Heparin-induced thrombocytopenia: pathophysiology, diagnosis and treatment

ABSTRACT

Introduction: Immune-mediated heparin-induced thrombocytopenia (HIT) is an infrequent complication following heparin exposure but with potentially fatal outcome due to thrombotic complications. Prompt suspension of heparin is necessary if HIT is suspected, followed by initiation of non-heparin anticoagulant therapy.

Areas covered: In this review, the pathophysiology and challenges in diagnosing HIT are elucidated. Current and emerging treatment options are discussed with special focus on parenteral thrombin inhibitors (argatroban, bivalirudin), parenteral factor Xa inhibitors (danaparoid, fondaparinux) and direct oral anticoagulants (DOACs [rivaroxaban, apixaban, dabigatran]) including dosing strategies for DOACs. The database PubMed was employed without time boundaries.

Expert opinion: Only argatroban holds regulatory approval for HIT treatment in both U.S. and Europe. This treatment is, however, challenged by the need for close monitoring and high costs. Fondaparinux has been increasingly used for off-label treatment and during recent years, evidence for the use of DOACs has emerged. Preliminary results from observational studies hold promise for future use of DOACs in the acute and subacute phase of HIT. However, so far, the use of DOACs in acute HIT should be reserved for clinically stable patients without severe thrombotic complications. Importantly, both fondaparinux and DOAC use is contraindicated in severe renal insufficiency.

KEYWORDS:

• Anticoagulant
• diagnosis
• heparin
• heparin antibody
• heparin-induced thrombocytopenia
• management
• thrombocytopenia
• thrombosis
• treatment

Article highlights

• The overall principle of treatment of heparin-induced thrombocytopenia (HIT) is suspension of heparin and initiation of a non-heparin anticoagulant drug

• Argatroban is the only available non-heparin anticoagulant drug holding regulatory approval for HIT treatment

• Due to cost and challenges of argatroban and danaparoid use in clinical practice, an increasing off-label use of fondaparinux and direct oral anticoagulants (DOACs) has emerged

• Current evidence suggests acceptable efficacy and safety of both fondaparinux and DOACs in HIT-patients without severe renal insufficiency, with DOACs having the most favorable profile due to oral administration

• Administration of high-dose intravenous immunoglobulin should be considered in HIT patients with refractory thrombocytopenia despite replacement of heparin by non-heparin anticoagulant therapy

Declaration of interest

The authors have no conflicts of interest regarding the present paper or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.