Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Int J Lab Hematol. 2019 Aug;41(4):493-502. doi: 10.1111/ijlh.13031. Epub 2019 May 3.
HIT is caused by platelet-activating IgG that recognize multimolecular PF4/heparin complexes. HIT antibodies are generally detectable by PF4-dependent enzyme immunoassay (EIA) and by platelet serotonin-release assay (SRA) at the beginning of the HIT-related platelet count fall. We determined whether an automated immunoassay for HIT, the latex immunoturbidimetric assay (LIA), also detects antibodies early during the course of HIT. The LIA was also used to evaluate a patient with putative SRA-negative HIT.
We evaluated the timing and magnitude of LIA reactivity in serial plasma samples obtained from 19 SRA-positive patients (17 with abnormal platelet count changes indicating HIT; two with subclinical seroconversion) and one putative SRA-negative HIT patient, all obtained from patients who participated in a clinical trial of heparin thromboprophylaxis. We determined LIA status at the onset of the HIT-related platelet count fall.
The LIA was positive in all 19 SRA-positive patients (median value, 7.3 U/mL [range, 1.2-35.5]; cutoff, 1.0 U/mL); for all 13 evaluable patients for whom an informative plasma sample was available at (or shortly before) the onset of the HIT-related platelet count fall, LIA reactivity was positive. Heterogeneity in seroconversion using the LIA was observed; some patients exhibited gradual increases in reactivity, whereas other patients showed rapid increase in reactivity over a few days. The single clinical trial patient who met clinical-pathological criteria for "SRA-negative HIT" tested LIA-positive.
The LIA detects HIT antibodies at the beginning of the HIT-associated platelet count fall. The LIA was also positive in a patient with SRA-negative HIT.
HIT 是由识别多分子 PF4/肝素复合物的血小板激活 IgG 引起的。HIT 抗体通常可通过 PF4 依赖性酶免疫分析（EIA）和血小板 5-羟色胺释放测定（SRA）在与 HIT 相关的血小板计数下降开始时检测到。我们确定了一种用于 HIT 的自动化免疫测定，即乳胶免疫比浊测定（LIA），是否也能在 HIT 过程的早期检测到抗体。LIA 还用于评估一名疑似 SRA 阴性 HIT 患者。
我们评估了来自 19 名 SRA 阳性患者（17 名血小板计数变化异常提示 HIT；两名亚临床血清转化）和一名疑似 SRA 阴性 HIT 患者的系列血浆样本中 LIA 反应的时间和幅度，所有患者均来自参加肝素预防血栓形成临床试验的患者。我们在与 HIT 相关的血小板计数下降开始时确定 LIA 状态。
19 名 SRA 阳性患者的 LIA 均为阳性（中位数为 7.3 U/mL [范围，1.2-35.5]；截断值为 1.0 U/mL）；对于所有 13 名可评估的患者，在与 HIT 相关的血小板计数下降开始时（或不久前）有信息性血浆样本，LIA 反应性为阳性。使用 LIA 观察到血清转化的异质性；一些患者表现出反应性逐渐增加，而其他患者在几天内反应性迅速增加。唯一符合“SRA 阴性 HIT”临床病理标准的临床试验患者 LIA 检测结果为阳性。
LIA 在与 HIT 相关的血小板计数下降开始时检测到 HIT 抗体。LIA 也在 SRA 阴性 HIT 患者中呈阳性。
