a Department of Hematology and Department of Clinical and Experimental Medicine , Linköping University , Linköping , Sweden.
b Department of Clinical Chemistry and Department of Clinical and Experimental Medicine , Linköping University , Linköping , Sweden.
Platelets. 2018 Jul;29(5):512-519. doi: 10.1080/09537104.2017.1349305. Epub 2017 Sep 12.
Platelet function disorders (PFDs) are common in patients with mild bleeding disorders (MBDs), yet the significance of laboratory findings suggestive of a PFD remain unclear due to the lack of evidence for a clinical correlation between the test results and the patient phenotype. Herein, we present the results from a study evaluating the potential utility of platelet function testing using whole-blood flow cytometry in a cohort of 105 patients undergoing investigation for MBD. Subjects were evaluated with a test panel comprising two different activation markers (fibrinogen binding and P-selectin exposure) and four physiologically relevant platelet agonists (ADP, PAR1-AP, PAR4-AP, and CRP-XL). Abnormal test results were identified by comparison with reference ranges constructed from 24 healthy controls or with the fifth percentile of the entire patient cohort. We found that the abnormal test results are predictive of bleeding symptom severity, and that the greatest predictive strength was achieved using a subset of the panel, comparing measurements of fibrinogen binding after activation with all four agonists with the fifth percentile of the patient cohort (p = 0.00008, hazard ratio 8.7; 95% CI 2.5-40). Our results suggest that whole-blood flow cytometry-based platelet function testing could become a feasible alternative for the investigation of MBDs. We also show that platelet function testing using whole-blood flow cytometry could provide a clinically relevant quantitative assessment of platelet-related hemostasis.
血小板功能障碍（PFD）在有轻度出血性疾病（MBD）的患者中很常见，但由于缺乏测试结果与患者表型之间的临床相关性的证据，实验室检查结果提示 PFD 的意义仍不清楚。在此，我们介绍了一项使用全血流动 cytometry 对 105 名接受 MBD 检查的患者进行血小板功能检测的潜在效用的研究结果。研究对象通过包含两种不同激活标志物（纤维蛋白原结合和 P-选择素暴露）和四种生理相关血小板激动剂（ADP、PAR1-AP、PAR4-AP 和 CRP-XL）的测试面板进行评估。通过与 24 名健康对照者的参考范围或整个患者队列的第五百分位数进行比较，确定异常测试结果。我们发现异常测试结果与出血症状严重程度相关，并且使用面板的子集进行比较，使用所有四个激动剂激活后的纤维蛋白原结合测量值与患者队列的第五百分位数（p=0.00008，危险比 8.7；95%CI 2.5-40）时，预测强度最大。我们的结果表明，基于全血流动 cytometry 的血小板功能检测可能成为 MBD 研究的可行替代方法。我们还表明，使用全血流动 cytometry 的血小板功能检测可以对血小板相关止血提供临床相关的定量评估。
