A novel diagnostic algorithm for heparin-induced thrombocytopenia

G Zheng; M B Streiff; D Allison; C M Takemoto; K Salimian; P Morris; J Jani; R McCord; T S Kickler

doi:10.1111/ijlh.12853

A novel diagnostic algorithm for heparin-induced thrombocytopenia

Int J Lab Hematol. 2018 Oct;40(5):527-532. doi: 10.1111/ijlh.12853. Epub 2018 May 13.

Authors

G Zheng¹, M B Streiff², D Allison¹, C M Takemoto³, K Salimian¹, P Morris¹, J Jani¹, R McCord¹, T S Kickler^{1

2}

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 29756276
DOI: 10.1111/ijlh.12853

Abstract

Introduction: While diagnostic algorithm using PF4-heparin enzyme-linked immunosorbent assay (ELISA) optical density (OD), and heparin neutralization assay (HNA), or 4T score have been proposed to replace serotonin-release assay (SRA) for heparin-induced thrombocytopenia (HIT), their performance against SRA is unclear. In this study, we proposed and validated the performance of a new algorithm combining PF4-heparin ELISA optical density (OD), HNA and 4T score against SRA for HIT diagnosis.

Methods: Heparin neutralization assays were performed on specimens submitted for HIT testing with positive PF4-heparin ELISA from December 2015 to September 2017, which were separated into a "training" and a "validation" data set. 4T scores were calculated for ELISA positive cases.

Results: A total of 123 consecutive unique patient samples had positive PF4-heparin ELISA with also HNA data, SRA data, and 4T scores available. Compared to SRA, a "laboratory criteria" (ELISA OD ≥ 1.4 and HNA ≥ 70%) had a sensitivity of 88% (14/16) and specificity of 91% (42/46), and a "combined criteria" (4T score = 8, or 4T score = 6 or 7 and ELISA OD ≥ 1.0, or 4T score = 4 or 5 and ELISA OD ≥ 2.0) had a sensitivity of 75% (12/16) and specificity of 98% (45/46) in the training data set. Laboratory and combined criteria had 90% (56/62) concordance rate. Importantly, for these concordant cases, the diagnostic specificity is 100% (46/46). Based on the data, a novel diagnostic algorithm combining these 2 criteria was proposed and validated prospectively.

Conclusion: A novel algorithm has high diagnostic accuracy and potentially could eliminate the need for SRA testing in at least 90% patients with suspected HIT.

Keywords: 4T score; PF4-heparin ELISA; heparin neutralization assay; heparin-induced thrombocytopenia; serotonin-release assay.