Impact of membrane choice and blood flow pattern on coagulation and heparin requirement - potential consequences on lipid concentrations

Background: We reasoned that procoagulant activity,and by implication heparin requirement, during haemodialysis areinfluenced, amongst other factors, by the type of membranes and thegeometry of the blood line system. In addition, there are indications thatheparin has dose-dependent effects on the lipid status of chronichaemodialysis patients. Methods: In a parallel groupdesign we compared patients treated with cuprophane (CU) andpolycarbonate-polyether (PC-PE) plate dialysers. In both groups, blood linegeometry was varied by including in a first phase and omitting in a secondphase drip chambers in the arterial blood line. End-points were changes incoagulation parameters, i.e. thrombin-antithrombin III complex (TAT),plasmin-anti-plasmin complex (PAP), and prothrombin fragment (F1+2)concentrations measured by sandwich ELISA. Subsequently all patients wereswitched to PC-PE dialysers for 6 months and the heparin dose was reducedin a stepwise fashion. Lipid levels and coagulation parameters weremonitored. Finally, in an ancillary study, the correlation between heparindose and LDL/HDL ratio was assessed in patients chronically exposed toPC-PE membranes and low doses of heparin. Results:Post-dialytic concentrations of coagulation and fibrinolysis parameterswere significantly lower in the PC-PE group (TAT 21.0±4.4&mgr;g/l; PAP 1180±1148 &mgr;g/l; F1+24.2±0.4 nmol/l) compared to the CU group (TAT57.3±10.8 &mgr;g/l; PAP 1789±185 &mgr;g/l;F1+2 8.8±1.0 nmol/l), independently of the use of an arterialdrip chamber. Omission of the arterial drip chamber led to lower TAT in theCU group (42.2±5.8 &mgr;g/l, P <0.05), but not in thePC-PE group. In contrast, PA and F1+2 concentrations did not changesignificantly in either group. Down-titration of heparin dose (from20.4±1.1 to (9.4±0.9 IU/kg/h) was associated with asignificant decrease in serum triglycerides (from 2.9±0.9 to2.0±0.6 mmol/l, P <0.05), LDL-cholesterol (from3.4±0.2 to2.7±0.4 mmol/l, P <0.05) andLDL/HDL-ratio (from 3.2±0.3 to 2.0±0.3, P<0.05) with no significant change of total or HDL-cholesterol after6 months. In an ancillary analysis, a correlation between lipid parameters(LDL/HDL ratio) and heparin dose was confirmed in 24 patients chronicallyexposed to PC-PE membranes (r=0.473, P <0.05).Conclusions: In a prospective exploratory study (I)heparin requirement is lower with the use of a polycarbonate-polyethermembrane compared to a cuprophane membrane, (ii) heparin requirement isinfluenced by blood line geometry (decreased with omission of an arterialdrip chamber), and (iii) in patients on polycarbonate-polyether membranesdown-titration of heparin is associated with a reduction of serumtriglycerides, LDL cholesterol, and LDL/HDL ratio. Our data suggest thatreduction of heparin dose improved lipid profile. These preliminaryobservations require confirmation by parallel group controlled studies withcontrolled dietary intake.