Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
J Thromb Haemost. 2018 Apr;16(4):680-688. doi: 10.1111/jth.13960. Epub 2018 Feb 28.
Essentials Mild antithrombin deficiency may increase the risk of recurrent venous thromboembolism (VTE). In a cohort study, we stratified patients with VTE to various cut-off antithrombin levels. A 1.6-3.7-fold increased risk of recurrent VTE was observed in the lowest antithrombin categories. Mild antithrombin deficiency (activity < 5th percentile of normal) increases recurrent VTE risk.
Background Mild antithrombin deficiency (previously defined as antithrombin activity below 70% or 80%) has been associated with a 2.4-3.5-fold increased risk of recurrent venous thromboembolism (VTE). This finding may have implications for duration of antithrombotic therapy in VTE patients with mild antithrombin deficiency. Objectives To externally validate whether mild antithrombin deficiency is a risk factor for recurrent VTE. Methods In a population-based cohort study, patients with a first VTE (n = 2357) were stratified according to percentile cut-off antithrombin levels (< 5th [< 87%], 5-10th [87-92%], > 10th percentile [> 92%]) and functional antithrombin levels (< 70%, 70-80%, > 80%). Results During a median follow-up of 7.4 years, 361 recurrent events occurred (incidence rate, 2.5/100 patient-years). We observed an increased risk of recurrent VTE in the lowest antithrombin activity category (< 5th percentile; < 87%) as compared with antithrombin activity that was > 10th percentile (> 92%), with an adjusted hazard ratio (HR) of 1.5 (95%CI, 1.0-2.3). When analyses were stratified to antithrombin cut-off criteria of< 70% vs. patients with antithrombin activity > 80%, the adjusted HR for venous recurrence was 3.7 (95% CI, 1.4-9.9). Mild antithrombin deficiency was able to predict recurrent VTE over at least 8 years of follow-up and the association remained present when the population was stratified to the presence or absence of thrombosis risk factors. Restriction analyses, where patients who used anticoagulation at time of blood draw and those who reported drinking ≥ 5 glasses alcohol daily were excluded, did not materially affect these outcomes. Conclusion This study confirms that mild antithrombin deficiency is a risk factor for recurrent VTE.
轻度抗凝血酶缺乏症（先前定义为抗凝血酶活性低于 70%或 80%）与静脉血栓栓塞症（VTE）复发的风险增加 2.4-3.5 倍相关。这一发现可能对 VTE 患者中轻度抗凝血酶缺乏症患者抗血栓治疗的持续时间产生影响。
外部验证轻度抗凝血酶缺乏症是否为 VTE 复发的危险因素。
在一项基于人群的队列研究中，根据抗凝血酶水平的百分位截断值（< 5 百分位[< 87%]、5-10 百分位[87-92%]、> 10 百分位[> 92%]）和功能性抗凝血酶水平（< 70%、70-80%、> 80%），对首次发生 VTE 的 2357 例患者进行分层。
在中位随访 7.4 年期间，有 361 例患者发生了复发事件（发生率为 2.5/100 患者年）。与抗凝血酶活性处于> 10 百分位（> 92%）的患者相比，我们观察到抗凝血酶活性处于最低水平（< 5 百分位；< 87%）的患者发生 VTE 复发的风险增加，校正后的危险比（HR）为 1.5（95%CI，1.0-2.3）。当根据抗凝血酶< 70%与抗凝血酶活性> 80%的截断值进行分层分析时，静脉血栓复发的校正 HR 为 3.7（95%CI，1.4-9.9）。轻度抗凝血酶缺乏症能够预测至少 8 年的随访中 VTE 的复发，当将人群分层为是否存在血栓形成危险因素时，这种关联仍然存在。排除在采血时使用抗凝剂的患者和每天报告饮用≥5 杯酒的患者的限制分析并没有对这些结果产生实质性影响。
本研究证实轻度抗凝血酶缺乏症是 VTE 复发的危险因素。
