Fibrinogen Supplementation Ex Vivo Increases Clot Firmness Comparable to Platelet Transfusion in Thrombocytopenia

Abstract

This study investigates how the use of fibrinogen concentrate ex vivo compares to the use of in vivo platelet transfusion (PT) to improve clot firmness in patients with thrombocytopenia (platelet count <150 10 L−1). While PT is currently first-line treatment to prevent bleeding in patients with clinically significant thrombocytopenia, PT carries significant risks, including viral or bacterial infection, febrile and nonfebrile transfusion reactions, and transfusion-related lung injury. Furthermore, the effectiveness of PT varies. The use of fibrinogen concentrate might be a useful tool to reduce PT, given its role in platelets activation and clot formation. Experimental data in animal models have indicated that fibrinogen concentrate can improve clot firmness better than PT. For this investigation, 100 patients aged between 18 and 35 years in need of PT were enrolled. Of the patients included, 88% were thrombocytopenic, and 65% had received antiplatelet medication. Indications for PTwere variable, but the most common indication was diffuse (microvascular) bleeding tendency. The enrolled patients’ blood samples were collected immediately before PT and 1 and 24 hours after PT. Using ROTEM (rotational thromboelastometry), the blood samples citrated with fibrinogen concentrate were analyzed at concentrations of 50, 100, 200, and 400mg kg−1 for the maximum clot firmness (MCF). ROTEM is a tool to predict, manage, and correct coagulation parameters. It was found that fibrinogen supplementation increasedMCF significantly and dose-dependently before and after PT. The effect of equivalent doses of 100 and 200 mg kg−1of fibrinogen concentrate ex vivo was comparable to that of PT in vivo. It was also noted that MCF improved markedly with 400 mg kg−1 compared with PT (P < 0.001). This study suggests that fibrinogen concentrate ex vivo compensates clot firmness to a similar degree as PT in vivo and could serve as an alternative treatment in appropriate situation. These results need to be confirmed in clinical trials.