Comparative effectiveness and safety of anticoagulants for the treatment of heparin‐induced thrombocytopenia

Abstract

Background 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. Methods 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. Results 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. Discussion 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.

Platelet Activation Mechanisms and Consequences of Immune Thrombocytopenia

“…In a recent meta-analysis, the application of argatroban appeared to associate with the lowest rates of thromboembolic events and of bleeding complications, on top of a shorter hospitalization length [ 87 ]. A systematic review concluded a similarity in the efficacy and safety of fondaparinux (heparin-derivative), bivalirudin or danaparoid [ 88 ].…”

Heparin-induced thrombocytopenia: An update for the COVID-19 era

“…a lack of adequate randomised controlled trials. [37] The choice of alternative anticoagulant will depend on clinician experience, drug availability, cost, expected drug-drug interactions, availability of laboratory testing for drug monitoring, patient age, organ function, weight, comorbidities and bleeding risk, as well as other established factors. [21] For most clinically stable patients without an excessive bleeding risk, fondaparinux or direct oral anticoagulants (DOACs) such as rivaroxaban are reasonable choices for the initial treatment of acute HIT.…”

Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

“…Numerous case reports, case series, and observational studies describing the use of DOACs in HIT have been published [ 34 , 35 , 36 ], but there remains a lack of high-quality randomized clinical trials (RCT) evaluating the efficacy and safety of DOACs in HIT patients. In the recently published systematic review and meta-analysis of 92 studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, DOACs, bivalirudin, and other hirudins) for acute HIT, Nilius et al [ 37 ] outlined significant bias in some studies linked to the lack of information about patient treatment, adherence to anticoagulant therapy, the lack of appropriate control groups, and the brief follow-up period. The rate of platelet recovery, risk of new or progressive thromboembolism, or occurrence of major bleeding complications were nonetheless not affected by patient populations (isolated HIT patients vs. HITT patients vs. all HIT and HITT patients), diagnostic testing strategy (PF4/H immunoassays vs. clinical criteria vs. SRA/HIPA), or study design (prospective study vs. RCT vs. retrospective study) which means that this study provides the best level of evidence available, according to the authors.…”

“…They reported a platelet count recovery (i.e., ≥150 G/L) in 96% (CI95%: 88–99%) of HIT patients treated with DOACs ( n = 74), where no significant difference with argatroban, danaparoid, or fondaparinux was noticed. Only bivalirudin was associated with a significant decreased rate of platelet count recovery (74%, CI95%: 58–85%) [ 37 ]. In 2019, Barlow et al [ 38 ] published an exhaustive compilation of literature data regarding the use of DOACs in HIT, where they regrouped biological and clinical features of 104 patients with probable HIT who were treated with DOACs.…”