Impaired haemostasis by intravenous administration of a gelatin-based plasma expander in human subjects.
The aim of this study was to investigate the effects of a gelatin-based plasma expander on blood coagulation and haemostasis in human subjects. Six healthy men were studied in a randomised, controlled cross-over study to investigate the effects of a 60 min intravenous infusion of either 1 l gelatin-based plasma substitute (Gelofusine) or 0.9% NaCl (control). The infusion of gelatin resulted in a 1.7 fold increase in bleeding time at 60 min and a 1.4 fold increase at 120 min, while saline had no effect (p <0.05). Aggregation studies revealed a significant impairment of ristocetin-induced platelet aggregation (p <0.05), associated with a substantial decrease of vWF:ag (-32% vs. -5%, p <0.05) and ristocetin co-factor (-29% vs. +1%, p <0.05) and without in vitro impairment of the platelet glycoprotein 1b receptor. Gelatin caused a decrease in thrombin-antithrombin complexes (-45% vs. -4%, p <0.05) and F1+2 (-40% vs. +1%, p <0.05). The decrease in circulating levels of vWF:ag, vWF R:Co, thrombin-antithrombin complexes and F1+2 was more than could be expected by the calculated plasma-dilution generated by Gelofusine. Our results demonstrated that the administration of a gelatin-based plasma substitute results in a significant impairment of primary haemostasis and thrombin generation. The defect in primary haemostasis appears to be related to a gelatin-induced reduction in von Willebrand factor, whereas the decreased thrombin generation may be due to the dilution of coagulation factors induced by Gelofusine.
de Jonge
E
E
Academic Medical Center, University of Amsterdam, Department of Intensive Care, The Netherlands.
Levi
M
M
Berends
F
F
van der Ende
A E
AE
ten Cate
J W
JW
Stoutenbeek
C P
CP
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005780:Gelatin / Q000009:adverse effects; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010952:Plasma Substitutes / Q000009:adverse effects*; D013917:Thrombin / Q000378:metabolism
D010952:Plasma Substitutes; D005780:Gelatin; D013917:Thrombin