Cardiac Transplantation after Heparin Induced Thrombocytopenia: A Patient-Level Meta-Analysis

Abstract

Purpose Heparin induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). However, data on management and outcomes are lacking. We sought to pool the existing evidence in a systematic review and meta-analysis. Methods Electronic search was performed to identify all relevant studies published on OHT in patients with HIT. Overall, 20 were selected comprising 30 patients with HIT who required OHT. Patient-level data were extracted for statistical analysis. Results Median patient age was 51 [IQR 41.8, 55.0] years old, with 73.3% (22/30) male. All patients had a clinical diagnosis of HIT, and PF4-Heparin antibodies were positive in 86.7% (26/30). Overall, 67% (20/30) required mechanical circulatory support preoperatively, including temporary support in 53% (16/30), and durable assist devices in 30% (9/30). Durable devices consisted of pulsatile 78% (7/9) and continuous-flow 22% (2/9) LVADs. Median duration from HIT to OHT was 21 [IQR 12, 61] days, and from MCS to OHT 28 [IQR 18, 66] days. Of 30 patients, 17 (56.7%) underwent OHT using unfractionated heparin (UFH), while 13 used other agents. In non-UFH patients, agents included 54% (7/13) Bivalirudin, 15% (2/13) Danaparoid, and 8% (1/13) each of enoxaparin, Argatroban or Lepirudin. Intraoperatively, non-UFH patients required more antifibrinolytics [54% (7/13) vs. 5.9% (5/17), p=0.01] and clotting factors [69.2% (9/13) vs. 11.8% (2/17) p=0.004]. Peri-operative thrombosis occurred in 53.8% (7/13) of non-UFH patients and 0% (0/17) of UFH patients (p=0.002). More non-UFH patients developed serious perioperative bleeding [62% (8/13) vs. 18% (3/17), p=0.04] and required post-operative transfusions [54% (7/13) vs. 0% (0/16), p=0.003]. Postoperative anticoagulation was utilized in 68.8% (11/16) of UFH patients and 7.7% (1/13) of non-UFH patients (p=0.003), with no difference in warfarin use [6.2% (1/16) vs.7.7% (1/13) respectively, p=1.00]. Median follow-up time was 20 [IQR 5, 24] months for UFH patients and 12 [IQR 10, 25] months for non-UFH patients (p=0.46). At the time of last follow-up, 82% (14/17) of UFH and 85% (11/13) of non-UFH patients were alive (p=1). Conclusion Non-UFH anticoagulation during OHT was associated with thrombotic and bleeding complications compared to UFH. However, there was no significant difference in overall survival.