A 45-year-old woman with pulmonary embolism receives weight-adjusted unfractionated heparin but the aPTT remains subtherapeutic despite escalating doses, with recurrence of thrombosis. Baseline aPTT was normal. The most likely explanation is:

• A Factor VIII inhibitor
• B Protein C resistance
• C Dysfibrinogenemia
• D Congenital antithrombin III deficiency ✓

Explanation

Heparin acts as a catalyst only when bound to antithrombin III; without adequate ATIII, heparin cannot inhibit thrombin and factor Xa effectively, so the aPTT fails to prolong and thrombosis can recur. Congenital antithrombin deficiency classically presents as recurrent venous thrombosis with heparin resistance and responds better to direct thrombin inhibitors or higher heparin doses with ATIII support. Factor VIII inhibitor and dysfibrinogenemia would alter clotting assays differently.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.