Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate

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Abstract
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 thrombelastographic 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 ×109 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.