Prospective evaluation of two specific IgG immunoassays (HemosIL^® AcuStar HIT‐IgG and HAT45G^®) for the diagnosis of heparin‐induced thrombocytopenia: A Bayesian approach

Abstract

Introduction The accurate diagnosis of heparin‐induced thrombocytopenia (HIT) is essential to ensure adequate treatment and prevent complications. First step diagnosis test are immunoassays including enzyme‐linked immunosorbent assays (ELISAs) and rapid immunoassays. Methods Using a Bayesian approach, we prospectively evaluated the performance of the IgG PF4/polyvinylsulfonate ELISA and a chemiluminescent immunoassay (CLIA), which are specific for IgG and use the same antigenic target to detect HIT antibodies. Results One hundred and eighty‐four 184 consecutive patients with an intermediate (n = 159) or high (n = 25) clinical pretest probability of HIT based on the 4Ts score or platelet pattern were included. Both immunoassays (IAs) were performed on all 184 samples, and definite HIT was confirmed with a positive serotonin release assay in 29 patients (12.7%). The sensitivity (Ss) and negative predictive value (NPV) of ELISA were excellent (100%) allowing HIT to be excluded with good confidence when the test was negative. In addition, the Ss and NPV of the CLIA equalled 93.1% and 98.6%, respectively, as it was negative in two definite HIT. When the CLIA was negative, the post‐test probability of HIT was 0.7% in case of intermediate risk. Although there was excellent agreement between CLIA and ELISA results, the quantitative values provided by the two IAs were not correlated. Conclusion AcuStar HIT® detects more than 90% of HIT, as do all rapid IAs, and appears to be a good tool for excluding HIT when the pretest probability is intermediate. A chemiluminescent signal higher than 10 IU/mL is highly predictive of definite HIT with a PPV of 100%.

Antibodies against Platelet Factor 4 and Their Associated Pathologies: From HIT/HITT to Spontaneous HIT-Like Syndrome, to COVID-19, to VITT/TTS

“…For HIT, the expected presentation of 5–10 days post-heparin initiation is much tighter that that expected for VITT, which may be of 5–42 days, albeit having a similar minimum presentation period of ~5 days [ 36 ]. For HIT, all immunological anti-PF4/H antibody assays can detect the anti-PF4/H antibodies with high sensitivity, albeit with differing specificity, with the rapid chemiluminescence assay perhaps showing highest specificity [ 10 , 11 , 12 ]. For VITT, only ELISA-based immunological assays are consistently sensitive to anti-PF4/X antibodies, with rapid assays, otherwise sensitive to anti-PF4/H antibodies in HIT, being mostly negative in VITT [ 23 , 28 , 37 ].…”

“…All such techniques are sensitive to detecting PF4/H (or HIT) antibodies but have variable specificity for pathophysiological HIT (or HITT). Among these assays, the chemiluminescence-based methods probably have the highest specificity for HITT [ 9 , 10 , 11 , 12 ]. Once PF4/H (or HIT) antibodies have been detected by these immunoassays, the presence of such antibodies is proved, but functional methods based on platelet activation and/or aggregation should be performed to identify if these antibodies are pathologically able to activate platelets [ 3 , 4 , 5 , 9 , 10 ].…”

Heparin-induced Thrombocytopenia: Perioperative Diagnosis and Management

“…an optical density of 1.4 or greater to 2 or greater (normal value, 0.3 to 0.5). 10,[31][32][33][34][35][36] However, variability in the institutional "in-house" functional confirmation assay rather than the result of the commercially available ELISA or the rapid immunoassay can be considered significant.…”

“…For example, for the chemiluminescent immunoassay, values of 3 U/ml or greater to 10 U/ml or greater (normal value, less than 1 U/ml) have been proposed, and for the ELISA, an optical density of 1.4 or greater to 2 or greater (normal value, 0.3 to 0.5). 10,31–36 However, variability in the institutional “in-house” functional confirmation assay rather than the result of the commercially available ELISA or the rapid immunoassay can be considered significant.…”