Fibrinogen concentrate and cryoprecipitate but not fresh frozen plasma correct low fibrinogen concentrations following in vitro haemodilution

Abstract

Introduction: Fibrinogen deficiency often develops during massive bleeding due to e.g. fluid resuscitation with colloid plasma expanders like hydroxyethyl starch. This study investigates the haemostatic effect of various sources of fibrinogen: fibrinogen concentrates (Haemocomplettan® (FC 1), CSL Behring and Clottagen® (FC 2), LFB Biomedicaments), fresh frozen plasma (FFP), and Cryoprecipitate (CP).

Methods: Whole blood samples provided by healthy individuals (n=8) were diluted 1:1 with HES or 0.9% isotonic saline as control. Various sources of fibrinogen was added to the HES diluted samples in concentrations equivalent to giving a 70 kg male either no correction, 2 grams of FC 1 or FC 2, 4 grams of FC 1 or FC 2, 15 ml/kg of FFP, 2 packs of CP or 4 packs of CP. Haemostatic effect was assessed by thromboelastometry initiated by tissue factor, with maximum clot firmness (MCF) as the primary endpoint. In addition thrombin generation was assessed for each intervention

Results: HES dilution reduced MCF significantly more than isotonic saline. High dose FC 1, 2 and CP corrected the MCF so that it did not differ significantly from the isotonic saline dilution group. Thrombin generation following isotonic saline and HES dilution was comparable and not decreased compared to whole blood. Fibrinogen concentrates supplementation did not increase thrombin generation whereas CP and FFP both increased thrombin generation

Conclusion: Fibrinogen concentrates investigated dose dependently and equally corrected the MCF and caused no increase in thrombin generation. Cryoprecipitate also corrected the MCF, but also increased thrombin generation. FFP failed to improve MCF, but increased thrombin generation.