Low molecular weight heparin improves peritoneal ultrafiltration and blocks complement and coagulation.
OBJECTIVE
Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell.


METHODS
Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations.


RESULTS
Exposure to PD fluid induced activation of IP complement [formation of C3a (desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin-antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration.


CONCLUSIONS
The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.
Bazargani
Farhan
F
Department of Anatomy and Cell Biology, University of Göteborg, Göteborg, Sweden.
Albrektsson
Ann
A
Yahyapour
Noushin
N
Braide
Magnus
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D003165:Complement System Proteins / Q000187:drug effects / Q000378:metabolism; D015314:Dialysis Solutions / Q000633:toxicity; D004195:Disease Models, Animal; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis / Q000009:adverse effects / Q000379:methods; D010537:Peritoneum / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D015314:Dialysis Solutions; D006495:Heparin, Low-Molecular-Weight; D003165:Complement System Proteins