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

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 (R)). 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 10(3) mm(-3), 50 x 1.03 mm(-3), and 100 x 10(3) 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 (R)) 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 10(3) mm(-3), whereas increases in MCE peaked and reached a plateau at platelet counts from 400 x 10(3) mm(-3). Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 x 10(3) mm(-3)). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopeluc 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 (R) (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.