Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy.
BACKGROUND
The biochemical mechanisms causing dilutional coagulopathy following infusion of hydroxyethyl starch 130/0.4 (HES) are not known in detail.


OBJECTIVE
To give a detailed biochemical description of the mechanism of coagulopathy following 30%in vivo dilution with HES, to present a systematic ex vivo test of various hemostatic agents, and to investigate the hypothesis that acquired fibrinogen deficiency constitutes the most important determinant of the coagulopathy.


METHODS
Dynamic whole blood clot formation assessed by thromboelastometry, platelet count, thrombin generation, and the activities of von Willebrand factor, coagulation factor II, FVII, FVIII, FIX, FX and FXIII were measured in 20 bleeding patients enrolled in a prospective clinical study investigating in vivo substitution of blood loss with HES up to a target level of 30%. Thromboelastometry parameters were further evaluated after ex vivo spiking experiments with fibrinogen, prothrombin complex concentrate (PCC), FXIII, activated recombinant FVIIa (rFVIIa), fresh frozen plasma, and platelets.


RESULTS
Hemodilution reduced maximum clot firmness (MCF), whereas whole blood clotting time (CT) and maximum velocity remained unaffected. All coagulation factor activities were reduced. Fibrinogen, FII, FXIII and FX activities decreased significantly below the levels expected from dilution. The endogenous thrombin potential was unchanged. Ex vivo addition of fibrinogen normalized the reduced MCF and increased the maximum velocity, whereas PCC, rFVIIa and platelets shortened the CT but showed no effect on the reduced MCF.


CONCLUSIONS
Acquired fibrinogen deficiency seems to be the leading determinant in dilutional coagulopathy, and ex vivo addition corrected the coagulopathy completely.
Department of Anaesthesiology, Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Aarhus, Denmark. chfen@dadlnet.dk
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C
Fenger-Eriksen
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Tønnesen
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Ingerslev
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B
Sørensen
D000368:Aged; D001778:Blood Coagulation Disorders / Q000139:chemically induced*; D001779:Blood Coagulation Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged
D001779:Blood Coagulation Factors; D006895:Hydroxyethyl Starch Derivatives