Hemostasis Disorders

sws42792's version from 2015-05-16 18:30

Primary Hemostasis

Question Answer
Immune thrombocytopenic purpura (ITP)Autoimmune production of IgG against platelet antigens, most common cause of thrombocytopenia, Abs produced in spleen and Ab-platelet complexes consumed by spleen, treat w/ corticosteroids, IVIG, splenectomy
Thrombotic thrombocytopenic purpura (TTP)decreased ADAMTS13, enzyme that normally cleaves vWF multimers into monomers for degradation, causes abnormal platelet adhesion and microthrombi, often due to acquired autoantibody, CNS involvement
Hemolytic uremic syndrome (HUS)endothelial damage by drugs or infection, children w/ E.coli 0157:H7 dysentery (verotoxin aka Shiga like toxin), renal insufficiency
Bernard-Soulier syndromegenetic GPIb deficiency, platelet adhesion impaired, decreased platelet lifespan, mild thrombocytopenia and increased platelet size
Glanzman thrombastheniagenetic GPIIb/IIIa deficiency, impaired aggregation
AspirinASA irreversibly inhibits COX, decrease TXA2 release impairs platelet aggregation
Uremiadisrupts platelet function, both aggregation and adhesion impaired

Secondary Hemostasis

Question Answer
Factor XII deficiencyasymptomatic (no increased bleeding)
Hemophelia Agenetic factor VIII deficiency, X-linked recessive, treat w/ recombinant FVIII, PTT is corrected in mixing study
Hemophelia Bgenetic factor IX deficiency, resembles hemophilia A clinically
Coagulation factor inhibitoracquired Ab against a coag factor, anti-FVIII is most common, clinical and lab findings are same as hemophilia A, but PTT does NOT correct in mixing study
VonWillebrand diseasegenetic vWF deficiency, autosomal dominant, mild mucosal and skin bleeding, low vWF impairs platelet adhesion, increased PTT b/c decrease FVIII half-life (vWF stabilized FVIII), abnormal ristocetin test, treat w/ desmopression (ADH analog)
Vitamin K deficiencyVit K activated by epoxide reductase in liver and is needed for gamma carboxylation of factors II, VII, IX, X, and protein C & S, occurs in newborns (prophylactic K injection), long-term antibiotic therapy, malabsorption
Liver failuredecreased production of clotting factors and Vit K activation by epoxide reductase - monitor PT
Large volume transfusiondilutes coagulation factors, relative deficiency

Other disorders of hemostasis

Question Answer
Causes of DICobstetric complications (tissue thromboplastin in amniotic fluid), sepsis (esp E.coli or N.meningitidis, endotoxin induces endothelia cells to make tissue factor), adenoCA (mucin), Acute promyelocytic leukemia (primary granules), rattlesnake bite (venom)
Radical prostatectomyrelease of urokinase activates plasmin - excessive cleavage of serum fibrinogen, no D-dimers
Cirrhosis of liver (fibrinolysis)reduced production of alpha 2-antiplasmin, excessive cleavage of fibrinogen, no D-dimers
Heparin-induced thrombocytopeniaplatelet destruction secondary to heparin therapy, Abs against Hep-PF4 (platelet factor 4) complex, destroyed platelet fragments activate remaining platelets leading to thrombosis, do NOT give warfarin, increased risk for skin necrosis


Question Answer
Vit B12/folate deficiencybuildup of homocysteine - increases risk of thrombosis
Cystathione beta synthase (CBS) deficiencyhigh homocystein levels w/ homocysteinuria, increased risk of vessel thrombosis (also mental retardation, lens dislocation, long slender fingers)
Protein C or S deficiencydecreases negative feedback on coag. cascade, normally inactivate factors V and VIII, increased risk for warfarin skin necrosis
Factor V Leidenmutated for of factor V that lack cleavage site for deactivation by proteins C and S
Prothrombin 20210Apoint mutation in prothrombin that results in increased gene expression, increased prothrombin and thrombin, thrombus formation
ATIII deficiencydecreases protective effect of heparin-like molecules from endothelial cells, increased risk for thrombus, ATIII inactivates thrombin and coag factors, PTT does not rise with standard heparin dosing, nephrotic syndrome causes selective loss of ATIII