- 學位論文
單劑量低分子量肝素應用於長期規則血液透析病患療效及安全性評估
A safety and efficacy evaluation of single infusion of low molecular weight heparin for hemodialysis patients
摘要
研究背景 目前國內血液透析病患數有日益增加的趨勢,而在血液透析過程中，目前國內應用最普遍的抗凝血劑是傳統肝素(Unfractionated heparin, UFH)，因為傳統肝素在臨床上存在有較嚴重的出血傾向，且生體可用率(Bioavailability) 低，個體差異大，易誘發血小板減少等副作用。但對於何種低分子量肝素，較適於使用在血液透析病患，則無一致之結論。而在血液透析病患，使用Enoxaparin與其他低分子量肝素作比較的研究，則至今付之闕如。本研究以前瞻性實驗設計在血液透析的過程中，使用低劑量的Enoxaparin，並檢測其抗凝血因子Xa (anti-Xa)活性的作用；此外，並在劑量與臨床效果上，與傳統肝素及另一種低分子量肝素Tinzaparin做比較。 研究目的 評估血液透析病患，使用傳統肝素及低分子量肝素，包括Heparin、Enoxaparin及Tinzaparin，其anti-Xa活性的差異；並評估治療時之臨床效果及安全性，希望可提供常規血液透析治療時的參考。 研究方法 研究對象為高雄縣某區域醫院血液透析中心，長期規則血液透析病患(連續血液透析超過三個月)。第一組25位病患，依原處方之Tinzaparin劑量，50位原使用Heparin病患之中25位，依原長期處方於血液透析開始時，及前3.5小時連續緩慢滴注Heparin，是為第二組。而另25位原使用Heparin病患，則將原處方Heparin之總劑量，換成單一劑量之Enoxaparin，於血液透析開始時靜脈給予，是為第三組。並於靜脈注射抗凝血藥物前、靜脈注射抗凝血藥物後4小時及靜脈注射抗凝血藥物後48小時，各抽取病患血液進行anti-Xa活性之檢測。同時於血液透析中及血液透析後，觀察病患之凝血及出血併發症。 研究結果 血液檢測血液透析病患在注射抗凝血藥物4小時及48小時後，血液中anti-Xa活性之變化情形。我們發現，在體重及劑量校正之後，Enoxaparin組之病患其4小時後血液中anti-Xa活性增加量，顯著高於Tinzaparin組之病患，但Enoxaparin組並未顯著高於Heparin組之病患。而Tinzaparin組與Heparin組兩組之比較，亦無顯著差異。 靜脈注射Heparin抗凝血藥物之病患在血液透析過程中及血液透析結束後，其出血比例為16.0%，明顯較注射Enoxaparin及Tinzaparin組病患來得高。而人工腎臟血液凝固的情形，則三組並無統計上的差異。 結論 本研究的結果證實，單劑量給予低分子量肝素，可達到與傳統肝素相當的抗凝血效果，至少持續4小時以上，且無增加出血的危險，因此可以安全且有效的使用於透析治療。而以anti-Xa活性的增加量而言，Enoxaparin似乎優於Tinzaparin。
並列摘要
Background: Low molecular weight heparin (LMWH) is an alternative to conventional unfractionated heparin (UFH) for anticoagulation during hemodialysis therapy. It is still controversial concerning about which kind of LMWH is more suitable to hemodialysis patients, and there is also no study to compare Enoxaparin with other LMWH in hemodialysis patients. We therefore performed a prospective study to compare the anti-factor Xa activity (anti-Xa), clinical performance and safety, between conventional heparin, Enoxaparin and Tinzaparin in 75 regular hemodialysis patients. Methods: As a matched control experimental design (matching factor: Age and Sex), all the 75 patients were assigned to 3 groups: Tinzaparin group (n=25), keeping their original Tinzaparin dosage with a single intravenous bolus before hemodialysis; Heparin group (n=25), keeping their original heparin dose with a single pre-dialysis intravenous bolus and then continuous drip for 3.5 hours; and Enoxaparin group (n=25), using the same dosage of Enoxaparin to replace their original total heparin dosage, giving with a single pre-dialysis intravenous bolus. Anti-Xa activity was measured before the start of hemodialysis therapy, end of 4 hours, and then 48 hours after the first dose. The complications including artificial kidney clotting and bleeding events during this 48-hour interval were all recorded. Results: The average dosages of anticoagulant were 36.82 ± 7.15 U/Kg in Tinzaparin group; 27.11 ± 5.98 U/Kg in Heparin group; and 34.32 ± 8.93 U/Kg in Enoxaparin group. The increments of anti-Xa activity after 4 hours of hemodialysis were significantly higher in Enoxaparin group compared with Tinzaparin group (0.43 ± 0.29 vs. 0.20 ± 0.21 IU/ml by anticoagulant 10000U/Kg, p= 0.010). There was no significant difference between Enoxaparin and Heparin groups, and also between Heparin and Tinzaparin groups. The analysis of the increments of anti-Xa activity 48 hours after showed the same trends as above. Concerning the clinical effects, Heparin group presented more bleeding events rate (16.0%), which is significantly higher than that of Tinzaparin group and Enoxaparin group. However, there was no significant difference between 3 groups in artificial kidney clotting rate. Conclusion: Our present study demonstrated that a single low dose of LMWH provides the same anti-coagulant effect as that of conventional heparin, sustains more than 4 hours, and do not increase the risk of bleeding. The LMWH is safe and effective in hemodialysis therapy. Concerning the efficacy in the increment of anti-Xa activity, Enoxaparin seems to be better than Tinzaparin。