British Journal of Anaesthesia 94 (3): 324–9 (2005) doi:10.1093/bja/aei052 Advance Access publication December 17, 2004 Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate C. Fenger-Eriksen 12 , E. Anker-Møller 1 , J. Heslop 1 , J. Ingerslev 2 * and B. Sørensen 2 1 Department of Anaesthesiology, Aarhus University Hospital, Aarhus Sygehus, Denmark. 2 Center for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby Sygehus, Denmark *Corresponding author. E-mail: [email protected] Background. Plasma substitutes such as hydroxyethyl starch (HES) and various dextrans may compromise the haemostatic system, thereby causing potentially dangerous bleeding. Whilst several mechanisms have been advanced to explain the nature of the coagulopathy induced by this colloid, there has been comparably little interest in devising ways to optimize haemostasis after a relative colloid overdose. Methods. Real-time whole blood (WB) clot formation profiles were recorded using a thromb- elastographic method employing activation with tissue factor. The coagulation tracings were transformed into dynamic velocity profiles of WB clot formation. WB from healthy individuals (n=20) was exposed to haemodilution of 55% with isotonic saline, HES 200/0.5, HES 130/0.4, and dextran 70, respectively. Possible modalities for improvement of the induced coagulopathy were explored, in particular ex vivo addition of a fibrinogen concentrate. Results. WB coagulation profiles changed significantly with decreased clot strength, and a compromised propagation phase of clot formation. The duration of the initiation phase of WB coagulation was unchanged. No statistical differences were detected amongst the HES solutions and dextran 70. However, dextran 70 returned a more suppressed clot development and strength compared with the HES solutions. Ex vivo haemostatic addition of washed platelets (75 ·10 9 litre 1 ) and factor VIII (0.6 IU ml 1 ) produced insignificant changes in clot initiation, propagation, and in the clot strength. In contrast, ex vivo addition of a fibrinogen concentrate (1 g litre 1 ) improved the coagulopathy induced by all of the three individual plasma expanders tested. Conclusion. Coagulopathy induced by haemodilution with either HES 200/0.5, HES 130/0.4, and dextran 70 may be improved by fibrinogen supplementation. Br J Anaesth 2005; 94: 324–9 Keywords: blood, coagulation; blood, haemodilution; blood, replacement; measurement techniques, thrombelastograph Accepted for publication: October 12, 2004 Correction of acute blood loss often requires the use of plasma substitutes to maintain blood pressure and to pre- serve microvascular circulation. Sterile solutions of artificial colloids such as hydroxyethyl starch (HES) and dextrans are in widespread use for plasma volume expansion. Clinical reports indicate that prolonged infusion of plasma sub- stitutes may result in an increased risk of spontaneous and potentially dangerous bleeding. 12 Various experi- mental studies have demonstrated that plasma substitute supplementation induces a coagulopathy characterized by a compromised clot development, 3 whereas the initiation phase of coagulation is unaffected. 45 Haemostatic deficits are reportedly related to the type and composition of the plasma substitute. Thus, HES solutions with a high mean molecular weight (MW), a high content of hydroxyethyl motifs, and a high C2/C6 ratio, seemingly suppress the co- agulation profile more than solutions composed of the more rapidly degradable low MW colloids. 6–8 Although results and conclusions appear somewhat inconsistent, 9 various mechanisms may be involved in the coagulopathy brought # The Board of Management and Trustees of the British Journal of Anaesthesia 2004. All rights reserved. For Permissions, please e-mail: [email protected]
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