Abnormal Hemostasis Flashcards
Thrombocytopenia
Decreased platelet count, results in bleeding
Thrombocytosis
Increased platelet count, benign
Thrombocythemia
Clonal proliferation (neoplastic) of platelets, bleeding and thrombosis may occur
Causes of Thrombocytopenia
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)
Causes of Thrombocytosis
Splenectomy: platelet function is normal Reactive thrombocytosis: due to cancer, infection, drugs Autonomous thrombocytosis (thrombocythemia): clonal disorder, increased # of platelets in circulation
Qualitative Disorders
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
Inherited disorders of Platelets
Congenital disorders resulting in bleeding diathesis
Inherited Disorders of Platelets
Glanzmann’s thrombasthenia
Autosomal recessive
GPIIb/IIIa defect
Aggregation defect
Bleeding time increased
Inherited Disorders of Platelets
Bernar-Soulier disease
Autosomal recessive
GPIb defec
Adhesion defection
Bleeding time increased
Inherited Disorders of Platelets
Storage Pool Disease
Decrease dense granule content
No aggregation
Inherited Disorders of Platelets
Other Disorders
Purpura of unknown origin
Gray platelet syndrome
Lack of alpha granules
Other Acquired Disorders of Platelets
Metabolic disorders: uremia (bleeding)
Myeloproliferative disorders: polycythemia vera, granulocytic leukemia, melofibrosis
Vascular Disorders
Non-thrombocytopenic purpuras
DO NOT result in sever bleeding diathesis
Platelet function and coagulation are normal
Easy bruising, bleeding from mucosa, purpura, vasculitis
Subendothelial Disorders
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)
Endothelial Disorders
Congenital: MOST COMMON, hereditary hemorrhagic, telangiectasia (HHT), arteriovenous malformation; giant hemangioma (Kasack-Merritt syndrome)
Acquired: inflammation, vasculitis (drugs, viruses, rickettsia)
Mechanical Disorders
Orthostatic purpura (sitting for too long) Mechanical purpural (elevator to 95th floor) INCREASED TRANSLUMINAL PRESSURE
Nutritional Disorders
Scurvy (vitamin C deficiency)
Hemophilia A
Classical Coagulation Factor Abnormality Intrinsic pathway Factor VIII APTT is elevated, no effect on platelets
Hemophilia B
Christmas Disease Coagulation Factor Abnormality Intrinsic Pathway Factor IX APTT is elevated, no effect on platelets
Coagulation Factor Abnormality
Extrinsic Pathways
Uncommon to have congenital defect of Factor VII
Warfarin can prolong PT
Von Willebrand’s Disease
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
Bleeding Disorders Due to Abnormalities of the Fibrinolytic System
Excessive activation of the fibrinolytic system can cause bleeding
Decrease in fibrinogen concentration and an increase in degradation product formation contribute to bleeding
Disorders in Fibrinolytic System
Primary Fibrinolysis
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
Disorders in Fibrinolytic System Secondary Fibrinolysis (DIC)
Both fibrin and fibrinogen are digested by plasmin, also associated with digestion of clotting factors and consumption of platelets. THIS IS SERIOUS
Deficiency of alpha2-antiplasmin
Results in increased fibrinolysis (bleeding)
a2-antiplasmin is an inhibitor of plasmin, thus inhibitor of fibrinolytic enzyme
Deficiency leads to uncontrolled fibrinolysis
Drug Induced Bleeding Disorders
Thromboyltic drugs
Anticoagulants (heparin)
Anti-platelet drugs
Thrombolytic drugs
Leads to drug induced thrombocytopenia or heparin induced thrombocytopenia (HIT)
Diagnosis of Bleeding Disorders
Bleeding time
Platelet count
Platelet function studies (adhesion, aggregation, activation)
