Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
University Hospital, Krakow, Poland.
J Thromb Haemost. 2019 Nov;17(11):1912-1922. doi: 10.1111/jth.14579. Epub 2019 Aug 8.
Compact fibrin clots relatively resistant to lysis are observed in patients at increased risk of venous thromboembolism (VTE) including malignancy. The citrullinated histone H3 (H3Cit) predicts VTE in cancer patients.
We performed a cohort study to investigate whether abnormal clot properties predict cancer diagnosis following unprovoked VTE.
In 369 consecutive patients aged <70 years without malignancy detected during routine screening, we determined plasma clot permeability (K ) and clot lysis time (CLT), along with several prothrombotic markers and H3Cit after 2 to 8 months since VTE.
During follow-up (median, 37; interquartile range, 33-39 months), malignancy was diagnosed in 22 patients (6%), who were older. This group had denser fibrin networks (-13% K ), impaired fibrinolysis (+25.5% CLT), increased endogenous thrombin potential (ETP,+7%), soluble P-selectin (+40.3%), and H3Cit (+169.2%) measured off anticoagulation after median 4 months since VTE. The K and CLT correlated with H3Cit (r = -.58 and r = .31, P < .05, respectively). The Kaplan-Meier survival analysis showed that reduced K (the first quartile, ≤6.2 × 10 cm ), prolonged CLT (the top quartile, >106 min), and higher ETP (the top quartile, >1657 nM × min) were predictors of cancer diagnosed during follow-up. The multivariable Cox proportional hazards model showed that patients with the prothrombotic clot phenotype (low K and long CLT) had the highest risk of cancer diagnosis [hazard ratio(HR), 23.4; 95% confidence interval (CI), 6.67-82.15].
Prothrombotic clot properties following unprovoked VTE might help identify patients at risk of a diagnosis of cancer within the first 3 years of follow-up.
在易发生静脉血栓栓塞症（VTE）的患者中，包括恶性肿瘤患者，可观察到相对不易被纤溶的致密纤维蛋白凝块。瓜氨酸化组蛋白 H3（H3Cit）可预测癌症患者的 VTE 风险。
我们进行了一项队列研究，旨在探究在无诱因 VTE 后，异常的血栓特性是否可以预测癌症的诊断。
在 369 例年龄<70 岁且在常规筛查中未发现恶性肿瘤的连续患者中，我们在 VTE 发生后 2 至 8 个月时，测定了血浆血栓通透性（K）和血栓溶解时间（CLT）以及几种促血栓形成标志物和 H3Cit。
在随访期间（中位数为 37 个月；四分位距为 33-39 个月），22 例（6%）患者被诊断出恶性肿瘤，这些患者年龄更大。该组的纤维蛋白网络更为致密（K 降低 13%），纤溶受损（CLT 延长 25.5%），内源性凝血酶潜能（ETP）增加（+7%），可溶性 P-选择素（+40.3%），且 H3Cit 升高（+169.2%），这些都是在 VTE 发生后中位 4 个月停用抗凝治疗时的测量结果。K 和 CLT 与 H3Cit 呈负相关（r=-.58 和 r=-.31，P<.05）。Kaplan-Meier 生存分析显示，降低的 K（第一四分位数，≤6.2×10cm）、延长的 CLT（最高四分位数，>106min）和较高的 ETP（最高四分位数，>1657 nM×min）是随访期间诊断出癌症的预测因素。多变量 Cox 比例风险模型显示，具有促血栓形成的血栓表型（低 K 和长 CLT）的患者发生癌症诊断的风险最高（危险比[HR]，23.4；95%置信区间[CI]，6.67-82.15）。
无诱因 VTE 后出现的促血栓形成的血栓特性可能有助于在随访的前 3 年内识别出有诊断为癌症风险的患者。
