Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Blood. 2024 Nov 14;144(20):2149-2154. doi: 10.1182/blood.2024024187.
Venous thromboembolism (VTE) is common among older individuals, but provoking factors are not identified in many cases. Patients with myeloid malignancies, especially myeloproliferative neoplasms (MPNs), are at increased risk for venous thrombosis. Clonal hematopoiesis of indeterminate potential (CHIP), a precursor state to myeloid malignancies, is common among older individuals 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 (HR) of 1.17 (95% confidence interval [CI], 1.09-1.3; P = .002) but was not significantly associated with prevalent VTE with an odds ratio (OR) of 1.02 (95% CI, 0.81-1.23; P = .81). TET2-mutant CHIP was associated with incident VTE with a HR of 1.33 (95% CI, 1.05-1.69; P = .02). JAK2 mutations were highly associated with both prevalent and incident VTE risk, with an OR of 6.58 (95% CI, 2.65-16.29; P = 4.7 × 10-5) and a HR of 4.2 (95% CI, 2.18-8.08; P = 1.7 × 10-5), respectively, consistent with the thrombophilia associated with JAK2-mutant MPN. The association between JAK2-mutant CHIP and VTE remained significant after excluding potential undiagnosed MPN based on laboratory parameters. JAK2-mutant CHIP was more strongly associated with VTE but was less common than heterozygous factor V Leiden and heterozygous prothrombin gene mutation. These results indicate that most individuals with CHIP do not have an altered risk of thrombosis, but individuals with JAK2-mutant CHIP have a significantly elevated risk of VTE.
静脉血栓栓塞症（VTE）在老年人中很常见，但在许多情况下，其诱发因素仍未明确。患有髓系恶性肿瘤的患者，特别是骨髓增生性肿瘤（MPN）患者，静脉血栓形成的风险增加。不确定潜能的克隆性造血（CHIP），是髓系恶性肿瘤的前体状态，在老年人中很常见，也可能同样易导致静脉血栓形成。我们评估了超过 400000 例来自英国生物银行的样本中 CHIP 与现患和新发 VTE 之间的总体和基因型特异性关联。CHIP 与新发 VTE 呈中度相关，风险比（HR）为 1.17（95%置信区间[CI]，1.09-1.3；P =.002），但与现患 VTE 无显著相关性，比值比（OR）为 1.02（95%CI，0.81-1.23；P =.81）。TET2 突变的 CHIP 与新发 VTE 相关，HR 为 1.33（95%CI，1.05-1.69；P =.02）。JAK2 突变与现患和新发 VTE 风险均高度相关，OR 为 6.58（95%CI，2.65-16.29；P = 4.7×10-5）和 HR 为 4.2（95%CI，2.18-8.08；P = 1.7×10-5），与 JAK2 突变的 MPN 相关的血栓形成相一致。根据实验室参数排除潜在未确诊的 MPN 后，JAK2 突变的 CHIP 与 VTE 之间的关联仍然显著。JAK2 突变的 CHIP 与 VTE 的相关性更强，但比杂合性因子 V Leiden 和杂合性凝血酶原基因突变少见。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 突变的 CHIP 患者 VTE 的风险显著升高。
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