Sacco Monica, Ranalli Paola, Lancellotti Stefano, Petrucci Giovanna, Dragani Alfredo, Rocca Bianca, De Cristofaro Raimondo
Servizio Malattie Emorragiche e Trombotiche Fondazione Policlinico Universitario "A. Gemelli" IRCCS Roma Italy.
Dipartimento di Medicina Interna e Chirurgia Traslazionale Facoltà di Medicina e Chirurgia "A. Gemelli" Università Cattolica del Sacro Cuore Roma Italy.
Res Pract Thromb Haemost. 2020 Feb 28;4(3):413-421. doi: 10.1002/rth2.12315. eCollection 2020 Mar.
Acquired von Willebrand factor (VWF) deficiency was described in Philadelphia-negative myeloproliferative neoplasms, especially in essential thrombocythemia (ET). VWF phenotype in contemporary patients with polycythemia vera (PV) remains less explored.
To characterize the VWF phenotype in PV and to compare VWF phenotype in PV with matched healthy subjects and ET patients.
PATIENTS/METHODS: We studied 48 PV patients, treated according to current recommendations (hematocrit ≤ 45%, on low-dose aspirin prophylaxis); 48 healthy and 41 subjects with ET, all sex, age, and blood group matched. We measured VWF antigen, activity, multimeric pattern, ADAMTS-13, and factor VIII (FVIII) antigen.
In patients with PV, VWF antigen and activity were significantly higher than in healthy subjects (antigen: 119[96-137] vs 93[79-107] IU/dL; activity: 114[95-128] vs 90[79-107] IU/dL, respectively, medians and interquartile, < 0.01), with normal multimeric distribution. ADAMTS-13 levels were similar between patients with PV and healthy subjects. FVIII levels were higher in PV than in healthy subjects (141[119-169] versus 98[88-123] IU/dL, respectively, < 0.01). By multivariable analysis, JAK2-p.V617F allelic burden, erythrocyte count, and male sex significantly predicted VWF antigen and activity levels. As compared to patients with ET, patients with PV showed similar VWF antigen levels but approximately 40% higher activity (79[49-104] vs 112[93-125] IU/dL, respectively, < 0.01).
Patients with PV show increased VWF and FVIII levels, predicted by JAK2-p.V617F burden and erythrocyte count. At variance with ET, acquired VWF defect was not observed in PV. High VWF/FVIII levels may sustain the thrombotic diathesis of PV and may be investigated as biomarkers for risk stratification.
在费城染色体阴性的骨髓增殖性肿瘤中发现了获得性血管性血友病因子（VWF）缺乏，尤其是在原发性血小板增多症（ET）中。真性红细胞增多症（PV）当代患者的VWF表型研究较少。
描述PV患者的VWF表型，并将PV患者的VWF表型与匹配的健康受试者和ET患者进行比较。
患者/方法：我们研究了48例PV患者，按照当前推荐方案进行治疗（血细胞比容≤45%，接受低剂量阿司匹林预防）；48名健康受试者和41名ET患者，所有受试者在性别、年龄和血型上均匹配。我们检测了VWF抗原、活性、多聚体模式、ADAMTS-13和凝血因子VIII（FVIII）抗原。
PV患者的VWF抗原和活性显著高于健康受试者（抗原：中位数和四分位数间距分别为119[96 - 137] vs 93[79 - 107] IU/dL；活性：114[95 - 128] vs 90[79 - 107] IU/dL，P < 0.01），多聚体分布正常。PV患者和健康受试者的ADAMTS-13水平相似。PV患者的FVIII水平高于健康受试者（分别为141[119 - 169] vs 98[88 - 123] IU/dL，P < 0.01）。多变量分析显示，JAK2-p.V617F等位基因负荷、红细胞计数和男性性别显著预测VWF抗原和活性水平。与ET患者相比，PV患者的VWF抗原水平相似，但活性高约40%（分别为79[49 - 104] vs 112[93 - 125] IU/dL，P < 0.01）。
PV患者的VWF和FVIII水平升高，由JAK2-p.V617F负荷和红细胞计数预测。与ET不同，PV未观察到获得性VWF缺陷。高VWF/FVIII水平可能维持PV的血栓形成倾向，可作为风险分层的生物标志物进行研究。
