Management of heparin-induced thrombocytopenia

Abstract

Background: Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic adverse effect of heparin treatment. The underlying cause is the formation of highly immunogenic complexes between negatively charged heparin and positively charged platelet factor 4 (PF4). Resulting antibodies against these PF4/heparin complexes can activate platelets via the platelet FcγIIa receptor, leading to thrombin generation and thus to the paradox of a prothrombotic state despite thrombocytopenia and application of heparin. Prompt diagnosis of HIT is important in order to change treatment to prevent severe thromboembolic complications. However, this is often difficult as thrombocytopenia is frequent in hospitalized patients and the commercially available laboratory tests for HIT antibodies have a high negative predictive value but only a poor positive predictive value. This leads to overdiagnosis and overtreatment of HIT, which also bear the risk for adverse outcomes.

Areas covered: This review aims at resuming recent data on HIT, thereby focusing on the role of new anticoagulants and providing a framework for diagnosis and treatment. Furthermore, it provides some insights into the pathogenesis of this peculiar adverse drug reaction and ventures a guess at its future relevance in clinical practice.

Expert opinion: New drugs which are strongly negatively charged should be assessed for their capacity to form complexes with PF4. If they do so, they bear the risk of inducing a HIT-like immune response. The immunology of HIT is still largely unresolved. Understanding HIT might provide insights into other immune and autoimmune response mechanisms.

Keywords::

• 4T score
• argatroban
• bivalirudin
• danaparoid
• fondaparinux
• heparin
• heparin-induced thrombocytopenia
• lepirudin
• thrombocytopenia
• thrombosis

Acknowledgements

The authors thank U Alpen for secretarial assistance. A Greinacher is the coauthor of more than 10 book chapters and reviews on HIT written during the last 24 months. This makes some forms of self-plagiarism unavoidable, as there will inevitably be some overlap in the content of some of these articles.

Notes

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