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心脏外科术后发生肝素诱导血小板减少症患者的临床特征分析及诊断指标评估

Analysis of Clinical Characteristics and Diagnostic Indicators in Patients With Heparin-induced Thrombocytopenia After Cardiac Surgery

  • 摘要:
    目的 探讨心脏外科术后疑似肝素诱导血小板减少症(heparin-induced thrombocytopenia, HIT)患者中HIT的确诊率、新发血栓发生率、血小板动态演变模式及临床特征;评估HIT抗体(hit-antibodies, HIT-Ab)、4T's评分和Lillo-Le Louet(LLL)评分对HIT的诊断价值。
    方法 采用回顾性队列研究,纳入2023年4月–2024年12月中国医学科学院阜外医院心脏外科术后疑似HIT患者307例,收集其临床与实验室数据。所有患者均接受4T's评分、LLL评分及HIT-Ab检测。根据最终临床诊断分为非HIT组(n=269)和HIT组(n=38),比较两组血小板演变模式及其他临床特征。根据HIT-Ab浓度分为四组:阴性组(<1.0 U/mL,n=257)、弱阳性组(1.0~4.9 U/mL,n=34)、中阳性组(5.0~9.9 U/mL,n=11)、强阳性组(≥10 U/mL,n=5),分析各组间新发血栓发生率及HIT确诊率等差异,并用受试者工作特征曲线(ROC曲线)评估HIT-Ab浓度、4T's评分和LLL评分对HIT的诊断效能。
    结果 HIT确诊率为12.38%(38/307),HIT组新发血栓率为63.16%,高于非HIT组34.57%(P<0.001)。76.32%HIT患者血小板呈双相下降模式(模式A),其发生HIT的风险显著高于模式B患者〔比值比(odds ratio, OR)=10.32, 95%置信区间(confidence interval, CI):4.64~22.95〕。新发血栓发生率随HIT-Ab升高阶梯式递增(阴性组32.7%→强阳性组100%,P<0.001),HIT确诊率从阴性组的0升至弱阳性组的64.71%,中/强阳性组确诊率达100%。HIT-Ab浓度、4T's评分和LLL评分诊断HIT的ROC曲线下面积分别为0.996(95%CI:0.991~1.000)、0.799(95%CI:0.727~0.870)和0.860(95%CI:0.811~0.908)。当HIT-Ab浓度为1 U/mL时,其诊断敏感度为100%,阴性预测值(negative predictive value, NPV)为100%。 与传统的HIT高危人群的诊断标准(4T's评分截断值为4分,LLL评分截断值为2分)相比, 以最大约登指数选定的4T's评分最佳截断值为5分,LLL评分最佳截断值为3分。
    结论 心脏术后疑似HIT患者新发血栓发生率随HIT-Ab水平升高呈阶梯上升趋势。LLL评分对HIT的诊断价值优于4T's评分。HIT-Ab检测具有较高的敏感度和阴性预测值,是指导早期停用肝素和排除HIT的可靠工具。结合HIT-Ab浓度、血小板演变模式及临床评分,有助于更精准地识别HIT风险、启动替代抗凝治疗及优化抗凝管理策略。

     

    Abstract:
    Objective To investigate the diagnosis rate of heparin-induced thrombocytopenia (HIT), the incidence of new thrombosis, the dynamic evolution pattern of platelets, and the clinical characteristics in patients with suspected HIT after cardiac surgery; and to evaluate the diagnostic value of HIT antibodies (HIT-Ab), 4T's score, and Lillo-Le Louet (LLL) score for HIT.
    Methods A retrospective cohort study was conducted. A total of 307 patients with suspected HIT after cardiac surgery at Fuwai Hospital of the Chinese Academy of Medical Sciences from April 2023 to December 2024 were included. Clinical and laboratory data were collected. All patients underwent 4T's score, LLL score, and HIT-Ab testing. Patients were divided into the non-HIT group (n = 269) and the HIT group (n = 38) based on the final clinical diagnosis. The platelet evolution patterns and other clinical characteristics of the two groups were compared. HIT-Ab concentration was divided into four groups: negative (< 1.0 U/mL, n = 257), weakly positive (1.0-4.9 U/mL, n = 34), moderately positive (5.0-9.9 U/mL, n = 11), and strongly positive (≥ 10 U/mL, n = 5). Differences in the incidence of new thrombosis and the diagnosis rate of HIT among the groups were analyzed, and the diagnostic efficacy of HIT-Ab concentration, 4T's score, and LLL score for HIT was evaluated using receiver operating characteristic (ROC) curves.
    Results The diagnosis rate of HIT was 12.38% (38/307), and the incidence of new thrombosis in the HIT group was 63.16%, higher than the 34.57% in the non-HIT group (P < 0.001). Among HIT patients, 76.32% showed a biphasic decline pattern of platelets (pattern A), and their risk of HIT was significantly higher than that of patients with pattern B (odds ratio OR = 10.32, 95% confidence interval CI: 4.64-22.95). The incidence of new thrombosis increased stepwise with higher HIT-Ab concentration (32.7% in the negative group to 100% in the strongly positive group, P < 0.001), and the diagnosis rate of HIT increased from 0 in the negative group to 64.71% in the weakly positive group, reaching 100% in the moderate/strong positive group. The areas under the ROC curves for HIT-Ab concentration, 4T's score, and LLL score for diagnosing HIT were 0.996 (95% CI: 0.991-1.000), 0.799 (95% CI: 0.727-0.870), and 0.860 (95% CI: 0.811-0.908), respectively. When the HIT-Ab concentration was 1 U/mL, the diagnostic sensitivity and negative predictive value (NPV) were both 100%. Compared with the traditional diagnostic criteria for high-risk HIT populations (4T's score cutoff of 4, LLL score cutoff of 2), the optimal cutoff value of 4T's score selected by the maximum Youden index was 5, and the optimal cutoff value of LLL score was 3.
    Conclusion The incidence of new thrombosis in patients with suspected HIT after cardiac surgery increases stepwise with higher HIT-Ab levels. The diagnostic value of the LLL score for HIT is superior to that of the 4T's score. HIT-Ab testing has high sensitivity and negative predictive value, making it a reliable tool for guiding early discontinuation of heparin and excluding HIT. Combining HIT-Ab concentration, platelet evolution pattern, and clinical scores helps more accurately identify HIT risk, initiate alternative anticoagulation therapy, and optimize anticoagulation management strategies.

     

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