Pooled Incidence of Heparin-Induced Thrombocytopenia and Anti-Platelet Factor 4 Antibody Formation Among Adults: A Systematic Review and Meta-Analysis

Heparin-induced thrombocytopenia (HIT) is an immune-mediated drug reaction. Patients with HIT show thrombocytopenia and increased thrombotic risk. Unfractionated heparin (UFH) is more immunogenic compared to low-molecular-weight heparin (LMWH), but estimates vary across clinical settings. The study aimed to determine the pooled incidence of thrombocytopenia and anti-platelet factor (PF)-4 antibody formation among adults exposed to UFH and LMWH. We systematically searched electronic databases, including PubMed, Cochrane CENTRAL, Embase (via Cochrane), the International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov, for studies published from 2010 to 2025. Eligible studies reported clinical HIT incidence or anti-PF4/heparin antibody formation in adults receiving UFH or LMWH. Two reviewers independently performed screening and data extraction. Bias risk was assessed using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I). Random-effects models pooled risk ratios (RRs) comparing UFH with LMWH. Twelve studies comprising 139,744 adults were included. Six studies reporting clinical HIT showed more risk with UFH (RR 3.4; I² = 55%). Four studies done on antibody formation showed higher seroconversion with UFH (RR 2.2; I² = 45%). The certainty of evidence (assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework) was low due to observational designs, diagnostic heterogeneity, and imprecision. UFH is associated with a higher incidence of clinical HIT and anti-PF4/heparin antibody formation compared with LMWH. Though certainty is low, the findings support using LMWH when clinically appropriate.