Heparin-Induced Thrombocytopenia from Venous Thromboembolism Treatment.
Authors: Begelman Susan M. , Hursting Marcie J. , Aghababian Richard V. , McCollum David 
Published: October 2019

Heparin therapy for any indication, including venous thromboembolism (VTE), can be complicated by heparin-induced thrombocytopenia (HIT). The purpose of this retrospective study was to characterize the clinical experience of patients in whom HIT complicated heparin therapy for VTE and who were switched to argatroban therapy. From the previously reported prospective, multicenter, historical-controlled Argatroban-911 and Argatroban-915 studies of argatroban therapy in HIT, we identified all patients who developed HIT while on heparin therapy for pulmonary embolism and/or deep venous thrombosis and in whom heparin was discontinued and argatroban therapy initiated. The primary study end point was a composite of death, amputation, or new thrombosis within 37 days of argatroban initiation; we also evaluated a 37-day composite end point of thrombosis-associated events, including death due to thrombosis, amputation secondary to HIT, or new thrombosis. A total of 145 patients with VTE and HIT were included in our analysis. During heparin therapy before HIT was diagnosed, platelet counts decreased from daily mean values greater than 175x109/L to a mean±SD nadir of 78±67x109/L over the course of 5 days, and new thrombosis developed in 75 (52%) patients. After heparin was discontinued, patients received argatroban (mean dose 2.1±1.2 mcg/kg/min) for 6.8±4.3 days achieving mean activated partial thromboplastin times during therapy of 63±12 s. By day 6 of argatroban therapy, the mean platelet count had risen to >150x109/L. The primary end point occurred in 41 (28.3%) patients, and the thrombotic composite in 23 (15.9%) patients (Table 1). Seventeen (11.7%) patients, including 12 who had also experienced thrombosis while on heparin, developed new thrombosis after argatroban initiation, typically on the day argatroban was discontinued or later (n=10). Death due to thrombosis occurred in only 1 (0.7%) patient. Seven (4.8%) patients experienced major bleeding. We conclude that in heparin-treated patients with VTE, HIT-associated thrombosis often occurs before HIT is recognized, emphasizing the importance of platelet count monitoring and a high degree of suspicion for HIT in this setting. For VTE patients with HIT, argatroban provides effective anticoagulation, with outcomes comparable with those reported for argatroban-treated patients in whom HIT developed following heparin therapy for any indication. New thrombosis occurring after switching to argatroban therapy more typically occurs in patients with existing HIT-associated thrombosis and at/after argatroban discontinuation.

Clinical Outcomes n(%) Outcome n=145 Primary (all cause)* Thrombosis-related†,¥ *All-cause death, all-cause amputation, or new thrombosis within 37 days. †Death due to thrombosis, amputation secondary to HIT, or new thrombosis within 37 days. ¥More than 1 outcome may have occurred in a single patient. Composite end point 41 (28.3) 23 (15.9) Individual components Death 19 (13.1) 1 (0.7) Amputation 8 (5.5) 6 (4.1) New thrombosis 17 (11.7) 17 (11.7)