Faculty Collaboration Database

A prospective, blinded study of a PF4-dependent assay for HIT diagnosis. Blood 2021 Feb 25;137(8):1082-1089

Date

09/09/2020

Pubmed ID

32898858

Pubmed Central ID

PMC7907721

DOI

10.1182/blood.2020008195

Scopus ID

2-s2.0-85098212078 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

Heparin-induced thrombocytopenia (HIT) is a life-threatening, prothrombotic, antibody-mediated disorder. To maximize the likelihood of recovery, early and accurate diagnosis is critical. Widely available HIT assays, such as the platelet factor 4 (PF4) heparin enzyme-linked immunosorbent assay (ELISA) lack specificity, and the gold-standard carbon 14-labeled serotonin release assay (SRA) is of limited value for early patient management because it is available only through reference laboratories. Recent studies have demonstrated that pathogenic HIT antibodies selectively activate PF4-treated platelets and that a technically simpler assay, the PF4-dependent P-selectin expression assay (PEA), may provide an option for rapid and conclusive results. Based upon predefined criteria that combined 4Ts scores and HIT ELISA results, 409 consecutive adults suspected of having HIT were classified as disease positive, negative, or indeterminate. Patients deemed HIT indeterminate were considered disease negative in the primary analysis and disease positive in a sensitivity analysis. The ability of PEA and SRA to identify patients judged to have HIT was compared using receiver operating characteristic curve statistics. Using these predefined criteria, the diagnostic accuracy of PEA was high (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.87-1.0) and similar to that of SRA (AUC, 0.91; 95% CI, 0.82-1.0). In sensitivity analysis, the AUCs of PEA and SRA were also similar at 0.88 (95% CI, 0.78-0.98) and 0.86 (95% CI, 0.77-0.96), respectively. The PEA, a technically simple nonradioactive assay that uses ∼20-fold fewer platelets compared with the SRA, had high accuracy for diagnosing HIT. Widespread use of the PEA may facilitate timely and more effective management of patients with suspected HIT.

Author List

Samuelson Bannow B, Warad DM, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Sharma R, Grill DE, Redman MW, Khalighi PR, Leger RR, Pruthi RK, Chen D, Sabath DE, Aster RH, Garcia DA, Padmanabhan A

Author

Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibodies
Anticoagulants
Enzyme-Linked Immunosorbent Assay
Female
Heparin
Humans
Immunoassay
Male
Middle Aged
P-Selectin
Platelet Factor 4
Prospective Studies
Thrombocytopenia