Kaksonen Matti, Simonen Piia, Lassila Riitta, Pentikäinen Markku
Heart and Lung Center, Cardiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Hematology, Coagulation Disorders Unit, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Ann Med. 2024 Dec;56(1):2404549. doi: 10.1080/07853890.2024.2404549. Epub 2024 Dec 3.
Factor Xa inhibitors (FXaI) are recommended for treatment of venous thromboembolism (VTE). However, in FXaI trials there is a 2-3% treatment failure rate. This observational study aimed to elucidate factors associated with recurrent VTE during coagulation FXaI treatment.
Ten consecutive FXaI failure cases were included. Various thrombosis risk scores were assessed, thrombophilia was screened, and coagulation activity was followed-up, to tailor individual anticoagulation strategies.
Our patients were young (mean age 37.5 years, range 22-55), six being women. Index VTE was pulmonary embolism (PE) in eight patients, and upon recurrent PE, six of them developed chronic thromboembolic pulmonary hypertension (CTEPH). Although initially many patients appeared to have unprovoked VTE, all had major VTE risk factors. Seven patients had chronic venous obstruction: five subclavian (thoracic outlet syndrome, TOS) even though only two had upper extremity deep vein thrombosis at index thrombosis, plus one common iliac, and one with chronic paraplegia. Five patients had multiple VTE risk factors and four had thrombophilia. VTE risk scores varied from the lowest (TOS patients) to the highest risk (multiple risk factors/thrombophilia). FXaI failure occurred on average at 97 days of therapy (range 15-279) without evident noncompliance. D-dimer levels declined from the index thrombosis to FXaI failure, and re-thrombosis resisted further anticoagulation, low D-dimer referring to impaired fibrinolysis. The majority (8/10) of patients required mechanical/surgical interventions.
Our results underline careful risk assessment upon PE and reoccurrence, with inclusion of TOS as a risk factor of VTE and CTEPH.
Xa因子抑制剂（FXaI）被推荐用于治疗静脉血栓栓塞症（VTE）。然而，在FXaI试验中存在2%-3%的治疗失败率。这项观察性研究旨在阐明与凝血FXaI治疗期间复发性VTE相关的因素。
纳入连续10例FXaI治疗失败的病例。评估各种血栓形成风险评分，筛查易栓症，并对凝血活性进行随访，以制定个体化的抗凝策略。
我们的患者较为年轻（平均年龄37.5岁，范围22-55岁），其中6例为女性。首发VTE为8例患者的肺栓塞（PE），复发性PE时，其中6例发展为慢性血栓栓塞性肺动脉高压（CTEPH）。尽管最初许多患者似乎有无诱因的VTE，但所有患者都有主要的VTE危险因素。7例患者存在慢性静脉阻塞：5例为锁骨下静脉阻塞（胸廓出口综合征，TOS），尽管首发血栓形成时只有2例有上肢深静脉血栓形成，另外1例为髂总静脉阻塞，1例为慢性截瘫。5例患者有多种VTE危险因素，4例有易栓症。VTE风险评分从最低（TOS患者）到最高风险（多种危险因素/易栓症）不等。FXaI治疗失败平均发生在治疗97天（范围15-279天），且无明显的不依从情况。D-二聚体水平从首发血栓形成到FXaI治疗失败呈下降趋势，再发血栓形成对抗凝治疗耐药，低D-二聚体提示纤维蛋白溶解受损。大多数（8/10）患者需要机械/手术干预。
我们的结果强调了对PE及复发情况进行仔细的风险评估，将TOS纳入VTE和CTEPH的危险因素。
