Johnsen Håkon S, Hindberg Kristian, Bjøri Esben, Brodin Ellen E, Brækkan Sigrid K, Morelli Vânia M, Hansen John-Bjarne
Department of Clinical Medicine, K.G Jebsen - Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway.
Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
TH Open. 2019 Mar 25;3(1):e77-e84. doi: 10.1055/s-0039-1683395. eCollection 2019 Jan.
Identification of patients at risk of major bleeding is pivotal for optimal management of anticoagulant therapy in venous thromboembolism (VTE). Studies have suggested that D-dimer may predict major bleeding during anticoagulation; however, this is scarcely investigated in VTE patients. We aimed to investigate the role of D-dimer, measured at VTE diagnosis, as a predictive biomarker of major bleeding. The study population comprised 555 patients with a first community-acquired VTE (1994-2016), who were identified among participants from the Tromsø study. Major bleeding events were recorded during the first year after VTE and defined according to the criteria of the International Society on Thrombosis and Haemostasis. Cox-regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, and duration of anticoagulant therapy. In total, 29 patients experienced major bleeding (incidence rate: 5.7/100 person-years, 95% CI: 4.0-8.2). The major bleeding risk was highest during the first 3 months, especially in patients with D-dimer ≥8.3 µg/mL (upper 20th percentile), with 28.8 major bleedings/100 person-years (95% CI: 13.7-60.4). Patients with D-dimer ≥8.3 µg/mL had a 2.6-fold (95% CI: 1.1-6.6) higher risk of major bleeding than patients with D-dimer ≤2.3 µg/mL (lower 40th percentile). Major bleeding risk according to D-dimer ≥8.3 versus ≤2.3 µg/mL was particularly pronounced among those with deep vein thrombosis (HR: 4.6, 95% CI: 1.3-16.2) and provoked events (HR: 4.2, 95% CI: 1.0-16.8). In conclusion, our results suggest that D-dimer measured at diagnosis may serve as a predictive biomarker of major bleeding after VTE, especially within the initial 3 months.
识别有大出血风险的患者对于静脉血栓栓塞症（VTE）抗凝治疗的优化管理至关重要。研究表明，D - 二聚体可能预测抗凝期间的大出血；然而，在VTE患者中对此研究甚少。我们旨在研究在VTE诊断时检测的D - 二聚体作为大出血预测生物标志物的作用。研究人群包括555例首次社区获得性VTE患者（1994 - 2016年），这些患者是从特罗姆瑟研究的参与者中识别出来的。在VTE后的第一年记录大出血事件，并根据国际血栓与止血学会的标准进行定义。使用Cox回归计算风险比（HRs）及95%置信区间（CIs），并对年龄、性别和抗凝治疗持续时间进行调整。共有29例患者发生大出血（发病率：5.7/100人年，95% CI：4.0 - 8.2）。大出血风险在最初3个月最高，尤其是D - 二聚体≥8.3 μg/mL（第80百分位数以上） 的患者，大出血发生率为28.8/100人年（95% CI：13.7 - 60.4）。D - 二聚体≥8.3 μg/mL的患者大出血风险比D - 二聚体≤2.3 μg/mL（第40百分位数以下）的患者高2.6倍（95% CI：1.1 - 6.6）。在深静脉血栓形成患者（HR：4.6，95% CI：1.3 - 16.2）和诱因明确的事件患者中（HR：4.2，95% CI：1.0 - 16.8），D - 二聚体≥8.3 μg/mL与≤2.3 μg/mL相比的大出血风险尤为明显。总之，我们的结果表明，诊断时检测的D - 二聚体可作为VTE后大出血的预测生物标志物，尤其是在最初3个月内。
