Comparative analysis of procoagulatory activity of haemodialysis, haemofiltration and haemodiafiltration with a polysulfone membrane (APS) and with different modes of enoxaparin anticoagulation.
BACKGROUND
Treatment modalities of renal replacement therapy differ in their diffusive and convective mass transfer characteristics. It was the goal of this study to clarify whether an increase in convective mass transfer as performed with haemofiltration (HF) and haemodiafiltration (HDF) in comparison with high-flux haemodialysis (HD) is associated with an alteration in procoagulatory activity or with complement activation.


METHODS
Ten stable chronic HD patients were monitored during 120 treatments in a randomized cross over design. A high-flux polysulfone dialyser (APS 900) was used for high-flux HD, pre-dilution HF and pre-dilution HDF. Constant flow of on-line substitution fluid for HF and HDF was 200 ml/min. The low molecular weight heparin (LMWH) enoxaparin was used for anticoagulation (i) as single bolus (50 IU/kg body weight, median 3700 IU) and (ii) as bolus of 1200 IU followed by a median continuous dose of 400 IU/h. Blood samples were collected before the LMWH bolus, after 10 min, 60 min, 120 min and at the end of treatment in venous and arterial blood lines to determine antiXa activity, thrombin-antithrombin-III complex (TAT), D-dimer and C5a generation.


RESULTS
Net ultrafiltration did not significantly differ between HD, HF and HDF but total ultrafiltration in HF and HDF far exceeded total ultrafiltration in HD. With conditions of single bolus, or bolus and continuous anticoagulation with enoxaparin, after comparable treatment times (median duration 4.25 h), TAT and D-dimer generation at identical anti-Xa levels revealed significantly higher coagulation activity during HF and HDF, compared with high-flux HD as assessed by comparative area under the curve (AUC) analysis. Plasma concentration of C5a in venous bloodlines did not significantly differ during HD, HF and HDF.


CONCLUSIONS
A higher convective mass transfer during HF and HDF, in comparison with high-flux HD caused by a greater total ultrafiltration volume was associated with increased procoagulatory activity in the extracorporeal circuit. Molecular markers assessing the activation of coagulation are appropriate to adjust the anticoagulation regime to high UF volumes in order to minimize bleeding risk and optimize patency of the extracorporeal circuit.
Klingel
Reinhard
R
Apheresis Research Institute, Stadtwaldguertel 77, D-50935 Cologne, Germany. afi@apheresis-research.de
Schaefer
Michael
M
Schwarting
Andreas
A
Himmelsbach
Frido
F
Altes
Ulrich
U
Uhlenbusch-Körwer
Ingrid
I
Hafner
Gerd
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000628:therapy*; D003167:Complement Activation / Q000187:drug effects; D017984:Enoxaparin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D017583:Hemodiafiltration / Q000009:adverse effects; D006440:Hemofiltration / Q000009:adverse effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D011108:Polymers / Q000009:adverse effects; D006435:Renal Dialysis / Q000009:adverse effects*; D013450:Sulfones / Q000009:adverse effects
D000925:Anticoagulants; D001672:Biocompatible Materials; D017984:Enoxaparin; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; C017662:polysulfone P 1700