B 细胞淋巴瘤、瓦尔登斯特伦巨球蛋白血症 (WM) 患者的临床特征包括血细胞减少、IgM 介导的高粘血症、疲劳、出血和瘀伤。布鲁顿酪氨酸激酶抑制剂 (BTK) 等治疗药物会加剧出血风险。尚未在 WM 患者中研究因血小板功能障碍、凝血功能改变或血管损伤引起的异常止血。评估 WM 患者样本的止血功能障碍。全血 (WB) 样本采集自 14 名未接受治疗的 WM 患者、5 名接受 BTK 的患者和 15 名健康捐献者 (HD)。通过流式细胞术测量血小板受体水平和网状结构，通过FRET测定测量血浆凝血酶生成±血小板，通过旋转血栓弹力测定法（ROTEM）测量WB凝血潜力，通过ELISA测量血浆可溶性糖蛋白VI（sGPVI）和血清血小板生成素（TPO）。在 WM 衍生 IgM 存在的情况下，评估了供体血小板的扩散、聚集和加速凝血酶生成的能力。 WM 血小板受体水平、对生理激动剂的反应和血浆 sGPVI 均在正常范围内。 WM 血小板网状结构减少 (p=0.0012)，而血清 TPO 水平升高 (p=0.0040)。 WM 血浆显示凝血酶生成较慢 (p=0.0080)，WM 血小板对内源性凝血酶潜力的贡献较小 (ETP，p=0.0312)。用 IgM (50-60 mg/mL) 孵育的 HD 血浆或血小板显示扩散 (p=0.0002)、聚集 (p<0.0001) 和 ETP (p=0.0081) 减少。在 WM 样本中检测到凝血酶电位和 WB 凝血的改变。 WM IgM 显着损害体外止血作用。管理良好的 WM 患者的血小板和凝血特性受到干扰。版权所有 © 2024 美国血液学会。

Clinical features in patients with the B-cell lymphoma, Waldenström Macroglobulinaemia (WM), include cytopenias, IgM-mediated hyperviscosity, fatigue, bleeding and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal haemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not been investigated in WM patients. To evaluate haemostatic dysfunction in samples from WM patients. Whole blood (WB) samples were collected from 14 WM patients not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation ± platelets by FRET assay, WB clotting potential by rotational thromboelastometry (ROTEM), and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by ELISA. Donor platelet spreading, aggregation and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (p=0.0012) while serum TPO levels were increased (p=0.0040). WM plasma displayed slower thrombin generation (p=0.0080) and WM platelets contributed less to endogenous thrombin potential (ETP, p=0.0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (p=0.0002), aggregation (p<0.0001) and ETP (p=0.0081). Alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired haemostasis in vitro. Platelet and coagulation properties are disturbed in well-managed WM patients.Copyright © 2024 American Society of Hematology.