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HEMOSTASIS
1. VASCULAR PHASE
2. PLATELET PHASE
3. COAGULATION PHASE
4. FIBRINOLYTIC PHASE
Lab Tests
Hemostasis •CBC-Plt
•BT,(CT)
BV Injury •PT
Tissue Factor •PTT
Neural
Reduced Platelet
Activation Fibrin
Blood flow formation
Plt Study
Morphology
Stable Hemostatic Plug Function
Antibody
NORMAL CLOTTING
Response to vessle injury
1. Vasoconstriction to reduce blood flow
2. Platelet plug formation (von willebrand factor binds
damaged vessle and platelets)
3. Activation of clotting cascade with generation of fibrin
clot formation
4. Fibrinlysis (clot breakdown)
CLOTTING CASCADE
Normally the ingredients, called factors, act like a row of
dominoes toppling against each other to create a chain
reaction.
If one of the factors is missing this chain reaction cannot
proceed.
VASCULAR PHASE
WHEN A BLOOD VESSEL IS
DAMAGED, VASOCONSTRICTION
RESULTS.
PLATELET PHASE
PLATELETS ADHERE TO THE
DAMAGED SURFACE AND FORM A
TEMPORARY PLUG.
COAGULATION PHASE
THROUGH TWO SEPARATE
PATHWAYS THE CONVERSION OF
FIBRINOGEN TO FIBRIN IS
COMPLETE.
THE CLOTTING MECHANISM
INTRINSIC EXTRINSIC
Collagen Tissue Thromboplastin
XII
XI VII
IX
VIII
V FIBRINOGEN
(I)
PROTHROMBIN THROMBIN
(II) (III) FIBRIN
FIBRINOLYTIC PHASE
ANTICLOTTING MECHANISMS ARE
ACTIVATED TO ALLOW CLOT
DISINTEGRATION AND REPAIR OF
THE DAMAGED VESSEL.
HEMOSTASIS
DEPENDENT UPON:
Vessel Wall Integrity
Adequate Numbers of Platelets
Proper Functioning Platelets
Adequate Levels of Clotting Factors
Proper Function of Fibrinolytic Pathway
LABORATORY EVALUATION
PLATELET COUNT
BLEEDING TIME (BT)
PROTHROMBIN TIME (PT)
PARTIAL THROMBOPLASTIN TIME (PTT)
THROMBIN TIME (TT)
PLATELET COUNT
NORMAL 100,000 - 400,000 CELLS/MM3
NORMAL VALUE
2-8 MINUTES
PROTHROMBIN TIME
Measures Effectiveness of the Extrinsic
Pathway
Mnemonic - PET
NORMAL VALUE
10-15 SECS
PARTIAL THROMBOPLASTIN TIME
NORMAL VALUE
25-40 SECS
THROMBIN TIME
NORMAL VALUE
9-13 SECS
So What Causes Bleeding
Disorders?
VESSEL DEFECTS ?
PLATELET DISORDERS
FACTOR DEFICIENCIES
OTHER DISORDERS
?
VESSEL DEFECTS
VITAMIN C DEFICIENCY
ACQUIRED &
HEREDITARY CONDITIONS
Vascular defect - cont.
Infectious and hypersensitivity vasculitides
- Rickettsial and meningococcal infections
- Henoch-Schonlein purpura (immune)
PLATELET DISORDERS
THROMBOCYTOPENIA
THROMBOCYTOPATHY
THROMBOCYTOPENIA
INADEQUATE NUMBER
OF PLATELETS
THROMBOCYTOPATHY
ADEQUATE NUMBER BUT
ABNORMAL FUNCTION
THROMBOCYTOPENIA
DRUG INDUCED
BONE MARROW FAILURE
HYPERSPLENISM
OTHER CAUSES
OTHER CAUSES
Lymphoma
HIV Virus
Idiopathic Thrombocytopenia Purpura (ITP)
THROMBOCYTOPATHY
UREMIA
INHERITED DISORDERS
MYELOPROLIFERATIVE DISORDERS
DRUG INDUCED
FACTOR DEFICIENCIES
(CONGENITAL)
HEMOPHILIA A
HEMOPHILIA B
LIVER DISEASE
MALABSORPTION
BROAD-SPECTRUM ANTIBIOTICS
INHIBITORS
30% of people with haemophilia develop an antibody to the
clotting factor they are receiving for treatment. These
antibodies are known as inhibitors.
These patients are treated with high does of FVIIa for bleeds or
surgery. This overrides defect in FVIII or FIX deficiency.
Major bleeding
Target: 80-100% q8-12h; 7-14 days (50U/kg)
CNS trauma, hemorrhage, lumbar puncture
Surgery
Retroperitoneal hemorrhage
GI bleeding
Adjunctive therapy
-aminocaproic acid (Amicar) or DDAVP (for mild disease only)
Complications of therapy
Formation of inhibitors (antibodies)
10-15% of severe hemophilia A patients
1-2% of severe hemophilia B patients
Viral infections
Hepatitis B Human parvovirus
Hepatitis C Hepatitis A
HIV Other
Viral infections in hemophiliacs
Negative 1 20
Hepatitis B virus only 1 1
Hepatitis C virus only 24 45
Hepatitis B and C 74 34
Blood 1993:81;412-418
Treatment of hemophilia B
Agent
Highpurity factor IX
Recombinant human factor IX
Dose
Initial
dose: 100U/kg
Subsequent: 50U/kg every 24 hours
von Willebrand Disease: Clinical Features
Diagnostic tests:
vonWillebrand type
Assay 1 2 3
Immunologic disorders
Severe allergic reaction
Transplant rejection
Disseminated Intravascular Coagulation (DIC)
Mechanism
Systemic activation
of coagulation
Release of
thromboplastic
material into Consumption of
circulation coagulation factors;
presence of FDPs
Coagulation Fibrinolysis
aPTT
PT
Fibrinogen TT
Plasmin
Thrombin Fibrinogen
Presence of plasmin
Fibrin FDP
Monomers Fibrin(ogen)
Degradation Intravascular clot
Products Platelets
Fibrin Schistocytes
Clot
Plasmin
(intravascular)
Disseminated Intravascular Coagulation
Treatment approaches
Treatment of underlying disorder
Platelet transfusion
Immune-mediated
Idioapthic
Drug-induced
Collagen vascular disease
Lymphoproliferative disease
Sarcoidosis
Non-immune mediated
DIC
Microangiopathic hemolytic anemia
Liver Disease and Hemostasis
INR >9; no bleeding Omit dose; vitamin K 3-5 mg po; repeat as necessary
Resume therapy at lower dose when INR therapeutic
Fibrin clot
Coagulation factor deficiencies
Summary
Sex-linked recessive
Factors VIII and IX deficiencies cause bleeding
Prolonged PTT; PT normal
Procedure:
Addthrombin with patient plasma
Measure time to clot
Variables:
Source and quantity of thrombin
Causes of prolonged Thrombin Time
Heparin
Hypofibrinogenemia
Dysfibrinogenemia
Elevated FDPs or paraprotein
Thrombin inhibitors (Hirudin)
Thrombin antibodies
Classification of thrombocytopenia
Associated with thrombosis Associated with bleeding
Thrombotic thrombocytopenic Immune-mediated
purpura thrombocytopenia (ITP)
Heparin-associated Most others
thrombocytopenia
Trousseau’s syndrome
DIC
Bleeding time and bleeding
5-10% of patients have a prolonged bleeding time
Most of the prolonged bleeding times are due to
aspirin or drug ingestion
Prolonged bleeding time does not predict excess
surgical blood loss
Not recommended for routine testing in
preoperative patients
Drugs and blood products used for
bleeding
Treatment Approaches to
the Bleeding Patient
Red blood cells
Platelet transfusions
Fresh frozen plasma
Cryoprecipitate
Amicar
DDAVP
Recombinant Human factor VIIa
RBC transfusion therapy
Indications
Improve oxygen carrying capacity of blood
Bleeding
Peri-operative management
Red blood cell transfusions
Special preparation
CMV-negative CMV-negative patients Prevent CMV
transmission
Non-immunologic reactions
HIV ~1/500,000
Hepatitis C 1/600,000
Hepatitis B 1/500,000
Hepatitis A <1/1,000,000
HTLV I/II 1/640,000
CMV 50% donors are sero-positive
Bacteria 1/250 in platelet transfusions
Creutzfeld-Jakob disease Unknown
Others Unknown
Platelet transfusions
Source
Platelet
concentrate (Random donor)
Pheresis platelets (Single donor)
Target level
Bone marrow suppressed patient (>10-20,000/µl)
Bleeding/surgical patient (>50,000/µl)
Platelet transfusions - complications
Transfusion reactions
Higher incidence than in RBC transfusions
Related to length of storage/leukocytes/RBC mismatch
Bacterial contamination
Splenic sequestration
Use
Factor VIII inhibitors
Bleeding with other clotting disorders
Warfarin overdose with bleeding
CNS bleeding with or without warfarin
Dose
90 µg/kg IV q 2 hr
“Adjust as clinically indicated”