Rapid and Accurate Bayesian Diagnosis of Heparin-induced thrombocytopenia

Abstract

Prompt diagnostic work-up of suspected heparin-induced thrombocytopenia (HIT) is critical for guiding initial patient management. We assessed the performance of three immunoassays detecting anti-PF4/heparin-antibodies, derived a diagnostic algorithm with a short analytical turnaround-time (TAT) and prospectively validated it. Plasma samples were analysed by Zymutest-HIA-IgG, HemosIL-AcuStar-HIT-IgG and ID-H/PF4-PaGIA in retrospective (n=221) and prospective (n=305) derivation cohorts. We calculated likelihood ratios (LR) of result intervals and cut-off values with 100% negative (NPV) and positive (PPV) predictive value for a positive gold-standard functional assay (HIPA). We established a diagnostic algorithm based on the Bayesian combination of pre-test probability and LR of first- and second-line immunoassays. Cut-offs with 100% PPV for positive HIPA were >3.0 U/ml (HemosIL-AcuStar-HIT-IgG) and titre {greater than or equal to}16 (ID-H/PF4-PaGIA); cut-offs with 100% NPV were <0.13 U/ml and {less than or equal to}1, respectively. During the prospective validation of the derived algorithm (n=687), HemosIL-AcuStar-HIT-IgG was used as unique testing in 566/687 cases (82.4%) (analytical TAT 30 min). In 121/687 unresolved cases (17.6%), ID-H/PF4-PaGIA was used as second-line testing (additional TAT 30 min). The algorithm accurately predicted HIT in 51/687 (7.4%) and excluded it in 604/687 (87.9%) patients, leaving only 20/687 (2.9%) cases unresolved. Additionally, we identified 12/687 (1.7%) positive predictions not confirmed by HIPA: 10 patients with probable HIT despite negative HIPA and two possible false positive algorithm predictions. The combination of pre-test probability with first- and second-line immunoassays for anti-PF4/heparin-antibodies is accurate for ruling in or out HIT in {greater than or equal to}95% of cases within 60 minutes. This diagnostic approach improves initial management of patients with suspected HIT.