d%s ibrino&enemia( Fe#er than 288 cases o a ibrino&enemia have been reported( This disorder is ascribed to an a!tosomal recessive mode o inheritance( The a ected individ!als are pres!mabl% homo6%&o!s or the trait( Bleedin& time ma% be mar$edl% prolon&ed in some patients beca!se ibrino&en is re0!ired or platelet a&&re&ation( 3onventional methods or meas!rin& ibrino&en in the plasma &ive a 6ero val!e" b!t imm!nolo&ic techni0!es ma% detect trace amo!nts o a ibrino&en*li$e protein( .atients have an inde initel% prolon&ed #hole*blood coa&!lation time" #hich can be corrected b% the addition o ibrino&en( The de icienc% !s!all% is less a clinical problem than is classical hemophilia" ho#ever( Bleedin& !s!all% be&ins earl% in li e" and bleedin& rom the !mbilical cord is a characteristic s%mptom( Bleedin& ma% ollo# operations" dental extraction" and tra!ma" b!t the most eared complication is intracranial bleedin& a ter minor in/!r% to the head( Less pro o!nd inherited de iciencies o ibrino&en have been observed and cate&ori6ed as con&enital h%po ibrino&enemia( T#o &ro!ps o h%po ibrino&enemic patients have been di erentiatedA those #ith ibrino&en val!es belo# 58 m&:dL and those #ith hi&her levels( The clinical mani estations depend on the ibrino&en concentration( Another con&enital disorder is d%s ibrino&enemia" in #hich there are str!ct!ral de ects in the ibrino&en molec!le( Both h%po ibrino&enemia and d%s ibrino&enemia have a dominant mode o inheritance( -%s ibrino&enemic patients are re0!entl% as%mptomatic b!t ma% have moderate or severe bleedin& associated #ith an operation( The% have a propensit% or thromboembolic disorders and have a hi&her incidence o #o!nd dehiscence a ter operative intervention( The thrombin clottin& time is dia&nostic or this &eneral cate&or% o abnormalities" b!t de inition o the precise abnormalit% re0!ires a series o complex laborator% st!dies( Treatment

Altho!&h the hemostaticall% optimal level o ibrino&en is not $no#n" a level &reater than +88 m&:dL is &enerall% re0!ired d!rin& an operation( The patient=s ibrino&en level sho!ld be raised above this be ore the proced!re( S!bstit!tion therap% ma% be e ected b% the in !sion o resh ro6en plasma or cr%oprecipitate( In order to achieve a ibrino&en level near +88 m&:dL or 29 h" an initial dose o 28 to 25 m& ibrino&en:$& o bod% #ei&ht sho!ld be administered" ollo#ed b% one*third the initial amo!nt &iven on a dail% basis thro!&ho!t the postoperative period( B!t appropriate corrections m!st be based on act!al ibrino&en meas!rements( Kormal ibrino&en concentration sho!ld be maintained !ntil #o!nd healin& is sho#n to be ade0!ate( Congenital )actor +III (eficiency This rare a!tosomal recessive disorder is mani est b% !mbilical bleedin& in the ne#born and slo# #o!nd healin& a ter an operation( In &eneral" most o the bleedin& mani estations are mild" b!t intracranial bleedin& ma% occ!r as a conse0!ence o minor tra!ma( Imm!nolo&ic assa%s have demonstrated de icienc% o the protein( Therap% is accomplished #ith resh ro6en plasma" cr%oprecipitate" or actor 4III concentrates( 7ith ma/or bleedin&" or accompan%in& s!r&ical intervention" the desired concentration o the recipient=s plasma is 8() to 8(5 mmol:mL( 7ith minor bleedin& or as proph%laxis" a level &reater than 8(85 mmol:mL is all that is re0!ired(

AC,-IRE( HE'#STATIC (E)ECTS

.latelet Abnormalities Thromboc%topenia is the most common abnormalit% o hemostasis that res!lts in bleedin& in the s!r&ical patient( The patient ma% have a red!ced platelet co!nt as a res!lt o a variet% o disease processes" s!ch as idiopathic thromboc%topenic p!rp!ra" thrombotic thromboc%topenic p!rp!ra" and s%stemic l!p!s er%thematos!s" or secondar% h%persplenism and splenome&al% o sarcoid" Ga!cher=s disease" l%mphoma" and portal h%pertension( In these circ!mstances the marro# !s!all% demonstrates a normal or increased n!mber o me&a$ar%oc%tes( B% contrast" #hen thromboc%topenia occ!rs in patients #ith le!$emia or !remia" and in patients on c%totoxic therap%" there is &enerall% a red!ced n!mber o me&a$ar%oc%tes in the marro#( Thromboc%topenia ma% occ!r ac!tel% as a res!lt o massive blood loss ollo#ed b% replacement #ith stored blood( Exchan&e o one blood vol!me '++ !nits in a ;5*$& man, decreases the platelet co!nt rom approximatel% 258"888:mm) to approximatel% G8"888:mm)( Thromboc%topenia ma% be ind!ced ac!tel% b% the administration o heparin and ma% be associated #ith thrombotic and hemorrha&ic complications( This sit!ation" #hich is tho!&ht to have an imm!nolo&ic basis" has been reported in 8(B percent o patients receivin& heparin( The lo#est platelet co!nts occ!r a ter 9 to +5 da%s o treatment in patients &iven heparin or the irst time and a ter 2 to < da%s in those &iven s!bse0!ent co!rses( Thromboc%topenia is o ten accompanied b% impaired platelet !nction( Impaired a&&re&ation a ter the addition o A-. has been demonstrated in patients receivin& a blood trans !sion o more than +8 !nits( Fremia ma% be associated #ith increased bleedin& time and impaired a&&re&ation" #hich can be corrected b% hemodial%sis or peritoneal dial%sis( -e ective a&&re&ation and platelet secretion can occ!r in patients #ith thromboc%themia" pol%c%themia vera" or m%elo ibrosis( A variet% o dr!&s inter ere #ith platelet !nction" incl!din& aspirin" indomethacin" ib!pro en"

dip%ridamole" phenothia6ines" penicillins" chelatin& a&ents" lidocaine" dextran" beta* adrener&ic bloc$ers" nitro&l%cerin" !rosemide" and antihistamines( The presence and extent o thromboc%topenia can be de ined rapidl% b% a platelet co!nt( In &eneral" B8"888 platelets:mm) is ade0!ate or normal hemostasis" b!t i there is associated platelet d%s !nction" there ma% be a poor correlation bet#een the platelet co!nt and the extent o bleedin&( The template bleedin& time is the most reliable in vivo test o platelet !nction( 7hen thromboc%topenia is present in a patient or #hom an elective operation is bein& considered" it is mana&ed on the basis o ho# m!ch the platelet co!nt is red!ced and the ca!se o the red!ction( A co!nt &reater than 58"888:mm) re0!ires no speci ic therap%( I thromboc%topenia is ca!sed b% ac!te alcoholism" dr!& e ect" or viral in ection" the platelet level #ill ret!rn to near normal #ithin + to ) #ee$s( Occasionall%" severe thromboc%topenia ma% be secondar% to vitamin B+2 or olic acid de icienc%" in #hich case it is associated #ith a me&aloblastic bone marro#( This condition &enerall% occ!rs 2 to ) %ears a ter total &astrectom% or in association #ith severe intestinal malabsorption( In either case" s!ppl%in& the appropriate n!trient #ill correct the thromboc%topenia in 2 to ) da%s( I the patient has idiopathic thromboc%topenia or l!p!s er%thematos!s" and a platelet co!nt less than 58"888:mm)" an attempt to raise the platelet co!nt #ith steroid therap% or plasmapheresis ma% prove s!ccess !l 'see 3hap( )*+,( The administration o platelet trans !sions in these patients #ith the spleen in place is &enerall% ine ective( The administration o &*&lob!lin ma% temporaril% increase the platelet co!nt( Splenectom% alone sho!ld not be per ormed to correct the thromboc%topenia associated #ith splenome&al% secondar% to portal h%pertension( .roph%lactic platelet administration as a ro!tine accompaniment to massive blood trans !sion is not re0!ired or indicated to prevent a hemostatic de ect( .latelet pac$s are administered preoperativel% to rapidl% increase the platelet co!nt in s!r&ical patients #ith thromboc%topenia d!e to marro# depression or in association #ith massive bleedin& and replacement #ith ban$ed blood( Special platelet trans !sion sets are !sed to red!ce the loss o platelets d!e to adherence( One !nit o platelet concentrate contains approximatel% 5(5 H +8+8 platelets and #o!ld be expected to increase the circ!latin& platelet co!nt b% abo!t +8 H +8<:L in the avera&e ;8*$& person( Hence a trans !sion o 9 to G pool platelet concentrates sho!ld raise the co!nt b% 98 to G8 H +8<:L and sho!ld provide ade0!ate hemostasis" as doc!mented b% bleedin& time and control o the hemorrha&ic mani estations( Fever" in ection" hepatosplenome&al%" and the presence o antiplatelet alloantibodies decrease the e ectiveness o platelet trans !sions( In patients re ractor% to standard platelet trans !sions" the !se o h!man l%mphoc%te anti&en 'HLA,*compatible platelets co!pled #ith special processors has proved e ective( .latelet a&&re&ometr% has been applied to screenin& or potential donors( Ac.uired Hy/ofi*rinogenemia -e ibrination S%ndrome The lar&est proportion o patients #ith ibrino&en*related problems o s!r&ical concern are in this &ro!p( The ibrino&en de icienc% rarel% is an isolated de ect" as

thromboc%topenia and actors II" 1" 1II" 1III" and 4 de iciencies o variable severit% !s!all% accompan% this state( The ma/orit% o patients #ith ac0!ired h%po ibrino&enemia s! er rom intravasc!lar coa&!lation" more properl% $no#n as de ibrination s%ndrome or cons!mptive coa&!lopath%" and it is to this &ro!p o patients that the term disseminated intravasc!lar coa&!lation '-I3, has been applied( S%stemic bleedin&" ho#ever" dominates the clinical mani estationsD thrombi are rarel% o!nd at a!tops%( The s%ndrome" no# reco&ni6ed #ith increasin& re0!enc%" is ca!sed b% the introd!ction o thromboplastic materials into the circ!lation( Beca!se this material is o!nd in most tiss!es" man% disease processes ma% activate the coa&!lation s%stem( Evidence o the thrombotic process incl!des patch% necrosis o the s$in" hemat!ria and oli&!ria" con !sion d!e to cerebral ischemia" &astrointestinal bleedin&" and hemorrha&e into the adrenal cortex ca!sin& ac!te onset o h%potension( The hemorrha&ic disasters o the perinatal period" e(&(" retained dead et!s" premat!re separation o the placenta" and amniotic l!id embol!s" are d!e primaril% to this pathoph%siolo&ic mechanism( The hemorrha&ic state that ollo#s hemol%tic trans !sion reaction is also related to this process( -e ibrination has been observed as a complication o extracorporeal circ!lation" head tra!ma" m!cin*prod!cin& and disseminated carcinoma" l%mphomas" thrombotic thromboc%topenia" ric$ettsial in ection" sna$ebite" b!rns" aortic s!r&er%" and shoc$ rom an% ca!se( Eelease o thromboplastic material has lon& been a reco&ni6ed complication o &ram* ne&ative sepsis and has been attrib!ted to the e ects o circ!latin& endotoxin on platelets( Septicemia ca!sed b% &ram*positive or&anisms ma% also be associated #ith -I3( The di erentiation o -I3 #ith secondar% protective ibrinol%sis rom primar% ibrinol%tic states can be extremel% di ic!lt beca!se the TT is prolon&ed in both cases" as is the .T and .TT( There is no laborator% test to con irm or excl!de the dia&nosis( The combination o a lo# platelet co!nt" a positive plasma protamine test indicatin& the presence o ibrin monomer* ibrino&en complexes in the plasma" and red!ced ibrino&en accompanied b% increased ibrin de&radation prod!cts vie#ed in the context o the patient=s !nderl%in& disease is hi&hl% s!&&estive o the dia&nosis( The ibrino&en level is &enerall% belo# +88 m&:dL #hen there is si&ni icant di !se bleedin&( Treatment The most important acets o treatment are relievin& the patient=s ca!sative primar% medical or s!r&ical problem and maintainin& ade0!ate capillar% lo#( The !se o intraveno!s l!ids to maintain vol!me" and sometimes vasodilators to open the arterioles" is indicated( I blood lo# de icienc% is related to the inabilit% o a dama&ed heart to p!mp" the !se o dr!&s s!ch as di&italis or isoproterenol ma% be indicated( 1iscosit% ma% be a ected b% an increased hematocrit concentration" and there ore a plasma expander ma% be bene icial( I there is active bleedin&" hemostatic actors sho!ld be replaced #ith resh ro6en plasma" #hich is !s!all% s! icient to correct the h%po ibrino&enemiaD cr%oprecipitate" #hich also provides ibrino&en '258 m&:+8 mL,D and platelet concentrates( There is little evidence that this replacement therap% #ill ? !el the ire@ and accelerate the pathoph%siolo&ic process( Most st!dies sho# that heparin is not help !l in ac!te orms o -I3" b!t the dr!& is indicated or p!rp!ra !lminans or veno!s thromboembolism(

Fibrinol%tic inhibitors s!ch as e *aminocaproic acid 'EA3A, ma% be !sed to bloc$ the acc!m!lation o de&radation prod!cts b!t are dan&ero!s i the thrombotic process is still active( The% sho!ld not be !sed #itho!t prior e ective antithrombotic treatment #ith heparin( )i*rinolysis The ac0!ired h%po ibrino&enemic state in the s!r&ical patient also can be d!e to patholo&ic ibrinol%sis( This ma% occ!r in patients #ith metastatic prostatic carcinoma" shoc$" sepsis" h%poxia" neoplasia" cirrhosis" and portal h%pertension and in those patients on extracorporeal b%pass( The patho&enesis o this bleedin& disorder is complex( Secondar% to shoc$ or h%poxia" a release o excessive plasmino&en activator into the circ!lation occ!rs( This is tho!&ht to consist o endo&eno!s $inases that can be released rom vasc!lar endotheli!m and other tiss!es( .harmacolo&ic activation o plasmino&en also occ!rs #ith p%ro&ens" epinephrine" nicotinic acid" and acet%lcholine( Electric shoc$ and pne!moencephalo&raph% have also been reported to ca!se activation( .atients #ith cirrhosis and portal h%pertension have a diminished abilit% to clear normal amo!nts o plasmino&en activator rom the blood( S! icient !ro$inase to ca!se ibrinol%sis can be released d!rin& operations on the prostate( The administration o exo&eno!s ibrinol%sins can also res!lt in di !se bleedin&( In addition to the red!ction in levels o plasma ibrino&en" dimin!tion o actors 1 and 1III also occ!rs" since the% also serve as s!bstrates or the en6%me plasmin( Thromboc%topenia is not an accompaniment o the p!rel% ibrinol%tic state( .ol%meri6ation o ibrin monomers" a step in normal ibrin ormation" is inter ered #ith b% the proteol%tic resid!e o ibrino&en and ibrin( The ibrin and ibrino&en brea$do#n prod!cts !s!all% disappear rom the circ!lation in a matter o ho!rs( The #hole blood clot l%sis time de ines increased ibrinol%tic activit% i a non* anticoa&!lated blood sample l%ses in a test t!be in less than G h( A e!&lob!lin l%sis time o 28 min or less provides a more rapid assessment( Treatment The s!ccess !l treatment o the !nderl%in& disorder !s!all% is ollo#ed b% rapid spontaneo!s recover%" since the severit% o ibrinol%tic bleedin& is dependent !pon the concentration o brea$do#n prod!cts in the circ!lation( EA3A" #hich is a s%nthetic amino acid" inter eres #ith ibrinol%sis b% inhibitin& plasmino&en activation( The dr!& ma% be administered intraveno!sl% or orall%( An initial dose o 5 & or the avera&e* si6ed ad!lt is ollo#ed b% another + & ever% + to 2 h !ntil the hemorrha&ic state s!bsides( Treatment rarel% is re0!ired or more than 2 or ) da%s( N!st as the administration o EA3A in a patient #ith cons!mptive coa&!lopath% is potentiall% dan&ero!s" the administration o heparin in the patient #ho has a primar% patholo&ic ibrinol%sis is ra!&ht #ith dan&er( Th!s ine clinical /!d&ment and reliable laboratories are needed to avoid therape!tic complications( Eestraint is recommended in de initive treatment o ibrinol%sis and cons!mptive coa&!lopath%" and meas!res desi&ned to reverse the shoc$ and stabili6e the patient are emphasi6ed( 'yelo/roliferati0e (iseases

The pol%c%themic patient" partic!larl% #ith mar$ed thromboc%tosis" is a ma/or s!r&ical ris$( Operations sho!ld be considered onl% or the most &rave s!r&ical emer&enc%( I possible" the operation sho!ld be de erred !ntil medical mana&ement has e ected normal blood vol!me" hematocrit level" and platelet co!nt( Spontaneo!s thrombosis is a complication o pol%c%themia vera and can be explained in part b% increased blood viscosit%" increased platelet co!nt" and increased tendenc% to#ard stasis( .aradoxicall%" a si&ni icant tendenc% to#ard spontaneo!s hemorrha&e also is noted in these patients( M%eloid metaplasia re0!entl% represents part o the nat!ral histor% o pol%c%themia vera( Approximatel% 58 percent o patients #ith m%eloid metaplasia are postpol%c%themic( There is evidence s!&&estin& 0!alitative platelet abnormalities in these patients( Abnormalities in platelet actor ) release and in platelet a&&re&ation #ith A-. have been demonstrated( Treatment Thromboc%tosis can be red!ced b% the care !l administration o al$%latin& a&ents s!ch as b!s!l an or chloramb!cil( Elective s!r&ical proced!res sho!ld be dela%ed #ee$s to months a ter instit!tion o treatment( Ideall% the hematocrit level sho!ld be $ept belo# 9G percent and the platelet co!nt !nder 988"888:mm)( Be ore operation" a thoro!&h laborator% examination o hemostatic !nction sho!ld be cond!cted( 7hen an emer&enc% proced!re is re0!ired" the er%thremic and thromboc%totic states sho!ld be red!ced b% phlebotom% and replacement o the blood removed #ith lactated Ein&er=s sol!tion( The operation" at all times" m!st be per ormed astidio!sl%(

#t er (iseases
Illnesses res!ltin& in severe impairment o hepatic !nction ma% limit s%nthesis o plasma actors essential to normal coa&!lation( The patient #ith advanced cirrhosis ma% be lac$in& in actors o the prothrombin complex 'II" 1" 1II" 4," as #ell as actor 4III( In addition" there ma% be increased ibrinol%sis as a res!lt o ail!re o the liver to clear plasmino&en activators( Other diseases" s!ch as macro&lob!linemia" ma% be associated #ith the abnormal prod!ction o proteins that coat the platelets and inter ere #ith their !nction( M!ltiple m%eloma and the disorders associated #ith the excessive prod!ction o cr%o&lob!lins ma% also bind certain blood*clottin& actors( Anticoa&!lation and Bleedin& Spontaneo!s bleedin& ma% be a complication o anticoa&!lant therap% #ith either heparin or the co!marin and indanedione derivatives( The incidence o bleedin& complications related to heparin is red!ced #ith a contin!o!s in !sion techni0!e" re&!latin& the .TT bet#een B8 and +88 s 'controlA )8 to )5 s,( An exa&&erated response to oral anticoa&!lants ma% occ!r i dietar% vitamin C is inade0!ate( The anticoa&!lant e ect o the co!marins is consistentl% red!ced in patients receivin& barbit!rates" and increased co!marin re0!irements have also been doc!mented in patients ta$in& contraceptives" other estro&en*containin& compo!nds" corticosteroids" and adrenocorticotropic hormone 'A3TH,( There ore" red!ced anticoa&!lant dosa&e sho!ld be instit!ted a ter discontin!ance o an% o these dr!&s( Medications $no#n to increase the e ect o oral anticoa&!lants incl!de phen%lb!ta6one" the cholesterol*

lo#erin& a&ent clo ibrate" anabolic steroids 'norethandrolone," d*th%roxine" &l!ca&on" 0!inidine" and a variet% o antibiotics( Fnexplained bleedin& in medical and paramedical personnel occasionall% is d!e to sel *ind!ced anticoa&!lation( The onset o hemat!ria or melena in the patient receivin& anticoa&!lants sho!ld be investi&ated" since it has been sho#n that anticoa&!lants ma% !nmas$ !nderl%in& t!mors( .atients #ith bleedin& secondar% to anticoa&!lation ma% present onl% #ith epistaxis" &astrointestinal hemorrha&e" or hemat!ria( .h%sical examination" ho#ever" almost al#a%s reveals other si&ns o bleedin& s!ch as ecch%moses" petechiae" or hematoma( Bleedin& secondar% to anticoa&!lation therap% is not an !ncommon ca!se o rect!s sheath hematoma" sim!latin& appendicitis" and intram!ral intestinal or retroperitoneal hematoma( S!r&ical intervention ma% prove necessar% in patients receivin& anticoa&!lation therap%( Increasin& experience s!&&ests that s!r&ical treatment can be !nderta$en #itho!t discontin!in& the anticoa&!lant pro&ram( The ris$ o thrombotic complications reportedl% is increased #hen anticoa&!lation therap% is discontin!ed s!ddenl%( I so" this ma% not be related to #hat has been called the ?rebo!nd phenomenon@ b!t ma% represent an event in a patient #ho has an !nderl%in& thrombotic tendenc%( 7hen the clottin& time is less than 25 min in the heparini6ed patient or #hen the .T is &reater than 28 percent o normal in a patient on a co!marin dr!&" reversal o anticoa&!lant therap% ma% not be necessar%( Metic!lo!s s!r&ical techni0!e is mandator%" and the patient m!st be observed closel%( 3ertain s!r&ical proced!res sho!ld not be per ormed in the ace o anticoa&!lation( In sites #here even minor bleedin& can ca!se &reat morbidit%" e(&(" the central nervo!s s%stem and the e%e" anticoa&!lants sho!ld be discontin!ed and" i necessar%" reversed( Beca!se o the added problem o local ibrinol%sis" prostatic s!r&ical treatment sho!ld not be carried o!t in a patient on anticoa&!lants( .roced!res re0!irin& blind needle introd!ction sho!ld be avoided( -eaths have been reported a ter s%mpathetic bloc$ or peripheral vasc!lar disease in patients receivin& anticoa&!lation( Emer&enc% operation occasionall% is necessar% in patients #ho have been heparini6ed as treatment or deep veno!s thrombosis( The irst step in mana&in& these patients is discontin!ation o heparinD this ma% be s! icient i the operation can be dela%ed or several ho!rs( For more rapid reversal" + m& o protamine s!l ate or ever% +88 !nits o heparin most recentl% administered is immediatel% e ective( For each ho!r that has elapsed since the last heparin dose" the amo!nt o protamine sho!ld be halved( The ormation o both extrinsic and intrinsic prothrombinase can be retarded" prolon&in& the one*sta&e .T test and the .TT test( Some patients exhibit the phenomenon o ?heparin rebo!nd@ a ter apparentl% ade0!ate heparin ne!trali6ation #ith protamineD prolon&ation o the clottin& time rec!rs a ter ade0!ate postoperative anta&onism o the heparin" #hich can contrib!te to postoperative bleedin&( In the a!thor=s experience" this is the ma/or ca!se o ?!nexplained@ postoperative bleedin& a ter cardiac and vasc!lar s!r&ical proced!res( Activation o ibrinol%sis and thromboc%topenia ma% also contrib!te to this problem( Bleedin& in re0!entl% is related to h%poprothrombinemia i the prothrombin concentration is &reater than +5 percent( In the elective s!r&ical patient receivin& co!marin*derivative therap% s! icient to e ect anticoa&!lation" the dr!& can be

discontin!ed several da%s be ore operation and the prothrombin concentration then chec$ed( A level &reater than 58 percent is considered sa e( I emer&enc% s!r&ical treatment is re0!ired" parenteral in/ection o vitamin C can be !sed( Since the reversal e ect ma% ta$e B h" trans !sion o #hole blood or" pre erabl%" reshl% ro6en plasma ma% be re0!ired( .arenteral administration o vitamin C also is indicated in elective s!r&ical treatment o patients #ith biliar% obstr!ction" malabsorption" and h%poprothrombinemia( The dr!& sho!ld res!lt in a normal .T( B% contrast" i the h%poprothrombinemia is related to hepatocell!lar d%s !nction" vitamin C therap% is ine ective and sho!ld not be prolon&ed over + #ee$ i no response is noted( 1itamin C is an oxidant" and one m!st be a#are that patients #ith red cell en6%me de iciencies ma% s!stain hemol%sis a ter its administration( Cardio/ulmonary By/ass Overheparini6ation" heparin rebo!nd" inade0!ate protamine ne!trali6ation" protamine excess" and thromboc%topenia all have been indicted as ca!ses o excessive bleedin& in patients !nder&oin& cardiop!lmonar% b%pass( -I3 is di ic!lt to doc!ment in most patients( The predisposin& actors that seem to be associated #ith excessive bleedin& are prolon&ed per !sion times" prior !se o oral anticoa&!lants" c%anotic heart disease" h%pothermia" and prior !se o antiplatelet dr!&s( It is c!rrentl% believed that the t#o actors most important in tri&&erin& excessive bleedin& associated #ith cardiop!lmonar% b%pass are excessive ibrinol%sis and platelet !nction de ects" #ith the latter the more important element( The laborator% eval!ation o patients #ith bleedin& sho!ld incl!de .T" .TT" complete blood co!nt '3B3, and platelet co!nt" peripheral blood smear examination" and meas!rement o ibrin de&radation prod!cts( Heparin assa% can indicate the heparin levelD plasmino&en and plasmin assa%s are also available( The mana&ement o cardiop!lmonar% b%pass hemorrha&e sho!ld incl!de the empiric administration o B to G !nits o platelet concentrates as rapidl% as possible( I h%perheparinemia is believed to be the ma/or actor" 25 percent o the calc!lated dose o protamine sho!ld be administered and repeated ever% )8 to B8 min !ntil the bleedin& ceases( I there is laborator% evidence o excess ibrinol%sis" EA3A sho!ld be &iven at an initial dose o 5 to +8 & ollo#ed b% + to 2 &:h !ntil bleedin& ceases( EA3A ma% be associated #ith ventric!lar arrh%thmia" h%potension" and h%po$alemia( Aprotinin" a protease inhibitor that acts as an anti ibrinol%tic a&ent" has been sho#n to red!ce trans !sion re0!irements associated #ith cardiac s!r&er% and orthotopic liver transplantation( -esmopressin acetate is also e ective in red!cin& blood loss d!rin& cardiac s!r&er%(

TESTS #) HE'#STASIS A$( B&##( C#A%-&ATI#$ 1TAB&E 3-32

The most important assessment o hemostasis is a care !l histor% and ph%sical examination( Onl% the histor% can indicate #hether the patient has a hemorrha&ic diathesis( Eather than as$in& a patient i he or she is a ?bleeder"@ speci ic 0!estions sho!ld be as$ed( These sho!ld incl!de 0!eries to determine #hether there #as !nto#ard bleedin& d!rin& a ma/or s!r&ical proced!re" or i there #as an% bleedin& a ter a minor operation s!ch as tonsillectom%" circ!mcision" or dental extraction" or i spontaneo!s bleedin& #as ever experienced( I there is an% s!&&estion o a bleedin&

diathesis" the a&e o onset and amil% histor% is help !l to determine #hether a hereditar% or ac0!ired de ect sho!ld be investi&ated( O!estions sho!ld !ncover a histor% o expos!re to toxic a&ents" oral anticoa&!lants" and dr!&s that mi&ht inter ere #ith hemostasis( Aspirin and ib!pro en are t#o o the more common medications in this cate&or%( A histor% o a recent re&imen o broad*spectr!m antibiotics sho!ld alert the ph%sician to the possibilit% o a de icienc% o vitamin C*dependent clottin& actors( .atients #ith mali&nant disease ma% have a variet% o abnormalities" s!ch as compensated intravasc!lar coa&!lation and increased circ!latin& ibrin complexes( 3omplex hemostatic disorders ma% accompan% liver and renal ail!re( Platelet Count Beca!se thromboc%topenia is the most common abnormalit% o hemostasis in the s!r&ical patient" determination o the level o circ!latin& platelets is a critical screenin& test( -irect en!meration o blood platelets can be accomplished 0!ite acc!ratel%( Spontaneo!s bleedin& onl% rarel% can be related to thromboc%topenia #ith platelet co!nts &reater than 98"888:mm)( .latelet co!nts o B8"888 to ;8"888:mm)!s!all% are s! icient to provide ade0!ate hemostasis a ter tra!ma or s!r&ical proced!res i other hemostatic actors are normal( An abnormal co!nt sho!ld be con irmed b% inspection o the blood smear( 7hen an area is examined #here the red blood cells displa% their c!stomar% central pallor and #here e# o the red blood cells overlap one another" +5 to 28 platelets per oil immersion ield sho!ld be noted( I the blood is not anticoa&!lated be ore the smear is prepared" as man% as hal o these ma% be in cl!mps o three or o!r platelets( A #ell*stained blood smear that ails to displa% more than three or o!r platelets in at least ever% other oil immersion ield can be considered si&ni icantl% thromboc%topenic( In this sit!ation" the patient=s platelet co!nt &enerall% is less than ;5"888:mm)( Blood smears that m!st be searched beca!se platelets appear in onl% ever% o!r or ive oil immersion ields !s!all% represent platelet co!nts o e#er than 98"888:mm)( I coverslip smears have been prepared" the coverslips al#a%s sho!ld be mo!nted as matched pairs( .latelets occasionall% stic$ to one o the coverslips" and examination o both #ill obviate a alse impression o thromboc%topenia( Li&htl% stained blood smears ma% appear thromboc%topenic i the platelets are not prominent eno!&h to attract the examiner=s attention( Inspection o the blood smear has the additional advanta&e o permittin& the examiner to identi % other patholo&ic eat!res that ma% have meanin& in the care o the patient( The presence o n!cleated red blood cells or abnormal #hite cells can provide in ormation important to the dia&nosis( The presence o &iant platelets or lar&e ra&ments o me&a$ar%oc%te c%toplasm #ill alert the examiner to possible patholo&ic platelet !nction( Bleeding Time Bleedin& time provides an assessment o both the interaction bet#een platelets and a dama&ed blood vessel and the ormation o the platelet pl!&( Bleedin& time ma% be abnormal in patients #ith thromboc%topenia" 0!alitative platelet disorders" von 7illebrand=s disease" and also in some patients #ith actor 1 de icienc% or h%po ibrino&enemia( Aspirin in&ested #ithin + #ee$ #ill a ect the res!lts( The tests can be per ormed b% a variet% o techni0!es that do not have the same normal times or the same de&ree o acc!rac%( The -!$e method o meas!rin& bleedin& time"

per ormed b% incisin& the most dependent portion o the earlobe and meas!rin& the time lapse !ntil the bleedin& ceases" normall% sho!ld not exceed )P min( The modi ied Iv% method has an !pper limit o normal o ; min( Other Tests o .latelet F!nction .latelet a&&re&ation can be assessed #ith a variet% o ind!ction a&ents to !ncover speci ic abnormalities( The res!lts ma% be a ected b% venip!nct!re" blood pH" temperat!re" d!ration o stora&e" and the e0!ipment itsel ( The de&ree o abnormalit% detected b% the test is not correlated #ith the extent o !nto#ard bleedin&( Aspirin is the most common ca!se o platelet a&&re&ation abnormalit%( Fail!re o platelets to a&&re&ate #ith the addition o arachidonic acid indicates an aspirin e ect( The ail!re o platelets to a&&re&ate #ith A-." epinephrine" and colla&en is characteristic o Glan6mann=s thrombasthenia( Abnormal platelet a&&re&ation #ith ristocetin occ!rs in von 7illebrand=s disease and in Bernard*So!lier s%ndrome( The abilit% o the platelets to liberate platelet actor ) 'phospholipid," essential in tin% amo!nts at several sta&es o the blood*clottin& process 'see Fi&( )*)," also can be meas!red( Impairment o platelet actor ) release has been reported in conditions described as thromboc%topathia( This de ect can represent a primar% disease entit%" b!t similar impairment has been described as a secondar% phenomenon in !remia and liver disease( The inabilit% o the platelet to ma$e platelet actor ) available or the clottin& process ma% be a part o a more !ndamental s!r ace membrane abnormalit%( The abilit% o A-." epinephrine" colla&en" and arachidonic acid to liberate serotonin" b*thrombo&lob!lin" or platelet actor 9 can be meas!red( Prot rom*in Time This test meas!res the speed o the events described earlier as the extrinsic path#a% o blood coa&!lation( A tiss!e so!rce o procoa&!lant 'thromboplastin," a lipoprotein" is added #ith calci!m to an ali0!ot o citrated plasma and the clottin& time determined( The laborator% sho!ld establish a normal dil!tion c!rve and normal val!es dail%( The .T #ill be prolon&ed in the presence o even min!te amo!nts o heparin( The presence o heparin" b% its antithrombin action" #ill arti iciall% prolon& the clottin& time o the mixt!re so that it appears that the prothrombin complex is lo#( Accordin&l%" an acc!rate prothrombin determination cannot be carried o!t in a patient receivin& anticoa&!lation treatment #ith heparin !ntil the heparin has disappeared rom the plasma( This sho!ld be at least 5 h a ter the last intraveno!s dose( The amo!nt o heparin !sed to maintain patenc% o an intraveno!s line is !s!all% ins! icient to alter the .T( The !se o tiss!e procoa&!lants in the test eliminates the roles o actors 1III" I4" 4I" 4II" and platelets( .roperl% done" the test #ill detect de iciencies o actors II" 1" 1II" 4" and ibrino&en( The one*sta&e .T is the pre erred method o controllin& anticoa&!lation #ith the co!marin and indanedione dr!&s( .artial Thromboplastin Time The .TT is a screenin& test or the intrinsic clottin& path#a%( The in vitro clottin& s%stem no# is sensitive to actors 1III" I4" 4I" and 4II" as #ell as the actors normall% detected b% the one*sta&e .T( The ran&e o normal #ith this test varies #ith the prod!ct !sed( The patient=s plasma m!st be compared #ith a normal control sample(

The .TT" #hen !sed in con/!nction #ith the one*sta&e .T" can help to place a clottin& de ect in the irst or second sta&e o the clottin& process( I the .TT is prolon&ed and the one*sta&e .T is normal" actors 1III" I4" 4I" or 4II ma% be de icient( I the .TT is normal and the one*sta&e .T is prolon&ed" a sin&le or m!ltiple de icienc% o actors II" 1" 1II" or 4 or o ibrino&en ma% be present( The .TT is also abnormal in the presence o circ!latin& anticoa&!lants or d!rin& heparin administration( It ma% be prolon&ed #hen heparin is !sed to maintain the patenc% o an intraveno!s line( The sensitivit% o the test is s!ch that onl% extremel% mild cases o actor 1III or I4 de icienc% ma% be missed( T rom*in Time This test is o val!e in detectin& 0!alitative abnormalities in ibrino&en and in detectin& circ!latin& anticoa&!lants and inhibitors o ibrin pol%meri6ation( The clottin& time o the patient=s plasma is meas!red a ter the addition o a standard amo!nt o thrombin to a ixed vol!me o plasma( 3ontrol samples o normal plasma m!st be r!n in parallel( Fail!re o the clot to orm" in the absence o circ!latin& inhibitors s!ch as heparin or the ibrinol%tic de&radation prod!cts o ibrin and ibrino&en" is consistent #ith severe dimin!tion o ibrino&en" !s!all% #ell belo# +88 m&:dL( It is also prolon&ed #hen ibrinol%sis is ta$in& place( Other Tests o 3oa&!lation T e fi*rinogen le0el can be determined b% clottin&*time meas!rements or &ravimetricall%( Speci ic assa%s o coa&!lation actors are per ormed b% meas!rin& the clottin& time o plasma rom patients con&enitall% lac$in& in one o these actors and notin& the e ect o the addition o each actor( Eelativel% simple tests permit identi ication o circ!latin& anticoa&!lants( The simplest o these are based on the retardation o clottin& o normal recalci ied plasma b% var%in& mixt!res o the test plasma( The sensitivit% o s!ch tests !s!all% can be increased b% inc!batin& the test plasma #ith the normal plasma or )8 min at bod% temperat!re be ore recalci ication( -etection o actor 4III de icienc% re0!ires a special test( Tests of )i*rinolysis Fibrin de&radation prod!cts 'F-., can be meas!red b% imm!nolo&ic methods( Kormall%" dissol!tion o a recentl% ormed blood clot #ill not occ!r or 9G h or more( 7hen ibrinol%sis is a si&ni icant actor in hemostatic ail!re" dissol!tion o the #hole blood clot is observed in 2 h or less( The test has the disadvanta&e o bein& time* cons!min& in a circ!mstance #here time ma% be o the essence( In addition" a alse impression o increased ibrinol%tic activit% ma% be &ained rom clots ormed in patients #ith hi&h hematocrit levels or in thromboc%topenia" in #hich red cells ma% all a#a% rom the clot( The e!&lob!lin clot l%sis time and dil!te #hole*blood or plasma*clot*l%sis time are more sensitive indices and permit more rapid eval!ation o ibrinol%sis( The thromboelasto&ram is a &raphic representation o clottin&( The record obtained provides in ormation abo!t the clottin& time" the speed o ibrin pol%meri6ation" and the clot=s stren&th and tendenc% to#ard dissol!tion( E3A&-ATI#$ #) THE S-R%ICA& PATIE$T AS A HE'#STATIC RIS4

.reoperative Eval!ation o Hemostasis The patient=s histor% provides meanin& !l cl!es to the presence o a bleedin& tendenc%( It is reasonable to !se a 0!estionnaire on #hich the patient indicatesA '+, prolon&ed bleedin& or s#ellin& a ter bitin& the lip or ton&!e" '2, br!ises #itho!t apparent in/!r%" '), prolon&ed bleedin& a ter dental extraction" '9, excessive menstr!al bleedin&" '5, bleedin& problems associated #ith ma/or and minor operations" 'B, medical problems receivin& a ph%sician=s attention #ithin the past 5 %ears" ';, medications incl!din& aspirin or remedies or headache ta$en #ithin the past +8 da%s" and 'G, a relative #ith a bleedin& problem( Fo!r levels o concern have been proposed on the basis o the histor% and s!r&ical proced!re bein& considered( At Level I" the histor% is ne&ative and the proced!re contemplated is relativel% minor" e(&(" breast biops% or hernia repairA no screenin& tests are recommended( At Level II" the histor% is ne&ative" screenin& tests ma% have been per ormed in the past" and a ma/or operation is planned" b!t the proced!re !s!all% is not attended b% si&ni icant bleedin&A a platelet co!nt and blood smear and .TT are recommended to detect an% thromboc%topenia" circ!latin& anticoa&!lant" or intravasc!lar coa&!lation( Level III pertains to the patient #hose histor% is s!&&estive o de ective hemostasis and also to the patient #ho is to !nder&o an operative proced!re in #hich hemostasis ma% be impaired" e(&(" operatin& !sin& p!mp ox%&enation or cell savers" or proced!res in #hich a lar&e" ra# s!r ace is anticipated( Level III also pertains to sit!ations in #hich minimal postoperative bleedin& co!ld be in/!rio!s" s!ch as intracranial operations( At this level" a platelet co!nt and bleedin& time test sho!ld be per ormed to assess platelet !nctionD a .T and .TT sho!ld be !sed to assess coa&!lation" and the ibrin clot sho!ld be inc!bated to screen or abnormal ibrinol%sis( Level I1 pertains to patients #ho present #ith a histor% hi&hl% s!&&estive o a hemostatic de ect( A hematolo&ist sho!ld be cons!lted" and" in addition to the tests prescribed or Level III patients" the bleedin& time test sho!ld be repeated 9 h a ter the in&estion o B88 m& o aspirin" provided that the operation is sched!led to ta$e place +8 or more da%s a ter this st!d%( In the case o an emer&enc% proced!re" platelet a&&re&ation tests !sin& A-." colla&en" epinephrine" and ristocetin sho!ld be per ormed" and a TT is indicated to detect an% d%s ibrino&enemia or a circ!latin&" #ea$" heparin*li$e anticoa&!lant( .atients #ith liver disease" renal ail!re" obstr!ctive /a!ndice" and the possibilit% o disseminated mali&nant disease sho!ld have a platelet co!nt" .T" and .TT per ormed preoperativel%( In !remic patients the most common de icit is a 0!alitative platelet abnormalit%( This is best detected b% the bleedin& time test( Eval!ation o Excessive Intraoperative or .ostoperative Bleedin& Excessive bleedin& d!rin& or shortl% a ter a s!r&ical proced!re ma% be d!e to one or more o the ollo#in& actorsA '+, ine ective local hemostasis" '2, complications o blood trans !sion" '), a previo!sl% !ndetected hemostatic de ect" '9, cons!mptive coa&!lopath%" and:or '5, ibrinol%sis( Excessive bleedin& rom the ield o the proced!re" !nassociated #ith bleedin& rom other sites" e(&(" central veno!s press!re line" intraveno!s line" or tracheostom%" !s!all% s!&&ests inade0!ate mechanical hemostasis rather than a de ect in the biolo&ic process( An exception to this r!le applies to operations on the prostate" pancreas" and liver beca!se operative tra!ma ma% stim!late local plasmino&en activation and lead to increased ibrinol%sis on the ra# s!r ace( In these circ!mstances 29 to 9G h interr!ption o plasmino&en activation b% the administration o EA3A ma% prove e ective(

Altho!&h one ma% be reasonabl% certain on clinical &ro!nds that s!r&ical bleedin& is related to local problems" laborator% investi&ation m!st be con irmator%( .rompt examination sho!ld be made o the blood smear to determine the n!mber o platelets" and an act!al platelet co!nt sho!ld be done i the smear is e0!ivocal( A .TT" a one* sta&e .T" and a TT all can be determined #ithin min!tes( 3orrect interpretation o the res!lts sho!ld con irm the clinical impression or identi % the problem( As pointed o!t previo!sl%" massive blood trans !sion is a #ell*doc!mented ca!se o thromboc%topenia( Altho!&h most patients #ho receive +8 !nits or more o ban$ed blood #ithin a period o 29 h #ill be meas!rabl% thromboc%topenic" this is !s!all% not associated #ith hemostatic ail!re( There ore" proph%lactic administration o platelets is not indicated" b!t i there is evidence o di !se bleedin&" G to +8 pac$s o resh platelet concentrates sho!ld be &iven empiricall%" beca!se no clear association has been doc!mented bet#een the platelet co!nt" bleedin& time" and the occ!rrence o pro !se bleedin&( Another ca!se o hemostatic ail!re related to the administration o blood is a hemol%tic trans !sion reaction( The irst hint o a trans !sion reaction in an anestheti6ed patient ma% be di !se bleedin& in an operative ield that had previo!sl% been dr%( The patho&enesis o this bleedin& is tho!&ht to be related to the release o A-. rom hemol%sed red cells" res!ltin& in di !se platelet a&&re&ation" a ter #hich the platelet cl!mps are s#ept o!t o the circ!lation( Eelease o procoa&!lants ma% res!lt in pro&ression o the clottin& mechanism and intravasc!lar de ibrination( In addition" the ibrinol%tic mechanism ma% be tri&&ered( Trans !sion p!rp!ra is an !ncommon ca!se o thromboc%topenia and associated bleedin& a ter trans !sion( 7hen this occ!rs the donor platelets are o the !ncommon .lA+ &ro!p( These platelets sensiti6e the recipient" #ho ma$es antibod% to the orei&n platelet anti&en( The orei&n platelet anti&en does not completel% disappear rom the recipient circ!lation b!t seems to attach to the recipient=s o#n platelets( The antibod%" #hich attains a s! icient titer #ithin B or ; da%s a ter the sensiti6in& trans !sion" then destro%s the recipient=s o#n platelets( The res!ltant thromboc%topenia and bleedin& ma% contin!e or several #ee$s( This !ncommon ca!se o thromboc%topenia sho!ld be considered i bleedin& ollo#s trans !sion b% 5 or B da%s( .latelet trans !sions are o little help in the mana&ement o this s%ndrome" since the ne# donor platelets !s!all% are s!b/ect to the bindin& o anti&en and dama&e rom the antibod%( 3orticosteroids ma% be o some help in red!cin& the bleedin& tendenc%( .osttrans !sion p!rp!ra is sel * limited" and the passa&e o several #ee$s inevitabl% leads to s!bsidence o the problem( -I3 and disseminated ibrinol%sis occ!r intraoperativel% or postoperativel% #hen control mechanisms ail to restrain the hemostatic process to the area o tiss!e dama&e( Either process can ca!se di !se bleedin& and can be ca!sed b% tra!ma" incompatible trans !sed blood" sepsis" necrotic tiss!e" at emboli" retained prod!cts o conception" toxemia o pre&nanc%" lar&e ane!r%sms" and liver diseases( It is important to distin&!ish bet#een the t#o processes or the dominant element ca!sin& intraoperative or postoperative bleedin&( Ko sin&le test can con irm or excl!de the dia&nosis or distin&!ish bet#een the t#o disorders( The combination o thromboc%topenia" de ined b% smear or platelet co!nt" positive plasma protamine test

or ibrin monomers" a lo# ibrino&en level" and an elevated level o F-. provides stron& indications or -I3( The e!&lob!lin l%sis time provides a method o detectin& di !se ibrinol%sis( -i !se intraoperative and postoperative bleedin& is a complication o biliar% tract s!r&er% in cirrhotic patients( This has been related to portal h%pertension and coa&!lopath% associated #ith chronic liver disease( The tests !sed to distin&!ish -I3 rom ibrinol%sis pertain( The therape!tic approach incl!des the intraveno!s administration o vasopressin to e ect a temporar% red!ction in portal h%pertension" and EA3A to correct the increased ibrinol%sis( An operation per ormed in a patient #ith sepsis sometimes is attended b% contin!ed bleedin&( Severe hemorrha&ic disorders d!e to thromboc%topenia have occ!rred as a res!lt o &ram*ne&ative sepsis( The patho&enesis o endotoxin*ind!ced thromboc%topenia has been st!died in detail" and it has been s!&&ested that a labile actor" possibl% actor 1" is necessar% or this interaction( -e ibrination and hemostatic ail!re also ma% occ!r #ith menin&ococcemia" 3lostridi!m per rin&ens sepsis" and staph%lococcal sepsis( Hemol%sis appears to be one mechanism in sepsis leadin& to de ibrination( Eval!ation o these patients incl!des platelet co!nt" .T" .TT" and TT( LO3AL HEMOSTASIS S!r&ical bleedin&" even #hen alarmin&l% excessive" is !s!all% ca!sed b% ine ective local hemostasis( The &oal o local hemostasis is to prevent the lo# o blood rom incised or transected blood vessels( This ma% be accomplished b% interr!ptin& the lo# o blood to the involved area or b% direct clos!re o the blood vessel #all de ect( The techni0!es ma% be classi ied as mechanical" thermal" or chemical( Mechanical .roced!res The oldest mechanical method o e ectin& clos!re o a bleedin& point or preventin& blood rom enterin& the area o disr!ption is di&ital press!re( 7hen press!re is applied to an arter% proximal to an area o bleedin&" pro !se bleedin& is red!ced" permittin& more de initive action( A classic example is the .rin&le mane!ver o occl!din& the hepatic arter% in the hepatod!odenal li&ament as a method o controllin& bleedin& rom a transected c%stic arter% or rom the s!r ace o the liver( -irect di&ital press!re over a bleedin& site" s!ch as a lateral rent in the in erior vena cava" is also e ective( The in&er has the advanta&e o bein& the least tra!matic vasc!lar hemostat( All clamps" incl!din& the so*called atra!matic vasc!lar clamps" do res!lt in dama&e to the intimal #all o the blood vessel( The most obvio!s disadvanta&e o di&ital press!re is that it cannot be !sed permanentl%( The hemostat also represents a temporar% mechanical device to stem bleedin&( In smaller and noncritical vessels" the tra!ma and ad/acent tiss!e necrosis associated #ith the application o a hemostat are o little conse0!ence( These minor disadvanta&es are o!t#ei&hed b% the mechanical advanta&e that the instr!ment o ers to s!bse0!ent li&ation( 7hen bleedin& occ!rs rom a vessel that sho!ld be preserved" relativel% atra!matic hemostats sho!ld be emplo%ed to limit the extent o intimal dama&e and s!bse0!ent thrombosis(

In &eneral" a li&at!re replaces the hemostat as a permanent method o e ectin& hemostasis in a sin&le vessel( 7hen a vessel is transected" a simple li&at!re !s!all% is s! icient( For lar&e arteries #ith p!lsation and lon&it!dinal motion" trans ixion s!t!re to prevent slippin& is indicated( 7hen the bleedin& site is rom a lateral de ect in the blood vessel #all" s!t!re li&at!res are re0!ired( The adventitia and media constit!te the ma/or holdin& orces #ithin the #alls o lar&e vessels" and there ore m!ltiple ine s!t!res are pre erable to e#er lar&er s!t!res( Historicall%" A!l!s 3orneli!s 3els!s devised the !se o li&at!res in the irst cent!r% a(d( Beca!se o the stron& in l!ence o Galen" #ho #as inclined to ca!ter%" this method did not &ain pop!larit%( .arQ" in +552" rediscovered the principle o li&at!re( In +G88 .h%sic$ !sed absorbable s!t!res o b!c$s$in and parchment( In +G5G Simpson introd!ced the #ire s!t!re" and in +GG+ Lister emplo%ed chromic cat&!t( Halsted" in the earl% +<88s" emphasi6ed the importance o incorporatin& as little tiss!e as possible in the s!t!re and indicated the advanta&es o sil$( In +<++ 3!shin& reported on the !se o silver clips to e ect hemostasis in delicate vessels in critical areas( A #ide variet% o staples made o di erent metals" relativel% inert in tiss!e" have been !sed( All s!t!res represent orei&n material" and their selection is based on the characteristics o the material and the state o the #o!nd( Konabsorbable s!t!res" s!ch as sil$" pol%eth%lene" and #ire" evo$e less tiss!e reaction than absorbable materials" s!ch as cat&!t" pol%&l%colic acid '-exon," and pol%&lactin '1icr%l,( The latter are pre erable" ho#ever" in the ace o overt in ection( The presence o nonabsorbable material in an in ected #o!nd can lead to extr!sion or sin!s tract ormation( 7ire is the least reactive o the nonabsorbable s!t!res b!t the most di ic!lt to handle( Mono ilament #ire and coated s!t!res have an advanta&e over m!lti ilament s!t!res in the presence o in ection( The latter tend to ra&ment and permit sin!s ormation( -i !se bleedin& rom m!ltiple transected vessels ma% be controlled b% mechanical techni0!es that emplo% press!re directl% over the bleedin& area" press!re at a distance" or &enerali6ed press!re( These techni0!es are based on the premise that as press!re and lo# are decreased in the area o vasc!lar disr!ption" a clot #ill develop( As a standard proced!re o militar% s!r&eons in the seventeenth cent!r%" press!re at a distance #as e ected b% application o to!rni0!ets and other press!re devices at press!re points proximal to bleedin& sites( Ko# it is &enerall% believed that direct press!re is pre erable and is not attended b% the dan&er o tiss!e necrosis associated #ith prolon&ed !se o to!rni0!ets( Gravitational s!its have been !sed to create &enerali6ed press!re and temporaril% decrease bleedin& rom r!pt!red ma/or intraabdominal vessels( -irect press!re applied b% means o pac$s a ords the best method o controllin& di !se bleedin& rom lar&e areas( Earel% is it necessar% to leave a pac$ at the bleedin& site and remove it at a second sittin&( I this is done" several da%s sho!ld elapse be ore removal" and the possibilit% o rec!rrent bleedin& sho!ld be anticipated( The 0!estion o #hether hot #et pac$s or cold #et pac$s sho!ld be applied has been investi&ated( Fnless the heat is so &reat as to denat!re protein" it ma% act!all% increase bleedin&" #hereas cold pac$s promote hemostasis b% ind!cin& vasc!lar spasm and increasin& endothelial adhesiveness( Bleedin& rom c!t bone ma% be controlled b% pac$in&

bees#ax in the area( This material e ects press!re and is relativel% nonirritatin& to the bod%( T ermal Agents Galen=s avorin& o ca!ter% in l!enced medicine or +588 %ears" !ntil the teachin&s o .arQ #ere appreciated( The !se o ca!ter% #as revitali6ed in +<2G" #hen 3!shin& and Bovie applied this techni0!e or e ectin& hemostasis o delicate vessels in recessed areas" s!ch as the brain( Heat achieves hemostasis b% denat!ration o protein" #hich res!lts in coa&!lation o lar&e areas o tiss!e( 7ith act!al ca!ter%" heat is transmitted rom the instr!ment b% cond!ction directl% to the tiss!eD #ith electroca!ter%" heatin& occ!rs b% ind!ction rom an alternatin&*c!rrent so!rce( 7hen electroca!ter% is emplo%ed" the amplit!de settin& sho!ld be hi&h eno!&h to prod!ce prompt coa&!lation b!t not so hi&h as to set !p an arc bet#een the tiss!e and the ca!ter% tip( This avoids b!rns o!tside the operative ield and prevents the exit o c!rrent thro!&h electrocardio&raphic leads or other monitorin& devices( A ne&ative plate sho!ld be placed beneath the patient #henever ca!ter% is emplo%ed to avoid severe s$in b!rns( The advanta&e o ca!ter% is that it saves timeD its disadvanta&e is that more tiss!e is necrosed than #ith precise li&at!re( 3ertain anesthetic a&ents cannot be !sed #ith electroca!ter% beca!se o the ha6ard o explosion( A direct c!rrent can also res!lt in electrical hemostasis( Since the protein moieties and cell!lar elements o blood have a ne&ative s!r ace char&e" the% are attracted to the positive pole" #here a thromb!s is ormed( -irect c!rrents in the 28* to +88*mA ran&e have been applied to control di !se bleedin& rom lar&e sero!s s!r aces( Ar&on &as has been applied s!ccess !ll% to the control o bleedin& rom s!per icial erosions( At the other end o the thermal spectr!m" coolin& has been applied to control bleedin&" partic!larl% rom the m!cosa o the esopha&!s and stomach( Generali6ed h%pothermia is o little avail" since in order to red!ce the blood lo# to visceral or&ans" the s%stemic temperat!re m!st be bro!&ht do#n to the level o )5R3( At this point shiverin& and ventric!lar ibrillation ma% occ!r( Thromboc%topenia ma% also be a conse0!ence o &enerali6ed coolin&( -irect coolin& #ith iced saline is e ective and acts b% increasin& the local intravasc!lar hematocrit concentration and decreasin& blood lo# b% vasoconstriction( Extreme coolin&" i(e(" cr%o&enic s!r&er%" has been applicable partic!larl% in &%necolo&% and ne!ros!r&er%( Temperat!res ran&in& bet#een *28 to* +G8R3 are !sed" and ree6in& occ!rs aro!nd the tip o the cann!la #ithin 5 s( At temperat!res o *28R3 or belo#" the tiss!e" capillaries" small arterioles" and ven!les !nder&o cr%o&enic necrosis( This is ca!sed b% deh%dration and denat!ration o lipid molec!les( The m!sc!lar #alls o lar&e arteries are an exception( Altho!&h the ma/or arteries and blood ma% be ro6en solid" the blood contained in these vessels does not clot( 7hen tha#in& occ!rs" normal circ!lation is res!med( C emical Agents 3hemical a&ents var% in their hemostatic action( Some are vasoconstrictive" #hile others have coa&!lant properties( Still others are relativel% inert b!t possess h%&roscopic properties #hich increase their b!l$ and aid in pl!&&in& disr!pted blood vessels(

Epinephrine" applied topicall%" ind!ces vasoconstriction" b!t extensive application can res!lt in considerable absorption and s%stemic e ects( The dr!& &enerall% is !sed on oo6in& sites in m!cosal areas" e(&(" d!rin& tonsillectom%( Historicall%" s$eletal m!scle #as one o the irst materials #ith locall% hemostatic properties to be emplo%ed" its !se havin& been introd!ced b% 3!shin& in +<++( Shortl% therea ter" hemostatic ibrin #as man! act!red( The properties re0!ired or local hemostatic materials incl!de handlin& ease" rapid absorption" hemostatic action independent o the &eneral clottin& mechanism" and the% sho!ld be nonirritatin&( The most #idel% !sed o the commerciall% available materials are &elatin oam 'Gel oam," oxidi6ed cell!lose 'Ox%cel," oxidi6ed re&enerated cell!lose 'S!r&icel," and microni6ed colla&en 'Avitene,( All these materials act" in part" b% transmittin& press!re a&ainst the #o!nd s!r ace" and the interstices provide a sca old on #hich the clot can or&ani6e 'Table )*9,( Gel oam is made rom animal s$in &elatin that has been denat!red( In itsel Gel oam has no intrinsic hemostatic action" b!t it can be !sed in combination #ith topical thrombin" or #hich it serves as an absorbable carrier( Its main hemostatic activit% is related to the contact bet#een blood and the lar&e s!r ace area o the spon&e and to the press!re exerted b% the #ei&ht o the spon&e and absorbed blood( Be ore Gel oam is applied" the spon&e sho!ld be moistened in saline or thrombin sol!tion and all the air sho!ld be removed rom the interstices( Ox%cel and S!r&icel are altered cell!lose materials capable o reactin& chemicall% #ith blood and prod!cin& a stic$% mass that !nctions as an arti icial clot( These s!bstances are relativel% inert and are removed b% li0!e action in + to 9 #ee$s( The% sho!ld be dr% #hen the% are applied( Li$e Gel oam" these materials are nontoxic and relativel% nonirritatin& b!t are some#hat detrimental to #o!nd healin& and re0!ire pha&oc%tosis to be removed( S!r&icel has been sho#n to have an antibacterial e ect( Microcr%stalline colla&en has been sho#n to be as e ective as other materials as a topical hemostatic a&ent or lar&e oo6in& s!r aces( Fibrin &l!e is commerciall% available in E!rope and 3anada b!t not in the Fnited States" beca!se o the potential o disease transmission #hen ibrino&en is obtained rom pooled plasma( Sin&le*donor ibrino&en can be mixed #ith bovine thrombin to ma$e the sealant( The &l!e is partic!larl% e ective in controllin& s!r ace bleedin& rom the liver and spleen(

TRA$S)-SI#$
Bac$&ro!nd In +<B;" the tercentennial anniversar% o the trans !sion o blood into h!man bein&s #as celebrated( In N!ne +BB; Nean*Baptiste -enis and a s!r&eon" Emmere6" trans !sed blood rom a sheep into a +5*%ear*old bo% #ho had been bled man% times as treatment or ever( The patient apparentl% improved" and a s!ccess !l experience #as reported sim!ltaneo!sl% in another patient( Beca!se o t#o s!bse0!ent deaths associated #ith trans !sion rom animals to h!mans" criminal char&es #ere bro!&ht a&ainst -enis( In April +BBG !rther trans !sions in h!mans #ere orbidden !nless

approved b% the Fac!lt% o Medicine in .aris( It #as not !ntil the nineteenth cent!r% that h!man blood #as reco&ni6ed as the onl% appropriate replacement( In +<88 Landsteiner and his associates introd!ced the concept o blood &ro!pin& and identi ied the ma/or A" B" and O &ro!ps( In +<)< the Eh &ro!p #as reco&ni6ed( The introd!ction o vario!s preservative sol!tions" s!ch as acid*citrate*dextrose 'A3-," citrate* phosphate*dextrose '3.-," and citrate*phosphate*do!ble*dextrose adenine '3.2-*A, and ne#er additive sol!tions extended the shel li e o blood to !p to B #ee$s( .reservation o blood and its constit!ents has been achieved b% ree6in&" and emphasis has been placed on the !se o plasma expanders and component therap%( 3haracteristics o Blood and Eeplacement Therap% Blood Blood has been described as a vehic!lar or&an that per !ses all other or&ans( It provides transportation o ox%&en to satis % the bod%=s metabolic demands and removes the b%*prod!ct carbon dioxide( Blood also transports chemical n!triments or" and #aste prod!cts rom" metabolic activit%( Homeostatic &overnors" incl!din& hormones" coa&!lation actors" and antibodies" are carried to and rom appropriate sites #ithin the l!id portion o the blood( Eed blood cells" #ith their ox%&en*carr%in& capacit%D #hite blood cells" #hich !nction in bod% de ense processesD and platelets" #hich contrib!te to the hemostatic process" comprise the ormed elements( Eeplacement Therap% Ban$ed 7hole Blood Ban$ed #hole blood is no# rarel% indicated and rarel% available( 7ith the ne# preservatives" the shel li e has been extended to 98 S 5 da%s( At least ;8 percent o the trans !sed er%throc%tes remain in the circ!lation or 29 h a ter trans !sion and are viable( The chan&es in the red cell that occ!r d!rin& stora&e incl!de red!ction o intracell!lar adenosine triphosphate 'AT., and 2")*diphospho&l%cerate '2")*-.G," #hich alters the c!rve o ox%&en dissociation rom hemo&lobin" decreasin& ox%&en transport !nction( Ban$ed blood is a poor so!rce o platelets beca!se platelets lose their abilit% to s!rvive trans !sion a ter 29 h o stora&e( Amon& the clottin& actors" II" 1II" I4" and 4I are stable in ban$ed blood( 7ithin 2+ da%s o stora&e" the pH decreases rom ;(88 to B(BG" and the lactic acid level increases rom 28 to +58 m&:dL( The potassi!m concentration rises steadil% to )2 mE0:dL" and the ammonia concentration rises rom 58 to BG8 m&:dL at the end o 2+ da%s or 3.- #hole blood( The hemol%sis that occ!rs d!rin& stora&e is insi&ni icant( T%pin& and 3rossmatchin& In selectin& blood or trans !sion" serolo&ic compatibilit% is established ro!tinel% or the recipients= and donors= A" B" O" and Eh &ro!ps( 3rossmatchin& bet#een the donors= red cells and the recipients= sera 'the ?ma/or@ crossmatch, is per ormed( As a r!le" Eh*ne&ative recipients sho!ld be trans !sed onl% #ith Eh*ne&ative blood( Since this &ro!p represents +5 percent o the donor pop!lation" the s!ppl% ma% be limited( I the recipient is an elderl% male #ho has not been trans !sed previo!sl%" the trans !sion o Eh*positive blood is acceptable i Eh*ne&ative blood is !navailable( Anti* Eh antibodies orm #ithin several #ee$s o trans !sion( I !rther trans !sions are needed #ithin a e# da%s" more Eh*positive blood can be !sed( Eh*positive blood sho!ld not be trans !sed to Eh*ne&ative emales #ho are capable o childbearin&(

Administration o h%perimm!ne anti*Eh &lob!lin to Eh*ne&ative #omen shortl% be ore or a ter childbirth lar&el% eliminates Eh disease in s!bse0!ent o sprin&( In the patient #ho is receivin& repeated trans !sions" ser!m dra#n not more than ;2 h be ore crossmatchin& sho!ld be !tili6ed or matchin& #ith cells o the donor( Emer&enc% blood trans !sion can be per ormed #ith t%pe O blood( O*ne&ative and t%pe*speci ic red blood cells are e0!all% sa e or emer&enc% trans !sion( .roblems are associated #ith the administration o 9 or more !nits o O*ne&ative blood beca!se there is a si&ni icant increase in the ris$ o a hemol%tic reaction( In patients #ith mali&nant l%mphoma and le!$emia" cr%o&lob!lins ma% be present" and the blood sho!ld be administered thro!&h a blood #armer( I these antibodies are present in hi&h titer" h%pothermia ma% be contraindicated( In patients #ith thalassemia #ho have been m!ltipl% trans !sed and" more partic!larl%" #ith ac0!ired hemol%tic anemia" t%pin& and crossmatchin& ma% be di ic!lt" and s! icient time sho!ld be allotted d!rin& the preoperative period to acc!m!late blood that ma% be re0!ired d!rin& the operation( 3rossmatchin& sho!ld al#a%s be carried o!t prior to the administration o dextran" since dextran inter eres #ith the t%pin& proced!re( Beca!se ban$ed blood ma% be stored or 98 S 5 da%s" the !se o a!tolo&o!s predeposit trans !sion is &ro#in&( In other#ise health%" nonanemic patients" !p to 5 or B !nits o blood ma% be collected or !se in elective s!r&ical proced!res( .atients ma% donate blood i the hemo&lobin level exceeds ++ &:dL or i the hematocrit concentration is &reater than )9 percent( The irst proc!rement is per ormed 98 da%s be ore the planned operation and the last one" ) da%s be ore the proced!re( -onations can be sched!led at intervals o 9 to 5 da%s( Eecombinant h!man er%thropoietin 'r* H!E.O, accelerates &eneration o red cells and allo#s or more re0!ent harvest or elective operative proced!res( )res 5 ole Blood This term re ers to blood that is administered #ithin 29 h o its donation( It is rarel% indicated( Beca!se o the time re0!irements o testin& or in ectio!s diseases" resh blood is onl% available !ntested( One !nit o platelet concentrate has more viable platelets than + !nit o resh #hole blood" #hich is also an inade0!ate so!rce o actor 1III( Pac6ed Red Cells and )ro"en Red Cells .ac$ed red cells is the prod!ct o choice or most clinical sit!ations( 3oncentrated s!spensions o cells can be prepared b% removin& most o the s!pernatant plasma a ter centri !&ation( The preparation red!ces b!t does not eliminate reaction ca!sed b% plasma components( It also red!ces the amo!nt o sodi!m" potassi!m" lactic acid" and citrate administered( Essentiall% it provides ox%&en*carr%in& capacit%( Fro6en red cells are not available or !se in emer&encies( The% are o ten !sed or patients #ho have been previo!sl% sensiti6ed beca!se the% have been selected or lac$ o certain anti&ens( The red cell viabilit% is improved" and the AT. and 2")*-.G concentrations are maintained(

&eu6ocyte-Poor 5as ed Cells This prod!ct is prepared b% aspiratin& the b! % coat and s!pernatant plasma and passin& them thro!&h a speci ic #hite*cell ilter( The red cells then are #ashed #ith sterile isotonic sol!tion( This sho!ld be done onl% or patients #ith demonstrated h%persensitivit% to le!$oc%tes or platelets 'b! % coat reactions,( Fs!all% this s%ndrome is mani est b% ever" chill% sensations" and !rticaria d!e to plasma proteins in the absence o hemol%sis( Platelet Concentrates The indications or platelet trans !sion are as ollo#sA thromboc%topenia d!e to massive blood loss and replacement #ith platelet*poor prod!cts" thromboc%topenia d!e to inade0!ate prod!ction" and 0!alitative platelet disorders( The preparations sho!ld be !sed #ithin +28 h o blood donation( One !nit o platelet concentrate has a vol!me o approximatel% 58 mL( .latelet preparations ma% transmit in ectio!s diseases and acco!nt or aller&ic reactions similar to those ca!sed b% #hole blood( 7hen treatin& thromboc%topenic bleedin& or preparin& some thromboc%topenic patients or s!r&er%" it is advisable to elevate the platelet levels to the ran&e o 58"888 to +88"888:mm) to provide contin!ed protection( The development o isoimm!nit% remains one o the most important actors limitin& the !se !lness o platelet trans !sion( Isoantibodies are demonstrable in abo!t 5 percent o patients a ter + to +8 trans !sions" in 28 percent a ter +8 to 28 trans !sions" and in G8 percent a ter more than +88 trans !sions( The !se o HLA*compatible platelets addresses this problem( )ro"en Plasma and 3olume E7/anders Fro6en plasma prepared rom reshl% donated blood or resh plasma is necessar% to provide actors 1 and 1III( The other plasma clottin& actors are present in ban$ed preparations( The ris$ o in ectio!s disease is the same #hether resh ro6en plasma or #hole blood:red cells is administered( Lactated Ein&er=s sol!tion or b! ered saline sol!tion administered in amo!nts t#o to three times the estimated blood loss" is e ective and is associated #ith e#er complications( -extran or a combination o lactated Ein&er=s sol!tion and normal h!man ser!m alb!min are pre erred or rapid plasma expansion( 3ommerciall% available dextran preparations probabl% sho!ld not be administered in amo!nts exceedin& + L:da%" since prolon&ation o bleedin& time and hemorrha&e can occ!r( Lo#*molec!lar* #ei&ht dextran" i(e(" molec!lar #ei&ht o )8"888 to 98"888" has become pop!lar beca!se it possesses a hi&her colloidal press!re than plasma and e ects some reversal o er%throc%te a&&l!tination( Concentrates Antihemophilic concentrates are prepared rom plasma and are available or the treatment o actor 1III de icienc%( Some o these concentrates are t#ent% to thirt% times as potent as an e0!al vol!me o resh ro6en plasma( The simplest actor 1III concentrate is the plasma cr%oprecipitate( Alb!min also has been concentrated" so 25 & ma% be administered and provide the osmotic e0!ivalent o 588 mL o plasma( The advanta&e o alb!min is that it is a hepatitis* ree prod!ct(

Indications for Re/lacement of Blood or Its Elements

Improvement in Ox%&en*3arr%in& 3apacit% Ox%&en*carr%in& capacit% is primaril% a !nction o the red cell( 7hen anemia can be treated b% speci ic therap%" s!ch as er%thropoietin" trans !sion sho!ld be #ithheld( Ac!te anemias" s!ch as hemol%tic anemia" are more disablin& ph%siolo&icall% than

chronic anemia" since most patients #ith chronic anemia have !nder&one an ad/!stment to the condition( In pre&nanc% there is a moderate drop in hematocrit level" and trans !sions are not indicated to correct the ph%siolo&ic anemia o pre&nanc% be ore s!r&ical treatment( The correction o chronic anemia be ore s!r&ical treatment" tho!&h o ten per ormed" is di ic!lt to /!sti %( A +<GG Kational Instit!tes o Health 3onsens!s Eeport challen&ed the dict!m that a hemo&lobin val!e o less than +8 &:dL or a hematocrit level o less than )8 percent indicates a need or a preoperative red cell trans !sion( It is s!&&ested that cardiac o!tp!t does not increase si&ni icantl% in health% individ!als !ntil the hemo&lobin val!e decreases to approximatel% ; &:dL( .atients #ith chronic anemia and a hemo&lobin val!e less than ; &:dL in #hom si&ni icant bleedin& intraoperativel% is not anticipated do not re0!ire a trans !sion preoperativel%( There is no correlation bet#een anemia and dehiscence or severit% o postoperative in ection( Blood vol!me ma% be replaced #ith dextran sol!tion or lactated Ein&er=s sol!tion #ith a red!ction o the hemo&lobin val!e to levels belo# +8 & and little demonstrable chan&e in the e ects o a red!ction in ox%&en*carr%in& capacit% or the capacit% to remove metabolic &aseo!s b%*prod!cts( A stroma* ree hemo&lobin sol!tion has been sho#n to have the abilit% to carr% and exchan&e ox%&en( Also" a #hole blood s!bstit!te" Fl!osol*-A" has been proposed as a sol!tion #ith ox%&en*handlin& capabilities( 1ol!me Eeplacement The most common indication or blood trans !sion in s!r&ical patients is the replenishment o the circ!latin& blood vol!me( It is di ic!lt to eval!ate the vol!me de icit acc!ratel%( 1al!es or ?normal blood vol!me@ are variable" and the techni0!es o meas!rement are relativel% inacc!rate #hen there is a rapidl% chan&in& sit!ation" s!ch as hemorrha&e( 3hronicall% ill and elderl% patients ma% have a dimin!tion o blood vol!me( In patients #ith cardiac decompensation" the blood vol!me ma% be &reater than normal( Man% patients #ith chronicall% red!ced blood vol!me are #ell accommodated to that vol!me( Meas!rement o hemo&lobin or hematocrit levels is also !sed to interpret blood loss( These meas!rements are misleadin& in the ace o ac!te blood loss" since the hematocrit level ma% be normal in spite o a severel% contracted blood vol!me( It has been sho#n that" a ter a health% ad!lt male lost approximatel% +888 mL o blood rapidl%" the veno!s hematocrit ell onl% ) percent d!rin& the irst ho!r" 5 percent at 29 h" B percent at 9G h" and G percent at ;2 h" th!s indicatin& the time re0!ired or the bod% to restore blood vol!me( Both the amo!nt and the rate o bleedin& are actors in the development o the si&ns and s%mptoms o blood loss( A health% person can lose 588 mL in +5 min #ith onl% minor e ects on the circ!lation and little chan&e in blood press!re or p!lse( Loss o +5 to )8 percent o blood vol!me 'class II hemorrha&e, is associated #ith tach%cardia and decreased p!lse press!re( Loss o )8 to 98 percent 'class III hemorrha&e, &enerall% res!lts in tach%cardia" tach%pnea" h%potension" oli&!ria" and chan&es in mental stat!s(

Loss o blood ma% be eval!ated in the operatin& room b% estimatin& the amo!nt o blood in the #o!nd and on the drapes and b% #ei&hin& spon&es( The loss determined b% #ei&hin& spon&es is onl% abo!t ;8 percent o tr!e loss( In patients #ho have normal preoperative blood val!es" blood loss !p to 28 percent o total blood vol!me 'TB1, is replaced #ith cr%stalloid sol!tions( Blood loss !p to 58 percent o TB1 is replaced #ith cr%stalloids and red blood cell concentrates( Blood loss above 58 percent o TB1 is replaced #ith cr%stalloids" red blood cells" and alb!min or plasma( 3ontin!ed bleedin& above 58 percent o TB1 sho!ld receive the same components and resh ro6en plasma( I electrol%te sol!tions are !sed to replace blood vol!me" an amo!nt three to o!r times the lost vol!me is re0!ired beca!se o immediate di !sion into the interstitial space( Re/lacement of Clotting )actors Trans !sion o platelets and:or proteins contrib!tin& to coa&!lation ma% be indicated in speci ic patients either be ore or d!rin& operation 'Table )*5,( In the treatment o certain hemorrha&ic conditions" it m!st be $ept in mind that the clottin& de ects ma% be m!ltiple( The e icac% o resh ro6en plasma in the mana&ement o coa&!lopath% in patients #ith liver disease and in patients receivin& lar&e amo!nts o vol!me replacement or ac!te blood loss is not #ell de ined( There are ins! icient data to speci % criteria or trans !sion o resh ro6en plasma( The initial vol!me o resh ro6en plasma needed or an e ect on coa&!lation ran&es rom B88 to 2888 mL administered in + to 2 h( The ri&id !se o the .T and .TT to anticipate the e ect o resh ro6en plasma is not /!sti ied( S/ecific Indications 'assi0e Transfusion The term massive trans !sion implies a sin&le trans !sion &reater than 2588 mL" or 5888 mL trans !sed over a period o 29 h( The approximate percenta&es o ori&inal blood vol!me remainin& a ter var%in& de&rees o hemorrha&e and trans !sion are sho#n in Table )*B( A variet% o problems ma% attend the !se o massive trans !sion( 3irc!lator% overload or -I3 ma% occ!r( -il!tional thromboc%topenia" impaired platelet !nction" and de iciencies o actors 1" 1III" and 4I ma% occ!r( Eo!tine al$alini6ation is not advisable" since this co!ld have an adverse e ect on the ox%hemo&lobin dissociation c!rve and presents an additional sodi!m load to a compromised patient( The increased potassi!m content o m!ltiple !nits o stored blood does not provide clinical e ects !nless the patient is severel% oli&!ric( 3itrate toxicit% ma% be associated #ith massive trans !sion" partic!larl% in %o!n& children and patients #ith severe h%potension or liver disease( This toxicit% is related to an excessive bindin& o ioni6ed calci!m and is !s!all% corrected b% spontaneo!s mobili6ation o calci!m rom bone( The ph%siolo&ic conse0!ences o citrate toxicit% rarel% have a si&ni icant e ect( The !nction o hemo&lobin is altered b% stora&e" since the concentration o 2")*-.G alls to a ne&li&ible level b% the third #ee$( This res!lts in an increased a init% o the red blood cells or ox%&en and a less e icient ox%&en deliver% s%stem( In itsel " red!ction o 2")*-.G ma% not have a si&ni icant e ect" b!t #hen combined #ith ac!te anemia it ma% be an important actor( 7hen lar&e trans !sions are administered" a heat exchan&er ma% be !sed to #arm the blood" since h%pothermia ma% ca!se a decrease in cardiac rate and o!tp!t and a red!ction in the blood pH( 7armin& the blood decreases si&ni icantl% the re0!enc% o intraoperative cardiac arrest(

The !se o blood rom man% donors increases the possibilit% o hemol%tic trans !sion reaction d!e to incompatibilit%( This can be red!ced b% screenin& each potential donor in the pool and eliminatin& those #ho sho# possible incompatibilit%( .aradoxicall%" patients #ho s!rvive a massive trans !sion do not have a hi&h probabilit% o developin& isoantibodies s!bse0!entl%" and the ris$ is no &reater than that rom a sin&le trans !sion( The ris$ o in ectio!s disease increases pro&ressivel% #ith each s!cceedin& !nit( 7hen administerin& massive trans !sions" the pH" blood &ases" and potassi!m sho!ld be meas!red re&!larl%( Acidosis and abnormalities sho!ld be corrected( I di !se bleedin& occ!rs" coa&!lation screenin& tests and platelet co!nts sho!ld be per ormed and de icits corrected #ith ro6en plasma and platelet concentrates( 'et ods of Administering Blood Eo!tine Administration The rate o trans !sion depends on the patient=s stat!s( Fs!all% 5 mL:min is administered or + min" a ter #hich +8 to 28 mL:min ma% be administered to complete ro!tine trans !sion( 7hen mar$ed oli&emia is bein& treated" the irst 588 mL ma% be &iven #ithin +8 min" and the second 588 mL ma% be &iven e0!all% rapidl% in most cases( 3old blood ma% be !sed or this amo!nt" b!t #hen lar&er amo!nts are administered" #arm blood is desirable( As m!ch as +588 mL:min can be administered thro!&h t#o ;(5F catheters( 7hen lar&e trans !sions are administered" it is important not to overload the circ!lation" and the !se o central veno!s press!re monitorin& is partic!larl% pertinent( There is no practical advanta&e in the !se o intraarterial trans !sion over the intraveno!s ro!te in the treatment o oli&emia( It has been sho#n that coronar% lo# and s%stemic arterial press!re respond as rapidl% and to the same extent #hether the blood is administered intraveno!sl% or intraarteriall%( #t er 'et ods Blood ma% be instilled intraperitoneall% or into the med!llar% cavit% o the stern!m and lon& bones( Intrasternal and intramed!llar% trans !sion ma% be pain !l" and the rate o administration is limited( Approximatel% <8 percent o red cells in/ected intraperitoneall% enter the circ!lation" b!t !pta$e is not complete or at least a #ee$" and there ore the method is not s!itable #hen immediate trans !sion is re0!ired( Intraoperative a!totrans !sion has become increasin&l% pop!larD it is a potentiall% li e* savin& ad/!nct to the mana&ement o tra!ma and is !se !l in elective operations in #hich m!ltiple trans !sions are li$el% to be re0!ired( Approximatel% 258 mL o blood can be retrieved" #ashed or iltered" and ret!rned to the patient over a 5* to B*min period( A comparison bet#een cell #ashin& and simple iltration revealed that iltration allo#ed a &reater percenta&e o blood to be ret!rned and #as associated #ith less thromboc%topenia( Another approach to anticipated intraoperative lar&e blood losses is hemodil!tion( At the onset o the proced!re" red cells are removed #hile the intravasc!lar vol!me is maintained #ith cr%stalloid or colloid( The red!ced blood viscosit% improves microcirc!lator% pro !sion( The removed blood can then be retrans !sed d!rin& the operation to replace lost blood or be rein !sed near the completion o the proced!re(

Com/lications Hemol%tic Eeactions The incidence o non atal hemol%tic trans !sion reactions is approximatel% + per B888 !nits o blood administered( Fatal hemol%tic trans !sion reactions occ!r once in ever% +88"888 !nits administered( Hemol%tic reactions d!e to incompatibilit% o A" B" O" and Eh &ro!ps or man% other independent s%stems ma% res!lt rom errors in the laborator% o a clerical or technical nat!re or the administration o the #ron& blood at the time o trans !sion( Hemol%tic reactions are characteri6ed b% intravasc!lar destr!ction o red blood cells and conse0!ent hemo&lobinemia and hemo&lobin!ria( 3irc!latin& hapto&lobin is capable o bindin& +88 m& hemo&lobin:dL plasma" and the complex is cleared b% the retic!loendothelial s%stem( 7hen the bindin& capacit% is exceeded" ree hemo&lobin circ!lates" and the heme is released and combines #ith alb!min to orm methemalb!min( Heme in plasma is detected b% a positive Sch!mm=s test( 7hen ree hemo&lobin exceeds 25 m&:dL plasma" some is excreted in the !rine" b!t in most s!b/ects hemo&lobin!ria occ!rs #hen the total plasma level exceeds +58 m&:dL( The renal lesions that ma% occ!r consist o t!b!lar necrosis and precipitation o hemo&lobin #ithin the t!b!les( Eed cell stromal lipid is liberated" and this ma% initiate a disseminated intravasc!lar coa&!lation( B!t -I3 is more li$el% initiated b% antibod%*anti&en complexes activatin& actor 4II end complement" leadin& to activation o the coa&!lation cascade( The $alli$rein*brad%$inin s%stem ma% be activated and a ect the circ!lator% s%stem( Minor incompatibilities ma% occ!r" ca!sin& hemol%sis #ithin the retic!loendothelial s%stem mani ested b% ever" a mild decrease in hemo&lobin" and an increase in bilir!bin( I the recipient has a lo# antibod% titer at the time o trans !sion" reaction ma% be dela%ed or several da%s( 3linical Mani estations There is an increased ha6ard in patients #ho have had a previo!s trans !sion reaction( I the patient is a#a$e" the most common s%mptoms are the sensation o heat and pain alon& the vein into #hich the blood is bein& trans !sed" l!shin& o the ace" pain in the l!mbar re&ion" and constrictin& pain in the chest( The patient ma% experience chills" ever" respirator% distress" h%potension" and tach%cardia rom amo!nts as small as 58 mL( In patients #ho are anestheti6ed and !nder&oin& operation" the t#o si&ns that ma% dra# attention are abnormal bleedin& and contin!ed h%potension despite ade0!ate replacement( The mortalit% and morbidit% res!ltin& rom hemol%tic reactions is hi&h i the patient receives a !ll !nit o incompatible blood( Ac!te hemorrha&ic diatheses occ!r in G to )8 percent o patients( There is a s!dden all in the platelet co!nt" an increase in ibrinol%tic activit%" and cons!mption o coa&!lation actors" especiall% 1 and 1III" d!e to disseminated intravasc!lar clottin&( E!do#s$i reported the ollo#in& incidences o clinical mani estations in a lar&e series #ith hemol%tic posttrans !sion reactionsA oli&!ria" 5G percentD hemo&lobin!ria" 5B percentD arterial h%potension" 58 percentD /a!ndice" 98 percentD na!sea and vomitin&" )8 percentD lan$ pain" 25 percentD c%anosis and h%pothermia" 22 percentD d%spnea" 28 percentD chills" +G percentD di !se bleedin&" +B percentD ne!rolo&ic si&ns" +8 percentD and aller&ic reaction" B percent( The laborator% criteria are hemo&lobin!ria #ith a concentration o ree hemo&lobin over 5 m&:dL" a ser!m hapto&lobin level belo# 58 m&:dL" and serolo&ic criteria to sho# anti&en incompatibilit% o the donor and recipient blood( The simplest clinical dia&nostic test is insertion o a bladder catheter and eval!ation o the color and vol!me o the excreted !rine" since hemo&lobin!ria

and oli&!ria are the most characteristic si&ns( A positive 3oombs= test indicatin& trans !sed cells coated #ith patient antibod% also provides evidence( Treatment I a trans !sion reaction is s!spected" the trans !sion sho!ld be stopped immediatel%" and a sample o the recipient=s blood sho!ld be dra#n and sent alon& #ith the s!spected !nit to the blood ban$ or comparison #ith the pretrans !sion samples( The ser!m bilir!bin level sho!ld be determined in the recipient( Each &ram o hemo&lobin is converted to abo!t 98 m& o bilir!bin( The hemol%tic reaction is characteri6ed b% an increase in the indirect reactin& raction( A Fole% catheter sho!ld be inserted and the ho!rl% !rine o!tp!t recorded( Since renal toxicit% is a ected b% the rate o !rinar% excretion and the pH" and since al$alini6in& the !rine prevents precipitation o hemo&lobin #ithin the t!b!les" attempts are made to initiate di!resis and to al$alini6e the !rine( This can be accomplished #ith mannitol or !rosemide pl!s 95 mE0 bicarbonate( I mar$ed oli&!ria or an!ria occ!rs" the l!id inta$e and potassi!m inta$e are restricted" and the patient is treated as a case o renal sh!tdo#n( In some instances" dial%sis is re0!ired( A ter recover% rom oli&!ria or an!ria" di!resis is o ten copio!s and ma% be associated #ith si&ni icant losses o potassi!m and sodi!m" #hich re0!ire replacement( )e*rile and Allergic Reactions These are relativel% re0!ent" occ!rrin& in abo!t + percent o trans !sions( Eeactions !s!all% are mild and are mani ested b% !rticaria and ever occ!rrin& #ithin B8 to <8 min o the start o trans !sion( In rare instances the reaction is severe eno!&h to ca!se anaph%lactic shoc$( Aller&ic reactions are ca!sed b% trans !sion o antibodies rom h%persensitive donors or the trans !sion o anti&ens to #hich the recipient is h%persensitive( Eeactions ma% occ!r a ter the administration o #hole blood" pac$ed red cells" plasma" and antihemophilic actor( Treatment consists o administration o antihistamines" epinephrine" and steroids" dependin& on the severit% o the reaction( Eepeated reactions can be prevented b% the !se o le!$oc%te* depleted or #ashed red cells( Bacterial Se/sis Bacterial contamination o in !sed blood is rare and ma% be ac0!ired either rom the contents o the container or the s$in o the donor( Gram*ne&ative or&anisms" especiall% coli orm and .se!domonas species" #hich are capable o &ro#th at 9R3" are the most common ca!se( 3linical mani estations incl!de ever" chills" abdominal cramps" vomitin&" and diarrhea( There ma% be hemorrha&ic mani estations and increased bleedin& i the patient is !nder&oin& s!r&ical treatment( In some instances bacterial toxins can prod!ce pro o!nd shoc$( I the dia&nosis is s!spected the trans !sion sho!ld be discontin!ed and the blood c!lt!red( Emer&enc% treatment incl!des administration o adrener&ic bloc$in& a&ents" ox%&en" antibiotics" and" in some cases" /!dicio!s trans !sion( Em*olism Altho!&h air embolism has been reported as a complication o intraveno!s trans !sion" health% animals tolerate lar&e amo!nts o air in/ected intraveno!sl% at a rapid rate( It has been s!&&ested that the normal ad!lt &enerall% can tolerate an embolism o 288 mL o air( Smaller amo!nts" ho#ever" can ca!se alarmin& si&ns and

ma% be atal( Mani estations o veno!s air embolism incl!de a rise in veno!s press!re" c%anosis" a ?mill #heel@ m!rm!r heard over the precordi!m" h%potension" tach%cardia" and s%ncope( -eath !s!all% is related to primar% respirator% ail!re( Treatment consists o placin& the patient on the le t side in a head*do#n position #ith the eet !p( Arterial air embolism is mani ested b% di66iness and aintin&" loss o conscio!sness" and conv!lsions( Air ma% be visible in the retinal arteries" and b!bbles o air ma% lo# rom transected vessels( .lastic t!bes !sed or trans !sion have also emboli6ed a ter the% have bro$en o #ithin the vein( .lastic t!bes have passed into the ri&ht atri!m and the p!lmonar% arter%" res!ltin& in death( Emboli6ed catheters have been removed s!ccess !ll%( T rom*o/ le*itis .rolon&ed in !sions into peripheral veins !sin& either needles" cann!lae" or plastic t!bes are associated #ith s!per icial veno!s thrombosis( Intraveno!s in !sions that last more than G h are more li$el% to be ollo#ed b% thrombophlebitis( There is an increased incidence in the lo#er limb as compared to !pper limb in !sions( Treatment consists o discontin!ation o the in !sion and local compression( Embolism rom s!per icial thrombophlebitis o this nat!re is rare( Overtrans !sion and .!lmonar% Edema Overloadin& the circ!lation is an avoidable complication( It ma% occ!r #ith rapid in !sion o blood" plasma expanders" and other l!ids" partic!larl% in patients #ith heart disease( In order to prevent this complication" the central veno!s press!re sho!ld be monitored in these patients and #henever lar&e amo!nts o l!id are administered( 3irc!lator% overloadin& is mani ested b% a rise in the veno!s press!re" d%spnea" and co!&h( Eales &enerall% can be heard at the base o the l!n&s( Treatment consists o stoppin& the in !sion" placin& the patient in a sittin& position" and" occasionall%" veno!s section or removal o blood( Altho!&h ac!te p!lmonar% edema occ!rs more re0!entl% a ter lar&e trans !sions" it has been reported in patients receivin& small trans !sions( A s%ndrome that can be con !sed #ith p!lmonar% edema consists o postoperative h%poxia" seen in patients #ho have !nder&one cardiac s!r&ical treatment and extracorporeal b%pass proced!res( A dama&in& actor apparentl% is carried b% the per !sin& blood" and immat!re plasma cells are o!nd in the interalveolar tiss!e( The illness represents an imm!ne response to blood( The incidence is red!ced b% emplo%in& the hemodil!tion techni0!e o p!mp primin&( Transmission of (isease Malaria" 3ha&as= disease" br!cellosis" and s%philis are amon& the diseases that can be transmitted b% blood trans !sion( S%philis has been reported a ter the trans !sion o platelets( The stora&e temperat!re !sed or all other blood components '9R3 or lo#er, $ills the spirochete( The inc!bation period ran&es rom 9 #ee$s to 9 months( The irst mani estation is the s$in rash o secondar% s%philis( 3!re is readil% achieved #ith brie penicillin therap%( Malaria can be transmitted b% all blood components" incl!din& platelets" resh ro6en plasma" and ro6en or de&l%ceroli6ed red cells( The species most commonl% implicated is .lasmodi!m malariae( The inc!bation period ran&es rom G to +88 da%sD the initial clinical mani estation is sha$in& chill and

spi$in& ever( 3%tome&alovir!s '3M1, in ection" ca!sin& a s%ndrome resemblin& in ectio!s monon!cleosis" #as commonl% observed a ter open*heart s!r&er% #hen lar&e amo!nts o heparini6ed blood #ere !sed to prime the p!mp( The most si&ni icant morbidit% and mortalit% occ!rs a ter trans !sion o 3M1*in ected blood in lo#*birth*#ei&ht in ants born o mothers #ho #ere 3M1 antibod%Tne&ative( .osttrans !sion viral hepatitis remains the most common atal complication o blood trans !sion( It is estimated that or ever% case o icteric posttrans !sion viral hepatitis there are o!r anicteric cases" man% o #hich are as%mptomatic( Hepatitis is ca!sed either b% hepatitis B vir!s" or the non*A" non*B vir!ses" incl!din& 3( The inc!bation period o the ormer is !p to B months" the latter=s ma% be as short as 2 #ee$s( Serolo&ic mar$ers or hepatitis B s!r ace anti&en 'HBsA&, and hepatitis 3 are available" and collectin& a&encies are re0!ired to test all !nits o blood or these anti&ens( The ris$ o hepatitis transmission per !nit o blood is 8(8)5 percent( The clinical mani estations o hepatitis incl!de lethar&% and anorexia as part o anicteric disease" icter!s" and chronic liver disease( HBsA& persists in abo!t )5 percent o patients #ho develop ser!m hepatitis o t%pe B( There is no ris$ rom h!man ser!m alb!min and other plasma protein ractions( Imm!ne &lob!lin is e ective in preventin& t%pe A hepatitis b!t is inconsistent in preventin& t%pe B hepatitis( Accidental sel *inoc!lation #ith material that is de initel% $no#n to contain HBsA&" or trans !sion o blood that is HBsA&*positive" constit!tes an indication or immediate !se o imm!no&lob!lin 'h!man, anti*HBsA&( The recommended dose is 8(82 to 8(8B mL:$& B7 o I&G &iven as an intram!sc!lar in/ection( A vaccine has been developed a&ainst HBsA&" and it is recommended that all s!r&eons !nder&o vaccination( The incidence o AI-S ollo#in& blood trans !sion has been estimated to be one case per 225"888 patients trans !sed" and blood collectin& a&encies have ta$en meas!res to precl!de donors in hi&h*ris$ &ro!ps and to appl% screenin& techni0!es( 'Biblio&raph% omitted in .alm version, Bac$ to 3ontents &raph% omitt