Lai Silvia, Barbano Biagio, Cianci Rosario, Gigante Antonietta, Di Donato Domenico, Asllanaj Bledian, Dimko Mira, Mariotti Amalia, Morabito Santo, Pugliese Francesco
Dipartimento di Nefrologia, Universita degli Studi, Roma, Italy.
G Ital Nefrol. 2010 Nov-Dec;27(6):649-54.
Cardiovascular mortality and morbidity are higher in patients with chronic renal disease than in the general population. Patients with chronic renal disease are in the highest risk group for thromboembolic disease and many clinical trials have demonstrated the greater safety and efficacy of low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH). LMWH is cleared only by the kidneys while UFH is cleared by the renal and hepatic routes. Furthermore, LMWH has a significant accumulative effect in patients with impaired renal function (creatinine clearance <30 mL/min). The aim of this study was to evaluate the risk of bleeding when LMWH is used as an anticoagulant in hemodialysis or for treatment of acute thromboembolic disease in patients with renal failure. Twenty-one adult patients were enrolled, 13 with end-stage renal disease requiring chronic hemodialysis and 6 with acute thromboembolic disease and severe renal insufficiency (creatinine clearance <30 mL/min). Group A consisted of 13 patients receiving LMWH (enoxaparin 60 IU/kg/day) for preventing thrombosis of the extracorporeal dialysis circuit. Group B consisted of 8 patients with acute thromboembolic disease receiving LMWH (enoxaparin 60 IU/kg/day). In all patients anti-Xa activity was measured by a chromogenic assay (HEMONOX). In the first group 2 blood samples were taken during the dialysis session (2-4 hours) and a third sample after the end of the session up to 48 hours following enoxaparin injection; in the second group a blood sample was taken 4 days after the start of LMWH treatment, 2 hours after its daily administration. In group A, all dialysis sessions were performed with no minor or major bleeding. Anti-Xa activity was highest 2 hours after the start and remained above 100 seconds after the end of the session, while 44 hours after injection, at the start of the next dialysis session, it was low or absent (<100 seconds). In the second group there were 2 major bleeding episodes, 2 minor bleeding episodes, 1 prolonged time to hemostasis after needle removal, and 2 bleeding episodes at the vascular access site (central venous catheter). Anti-Xa activity was consistently higher than 200 seconds (therapeutic target range:100-200 seconds) and showed interindividual variability (in 2 patients the anti-Xa time was more than 900 seconds), indicating a high risk of bleeding. LMWH seems to be as effective and safe as UFH in terms of bleeding complications and in preventing extracorporeal circuit thrombosis in patients on hemodialysis. Our results indicate that it is preferable to avoid invasive procedures for 12 hours following a dialysis session performed with LMWH anticoagulation because the anticoagulant effect lasted at least 4 hours after its injection. These data suggest that in patients with acute thromboembolic events and severe renal insufficiency, standard anticoagulation with LMWH is not recommended because of an increased risk of major and minor bleeding.
慢性肾病患者的心血管死亡率和发病率高于普通人群。慢性肾病患者属于血栓栓塞性疾病的最高风险组,许多临床试验已证明低分子量肝素(LMWH)相对于普通肝素(UFH)具有更高的安全性和有效性。LMWH仅通过肾脏清除,而UFH通过肾脏和肝脏途径清除。此外,LMWH在肾功能受损(肌酐清除率<30 mL/分钟)的患者中有显著的蓄积作用。本研究的目的是评估LMWH用作血液透析抗凝剂或用于治疗肾衰竭患者急性血栓栓塞性疾病时的出血风险。招募了21名成年患者,其中13名患有需要长期血液透析的终末期肾病,6名患有急性血栓栓塞性疾病和严重肾功能不全(肌酐清除率<30 mL/分钟)。A组由13名接受LMWH(依诺肝素60 IU/kg/天)以预防体外透析回路血栓形成的患者组成。B组由8名患有急性血栓栓塞性疾病并接受LMWH(依诺肝素60 IU/kg/天)的患者组成。所有患者均通过发色底物法(HEMONOX)测量抗Xa活性。在第一组中,在透析过程中(2 - 4小时)采集2份血样,并在依诺肝素注射后48小时内透析结束后采集第三份血样;在第二组中,在LMWH治疗开始4天后、每日给药后2小时采集血样。在A组中,所有透析过程均未发生轻微或严重出血。抗Xa活性在开始后2小时最高,透析结束后仍高于100秒,而在注射后44小时,在下一次透析开始时,活性较低或无活性(<100秒)。在第二组中,发生了2次严重出血事件、2次轻微出血事件、1次拔针后止血时间延长以及2次血管通路部位(中心静脉导管)出血事件。抗Xa活性持续高于200秒(治疗目标范围:100 - 200秒),并显示出个体差异(2名患者的抗Xa时间超过900秒),表明出血风险高。就出血并发症和预防血液透析患者体外回路血栓形成而言,LMWH似乎与UFH一样有效和安全。我们的结果表明,在使用LMWH抗凝进行透析后12小时内最好避免进行侵入性操作,因为抗凝作用在注射后至少持续4小时。这些数据表明,对于急性血栓栓塞事件和严重肾功能不全的患者,不建议使用LMWH进行标准抗凝,因为发生轻微和严重出血的风险增加。