Department of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland.
Department of Medicine and Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Am J Hematol. 2021 Jul 1;96(7):805-815. doi: 10.1002/ajh.26194. Epub 2021 May 3.
The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability.
Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed.
Out of 3194 articles screened, 92 studies with 119 treatment groups describing 4698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article.
Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice.
非肝素抗凝剂治疗肝素诱导的血小板减少症(HIT)的有效性和安全性尚未完全确定,最佳治疗策略尚不清楚。在一项系统评价和荟萃分析中,我们旨在确定所有非肝素抗凝剂的血小板恢复、新发或进展性血栓栓塞(TE)、大出血和死亡的确切发生率,并研究潜在的变异性来源。
根据详细的方案(PROSPERO:CRD42020219027),在 EMBASE 和 Medline 中搜索所有报告非肝素抗凝剂(阿加曲班、达那肝素、磺达肝素、直接口服抗凝剂[DOAC]、比伐卢定和其他水蛭素)治疗急性 HIT 患者临床结局的研究。使用随机效应模型对每种药物的感兴趣结局患者的比例进行汇总。评估了患者人群、使用的诊断测试、研究设计和文章类型的影响。
在筛选出的 3194 篇文章中,有 92 项研究共 119 个治疗组,描述了 4698 例患者,纳入本研究。血小板恢复的汇总率范围为 74%(比伐卢定)至 99%(磺达肝素),TE 为 1%(磺达肝素)至 7%(达那肝素),大出血为 1%(DOAC)至 14%(比伐卢定),死亡为 7%(磺达肝素)至 19%(比伐卢定)。置信区间大多重叠,结果不受患者人群、使用的诊断测试、研究设计或文章类型的影响。
各种抗凝剂的有效性和安全性结局相似,未确定影响这些结局的重要因素。这些发现支持磺达肝素和 DOAC 作为治疗临床实践中急性 HIT 的常规抗凝剂的可行替代药物。