Hospital Universitario Morales Meseguer, Murcia, Spain; Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII, Murcia, Spain.
Hospital Universitario Morales Meseguer, Murcia, Spain.
Lancet Haematol. 2024 Aug;11(8):e606-e616. doi: 10.1016/S2352-3026(24)00138-8. Epub 2024 Jun 12.
Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA.
In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing.
We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034).
This evaluation of a large patient cohort demonstrates the high thrombotic burden of IVCA. We have identified two distinct forms of IVCA, hepatic and extrahepatic, suggesting different underlying mechanisms. Beyond clinical characterisation, we draw attention to this orphan disease and highlight the need for its study and improved care.
Spanish Society of Thrombosis and Haemostasis, Instituto de Salud Carlos III, FEDER, Fundación Séneca.
下腔静脉发育不全（IVCA）是一种罕见的异常，使受影响的人下肢静脉血栓形成的频率较低，但肺栓塞的频率较低。产前血栓形成和遗传性血栓形成倾向已被认为是 IVCA 的原因。然而，关于这种疾病的临床过程和管理，证据很少。我们设计了一个患者登记处来评估 IVCA 的血栓形成风险和特征。
在这项多中心、回顾性、观察性研究中，我们纳入了 18 名来自西班牙、1 名来自葡萄牙和 1 名来自意大利的 20 家医院通过常规影像学诊断为 IVCA 的患者（n=18）。通过使用数据提取软件在放射学数据库中进行系统搜索（队列 A），或在无法进行系统方法时在病历中进行替代搜索来确定患者（队列 B；选项允许）。主要结局为临床和影像学特征、血栓形成风险、IVCA 相关血栓形成的表型、抗凝治疗和血栓形成倾向检测的结果。
我们纳入了 2010 年 1 月 1 日至 2022 年 12 月 31 日期间通过常规影像学研究诊断为 IVCA 的患者。在系统搜索中，从 8 个中心的放射学数据库中筛选了 4341333 次影像学检查。在队列 A 中，共纳入了 122 名符合条件的患者。在 12 个中心通过筛查病历又确定了 95 名符合条件的患者，其中 88 名符合条件并纳入队列 B，因此共有 210 名患者纳入了联合队列。210 名患者中，96 名（46%）为女性，200 名（95%）为欧洲或西班牙裔。60 名（29%）患者有肝下腔静脉中断，而 150 名（71%）患者有肝外 IVCA。在队列 A 中，122 名患者中有 65 名（53%）有静脉血栓形成，估计每年的风险为 1.15%（95%CI 0.89-1.46）。肝外 IVCA 与静脉血栓形成的风险高于肝内 IVCA（84 名患者中有 56 名[67%] vs 38 名患者中有 9 名[24%]，比值比 5.31，95%CI 2.27-12.43；p<0.0001）。对来自队列 A 和 B 的 126 名静脉血栓形成患者进行分析显示，发病早（中位数年龄 34.6 岁，IQR 23.3-54.3）和复发事件（126 名患者中有 50 名[40%]）。肝外 IVCA 患者下肢静脉血栓形成（95[87%]例 vs 17 例中的 9 例[53%]，p=0.0010）和复发（48[44%]例 vs 17 例中的 2 例[12%]，p=0.015）的比例更高，而肺栓塞（99 例中的 10[10%] vs 12 例中的 4 例[33%]，p=0.044）的比例较低。122 名有血栓形成的患者中，77 名（63%）接受了无限期抗凝治疗。111 名有血栓形成的患者中有 32 名（29%）（有血栓形成的 86 名患者中有 32 名[34%]）存在共存的血栓形成倾向。接受无限期抗凝治疗的患者复发风险较低（调整后的比值比 0.24，95%CI 0.08-0.61；p=0.010），而存在血栓形成倾向的患者复发风险较高（3.19，1.09-9.32；p=0.034）。
这项对大量患者队列的评估表明，IVCA 的血栓形成负担很高。我们已经确定了两种不同形式的 IVCA，即肝内和肝外，提示潜在机制不同。除了临床特征外，我们还提请注意这种孤儿病，并强调需要对其进行研究和改善护理。
西班牙血栓形成和止血学会、西班牙卡洛斯三世卫生研究所、欧盟、塞内卡基金会。
