Molecular and Clinical Risk Factors Associated with Thrombosis and Bleeding in Myelofibrosis Patients.

IF 2.7 4区医学 Q2 HEMATOLOGY

Hamostaseologie Pub Date : 2024-12-21 DOI:10.1055/a-2410-8530

Olga Morath, Carl Crodel, Jenny Rinke, Inken Sander, Aysun Tekbas, Manja Meggendorfer, Constance Baer, Andreas Hochhaus, Thomas Ernst

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Abstract

Background: The risk of thrombosis and bleeding in myelofibrosis (MF) has been historically underappreciated. We sought to investigate potential molecular and clinical risk factors for venous (VTE) and arterial (ATE) thrombotic events as well as bleeding episodes.

Methods: Data from 246 consecutive MF patients were analyzed. Driver mutations were tested in 191 patients.

Results: In total, 181 mutations were found in 177 MF patients: 118 (61.8%) patients showed JAK2-V617F, 50 patients (26.2%) showed CALR, and 6 patients (3.1%) showed MPL mutations. Two patients were JAK2-V617F and MPL positive and one patient was positive for all three genes. Fourteen (7.3%) patients were triple negative. The JAK2-V617F allele burden was assessed in 63 JAK2-V617F-mutated patients, revealing a median of 35.6% (range: 5.0-96.0). At the time of MF diagnosis and during follow-up, 84 thrombotic events (52 VTEs and 32 ATEs) were observed, corresponding to 6.6% of patients per year. A significant association was found between JAK2-V617F mutation (OR: 2.5, 95% CI: 1.1-5.6) and prior VTE (OR: 7.6, 95% CI: 2.1-27.1) with an increased risk of VTE. Patients with prefibrotic MF had a higher rate of ATE than patients with overt MF. Hemorrhagic events occurred in 34 (13.8%) patients, corresponding to 3.8% of patients per year. Fibrosis grade 3 was associated with bleeding risk (OR: 3.4, 95% CI: 1.2-9.2, p = 0.02).

Conclusions: The presence of the JAK2-V617F mutation, regardless of allele burden, and prior thrombosis were strongly associated with an increased risk of VTE. Patients with prefibrotic MF might be considered at high risk for developing ATE.

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与骨髓纤维化患者血栓和出血相关的分子和临床危险因素。

背景：骨髓纤维化（MF）的血栓和出血风险历来被低估。我们试图研究静脉（VTE）和动脉（ATE）血栓形成事件以及出血发作的潜在分子和临床危险因素。方法：对246例连续MF患者的资料进行分析。191例患者检测了驱动突变。结果：177例MF患者共发现181个突变，其中JAK2-V617F突变118例（61.8%），CALR突变50例（26.2%），MPL突变6例（3.1%）。2例患者JAK2-V617F和MPL阳性，1例患者3种基因均阳性。14例（7.3%）为三阴性。在63名JAK2-V617F突变患者中评估了JAK2-V617F等位基因负荷，显示中位数为35.6%（范围：5.0-96.0）。在MF诊断时和随访期间，观察到84例血栓形成事件（52例vte和32例te），相当于每年6.6%的患者。JAK2-V617F突变（OR: 2.5, 95% CI: 1.1-5.6）和既往静脉血栓栓塞（OR: 7.6, 95% CI: 2.1-27.1）与静脉血栓栓塞风险增加之间存在显著关联。纤维化前MF患者ATE发生率高于显性MF患者。34例（13.8%）患者发生出血事件，相当于每年3.8%的患者。纤维化3级与出血风险相关（OR: 3.4, 95% CI: 1.2-9.2, p = 0.02）。结论：JAK2-V617F突变的存在（无论等位基因负荷如何）和既往血栓形成与VTE风险增加密切相关。纤维化前MF患者可能被认为是发生ATE的高风险人群。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hamostaseologie HEMATOLOGY-

CiteScore

5.50

自引率

6.20%

发文量

审稿时长

6-12 weeks

期刊介绍： Hämostaseologie is an interdisciplinary specialist journal on the complex topics of haemorrhages and thromboembolism and is aimed not only at haematologists, but also at a wide range of specialists from clinic and practice. The readership consequently includes both specialists for internal medicine as well as for surgical diseases.