PTT

PTT assesses the intrinsic pathway (factors XII, XI, IX, VIII) and common pathway (factors X, V, II, fibrinogen) of the coagulation cascade. The test involves adding a contact activator, phospholipid, and calcium to plasma, then measuring the time to clot formation (normal range ~25-35 seconds).

Clinical uses and associations: - Monitoring unfractionated heparin therapy (heparin inhibits thrombin and factor Xa via antithrombin III, prolonging PTT) - Screening for hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency), both of which cause isolated PTT prolongation - Detecting Lupus anticoagulant (antiphospholipid antibody syndrome) - paradoxically prolongs PTT in vitro despite being associated with thrombosis in vivo - Von Willebrand disease can show prolonged PTT if factor VIII is sufficiently reduced (vWF stabilizes factor VIII) - Factor XII deficiency prolongs PTT but is NOT associated with bleeding (contact pathway not essential in vivo)

Mixing studies help differentiate factor deficiency from inhibitor presence: if PTT corrects with mixing (1:1 with normal plasma), it suggests factor deficiency; if it doesn't correct, an inhibitor (e.g., lupus anticoagulant, factor-specific antibody) is present.

PTT is compared with PT/INR, which measures the extrinsic (factor VII) and common pathway, and is used to monitor warfarin therapy. Together, PT and PTT help localize coagulation factor deficiencies: - Isolated prolonged PTT: intrinsic pathway defect (XII, XI, IX, VIII) - Isolated prolonged PT: extrinsic pathway defect (VII) - early liver disease, warfarin, vitamin K deficiency - Both prolonged: common pathway defect (X, V, II, fibrinogen) or combined deficiencies, DIC, severe liver disease