Heparin induced thrombocytopenia in critically ill: Diagnostic dilemmas and management conundrums

Abstract

Thrombocytopenia is often noted in critically ill patients. While there are many reasons for thrombocytopenia, the use of heparin and its derivatives is increasingly noted to be associated with thrombocytopenia. Heparin induced thrombocytopenia syndrome (HITS) is a distinct entity that is characterised by the occurrence of thrombocytopenia in conjunction with thrombotic manifestations after exposure to unfractionated heparin or low molecular weight heparin. HITS is an immunologic disorder mediated by antibodies to heparin-platelet factor 4 (PF4) complex. HITS is an uncommon cause of thrombocytopenia. Reported incidence of HITS in patients exposed to heparin varies from 0.2% to up to 5%. HITS is rare in ICU populations, with estimates varying from 0.39%-0.48%. It is a complex problem which may cause diagnostic dilemmas and management conundrum. The diagnosis of HITS centers around detection of antibodies against PF4-heparin complexes. Immunoassays performed by most pathology laboratories detect the presence of antibodies, but do not reveal whether the antibodies are pathological. Platelet activation assays demonstrate the presence of clinically relevant antibodies, but only a minority of laboratories conduct them. Several anticoagulants are used in management of HITS. In this review we discuss the incidence, pathogenesis, diagnosis and management of HITS.

Keywords: Critically ill; Diagnosis; Heparin; Management; Thrombocytopenia.

Figure 1

Iceberg model for heparin induced thrombocytopenia syndrome heparin induced thrombocytopenia syndrome as proposed by Warkentin et al[37]. The size of various iceberg sections and the portion seen, can vary in proportion to the other sections depending on the population of patients, preparation of heparin used, etc.

Figure 2

Diagnostic algorithm for Heparin induced thrombocytopenia syndrome. Note that Confirmatory assays for HITS should be considered on the basis of pre test probability rather than ELISA alone. HITS: Heparin induced thrombocytopenia syndrome; SRA : Serotonin release assay. ELISA : Enzyme linked immunosorbent assay.

Figure 3

Suggested approach for patients with heparin induced thrombocytopenia syndrome needing cardiopulmonary bypass. HITS: Heparin induced thrombocytopenia syndrome; CPB: Cardiopulmonary bypass.