Potential of whole blood coagulation reconstitution by desmopressin and fibrinogen under conditions of hypothermia and acidosis – an in vitro study using rotation thrombelastometry

Abstract

Background. Desmopressin (DDAVP) and fibrinogen improve platelet function and clot stability. We investigated the influence of DDAVP and fibrinogen on whole blood coagulation in an in vitro model of hypothermia and acidosis. Methods. After IRB approval and written consent blood samples were taken from 10 healthy volunteers. Samples were prepared with hydrochloric acid to maintain – beside normal pH – reduced pH (∼7.2) and severely reduced pH (∼7.0), and were assigned to four treatment groups: addition of either isotonic saline for compensation of dilutional effects (ISO), desmopressin (DDAVP+), fibrinogen (FIB+), or both substances (DDAVP+FIB+). Baseline was ISO at 37°C and normal pH. Remaining samples were incubated for 30 min and measured at 32°. Rotation thrombelastometry (ROTEM) after extrinsically activation and fibrin polymerization was tested. Repeated measures ANOVA were performed (p < 0.05). Results. Hypothermia and acidosis synergistically impaired whole blood coagulation. DDAVP+ normalized maximum clot firmness (MCF) at normal pH. Coagulation time (CT) was not affected. FIB+ normalized MCF at pH 7.35 and pH 7.2. CT was normalized independently of pH. DDAVP+FIB+ did not show additional effects to FIB+. Fibrin polymerization was increased by FIB+ and DDAVP+FIB+ independently of pH. DDAVP+ did not alter fibrin polymerization. Conclusion. DDAVP and fibrinogen increased whole blood coagulation under hypothermia. Acidosis diminished this effect. Thus, acidosis should be corrected first and then both substances could be used for bridging until normothermia can be achieved. In combination, the effects of fibrinogen were overwhelming DDAVP effects. Thus, combined administration did not show any benefit compared to fibrinogen administration alone.

Key Words::

• Acidosis
• coagulation
• desmopressin
• fibrinogen
• hypothermia

Acknowledgements

The authors would like to thank Brigitte Buchalik for invaluable support in the laboratory.

The presented work was financially supported by CSL Behring, Marburg, Germany.

Declaration of interest: Dr Hanke, Dr Rahe-Meyer, Dr Schöchl, and Dr Johanning have received speaker fees from CSL Behring, Marburg, Germany, Dr Görlinger has received speaker fees from CSL Behring, Marburg, Germany, and TEM international, Munich, Germany.