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CARDIOVASCULAR ANESTHESIOLOGY

The Effects of Fibrinogen Levels on Thromboelastometric Variables in the Presence of Thrombocytopenia

Thomas Lang, MD^*, Kai Johanning, MD^*, Helfried Metzler, MD, Siegfried Piepenbrock, MD^*, Cristina Solomon, MD^*, Niels Rahe-Meyer, MD, PhD^*, and Kenichi A. Tanaka, MD, MSc

From the *Department of Anesthesiology, Medical School, Hannover, Germany; Werlhof Institut, Hannover, Germany, Department of Anesthesiology, University Medical School, Graz, Austria; and Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.

Address correspondence and reprint requests to Thomas Lang, MD, Werlhof Institut, Karl-Wiechert-Allee 1a, 30625 Hannover, Germany. Address e-mail to tl{at}lipidstoffwechsel.de.

Abstract

BACKGROUND: The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational thromboelastometry (ROTEM®). In this study, we investigated the effect of fibrinogen concentration and its relative contribution to overall clot strength using ROTEM.

METHODS: Blood samples were collected from healthy volunteers. The effects of platelet count on clot strength, determined by maximum clot elasticity (MCE), were evaluated on ROTEM using platelet-rich plasma (PRP) adjusted with autologous plasma to generate a range of platelet counts. PRPs were adjusted to 10 x 10³ mm^–3, 50 x 10³ mm^–3, and 100 x 10³ mm^–3 and spiked with fibrinogen concentrates at 550 and 780 mg/dL. The effect of fibrin polymerization on clot strength, independent of platelet attachment, was analyzed by the cytochalasin D-modified thromboelastometry (FIBTEM®) method. Additional retrospective analysis of clot strength (MCE) in two groups of thrombocytopenic patients was conducted.

RESULTS: Clot strength (MCE) decreased at a platelet count below 100 x 10³ mm^–3, whereas increases in MCE peaked and reached a plateau at platelet counts from 400 x 10³ mm^–3. Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 x 10³ mm^–3). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopenic patients.

CONCLUSIONS: These in vitro and clinical data indicate that the clot strength increases in a fibrinogen concentration-dependent manner independent of platelet count, when analyzed by ROTEM. The maintenance of fibrinogen concentration is critical in the presence of thrombocytopenia. EXTEM® (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.