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

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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 × 103 mm−3, 50 × 103 mm−3, and 100 × 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 × 103 mm−3, whereas increases in MCE peaked and reached a plateau at platelet counts from 400 × 103 mm−3. Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 × 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.

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