How Frequently Is Venous Thromboembolism in Heparin-Treated Patients Associated with Heparin-Induced Thrombocytopenia?.

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are routinely used for prophylaxis or treatment of venous thromboembolism (VTE) yet paradoxically can promote VTE in a patient with heparin-induced thrombocytopenia (HIT), an immune-mediated prothrombotic reaction to heparins. The purpose of this meta-analysis was to estimate how frequently new or recurrent VTE in heparin-treated patients is HIT-associated. Studies using UFH or LMWH for prophylaxis or treatment of thrombosis in which an outcome variable was new or recurrent VTE and in which information was available for the determination of HIT were abstracted to determine the proportion of patients with VTE that was associated with HIT. From a comprehensive literature search, we identified 10 studies (6 randomized trials, 3 prospective cohort studies, 1 retrospective cohort study) of intravenous (iv) or subcutaneous (sc) UFH or LMWH therapy that reported objectively confirmed VTE (at least 1 event per study) both overall and in patients with comorbid HIT, which was prospectively defined in each study (typically a platelet count <100–150 x10⁹/L or a 30–50% decrease in count, with serologic confirmation). In each study, which may have included 2 treatment groups, medical or surgical patients received UFH iv (5 studies), UFH sc (3 studies), or LMWH sc (5 studies) therapy typically for 7–10 days and were followed in hospital or for 10 to 90 days for new or recurrent VTE. Across the studies in a total of 6219 heparin-treated patients, 386 patients had new or recurrent VTE, and 34 had HIT-associated VTE. The frequency of HIT-associated VTE among heparin-treated patients with VTE was not different between iv and sc UFH therapy (13.2% versus 12.4%, P>0.99) but was significantly different between UFH and LMWH therapy (12.8% versus 0.7%, P<0.001) (Table 1). These data indicate that new or recurrent VTE is HIT-associated infrequently (<1%) in LMWH-treated patients yet often (approximately 1 in 8 cases) in UFH-treated patients. Because continued or repeated exposure to heparins can be catastrophic in HIT, physicians should have a high degree of suspicion for HIT in patients developing VTE during or soon after UFH therapy and should use alternative anticoagulation until HIT has been excluded.