Ivan Budnik1, Boris Shenkman2, Olga Morozova1, Yulia Einav3. 1. Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. 2. National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel. 3. Faculty of Engineering, Holon Institute of Technology, Holon, Israel. yulia_e@hit.ac.il.
Abstract
PURPOSE: Coagulation abnormalities are common following major trauma. The aim of this study was to assess the improvement of trauma-induced coagulopathy (TIC) in an in vitro model. METHODS: TIC was created on blood taken from healthy individuals by inducing hemodilution, acidosis, hypothermia and fibrinolysis. Next, blood samples were subjected to rotational thromboelastometry to assess the effect of hemostasis modulators on blood coagulation and fibrinolysis. RESULTS: Introducing to blood fibrinogen at 0.75 mg/mL, prothrombin complex concentrate at 0.66 IU/mL or tranexamic acid at 95 µg/mL increased clot strength. Higher effect was observed by combination of fibrinogen with tranexamic acid and prothrombin complex with tranexamic acid, whereas the maximal effect was achieved using all agents together. Fibrinolysis was inhibited by tranexamic acid and stronger by triple combination of the agents. Selective treating the TIC blood with fibrinogen, prothrombin complex or tranexamic acid at two time lower concentrations did not affect clot strength. Combining fibrinogen with prothrombin complex or with tranexamic acid stimulated clot strength but at lower extent compared to higher concentrations. Lysis onset time was prolonged by tranexamic acid. Maximal effect on both clot formation and fibrinolysis was achieved using all three agents together. CONCLUSIONS: Blood clotting stimulation and fibrinolysis inhibition in the TIC model was enough combining subthreshold concentrations of fibrinogen, prothrombin complex and tranexamic acid. Further experiments are warranted in both in vitro and in vivo conditions with minimally effective concentrations of both pro-coagulant and anti-fibrinolytic drugs assuming that this combinatorial approach may not only improve coagulopathy but also minimize the risk of thrombotic complications.
PURPOSE:Coagulation abnormalities are common following major trauma. The aim of this study was to assess the improvement of trauma-induced coagulopathy (TIC) in an in vitro model. METHODS:TIC was created on blood taken from healthy individuals by inducing hemodilution, acidosis, hypothermia and fibrinolysis. Next, blood samples were subjected to rotational thromboelastometry to assess the effect of hemostasis modulators on blood coagulation and fibrinolysis. RESULTS: Introducing to blood fibrinogen at 0.75 mg/mL, prothrombin complex concentrate at 0.66 IU/mL or tranexamic acid at 95 µg/mL increased clot strength. Higher effect was observed by combination of fibrinogen with tranexamic acid and prothrombin complex with tranexamic acid, whereas the maximal effect was achieved using all agents together. Fibrinolysis was inhibited by tranexamic acid and stronger by triple combination of the agents. Selective treating the TIC blood with fibrinogen, prothrombin complex or tranexamic acid at two time lower concentrations did not affect clot strength. Combining fibrinogen with prothrombin complex or with tranexamic acid stimulated clot strength but at lower extent compared to higher concentrations. Lysis onset time was prolonged by tranexamic acid. Maximal effect on both clot formation and fibrinolysis was achieved using all three agents together. CONCLUSIONS: Blood clotting stimulation and fibrinolysis inhibition in the TIC model was enough combining subthreshold concentrations of fibrinogen, prothrombin complex and tranexamic acid. Further experiments are warranted in both in vitro and in vivo conditions with minimally effective concentrations of both pro-coagulant and anti-fibrinolytic drugs assuming that this combinatorial approach may not only improve coagulopathy but also minimize the risk of thrombotic complications.
Authors: Annabel Blasi; Vishal C Patel; Eva N H E Spanke; Jelle Adelmeijer; Marilena Stamouli; Ane Zamalloa; Eleanor Corcoran; Andrea Calvo; Javier Fernandez; William Bernal; Ton Lisman Journal: Liver Int Date: 2021-12-20 Impact factor: 8.754