Low molecular weight heparin and haemodialysis: neutralization by protaminchloride

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.