静脉血栓栓塞 (VTE) 在老年人中很常见，但在许多情况下尚未确定诱发因素。患有骨髓恶性肿瘤，尤其是骨髓增生性肿瘤的患者发生静脉血栓的风险增加。不确定潜能克隆造血（CHIP）是骨髓恶性肿瘤的一种先兆状态，在老年人中很常见，并且可能同样容易形成静脉血栓。我们评估了英国生物银行超过 400,000 个样本中 CHIP 与流行和意外 VTE 之间的总体关联和基因型特异性关联。 CHIP 与 VTE 事件有一定相关性，风险比为 1.17（95% 置信区间 (CI) 1.09-1.3；p= 0.002），但与流行的 VTE 没有显着相关性，比值比为 1.02（95% CI 0.81-1.23） ；p=0.81）。 TET2 突变 CHIP 与 VTE 事件相关，风险比为 1.33（95% CI 1.05-1.69；p= 0.02）。 JAK2 突变与 VTE 患病风险和事件风险高度相关，比值比为 6.58 (95% CI 2.65-16.29；p= 4.7 x 10-5)，风险比为 4.2 (95% CI 2.18-8.08；p= 1.7 x 10-5)，分别与 JAK2 突变型骨髓增生性肿瘤相关的血栓形成倾向一致。根据实验室参数排除潜在的未确诊骨髓增生性肿瘤后，JAK2 突变 CHIP 与 VTE 之间的关联仍然显着。与杂合因子 V Leiden 和杂合凝血酶原基因突变相比，JAK2 突变 CHIP 与 VTE 的相关性更强，但不太常见。这些结果表明，大多数 CHIP 患者的血栓形成风险没有改变，但 JAK2 突变 CHIP 患者的 VTE 风险显着升高。版权所有 © 2024 美国血液学会。

Venous thromboembolism (VTE) is common among older individuals, but provoking factors are not identified in many cases. Patients with myeloid malignancies, especially myeloproliferative neoplasms, are at increased risk for venous thrombosis. Clonal hematopoiesis of indeterminate potential (CHIP), a precursor state to myeloid malignancies, is common among the elderly and may similarly predispose to venous thrombosis. We evaluated overall and genotype-specific associations between CHIP and prevalent and incident VTE in >400,000 samples from the UK Biobank. CHIP was modestly associated with incident VTE with a hazard ratio of 1.17 (95% confidence interval (CI) 1.09-1.3; p= 0.002) but was not significantly associated with prevalent VTE with an odds ratio of 1.02 (95% CI 0.81-1.23; p= 0.81). TET2-mutant CHIP was associated with incident VTE with a hazard ratio of 1.33 (95% CI 1.05-1.69; p= 0.02). JAK2 mutations were highly associated with both prevalent and incident VTE risk with odds ratio of 6.58 (95% CI 2.65-16.29; p= 4.7 x 10-5) and hazard ratio of 4.2 (95% CI 2.18-8.08; p= 1.7 x 10-5), respectively, consistent with the thrombophilia associated with JAK2-mutant myeloproliferative neoplasms. The association between JAK2-mutant CHIP and VTE remained significant after excluding potential undiagnosed myeloproliferative neoplasms based on laboratory parameters. Compared to heterozygous factor V Leiden and heterozygous prothrombin gene mutation, JAK2-mutant CHIP was more strongly associated with VTE but was less common. These results indicate that most individuals with CHIP do not have an altered risk of thrombosis, but that individuals with JAK2-mutant CHIP have a significantly elevated risk of VTE.Copyright © 2024 American Society of Hematology.