Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
J Thromb Haemost. 2020 Jun;18(6):1435-1446. doi: 10.1111/jth.14794. Epub 2020 Apr 27.
HIT diagnosis typically uses complementary diagnostic assays (eg, a PF4-dependent enzyme-immunoassay [EIA] and a platelet activation assay such as the serotonin-release assay [SRA]).
To determine whether the combination of two automated assays-a latex immunoturbidimetric assay (LIA) that evaluates competitive inhibition of a HIT-like monoclonal antibody and a chemiluminescence immunoassay (CLIA) for detecting anti-PF4/heparin IgG-optimizes diagnostic sensitivity while also yielding good specificity, particularly at high assay reactivities.
PATIENTS/METHODS: We determined operating characteristics using combined LIA/CLIA results from a HIT observational trial (n = 430; derivation cohort) and 147 consecutive patients with HIT (n = 147; supplementary derivation cohort). We also evaluated 678 consecutive samples referred for HIT testing (replication cohort). LIA/CLIA reactivities were scored individually as "negative" (<1.00 U/mL, 0 points), "weak" (1.00-4.99 U/mL, 1 point), "moderate" (5.00-15.99 U/mL, 2 points) and "strong" (≥16.00 U/mL, 3 points), thus contributing up to 6 points (maximum) when LIA/CLIA results were combined. We also examined whether higher LIA/CLIA scores predicted presence of platelet-activating antibodies by conventional and modified (PF4- or PF4/heparin-enhanced) SRA.
Combined LIA/CLIA testing yielded high diagnostic sensitivity (99%) similar to EIA. Interpretation of LIA/CLIA results using the 6-point scale indicated progressively greater likelihood for the presence of platelet-activating antibodies with increasing scores (semi-quantitative reactivity). A LIA/CLIA score ≥ 4 points predicted the presence of platelet-activating antibodies by SRA or PF4-enhanced SRA with high probability (98%).
Combined LIA/CLIA testing optimizes diagnostic sensitivity, with progressively greater probability of detecting platelet-activating antibodies with higher assay reactivity that reaches 98% when both automated assays yield moderate or strong results.
肝素诱导的血小板减少症（HIT）的诊断通常采用互补诊断检测方法（如，依赖 PF4 的酶免疫分析（EIA）和血小板活化检测，如 5-羟色胺释放检测[SRA]）。
旨在确定两种自动化检测方法（评价 HIT 样单克隆抗体竞争性抑制的乳胶免疫比浊测定法[LIA]和检测抗 PF4/肝素 IgG 的化学发光免疫测定法[CLIA]）的联合应用是否可在提高诊断灵敏度的同时保持良好的特异性，尤其是在高检测反应性时。
患者/方法：我们使用来自 HIT 观察性试验（n=430；推导队列）和 147 例连续 HIT 患者（n=147；补充推导队列）的联合 LIA/CLIA 结果确定了检测性能。我们还评估了 678 例连续送检进行 HIT 检测的样本（验证队列）。单独对 LIA/CLIA 反应性进行评分，结果为“阴性”（<1.00 U/mL，0 分）、“弱阳性”（1.00-4.99 U/mL，1 分）、“中度阳性”（5.00-15.99 U/mL，2 分）和“强阳性”（≥16.00 U/mL，3 分），因此，当 LIA/CLIA 结果联合时，最高可达 6 分（最高分）。我们还研究了较高的 LIA/CLIA 评分是否可以通过传统和改良（PF4 或 PF4/肝素增强）SRA 预测血小板活化抗体的存在。
联合 LIA/CLIA 检测的诊断灵敏度较高（99%），与 EIA 相似。使用 6 分制解释 LIA/CLIA 结果表明，随着评分的增加（半定量反应性），血小板活化抗体存在的可能性逐渐增加。LIA/CLIA 评分≥4 分通过 SRA 或 PF4 增强 SRA 预测血小板活化抗体的存在，具有较高的可能性（98%）。
联合 LIA/CLIA 检测可优化诊断灵敏度，检测反应性较高时，检测血小板活化抗体的可能性逐渐增加，当两种自动化检测均产生中度或强结果时，可达到 98%。
