Disorders of Coagulation and Hemostasis
Separate primary hemostasis (platelets, von Willebrand factor) from secondary hemostasis (coagulation cascade) and fibrinolysis. Screening tests: PT/INR (extrinsic and common pathway), aPTT (intrinsic and common), thrombin time, fibrinogen, and mixing studies. A prolonged aPTT that corrects with normal plasma suggests factor deficiency; failure to correct suggests an inhibitor (e.g., lupus anticoagulant, factor VIII inhibitor).
Know factor deficiencies: hemophilia A (VIII) and B (IX) show prolonged aPTT with normal PT. Von Willebrand disease shows prolonged bleeding time/PFA-100 with variable aPTT. Disseminated intravascular coagulation shows prolonged PT/aPTT, low fibrinogen, elevated D-dimer, and thrombocytopenia. Liver disease affects all factors.
Anticoagulant monitoring: heparin by aPTT or anti-Xa; warfarin by INR; direct oral anticoagulants have specific assays. Understand heparin-induced thrombocytopenia (platelet factor 4 antibodies) and the paradox of thrombosis.
Worked example: a patient with a prolonged aPTT, no bleeding, and a positive mixing study that does not correct-consider lupus anticoagulant; confirm with phospholipid-dependent tests.
Trap: assuming a prolonged aPTT always means bleeding risk-lupus anticoagulant prolongs aPTT in vitro but is associated with thrombosis.