Andrassy K
Department of Medicine, University Hospital, Heidelberg, Germany.
Blood Coagul Fibrinolysis. 1993 Dec;4 Suppl 1:S39-43.
Unfractionated heparin (UFH) is the most widely used agent in preventing clot formation in the extracorporeal circuit. The dose of heparin varies and is dependent on biocompatibility of membranes, the construction of the dialyser and the roller pump segment besides the individual patient's sensitivity. The risk of bleeding might be increased in patients with acute renal failure, particularly with multiple organ failure. Alternative strategies were elaborated, one of which is the use of low molecular weight heparin (LMWH). LMWH has a similar antithrombotic activity as UFH but a lower haemorrhagic tendency and a longer plasma half-life in patients with renal insufficiency. Various studies with LMWH--which are only comparable if the same dialyser and equipment are used--clearly show that the anti-factor Xa level must exceed 0.5 U/ml to prevent clot formation. With these levels LMWH is as effective and safe as UFH in inhibiting coagulation during chronic dialysis. Anti-factor Xa levels > 0.5 U/ml will, however, simultaneously increase bleeding tendency, in patients at risk. Therefore, lower doses of LMWH have to be administered to patients with acute renal failure and risk of bleeding. This haemorrhagic tendency may be neutralized by protamine. The present investigation with protamine chloride and different concentrations of LMWH (Clivarin) shows that clotting tests (thrombin time, aPTT) were immediately antagonized. Anti-factor Xa activity was neutralized by only 20-40%. The gradual decline of anti-factor Xa activity thereafter corresponds to the biological half-life of Clivarin. Whether the remaining anti-factor Xa activity is associated with any increased bleeding risk remains to be seen.
普通肝素（UFH）是体外循环中预防血栓形成应用最广泛的药物。肝素剂量因人而异，取决于膜的生物相容性、透析器的构造、滚压泵部分以及患者个体的敏感性。急性肾衰竭患者，尤其是合并多器官功能衰竭的患者，出血风险可能会增加。人们制定了替代策略，其中之一是使用低分子量肝素（LMWH）。LMWH具有与UFH相似的抗血栓活性，但在肾功能不全患者中出血倾向较低且血浆半衰期较长。使用LMWH的各种研究（只有在使用相同透析器和设备时才具有可比性）清楚地表明，抗Xa因子水平必须超过0.5 U/ml才能预防血栓形成。在这些水平下，LMWH在慢性透析期间抑制凝血方面与UFH一样有效和安全。然而，抗Xa因子水平>0.5 U/ml会同时增加高危患者的出血倾向。因此，对于有急性肾衰竭和出血风险的患者，必须给予较低剂量的LMWH。这种出血倾向可用鱼精蛋白中和。目前关于氯化鱼精蛋白和不同浓度LMWH（克赛）的研究表明，凝血试验（凝血酶时间、活化部分凝血活酶时间）立即受到拮抗。抗Xa因子活性仅被中和20 - 40%。此后抗Xa因子活性的逐渐下降与克赛的生物半衰期相对应。剩余的抗Xa因子活性是否与出血风险增加有关还有待观察。
