Abnormal Hemostasis

Question 1

Thrombocytopenia

Answer 1

Decreased platelet count, results in bleeding

Question 2

Thrombocytosis

Answer 2

Increased platelet count, benign

Question 3

Thrombocythemia

Answer 3

Clonal proliferation (neoplastic) of platelets, bleeding and thrombosis may occur

Question 4

Causes of Thrombocytopenia

Answer 4

Alterations in bone marrow
Hereditary thrombocytopenia (May Hegglin anomaly, Fanconi’s anemia, etc)
Abnormal hematopoeisis (acquired): B12/Folate deficiency, pre-leukemia
Drug Induced thrombocytopenia: heparin, gold, quinine, sulfonamides, GPIIb/IIIa inhibitors
Dilutional: hemodialysis, heart-lung machine
ITP: Immune thrombocytopenic purpura (IgG mediated)
TTP: Thrombotic thrombocytopenic purpural (abnormal vWF multimers), arterial thrombi (platelet-rich)

Question 5

Causes of Thrombocytosis

Answer 5

Splenectomy: platelet function is normal
Reactive thrombocytosis: due to cancer, infection, drugs
Autonomous thrombocytosis (thrombocythemia): clonal disorder, increased # of platelets in circulation

Question 6

Qualitative Disorders

Answer 6

Platelet numbers are usually normal, however, platelet function is impaired

Disease induced platelet defects: liver disorders, paraproteinemia
Drug induced platelet defects: ASA, NSAIDS
Diet induced platelet defects: omega 3 fatty acids, onion, garlic, cayenne pepper

Question 7

Inherited disorders of Platelets

Answer 7

Congenital disorders resulting in bleeding diathesis

Question 8

Inherited Disorders of Platelets

Glanzmann’s thrombasthenia

Answer 8

Autosomal recessive
GPIIb/IIIa defect
Aggregation defect
Bleeding time increased

Question 9

Inherited Disorders of Platelets

Bernar-Soulier disease

Answer 9

Autosomal recessive
GPIb defec
Adhesion defection
Bleeding time increased

Question 10

Inherited Disorders of Platelets

Storage Pool Disease

Answer 10

Decrease dense granule content

No aggregation

Question 11

Inherited Disorders of Platelets

Other Disorders

Answer 11

Purpura of unknown origin
Gray platelet syndrome
Lack of alpha granules

Question 12

Other Acquired Disorders of Platelets

Answer 12

Metabolic disorders: uremia (bleeding)

Myeloproliferative disorders: polycythemia vera, granulocytic leukemia, melofibrosis

Question 13

Vascular Disorders

Answer 13

Non-thrombocytopenic purpuras
DO NOT result in sever bleeding diathesis
Platelet function and coagulation are normal
Easy bruising, bleeding from mucosa, purpura, vasculitis

Question 14

Subendothelial Disorders

Answer 14

Congenital: Ehler Danlos Syndrome, hypermobile joints, hyperflexible skin, osteogensis imperfecta, drugs, infections, amyloidosis
Aquired: Purpura simplex, amyloids, drugs, steroid purpura (prednisone), Cushing’s syndrome (steroid excess), Henoch-schonlin purpura (usually drug induced)

Question 15

Endothelial Disorders

Answer 15

Congenital: MOST COMMON, hereditary hemorrhagic, telangiectasia (HHT), arteriovenous malformation; giant hemangioma (Kasack-Merritt syndrome)
Acquired: inflammation, vasculitis (drugs, viruses, rickettsia)

Question 16

Mechanical Disorders

Answer 16

Orthostatic purpura (sitting for too long)
Mechanical purpural (elevator to 95th floor)
INCREASED TRANSLUMINAL PRESSURE

Question 17

Nutritional Disorders

Answer 17

Scurvy (vitamin C deficiency)

Question 18

Hemophilia A

Answer 18

Classical
Coagulation Factor Abnormality
Intrinsic pathway
Factor VIII
APTT is elevated, no effect on platelets

Question 19

Hemophilia B

Answer 19

Christmas Disease
Coagulation Factor Abnormality
Intrinsic Pathway
Factor IX
APTT is elevated, no effect on platelets

Question 20

Coagulation Factor Abnormality

Extrinsic Pathways

Answer 20

Uncommon to have congenital defect of Factor VII

Warfarin can prolong PT

Question 21

Von Willebrand’s Disease

Answer 21

Hemostatic defect from vWF defect
Platelets cannot adhere to subendothelium
Type 1 and 3 are quantititave (decrease in circulating level of factor)
Type 2 is qualitative (molecular/structural defect)
Bleeding time is elevated

Question 22

Bleeding Disorders Due to Abnormalities of the Fibrinolytic System

Answer 22

Excessive activation of the fibrinolytic system can cause bleeding
Decrease in fibrinogen concentration and an increase in degradation product formation contribute to bleeding

Question 23

Disorders in Fibrinolytic System

Primary Fibrinolysis

Answer 23

Only fibrinogen is converted into fibrinogen degradation products
This condition is seen in dead fetus syndrome (Abruptio Placenta)
Plasmin breaks down fibrinogen
Excessive fibrinolysis can result in bleeding due to decreased fibrinogen levels
Fibrinogen degradation products can also produce anticoagulant effects
Overdosage of thrombolytic agents can result in primary fibrinolytic state and cause bleeding

Question 24

Disorders in Fibrinolytic System
Secondary Fibrinolysis (DIC)

Answer 24

Both fibrin and fibrinogen are digested by plasmin, also associated with digestion of clotting factors and consumption of platelets. THIS IS SERIOUS

Question 25

Deficiency of alpha2-antiplasmin

Answer 25

Results in increased fibrinolysis (bleeding)
a2-antiplasmin is an inhibitor of plasmin, thus inhibitor of fibrinolytic enzyme
Deficiency leads to uncontrolled fibrinolysis

Question 26

Drug Induced Bleeding Disorders

Answer 26

Thromboyltic drugs
Anticoagulants (heparin)
Anti-platelet drugs
Thrombolytic drugs

Leads to drug induced thrombocytopenia or heparin induced thrombocytopenia (HIT)

Question 27

Diagnosis of Bleeding Disorders

Answer 27

Bleeding time
Platelet count
Platelet function studies (adhesion, aggregation, activation)