TY - JOUR
T1 - A prospective, blinded study of a PF4-dependent assay for HIT diagnosis
AU - Samuelson Bannow, Bethany
AU - Warad, Deepti M.
AU - Jones, Curtis G.
AU - Pechauer, Shannon M.
AU - Curtis, Brian R.
AU - Bougie, Daniel W.
AU - Sharma, Ruchika
AU - Grill, Diane E.
AU - Redman, Mary W.
AU - Khalighi, Parisa R.
AU - Leger, Rachel R.
AU - Pruthi, Rajiv K.
AU - Chen, Dong
AU - Sabath, Daniel E.
AU - Aster, Richard H.
AU - Garcia, David A.
AU - Padmanabhan, Anand
N1 - Funding Information:
The authors acknowledge Allison Ujcich, Mia Sullivan, and Zaira Arteaga from the Platelet & Neutrophil Immunology Laboratory, Versiti Wisconsin, for logistic and technical assistance for SRA studies. This work was supported, in part, by National Institutes of Health, National Heart Lung and Blood Institute grants HL133479 (A.P.), HL013629 (R.H.A.), and 2T32HL007093-41 (Hematology Training Grant; B.S.B.).
Funding Information:
This work was supported, in part, by National Institutes of Health, National Heart Lung and Blood Institute grants HL133479 (A.P.), HL013629 (R.H.A.), and 2T32HL007093-41 (Hematology Training Grant; B.S.B.).
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/2/25
Y1 - 2021/2/25
N2 - 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. Key Points: • The PEA is a technically simple nonradioactive functional HIT assay. • In a prospective blinded study, the PEA was highly accurate for the diagnosis of HIT classified by predefined clinicopathologic criteria.
AB - 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. Key Points: • The PEA is a technically simple nonradioactive functional HIT assay. • In a prospective blinded study, the PEA was highly accurate for the diagnosis of HIT classified by predefined clinicopathologic criteria.
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U2 - 10.1182/blood.2020008195
DO - 10.1182/blood.2020008195
M3 - Article
C2 - 32898858
AN - SCOPUS:85098212078
SN - 0006-4971
VL - 137
SP - 1082
EP - 1089
JO - Blood
JF - Blood
IS - 8
ER -