Combinations of rapid immunoassays for a speedy diagnosis of heparin-induced thrombocytopenia

Abstract

Background: Early recognition and treatment of heparin-induced thrombocytopenia (HIT) are key to prevent severe complications.

Objective: To assess the diagnostic performance of rapid immunoassays (IA) in detecting anti-PF4/heparin-antibodies.

Methods: Diagnostic performances of lateral-flow IA (LFIA; STic Expert HIT) and latex IA (LIA; HemosIL HIT-Ab) were analyzed in pilot (n = 74) and derivation cohorts (n = 267). Two novel algorithms based on the combination of HIT clinical probability with sequentially performed LIA and chemiluminescent IA (CLIA; HemosIL AcuStar-HIT-IgG) were compared with published rapid diagnostic algorithms: the "Lausanne algorithm" sequentially combining CLIA and particle-gel IA (PaGIA) and the "Hamilton algorithm" based on simultaneously performed LIA and CLIA.

Results: LFIA missed 6/30 HIT. The sensitivity and specificity of LIA were 90.9% and 93.5%. The Lausanne algorithm correctly predicted HIT in 19/267 (7.1%), excluded it in 240/267 (89.9%), leaving 8/267 (3%) cases unsolved. The algorithm sequentially combining CLIA and LIA predicted HIT in 19/267 (7.1%) with 1/19 wrong prediction, excluded it in 236/267 (88.4%), leaving 11/267 (4.1%) cases unsolved. The algorithm employing LIA as a first assay predicted HIT in 22/267 (8.2%), excluded it in 235/267 (88%), leaving 9/267 (3.4%) cases unsolved. Finally, the Hamilton algorithm correctly predicted HIT in 10/267 (3.7%), excluded it in 229/267 (85.7%), leaving 28/267 (10.5%) cases unsolved.

Conclusion: LFIA cannot be used to exclude or predict HIT when using frozen plasma. A Bayesian approach sequentially employing two rapid immunoassays for anti-PF4/heparin antibodies is most effective for the accurate diagnosis of HIT. Based on retrospective data, the combination LIA/CLIA is a candidate for a prospective validation.

Keywords: Bayesian inference; anti-PF4/heparin antibodies; diagnostic algorithm; heparin-induced thrombocytopenia; rapid immunoassays.