Potential Role of Direct Oral Anticoagulants in the Management of Heparin‐induced Thrombocytopenia

Abstract

Heparin‐induced thrombocytopenia (HIT) is a rare, potentially life‐threatening condition secondary to unfractionated heparin or low molecular weight heparin exposure. This immune‐mediated drug reaction manifests as thrombocytopenia with a paradoxical hypercoagulable state that can result in life‐threatening thrombosis. It is imperative to ensure cessation of heparin‐based products as soon as HIT is identified. Traditional treatment options include argatroban, bivalirudin, fondaparinux, and danaparoid with a transition to warfarin upon platelet recovery. These anticoagulants are notwithstanding limitations including parenteral administration and routine laboratory monitoring leading to prolonged hospitalizations, emphasizing the need for new therapies. Direct oral anticoagulants (DOACs) have been increasingly investigated for the management of HIT and may overcome the aforementioned challenges of current therapies. The objective of this narrative review is to summarize the current HIT guidelines, discuss limitations to contemporary treatment options, provide insight into the emerging evidence for the DOACs rivaroxaban, apixaban, and dabigatran, and conclude with a clinical summary for their use in this setting. The PubMed, Google Scholar, and MEDLINE databases were searched for peer‐reviewed literature from January 1, 2012, to June 31, 2018. Twenty‐seven articles met inclusion criteria for review: 1 prospective trial, 5 retrospective cohort studies, and 21 case reports totaling 104 patients treated with a DOAC for HIT. The DOACs prevented new and recurrent thrombosis in 98% (n=102) of cases, and bleeding complications occurred in 3% (n=3). While current literature remains limited, it is suggestive of a potential role of DOACs for HIT, which has led to their integration into the 2018 American Society Hematology Guidelines with a conditional recommendation.

Prevention and Treatment of Venous Thromboembolism Associated with Coronavirus Disease 2019 Infection: A Consensus Statement before Guidelines

“…24 Considering all comorbidities, patient frailty, and potential drug-drug interactions, others nonheparin drug use, such as rivaroxaban or fondaparinux, are quite problematic in this complex clinically instable context. 25,26 During the prevention of VTE, bleeding or coagulation abnormalities may occur following the administration of anticoagulant drugs. Once it happens, drug administration should be stopped immediately, and appropriate actions can be taken.…”

Recommendations on the use of anticoagulants for the treatment of patients with heparin-induced thrombocytopenia in Switzerland

“…DOACs may be considered when switching to oral anticoagulation if there are neither renal insufficiency nor liver impairment. Of the DOACs, we would give preference to rivaroxaban, given that the most experience is available for this DOAC [12,66]. Moreover, because current literature for the use of DOACs in this setting remains limited, DOACs should not be the first option when an arterial thrombotic event occurred during HIT [12,66].…”

Superior outcomes with Argatroban for heparin-induced thrombocytopenia: a Bayesian network meta-analysis

“…Given the lack of quantitative data, a subgroup analysis according to the initial and maintenance doses could not be performed. Parenteral anticoagulants are frequently chosen for the management of HIT [ 22 , 57 ]. While many options for anticoagulant therapy are available, the present study focused on the effects of parenteral anticoagulation.…”