TRANSFUSION PRACTICE Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders Christian Fenger-Eriksen, GaryW. Moore, Savita Rangarajan, Jørgen Ingerslev, and Benny Sørensen BACKGROUND: Measurement of plasma fibrinogen is often required in critically ill patients or massively bleed- ing patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated sig- nificantly higher in plasma diluted with colloid plasma expander compared with isotonic saline. STUDY DESIGN AND METHODS: Fibrinogen mea- surements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo-optical Clauss methods, one mechanical Clauss method, a prothrombin-derived method, and viscoelastic measurement through throm- boelastometry. RESULTS: Measurement of fibrinogen levels was sig- nificantly different when performed on alternate analyti- cal platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo-optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin. CONCLUSION: This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss. R ecent studies have shown that levels of fibrino- gen and hemostatic intervention with fibrino- gen may serve as an important marker and effective treatment in management of periop- erative bleeding. Recommendations have repeatedly stressed a threshold level of 1.0 g/L warranting replace- ment therapy in bleeding patients. 1,2 New studies suggest that the critical level of fibrinogen may be considerably higher and possibly influenced by underlying disorders. 3,4 Laboratory measurements and preanalytical vari- ables represent important aspects in assessing the need for treatment with fibrinogen. Various methods are used to record fibrinogen. 5 Most commonly fibrinogen is esti- mated based on the activity method devised by Clauss. 6 In principle, diluted citrated plasma is activated with throm- bin, and the clotting time is inversely proportional with the functional fibrinogen concentration. Fibrinogen mea- surements are usually performed using automated coa- gulation analyzers adopting two different principles: photometric or mechanical detection of fibrin formation. Photometric methods records change in turbidity or opacity, whereas mechanical methods detect removal of a metal ball from a magnetic field upon clot formation. Thromboelastometry/thrombelastography is being used more and more frequently for bedside hemostasis ABBREVIATION: PT = prothrombin time. From the Department of Anaesthesiology and the Center for Haemophilia and Thrombosis, Department of Clinical Bio- chemistry, Aarhus University Hospital, Denmark; and the Hae- mostasis Research Unit, Centre for Haemostasis and Thrombosis, Guy’s and St Thomas Hospital, London, UK. Address reprint requests to: Christian Fenger-Eriksen, Department of Anaesthesiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark; e-mail: chfen@dadlnet.dk. Received for publication February 23, 2010; revision received May 5, 2010; and accepted May 5, 2010. doi: 10.1111/j.1537-2995.2010.02752.x TRANSFUSION 2010;50:2571-2576. Volume 50, December 2010 TRANSFUSION 2571