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 are influenced, amongst other factors, by the type of membranes and the geometry of the blood line system. In addition, there are indications that heparin has dose-dependent effects on the lipid status of chronic haemodialysis patients. Methods: In a parallel group design we compared patients treated with cuprophane (CU) and polycarbonate-polyether (PC-PE) plate dialysers. In both groups, blood line geometry was varied by including in a first phase and omitting in a second phase drip chambers in the arterial blood line. End-points were changes in coagulation 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 were switched to PC-PE dialysers for 6 months and the heparin dose was reduced in a stepwise fashion. Lipid levels and coagulation parameters were monitored. Finally, in an ancillary study, the correlation between heparin dose and LDL/HDL ratio was assessed in patients chronically exposed to PC-PE membranes and low doses of heparin. Results: Post-dialytic concentrations of coagulation and fibrinolysis parameters were significantly lower in the PC-PE group (TAT 21.0±4.4 &mgr;g/l; PAP 1180±1148 &mgr;g/l; F1+2 4.2±0.4 nmol/l) compared to the CU group (TAT 57.3±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 arterial drip chamber. Omission of the arterial drip chamber led to lower TAT in the CU group (42.2±5.8 &mgr;g/l, P <0.05), but not in the PC-PE group. In contrast, PA and F1+2 concentrations did not change significantly in either group. Down-titration of heparin dose (from 20.4±1.1 to (9.4±0.9 IU/kg/h) was associated with a significant decrease in serum triglycerides (from 2.9±0.9 to 2.0±0.6 mmol/l, P <0.05), LDL-cholesterol (from 3.4±0.2 to2.7±0.4 mmol/l, P <0.05) and LDL/HDL-ratio (from 3.2±0.3 to 2.0±0.3, P <0.05) with no significant change of total or HDL-cholesterol after 6 months. In an ancillary analysis, a correlation between lipid parameters (LDL/HDL ratio) and heparin dose was confirmed in 24 patients chronically exposed 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-polyether membrane compared to a cuprophane membrane, (ii) heparin requirement is influenced by blood line geometry (decreased with omission of an arterial drip chamber), and (iii) in patients on polycarbonate-polyether membranes down-titration of heparin is associated with a reduction of serum triglycerides, LDL cholesterol, and LDL/HDL ratio. Our data suggest that reduction of heparin dose improved lipid profile. These preliminary observations require confirmation by parallel group controlled studies with controlled dietary intake.