An update on heparin-induced thrombocytopenia: diagnosis and management

ABSTRACT

Introduction: Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. A subset of anti-PF4/heparin antibodies are capable of intravascular platelet activation by cross-linking Fcgamma receptor IIA leading to platelet count decrease and/or thrombosis. HIT can be potentially associated with devastating complications such as life-threatening thrombosis making it one of the most serious adverse drug reactions. Diagnosis of HIT based on clinical information is often difficult.

Area covered: This review highlights the pathophysiology of HIT, emphasizing characteristic clinical features and the role of laboratory assays in the diagnosis of HIT. In addition, a summary of current therapeutic options for patients with HIT will be provided.

Expert opinion: A combination of clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. If HIT is strongly suspected, all sources of heparin must be stopped and an alternative non-heparin anticoagulant should be started to prevent new thromboembolic complications. However, heparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. A better understanding of clinical and laboratory features of HIT may help developing strategies to avoid complications induced by this serious adverse reaction against heparin.

KEYWORDS:

• Antibody
• heparin
• thrombocytopenia
• thrombosis

Article highlights

• The diagnosis of HIT is based on clinical criteria and confirmed by in vitro demonstration of platelet-activating anti-PF4/heparin antibodies.

• Immunoassays to detect anti-PF4/heparin antibodies have an excellent sensitivity; their ability to distinguish pathogen from non-pathogen antibodies is, however, unsatisfactory.

• Including systematic approaches to assess the likelihood of HIT, such as 4T score, into the hospital’s standard operating procedures may reduce overdiagnosis of HIT.

• Once HIT is strongly-suspected, all source of heparin must be stopped and an alternative non-heparin anticoagulant should be applied.

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Acknowledgments

The author thanks Drs Andreas Greinacher and Theodore Warkentin for helpful discussion. T.B. was supported by a grant from the German Research Foundation (DFG; BA-5158-1).

Declaration of interest

The author has no relevant affiliations 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.