Serotonin-release assay-negative heparin-induced thrombocytopenia
Serotonin-release assay-negative heparin-induced thrombocytopenia
复制标题
DOI：
10.1002/ajh.25660
复制
发表时间：
2019-11-06
影响因子：
12.8
通讯作者：
Arnold, Donald M.
中科院分区：
文献类型：
--
作者：
Warkentin, Theodore E.;Nazy, Ishac;Arnold, Donald M.
肝素诱导的血小板减少症（HIT）是由血小板活化抗血小板因子4（PF 4）/肝素抗体引起的血栓前药物反应。病原性HIT抗体可通过血小板活化试验-降钙素释放试验（SRA）检测。我们认为在我们的医学界进行的SRA（“McMaster”SRA）具有高灵敏度和特异性。最近，“SRA阴性HIT”的概念已被提出用于具有HIT相容临床表现的酶免疫测定（EIA）阳性/SRA阴性患者，其在PF 4增强血小板活化测定中测试为阳性。在确定SRA阴性HIT的指示病例后，我们通过在来自评估HIT的临床和实验室诊断的队列研究的EIA阳性患者中进行“PF 4-SRA”（使用高浓度添加的PF 4而不是肝素的改良SRA）来估计这种情况的频率。我们将SRA阴性HIT定义为符合三个标准的患者：临床表现与HIT一致（4 Ts ≥ 4分）; EIA阳性（≥ 1.00单位）; PF 4-SRA阳性。430例患者中，35例EIA阳性/SRA阳性，27例EIA阳性/SRA阴性。在这27例SRA阴性患者中，通过PF 4-SRA发现3例具有亚阈值水平的血小板活化抗体，其中1例符合SRA阴性HIT的临床标准。因此，基于在发现35例SRA阳性HIT患者的队列研究中识别出1例SRA阴性HIT患者，我们估计McMaster SRA诊断HIT的灵敏度为35/36（97.2%; 95% CI，85.8-99.9%）。尽管McMaster SRA对HIT高度敏感，但偶尔强烈怀疑患有HIT的SRA阴性但EIA阳性患者可以通过PF 4增强的活化测定（如PF 4-SRA）进行诊断。
Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Pathogenic HIT antibodies can be detected by the serotonin-release assay (SRA), a platelet activation test. We have regarded the SRA performed in our medical community ("McMaster" SRA) as having high sensitivity and specificity. Recently, the concept of "SRA-negative HIT" has been proposed for enzyme-immunoassay (EIA)-positive/SRA-negative patients with a HIT-compatible clinical picture, who test positive in a PF4-enhanced platelet activation assay. After identifying an index case of SRA-negative HIT, we estimated the frequency of this condition by performing the "PF4-SRA" (modified SRA using high concentrations of added PF4 rather than heparin) in EIA-positive patients from a cohort study evaluating clinical and laboratory diagnosis of HIT. We defined SRA-negative HIT as patients meeting three criteria: clinical picture compatible with HIT (4Ts >= 4 points); EIA-positive (>= 1.00units); and PF4-SRA-positive. Among 430 patients, 35 were EIA-positive/SRA-positive and 27 were EIA-positive/SRA-negative. Among these 27 SRA-negative patients, three were found to have subthreshold levels of platelet-activating antibodies by PF4-SRA, of whom one met clinical criteria for SRA-negative HIT. Thus, based on identifying one patient with SRA-negative HIT within a cohort study that found 35 SRA-positive HIT patients, we estimate the sensitivity of the McMaster SRA for diagnosis of HIT to be 35/36 (97.2%; 95% CI, 85.8-99.9%). Although the McMaster SRA is highly sensitive for HIT, occasional SRA-negative but EIA-positive patients strongly suspected of having HIT can have this diagnosis supported by a PF4-enhanced activation assay such as the PF4-SRA.