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Further coagulation tests

•  Mixing study: useful if ↑ PT or PTT; mix Pt’s plasma 1:1 w/ normal plasma and retest PT/PTT normalizes → factor deficiency; PT/PTT remains elevated → factor inhibitor

•  Coagulation factor levels: useful if mixing study suggests factor deficiency

DIC → all factors consumed; ∴ ↓ factors V and VIII liver disease → ↓ all factors except VIII; ∴↓ factor V, normal factor VIII vitamin K deficiency → ↓ factors II, VII, IX, X (and protein C, S); ∴ normal V and VIII

•  DIC screen: fibrinogen (consumed), fibrin degradation products (FDPs,  due to intense fibrinolysis), D-dimer (more specific FDP test that detects degradation of X-linked fibrin)

Hemophilias (NEJM 2001;344:1773)

•  X-linked recessive factor VIII (hemophilia A) or factor IX (hemophilia B) deficiency

•  Classification: mild (5–25% normal factor activity), moderate (1–5%) or severe (<1%)

•  Clinical manifestations: hematomas, hemarthroses, bruising, bleeding (mucosal, GI, GU)

•  Diagnosis: ↑ PTT (normalizes w/mixing study), normal PT & vWF, ↓ factor VIII or IX

•  Treatment: purified/recomb. factor VIII or IX concentrate, desmopressin (mild disease), aminocaproic acid; recomb. factor VIIa if factor inhib., cryo (only has factor VIII)

Coagulation factor inhibitors

•  Etiologies: hemophilia (treated with factor replacement); postpartum; lymphoproliferative disorders and other malignancies; autoimmune diseases; most commonly anti–factor VIII

•  Diagnosis: ↑ PTT (does not normalize w/mixing study); Bethesda assay quantitates titer

•  Treatment: high titer → recomb. factor VIIa, porcine factor concentrates, activated prothrombin complex; others → high-purity human factor, plasmapheresis, immunosupp. w/ steroids, cyclophosphamide and/or rituximab (Curr Opin Hematol 2008;15:451)

Disseminated intravascular coagulation (DIC) (NEJM 1999;341:586)

•  Etiologies: trauma, shock, infection, malignancy (esp. APL), obstetric complications

•  Pathogenesis: massive activation of coagulation that overwhelms control mechanisms thrombosis in microvasculature → ischemia + microangiopathic hemolytic anemia acute consumption of coagulation factors and platelets → bleeding chronic DIC → able to replete factors and platelets → thrombosis

•  Diagnosis: ↑ PT, ↑ PTT, ↓ fibrinogen (may be nl b/c acute phase),  FDP/D-dimer, ↓ plts,  schistos, ↑ LDH, ↓ hapto; chronic DIC:  FDP/D-dimer, variable plts, other labs nl

•  Treatment: treat underlying process; support with FFPcryoprecipitate (goal fibrinogen

>100 mg/dL) and platelets; no role for activated protein C in sepsis (NEJM 2012;366:2055)

Vitamin K deficiency

•   Etiologies: malnutrition, ↓ absorption (antibiotic suppression of vitamin K-producing intestinal flora or malabsorption), liver disease (↓ stores), warfarin