Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

Abstract

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. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options.

Keywords: heparin; thrombocytopenia; thrombosis.

Figure 1.

A suggested approach to diagnosis and initial management of patients with suspected HIT.This approach to the diagnosis and initial management of patients with suspected HIT is based on clinical assessment supported by complementary laboratory investigations. Results of Immunoassays can be devided into neagtive, weakly positive (OD < 1.0) and strong positive (OD>1.0). The decision whether weakly positive results need to be further verfied using functional assays or not depends on the clinical probabilty. As indeterminate results may be occasionally obtained using laboratory tests, re-evaluating the clinical probability of HIT in an individual patient may be helpful to overcome some diagnostic uncertainty.