Julius Arkhe Arevalo Atacador UPMSHS MD 14th Batch

Blood transfusion became practical early in the twentieth century with the discovery of blood group antigens and methods for typing and matching donor to recipient. development of fortified anticoagulants to improve red blood cell preservation, the biocompatible plastic bag system that allows blood fractionation, and expanded testing to prevent disease transmission, modern concepts of blood component therapy gradually evolved

Transfusion practice is now a complex therapeutic discipline, requiring all the skills of a trained clinician. The transfusion of a blood component can never be taken lightly; it should only be given for a good reason after careful evaluation of the clinical situation.

has largely been replaced by component therapy some blood centers do offer modified whole blood (whole blood minus the platelet component) for the treatment of large-volume blood loss can save time, cost less, and expose the recipient to fewer donors

In the patient with massive blood loss, transfusion of modified whole blood sustains coagulation factor levels in plasma, but platelets need to be replaced separately

BLOOD COMPONENTS FOR TRANSFUSION 1. Red blood cells Packed red blood cells Leukodepleted red cells Washed red cells Irradiated red cells Frozen (deglycerolized) red cells CMV-negative red cells 2. Platelets Pooled random donor platelets Single donor pheresis platelets HLA-matched single donor platelets 3. Coagulation factors Fresh frozen plasma Cryoprecipitate

used to treat most anemias, regardless of cause, to improve oxygen delivery to tissues A unit of packed cells contains all of the red blood cells from a 450-mL unit of whole blood (~200 mL of red blood cells) suspended in 130 mL of plasma/acid citrate dextrose (ACD) solution to give a hematocrit of about 60%

A red blood cell unit also contains sufficient white blood cells and platelets to induce alloimmunization to HLA antigens, and with storage, to increase levels of cytokines capable of producing a febrile transfusion reaction

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Leukodepleted red blood cells

Packed red blood cells can be passed through a microfiber filter to remove 99.9% of leukocytes, with a loss of 1520% of the red blood cells. reduces the risk of HLA alloimmunization, cytomegalovirus (CMV) transmission, and if the cells are filtered prior to storage, cytokine-induced febrile reactions.

- This product should always be used in a patient with a history of febrile reactions and is the preferred product for patients in need of long-term transfusion support (eg, hematopoietic malignancies, aplastic anemia, transplantation).

2. Washed red blood cells - are suspended in saline after repeated saline washes - This procedure removes 85% of the leukocytes and 99% of the original plasma - indicated for patients with paroxysmal nocturnal hemoglobinuria and cold agglutinin disease (IgM cold antibody hemolytic anemia), where transfused complement in the plasma could exacerbate the disease process

These units are also used in IgA-deficient patients who because of their tendency to form anti-IgA antibodies are at risk for an anaphylactic reaction when receiving a transfusion containing normal plasma

3. Frozen (deglycerolized) red blood cells - cryopreserved red blood cells - once deglycerolized, are suspended in saline for transfusion - they can be used for the same indications as washed cells - principal use of frozen red blood cells, however, is their long-term storage for the treatment of patients with rare blood types who are difficult to crossmatch.

4. Irradiated red blood cells - This product is indicated for markedly immunocompromised patients in whom transfused lymphocytes might induce TAGVHD - Red blood cells are exposed to a minimum dose of 2500 rads prior to transfusion

5. CMV-negative red blood cells - This is a preferred product for CMVnegative recipients, especially those who are undergoing bone marrow transplantation.

Hospitals have strict transfusion guidelines that spell out when red blood cell transfusions are indicated whether for blood loss related to a procedure, significant anemia (hemoglobin level < 7-8 g/dL unless age, illness, or cardiopulmonary disease mandates a higher hemoglobin level), or ongoing hemorrhage

red blood cells do provide some volume expansion, actively bleeding patients will require further volume support with electrolyte, colloid, or plasma transfusions Each unit of packed red blood cells given to an average-sized adult will increase the hemoglobin level by 1 g/dL (~3% hematocrit rise).

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ABO System To avoid a major adverse reaction, transfused blood must be type specific. Type O patients have both anti-A and anti-B in their serum and, therefore, must receive type O blood. Type B patients carry anti-A, and type A patients carry anti-B. Only type AB patients can accept red blood cells of any type without risk. Type O red blood cells, because they are antigenically silent, can be given to A, B, and AB patients in an emergency. Life-threatening hemolytic transfusion reactions are generally associated with transfusions of type A blood to type O recipients, especially those who carry a high-titer hemolytic anti-A alloantibody

2. Rh System - The Rh blood group system includes five important antigens D, C, c, E, and e, coded by two highly homologous genes on chromosome 1 - prevalence of Rh-negative (D-negative) people varies by race, from as high as 15% in Caucasians to less than 1% in Asians - D-negativity is most often due to a deletion of the entire RHD gene, setting the stage for a strong immune response upon exposure to D antigen with transfusion or pregnancy - formation of anti-D is not a certainty; naive Rh-negative women come to term without sensitization by a D-positive fetus more often than not. - the risk of Rh immunization can be reduced to near zero by the administration of hyperimmune anti-D serum (Rh immune globulin) within 72 hours postpartum or following a mismatched transfusion. - hemolytic disease of the newborn can result from antibody formation to C, c, E, and e or a minor blood group antigen.

3. Kell System - The Kell antigens are coded by a gene on chromosome 7. - Antibodies to the Kell blood group system (anti-K) have been associated with rapid destruction of Kell-positive red blood cells following transfusion and an anemia of the newborn secondary to marrow suppression, not hemolysis.

4. Duffy System - The Duffy system consists of two polymorphic antigens Fya and Fyb, reflecting a single amino acid difference. - Most African Americans (and 100% of West Africans) are Fy(a-b-), perhaps through natural selection inasmuch as the Duffy antigen is an obligate receptor for Plasmodium vivax and Plasmodium knowlesi. - Patients with this phenotype may form antiFya after transfusion but not anti-Fyb because the Fy(a-b-) recessive gene still encodes normal amounts of Fyb protein in nonhematopoietic tissues.

5. Other minor blood group antigens a. The Kidd genelocated on chromosome 18, codes for two antithetical antigens-aJka and Jkb as well as Jk3. Anti-Jkb and Jk are potent antibodies capable of delayed hemolysis after transfusion. b. The Diego antigens- Dia and Dib, have also been implicated as a cause of hemolytic disease of the newborn. Deficiency in band 3, which carries both the Diego and Wright antigens, has been associated with hereditary spherocytosis.

c. The MNSs system- is expressed on the red blood cell surface as two homologous proteins, glycophorin A (M and N antigens) and glycophorin B (S and s antigens). S and s antibodies have been associated with hemolysis, while M and N antibodies have not. d. Lewis antigens- (Lea and Leb), P antigen, and the Ii antigen system are targets for IgM cold-reacting antibodies seen with cold agglutinin disease, Epstein-Barr virus and mycoplasma infections, and lymphomas. - The rare P- or I-negative patient can form strong alloantibodies with transfusion.

Each unit of donated blood is routinely typed prior to storage for both ABO and Rh (D) antigens the plasma from the unit is tested for the presence of anti-A and anti-B and for other minor blood group antibodies using the indirect antiglobulin test For the purpose of screening, this test uses a standard set of red blood cells, which express a full range of blood group antigens, to detect plasma IgG antibodies against minor blood group antigens

Prior to transfusion, the donor and the recipient must be matched for compatibility. This process includes selecting ABO and Rh type-specific blood, screening the recipient for serum antibodies, and performing a major crossmatch (testing donor cells against patient serum for ABO compatibility). This process is made much more difficult if the patient has a positive indirect antiglobulin test for minor blood group antibodies. In this situation, the antigen specificity of the antibodies must be identified to permit selection of donor units that lack the target antigen

Transmissible Disease Tests

Agent T pallidum (syphilis) Hepa B (HBV) Hepa C (HCV) CMV HIV-1 and -2 HTLV-1 and -2 Antibody HBsAg, nucleic acid testing Viral protein antibody, nucleic acid testing Virall antibody Viral antibodies, nucleic acid testing Viral antibody Test

West Nile virus Babesiosus

Nucleic acid testing Antibody, nucleic acid testing (experimental)

Fully crossmatched red blood cells: Patients requiring an elective transfusion of red blood cells should receive fully crossmatched blood. includes typing, screening for antibodies, and performing a major crossmatch of each unit Depending on the workload in the blood bank, several hours may be required before blood will be available for transfusion

Type and screen: For surgical procedures where blood is only occasionally needed, it is common practice to determine the patient's ABO and Rh type and test the serum for red blood cell antibodies. - If none are detected, type-specific blood is set aside but the major crossmatch is not performed. - if the patient requires transfusion, crossmatched red blood cells can be made available within 15 minutes, or if it is an emergency, the type-specific blood can be transfused and the crossmatch performed post facto to detect any mismatch.
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Emergency crossmatch: - When blood is needed urgently, the blood bank can type and crossmatch red blood cells in 15- 30 minutes, once a sample of the patient's blood is available. F - or patients who have already received transfusions, the blood bank usually has a sample on hand. If not, an extra delay can result. - Antibody screening results will generally not be available prior to transfusion, but this poses almost no risk to the patient.

Uncrossmatched/type-specific red blood cells: If a patient cannot wait the 15- 30 minutes required to obtain crossmatched blood, ABO type-specific or, in a situation where the patient's blood type is unknown, type O-(Rh)negative red blood cells can be transfused. When the supply of O-negative cells is exhausted, Opositive red blood cells can be substituted with little risk to the recipient. chance of a reaction to Rh-positive cells is very small; < 0.5% of patients will both be Rh negative and have an anti-D antibody. risk of inducing an antibody is only of importance in young women with childbearing potential. A tube of the patient's blood should always be drawn prior to transfusion to avoid confusion and allow the blood bank to start crossmatching additional units. Since the supply of O-negative red blood cells is always limited, conversion of the patient to typespecific, crossmatched blood should occur as soon as possible.

RBC should never be administered without the informed consent of the patient. The risks involved and the alternatives to transfusion need to be explained, and the patient's consent needs to be documented. It is essential that any transfusion be taken very seriously

Filter sets Red blood cells are administered intravenously The traditional filter set traps clots and any large particulate debris. Microaggregate filters have been used to exclude platelet, leukocyte, and fibrin microemboli, which may play a role in acute respiratory distress syndrome and complications of cardiovascular surgery. However, microfiber leukodepletion filters have largely replaced the use of microaggregate filters. They have the added benefit of reducing the incidence of febrile reactions to leukocyte products and preventing CMV transmission

Rate of administration will vary with the clinical situation. When red blood cells are given electively to treat a chronic anemia, the first 25- 50 mL of each unit should be administered slowly over 10-15 minutes, while closely monitoring the patient. If no immediate adverse reaction is observed, the rate can then be increased. The overall rate will vary depending on the patient's cardiovascular status, the number of units to be transfused, and the patient's tolerance. Signs of volume overload or the appearance of a delayed transfusion reaction, such as fever and chills, will necessarily cut short the transfusion event.

Red blood cells should never be diluted to decrease viscosity and improve the rate of infusion. The use of fortified anticoagulant solutions (Adsol, etc) for storage maintains the unit's hematocrit at about 60%, so infusion flow rates should not be a problem. If red blood cells are piggybacked to an existing indwelling catheter, only isotonic saline solution should be used in the main line. Exposure to even small amounts of dextrose in water or hypotonic saline can result in clumping and hemolysis; lactated Ringer's solutions can cause clot formation. When a higher rate of infusion is required, as with massive blood loss, a pressure bag or cuff can be used to speed delivery. However, flow will not significantly increase unless a large-bore catheter or needle (18 gauge or higher) is in place.

Warming is rarely necessary when red blood cells are given slowly. It is recommended, however, when multiple units are given at rates exceeding 50 mL per minute, the patient has a high-titer cold agglutinin, or for a newborn receiving an exchange transfusion. should always be done using an approved device designed specifically for blood warming. Never use a microwave to warm blood! Hypocalcemia secondary to citrate toxicity is rarely seen with red blood cell transfusions, even when multiple units are given in cases of massive blood loss. It is seen in adults undergoing pheresis procedures and newborns needing exchange transfusion.

Hemolytic reactions ABO-incompatible, intravascular hemolysis Delayed, extravascular hemolysis Febrile reactions Cytokine-induced fever HLA alloimmunization reactions Allergic reactions Alloimmunization, decreased platelet survival IgE-related histamine reactions IgA-deficient anaphylaxis Acute lung injuryleukocyte antibodies Immune compromise Transfusion-associated GVHD Post-transfusion immunomodulation Infectious agent transmission Bacterial contamination Cytomegalovirus EBV seroconversion Viral hepatitis (B, C, other) HIV and HTLV-1 Other adverse effects Circulatory overload Iron overload

The key to preventing a life-threatening reaction to transfusion is to closely monitor the patient during and after the transfusion. The most frequent signs and symptoms that accompany a hemolytic reaction include fever, chills, chest and low back pain, hypotension, and often a feeling of impending doom. The transfusion must be discontinued immediately and a venous blood sample drawn to look for intravascular hemolysis and to repeat the crossmatch.

Delayed hemolytic transfusion reactions seen in patients who develop antibodies to one of the minorr blood group antigens, most often to the Rh system (E or c), Kell, Fya, or Jka. this occurs in a patient who has already been immunized from a past pregnancy or transfusion but is not detected by the routine serum antibody screen. The extravascular red blood cell hemolysis that results is usually clinically silent, other than a surprising fall in the hematocrit within a few days or even weeks. If this happens, a repeat of the serum antibody screen will usually detect the antibody.

Patients who have had multiple transfusions and patients receiving red blood cells that have been stored for long periods without leukodepletion often experience fever and/or chills, beginning, during, or several hours after the transfusion. This effect is not a hemolytic reaction. It is caused by cytokines released by contaminating leukocytes or alloantibodies to leukocyte and platelet HLA antigens. Transfusion with leukodepleted red blood cells, together with premedicating the patient with hydrocortisone and/or acetaminophen can greatly ameliorate this reaction. Patients who have had several febrile reactions to blood should receive only leukodepleted red blood cells, preferably cells leukodepleted at the time of donation.

Simple allergic reactions are common with transfusion. - The incidence of hives and mild bronchospasm, perhaps related to IgErelated histamine response to infused plasma proteins, cytokines, or both, has been estimated to occur in 2-10% of transfusions. o Atopic individuals may be at greater risk - Treatment of affected patients with diphenhydramine, 25- 50 mg orally or intravenously, usually ameliorates this reaction so that transfusion can be completed.

IgA-deficient patients are at considerable risk for a severe anaphylactic reaction, if they have formed anti-A antibodies. Once identified, they should only receive a transfusion of washed or deglycerolized red blood cells. Any plasma component transfusion should be with product from an IgAdeficient donor.

Red blood cell transfusions carry a special risk for the severely immunocompromised patient. Only irradiated red blood cells and, if the patient is CMV negative, CMV-negative units should be used. Unirradiated red blood cells contain enough viable lymphocytes to cause GVHD. Red blood cell transfusions are also believed to modulate the immune system. They have been used to induce tolerance in patients receiving renal transplants and may be associated with a higher incidence of postoperative infection and second cancers

Although the risk of disease transmission is very small, bacterial and viral infections secondary to transfusion still do occur. - The risk of infection for hepatitis B, HCV, and HIV from well-screened, fully tested blood is approximately 1 in 50,000 to 1.5 million units/components transfused.

Transfusion-related acute lung injury a severe, sometimes fatal pulmonary reaction characterized by noncardiogenic pulmonary edema and hypotension, has been described in association with leukocyte or HLAspecific complement-activating antibodies in transfused plasma. The passive transfer of these antibodies to the donor's leukocytes results in aggregation, activation, and microvascular pulmonary damage

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Autologous Blood opportunity still exists for a clerical error or mistake in patient-unit identification. Bacterial contamination can still occur. There is also a limited set of circumstances when autologous blood storage makes sense, such as in an elective surgery procedure where transfusion of 2- 4 units of red blood cells is predictable and sufficient. Orthopedic procedures such as total hip and major knee operations are another example. storage is unnecessary in elective surgeries where blood loss is usually minimal (< 1-2 units) or major procedures requiring more than 4 units. Red blood cell salvage also has been used in major surgical procedures to reduce the need for allogeneic transfusion.

2. Perioperative erythropoietin therapy - Is expensive, can reduce the need for transfusion. - It has been used to increase the amount of autologous blood donated and stored. - It has also been shown to increase in vivo erythropoiesis preoperatively and postoperatively. - When given for a week or more before and continuing for up to 10 days after major elective surgery, the immediate postoperative anemia is less and a 5-6% rise in the hematocrit level can be seen by the tenth postoperative day. - The number of units of red blood cells transfused is also less. - Success, however, is very much dependent on the level of iron supply during treatment, so aggressive iron supplementation is essential.

concentrates can be prepared from individual units of donated blood (random donor platelets) or harvested from a single donor by cytapheresis (pheresis platelets). In the United States, where blood is routinely collected using a multibag system, platelet rich plasma (PRP) is separated from red blood cells by centrifugation at a low G force. The PRP is then transferred to a smaller connected bag, where following a second spin at a higher G force to further concentrate the platelets, excess supernatant plasma is transferred to a third bag. About 50 mL of plasma/ACD solution is left behind. This method recovers about 60- 70% of the platelets from the original unit of blood, together with a portion of the leukocytes and a few red blood cells (< 0.3 mL). E:\Hematology in Clinical practice.CHM Most platelet concentrates contain 108 or more leukocytes, which is enough to induce alloimmunization and cause febrile transfusion reactions

Random donor platelet concentrates can be stored for up to 5 days at 20- 24C. the normal survival of platelets is 10 days, recovery after transfusion is predictably reduced by 25% or more, mostly because of splenic sequestration. At the time of transfusion, 4- 8 units of random donor platelets are pooled. When transfused into an average-sized adult, 6 units (a six-pack) of random donor pooled platelets increase the platelet count by ~50,000/L, usually enough to control any bleeding tendency. In patients with a qualitative platelet defect (eg, aspirin treatment), transfusion of platelets in an amount equivalent to 10- 20% of the circulating platelet count generally is sufficient to stop the bleeding

Platelets in amounts equivalent to 6- 10 pooled random donor units can be harvested from a single donor by cytapheresis. Each plateletpheresis unit has a volume of 200- 500 mL and contains ~3 1011 platelets. apheresis platelets can be stored for up to 5 days at 20-24C. Single donor apheresis platelet units are processed like platelets prepared from a unit of whole blood. They are ABO and Rh typed and tested for transmissible disease and, therefore, are only available for transfusion once testing results are known, usually 24 hours after the draw. Most blood centers also provide single-donor apheresis platelets drawn from a registry of HLAtyped donors, as a strategy to improve platelet recovery in the patient who has become alloimmunized.

The routine availability of platelet concentrates for transfusion has revolutionized the management of thrombocytopenia. Myeloablative chemotherapy for hematologic malignancies and bone marrow transplantation are two situations where platelet transfusions are an absolutely essential part of the therapeutic regimen. Platelet therapy is used both to prevent bleeding and to treat the actively bleeding patient with thrombocytopenia.

platelets should be ABO type-specific if possible. A-antigen is absorbed to the surface of platelets of type A patients, so a transfusion of incompatible platelets may result in a somewhat shortened survival. ABO-incompatible platelets can be given when the supply of type-specific platelets runs short, without risk to the patient. If large volumes of type-O donor plasma (> 500 mL), containing anti-A and anti-B, are transfused to a type A, B, or AB patient, the direct antiglobulin test may turn positive and both transfused platelet and patient red blood cell survivals may be reduced. Rh antigens are not present on the platelet surface, so the Rh type need not be considered. However, the small number of red blood cells present in platelet preparations from Rh-positive donors can induce anti-D antibody in an Rh-negative patient. This will not affect platelet survival and is only of consequence when the patient is of childbearing age.

Patients receiving transfusions of multiple units of platelets are likely to become refractory, defined as a failure to achieve a respectable platelet count increment immediately following or within 1 hour of transfusion. Depending on the clinical illness, the cause may be multifactorial. Antiplatelet antibodies in the patient with idiopathic thrombocytopenic purpura or nonimmune factors such as sepsis, disseminated intravascular coagulation, and hypersplenism can all be responsible. alloimmunization to platelet and leukocyte HLA antigens also must be considered, especially for those patients who receive platelet transfusions over a long period, such as patients with hematologic malignancies or aplastic anemia. Patients receiving transfusions primarily with single-donor apheresis platelets may be at lower risk, perhaps because of less donor exposure. Prestorage leukodepletion of platelet units also reduces the risk of alloimmunization.

To rule in alloimmunization, patients are cross-matched with multiple donors, usually an index pool drawn from the central donor institution. When there is a high percentage of reactivity, the patient is considered to be alloimmunized. Such patients should then receive transfusions with 2-dayold ABO identical, HLA-matched platelets, drawn from a matched sibling or an HLA-matched unrelated community donor(s). This approach often yields an improved post-transfusion recovery, confirming a significant component of alloimmunization. Platelet crossmatching using a solid-phase red blood cell adherence assay has also been used to identify compatible donors and may be superior to HLA matching. When crossmatched or HLA-matched platelets fail, continued transfusion of random donor platelets may be of clinical benefit even though there is no apparent improvement in the platelet count

platelets should be transfused using a standard filter set to exclude fibrin clots and debris. Microfiber filters are available to leukodeplete the platelet unit at the time of transfusion at the cost, however, of a 20- 25% loss of platelets. Leukodepletion also helps prevent CMV transmission and alloimmunization, whether random or apheresis platelets are used. Platelet units should be leukodepleted prior to storage to decrease cytokine production; this will reduce the severity of fever and chills in the sensitized patient. Sensitized patients should be premedicated and the platelets infused at a slower rate. Even in the face of severe fever and chills, platelet recovery may be respectable. Immunocompromised patients should receive irradiated platelets.

The effectiveness of a platelet transfusion can only be determined by its impact on the patient's platelet count and the control of ongoing hemorrhage . Measurement of the patient's platelet count at 1, 4, and 24 hours following transfusion can ideally be used to assess recovery (the incremental rise in the platelet count at 1 hour), and survival (the fall in the platelet count at 4 and 24 hours). This information is essential for planning subsequent platelet transfusions. The pattern of the response may also help identify the cause of apparent refractoriness.

Because platelets are stored at room temperature, the risk of bacterial contamination is significantly increased. The rate of contamination of platelets is estimated to be as high as 0.1% of units transfused, although apheresis platelets generally pose a lower risk. Sepsis or high (> 102 F/39C) or persistent fever following transfusion should be reason to draw blood cultures and, if available, culture the remnant of the transfused unit. The FDA has now mandated that all platelet units be tested for bacterial contamination prior to transfusion. Whether this will eradicate post-transfusion sepsis should be apparent within a few years.

As an integral part of blood component therapy, blood centers prepare FFP and cryoprecipitate as respective sources of coagulation factors at physiologic levels and a concentrated product containing fibrinogen, vWF, and factor XIII. FFP is most often used in patients with liver disease or in patients who require immediate reversal of coumadin anticoagulation. Both products are used for massive blood loss, where low factor levels can result from the combination of colloid or electrolyte infusions and large volume red cell transfusions. Low levels of coagulation factors, especially fibinogen and the common pathway factors, also can result from the consumptive coagulopathy associated with trauma.

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Fresh Frozen Plasma is harvested from donated whole blood as part of the preparation of platelet concentrates. Using a three-bag system, the excess plasma/ACD solution left after the platelet concentrate centrifugation step (~250 mL) is transferred to the third bag, separated, and frozen within 8 hours of collection. can then be stored for up to 1 year at 20C. At the time of transfusion, it is thawed at 37C, a process that takes 30- 60 minutes. Once thawed, it should be transfused within 12 hours to guarantee adequate coagulation factor levels and sterility. It should be ABO compatible with the patient's red blood cells.

used in several clinical situations. The dose will depend on the type and severity of the coagulation abnormality. To sustain factor levels in a patient with massive blood loss, the number of FFP units transfused is determined by the clinical setting, number of red blood cell units used to resuscitate the patient (the dilution factor), and results of coagulation tests [prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen levels]. Microvascular bleeding is most often related to thrombocytopenia or platelet dysfunction and should be treated with platelet transfusions. As a general rule, a six-pack of platelets should be transfused for every 6- 10 units of red blood cells transfused, with additional platelets given according to the clinical situation.

When used to treat a PT or PTT > 1.5-2 times control (factor levels below 15- 25% of normal), at least 6 units must be given to achieve factor levels of > 30%. Each unit increases coagulation factor levels by only 2-3%. This may involve the transfusion of close to 1500 mL of plasma/ACD solution, and unless the patient is actively bleeding, can result in volume overload and congestive failure. subsequent infusions may be limited by the large volumes required for an appreciable impact on factor levels. In addition, any sustained benefit from FFP therapy requires a normal level of coagulation factor production by the liver. Patients with severe liver disease will benefit only briefly, often for only a few hours and no more than a day, before the transfused coagulation factors, especially factor VII, decline and the PT rises once again.

Allergic reactions to FFP are similar to but frequently more intense than those seen with red blood cells and platelets. Urticaria, bronchospasm, and laryngeal spasm are common. An immediate and impressive leakage of oncotic protein out of the intravascular space can result in a fall in blood pressure and a rise in hematocrit level. This effect can add considerable confusion to the management of a surgery patient or a patient experiencing a major blood loss. Infusions of FFP have also been associated with sudden marked symptomatic thrombocytopenia, so-called post-transfusion purpura. Febrile reactions are uncommon, since FFP is free of leukocytes, platelets, and cytokines.

2. Cryoprecipitate is prepared by flash freezing fresh plasma and then thawing it at 4C. This process leaves a residual precipitate, once the plasma/ACD supernatant is removed, of cryoproteins, including fibrinogen, von Willebrand factor (vWF), and factors VIII and XIII. The procedure recovers 150-200 mg of fibrinogen and 80-100 units of factor VIII/vWF in 15 mL of residual plasma, a tenfold concentration over FFP. can then be stored for up to 1 year at 20C. In treating a patient, several units are thawed, pooled, and transfused within 4 hours.

Each unit will raise a patient's fibrinogen level by only 5-10 mg/dL. when it is used to treat hypofibrinogenemia (fibrinogen levels < 100 mg/dL), a minumum of 10 units need to be pooled, sufficient to increase the circulating fibrinogen level in an average-sized adult by at least 100 mg/dL. Following transfusion, the fibrinogen level should be monitored and repeated infusions given to maintain levels > 100 mg/dL. The amount required will vary with the rate of fibrinogen consumption

The treatment of von Willebrand disease is often empirical and depends on the disease subtype. In the past, doses of cryoprecipitate ranged from 20 to 30 pooled U/day in an adult with severe type 1 or 3 disease to < 10 U/day with mild disease. With the development of virally inactivated, highly purified factor VIII concentrates, cryoprecipitate is no longer the product of choice in the treatment of vWD. Cryoprecipitate is used in the operating room for the preparation of fibrin glue for topical surgical hemostasis.

Like FFP, it can cause an immediate IgEhistamine-driven allergic reaction. In the past, hemophiliac children who received large volumes of cryoprecipitate were frequently exposed to HCV. Human parvovirus B19 also can be transmitted by cryoprecipitate. Although parvovirus infection is characterized by little more than transient polyarthritis and an exanthema in children and young adults, pregnant women and patients with hemolytic anemias are at special risk, such as for the development of severe red blood cell aplasia. Testing for the presence of HPV-B19 viremia in the donor is not yet possible

Fresh Frozen Plasma Massive blood loss/transfusion Emergency reversal of warfarin therapy Factor replacement in DIC Treatment of hereditary coagulopathies Liver disease

Cryoprecipitate - Treatment of factor XIII deficiency - Fibrinogen replacement

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Purified and recombinant factor preparations Inherited factor deficiencies

The treatment of the inherited coagulopathies has changed dramatically first with the purification of individual factors from pooled plasma, then with viral inactivation methodology, and now with the synthesis of recombinant factors and growth factors, especially thrombopoietin. Recombinant technology has opened the door to a highly sophisticated approach to the management of both bleeding disorders and some thrombopathies.