L36-L37 Abnormal Hemostasis Flashcards
Thrombotic and bleeding disorders can result from abnormalities of what three things?
- Platelets
- Endothelial function
- Coagulation abnormalities
Both ___ and ___ disorders of platelets result in bleeding and thrombotic disorders (may be acquired or congenital).
Quantitative; qualitative
What are quantitative platelet disorders?
Diseases that result in a decrease or increase in the # of platelets
What is thrombocytopenia?
Decreased platelet count; results in bleeding
What is thrombocytosis?
Increased platelet count (benign); bleeding and thrombosis may occur
What is thrombocythemia?
Increased platelet count (clonal proliferation)
What are the general causes of thrombocytopenia?
- Alterations in bone marrow
- Hereditary thrombocytopenia
- Abnormal hematopoiesis (acquired)
- Drug induced thrombocytopenia
- Dilutional
What is ITP?
Immune thrombocytopenic purpura (IgG mediated, induced by autoantibody)
What is TTP?
Thrombotic thrombocytopenic purpura (abnormal vWF multimers form and bind lots of platelets, creating arterial thrombi)
Thrombocytopenia is also seen in ___, which can be confused with TTP.
HUS
What are the general causes of thrombocytosis?
- Splenectomy
- Reactive (cancer, infection, drugs)
- Autonomous (clonal disorder)
What are qualitative platelet disorders?
Platelet numbers are normal; function is impaired
- Disease-induced (liver disorders, paraproteinemia)
- Drug-induced (aspirin, NSAIDs)
- Diet-induced (omega 3 fatty acids)
What are 3 congenital disorders of platelets resulting in bleeding?
- Glanzmann’s thrombasthenia
- Bernard-Soulier disease
- Storage pool disease
What is Glanzmann’s thrombasthenia?
Autosomal recessive defect of 2b3a leading to defective aggregation and increased bleeding time
What is Bernard-Soulier disease?
Autosomal recessive defect of 1b leading to defective adhesion and increased bleeding time
What is storage pool disease?
Decreased dense granule content, no aggregation
What are 2 other acquired disorders of platelets?
- Metabolic disorders (uremia)
2. Myeloproliferative disorders (polycythemia vera, granulocytic leukemia, myelofibrosis)
What are vascular disorders?
Non-thrombocytopenic purpuras; no serious bleeding, platelet function and coagulation are normal, easy bruising, bleeding from mucosa, purpura, vasculitis
What is an important congenital subendothelial disorder?
Ehler Danlos syndrome (hyperflexible skin, hypermobile joints)
What are two mechanical disorders?
- Orthostatic purpura
2. Mechanical purpura
What is one nutritional disorder?
Scurvy (vitamin C deficiency)
What is a PT test used for?
Diagnosis of issues in the extrinsic pathway (2, 5, 7, 10, fibrinogen)
What is the APTT test used for?
Diagnosis of issues in the intrinsic pathway (8, 9, 11, 12 - technically measures all factors except 7, 13, C, and S)
Most defects due to coagulation factors result in ___.
Bleeding
What is Hemophilia A?
Factor 8 coagulant deficiency
What is Hemophilia B?
Factor 9 deficiency (Christmas disease)
Hemophilia A and B are transmitted as ___.
Sex-linked recessive
What is von Willebrand’s disease?
Hemostatic defect due to von Willebrand factor defect
What are the 3 types of VW disease?
Type 1 and 3: decrease in circulating level of factor
Type 2: qualitative defect
Compare the APTT result in hemophilia vs. VW disease.
H: prolonged
VW: slightly elevated due to mild reduction in factor 8
Compare the platelet function in hemophilia vs. VW disease.
H: normal
VW: hemostatic function impaired due to impaired adhesion of platelets to collagen
Compare the bleeding time in hemophilia vs. VW disease.
H: no effect
VW: increased
Excessive activation of the fibrinolytic system can cause ___.
Bleeding
What aspects of the fibrinolytic system contribute to bleeding?
Decrease in the fibrinogen concentration; increase in degradation product formation
What happens in primary fibrinolysis?
Only fibrinogen is converted into fibrinogen degradation products (rather than fibrin) –> no clotting
Primary fibrinolysis is seen in what syndrome?
Dead fetus syndrome (abruptio placenta)
What happens in secondary fibrinolysis?
Both fibrin and fibrinogen are digested by plasmin; also associated with digestion of clotting factors and consumption of platets; leads to DIC
Discuss the pathogenesis of sepsis associated DIC - what causes release of tissue factor?
- Massive tissue destruction
- Sepsis
- Endothelial injury
Discuss the pathogenesis of sepsis associated DIC - release of tissue factor causes what?
Widespread microvascular thrombosis
Discuss the pathogenesis of sepsis associated DIC - what does widespread microvascular thrombosis cause?
- Activation of plasmin; this leads to fibrinolysis and fibrin split products, which inhibit clotting, as well as proteolysis of clotting factors
- Vascular occlusion, which leads to ischemic tissue damage
- Consumption of clotting factors and platelets
All of this leads to bleeding
What is caused by a deficiency of alpha2-antiplasmin?
Increased fibrinolysis and bleeding
