Case Report: Heparin resistance as the harbinger of heparin-induced thrombocytopenia in acute pulmonary embolism.

Heparin-induced thrombocytopenia (HIT) is a severe, prothrombotic complication of heparin therapy. While thrombocytopenia is a hallmark, diagnosis can be obscured when preceded by unexplained heparin resistance and progressive thrombosis. We present the case of a 50-year-old man with intermediate- to high-risk acute pulmonary embolism (PE), deep vein thrombosis and a right ventricular mass. Despite timely and progressive dose escalation of intravenous unfractionated heparin [UFH; up to 1,850 U/h (~24.7 U/kg/h)], monitoring by activated partial thromboplastin time (APTT) revealed a failure to achieve therapeutic anticoagulation (heparin resistance), and he suffered two recurrent episodes of hemodynamic instability on treatment days 3 and 6, requiring rescue thrombolysis. Follow-up imaging revealed thrombus progression. On day 8 of heparin therapy, thrombocytopenia (platelets 104 × 109/L) and a high 4Ts score (6 points) prompted HIT suspicion. Heparin was immediately discontinued and replaced with intravenous argatroban (initiated at 2 μg/kg/min), resulting in prompt attainment of the target therapeutic APTT range. HIT was confirmed by positive anti-platelet factor 4 (PF4)/heparin immunoglobulin G (IgG) antibodies. After platelet count recovery (to >150 × 109/L), argatroban was discontinued and anticoagulation was switched to oral rivaroxaban. Follow-up studies at discharge and 3 months showed significant thrombus resolution, with normalized cardiac function and complete resolution of the intracardiac mass. This case underscores that unexplained heparin resistance with thrombotic progression, even preceding significant thrombocytopenia, a recognized harbinger of HIT-associated thrombosis, is a critical indicator of HIT. Immediate diagnostic evaluation and switch to non-heparin anticoagulants are imperative to avert life-threatening complications.