L36-L37 Abnormal Hemostasis

Question 1

Thrombotic and bleeding disorders can result from abnormalities of what three things?

Answer 1

1. Platelets
2. Endothelial function
3. Coagulation abnormalities

Question 2

Both ___ and ___ disorders of platelets result in bleeding and thrombotic disorders (may be acquired or congenital).

Answer 2

Quantitative; qualitative

Question 3

What are quantitative platelet disorders?

Answer 3

Diseases that result in a decrease or increase in the # of platelets

Question 4

What is thrombocytopenia?

Answer 4

Decreased platelet count; results in bleeding

Question 5

What is thrombocytosis?

Answer 5

Increased platelet count (benign); bleeding and thrombosis may occur

Question 6

What is thrombocythemia?

Answer 6

Increased platelet count (clonal proliferation)

Question 7

What are the general causes of thrombocytopenia?

Answer 7

1. Alterations in bone marrow
2. Hereditary thrombocytopenia
3. Abnormal hematopoiesis (acquired)
4. Drug induced thrombocytopenia
5. Dilutional

Question 8

What is ITP?

Answer 8

Immune thrombocytopenic purpura (IgG mediated, induced by autoantibody)

Question 9

What is TTP?

Answer 9

Thrombotic thrombocytopenic purpura (abnormal vWF multimers form and bind lots of platelets, creating arterial thrombi)

Question 10

Thrombocytopenia is also seen in ___, which can be confused with TTP.

Answer 10

HUS

Question 11

What are the general causes of thrombocytosis?

Answer 11

1. Splenectomy
2. Reactive (cancer, infection, drugs)
3. Autonomous (clonal disorder)

Question 12

What are qualitative platelet disorders?

Answer 12

Platelet numbers are normal; function is impaired

1. Disease-induced (liver disorders, paraproteinemia)
2. Drug-induced (aspirin, NSAIDs)
3. Diet-induced (omega 3 fatty acids)

Question 13

What are 3 congenital disorders of platelets resulting in bleeding?

Answer 13

1. Glanzmann’s thrombasthenia
2. Bernard-Soulier disease
3. Storage pool disease

Question 14

What is Glanzmann’s thrombasthenia?

Answer 14

Autosomal recessive defect of 2b3a leading to defective aggregation and increased bleeding time

Question 15

What is Bernard-Soulier disease?

Answer 15

Autosomal recessive defect of 1b leading to defective adhesion and increased bleeding time

Question 16

What is storage pool disease?

Answer 16

Decreased dense granule content, no aggregation

Question 17

What are 2 other acquired disorders of platelets?

Answer 17

1. Metabolic disorders (uremia)

2. Myeloproliferative disorders (polycythemia vera, granulocytic leukemia, myelofibrosis)

Question 18

What are vascular disorders?

Answer 18

Non-thrombocytopenic purpuras; no serious bleeding, platelet function and coagulation are normal, easy bruising, bleeding from mucosa, purpura, vasculitis

Question 19

What is an important congenital subendothelial disorder?

Answer 19

Ehler Danlos syndrome (hyperflexible skin, hypermobile joints)

Question 20

What are two mechanical disorders?

Answer 20

1. Orthostatic purpura

2. Mechanical purpura

Question 21

What is one nutritional disorder?

Answer 21

Scurvy (vitamin C deficiency)

Question 22

What is a PT test used for?

Answer 22

Diagnosis of issues in the extrinsic pathway (2, 5, 7, 10, fibrinogen)

Question 23

What is the APTT test used for?

Answer 23

Diagnosis of issues in the intrinsic pathway (8, 9, 11, 12 - technically measures all factors except 7, 13, C, and S)

Question 24

Most defects due to coagulation factors result in ___.

Answer 24

Bleeding

Question 25

What is Hemophilia A?

Answer 25

Factor 8 coagulant deficiency

Question 26

What is Hemophilia B?

Answer 26

Factor 9 deficiency (Christmas disease)

Question 27

Hemophilia A and B are transmitted as ___.

Answer 27

Sex-linked recessive

Question 28

What is von Willebrand's disease?

Answer 28

Hemostatic defect due to von Willebrand factor defect

Question 29

What are the 3 types of VW disease?

Answer 29

Type 1 and 3: decrease in circulating level of factor Type 2: qualitative defect

Question 30

Compare the APTT result in hemophilia vs. VW disease.

Answer 30

H: prolonged VW: slightly elevated due to mild reduction in factor 8

Question 31

Compare the platelet function in hemophilia vs. VW disease.

Answer 31

H: normal VW: hemostatic function impaired due to impaired adhesion of platelets to collagen

Question 32

Compare the bleeding time in hemophilia vs. VW disease.

Answer 32

H: no effect VW: increased

Question 33

Excessive activation of the fibrinolytic system can cause ___.

Answer 33

Bleeding

Question 34

What aspects of the fibrinolytic system contribute to bleeding?

Answer 34

Decrease in the fibrinogen concentration; increase in degradation product formation

Question 35

What happens in primary fibrinolysis?

Answer 35

Only fibrinogen is converted into fibrinogen degradation products (rather than fibrin) --> no clotting

Question 36

Primary fibrinolysis is seen in what syndrome?

Answer 36

Dead fetus syndrome (abruptio placenta)

Question 37

What happens in secondary fibrinolysis?

Answer 37

Both fibrin and fibrinogen are digested by plasmin; also associated with digestion of clotting factors and consumption of platets; leads to DIC

Question 38

Discuss the pathogenesis of sepsis associated DIC - what causes release of tissue factor?

Answer 38

1. Massive tissue destruction 2. Sepsis 3. Endothelial injury

Question 39

Discuss the pathogenesis of sepsis associated DIC - release of tissue factor causes what?

Answer 39

Widespread microvascular thrombosis

Question 40

Discuss the pathogenesis of sepsis associated DIC - what does widespread microvascular thrombosis cause?

Answer 40

1. Activation of plasmin; this leads to fibrinolysis and fibrin split products, which inhibit clotting, as well as proteolysis of clotting factors 2. Vascular occlusion, which leads to ischemic tissue damage 3. Consumption of clotting factors and platelets All of this leads to bleeding

Question 41

What is caused by a deficiency of alpha2-antiplasmin?

Answer 41

Increased fibrinolysis and bleeding