The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl(-1) as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.
ROTEM variables demonstrated clinically relevant correlations with PLT counts and fibrinogen levels. In particular, decreasing levels of fibrinogen can be quickly determined (<15-20 min) using FIBTEM.
We demonstrated in vitro and in vivo that progressive haemodilution decreases endogenous antifibrinolytic proteins including alpha(2)-antiplasmin and thrombin-activatable fibrinolysis inhibitor, resulting in increased fibrinolytic tendency. Therefore, early fluid replacement therapy with FFP might be advantageous after massive haemorrhage.
Fibrinogen plays several key roles in the maintenance of hemostasis. Its cleavage by thrombin and subsequent polymerization to form fibrin strands provides the structural network required for effective clot formation. During cases of acute blood loss, attempts to maintain circulating volume and tissue perfusion often involve the infusion of crystalloids, colloids, and red blood cells. Intravascular volume resuscitation, although vital, frequently results in dilution of the remaining clotting factors and onset of dilutional coagulopathy. In such cases, fibrinogen is the first coagulation factor to decrease to critically low levels. There currently is a lack of awareness among physicians regarding the significance of fibrinogen during acute bleeding and, at many centers, fibrinogen is not monitored routinely during treatment. We reviewed current studies that demonstrate the importance of considering fibrinogen replacement during the treatment of acquired bleeding across clinical settings. If depleted, the supplementation of fibrinogen is key for the rescue and maintenance of hemostatic function; however, the threshold at which such intervention should be triggered is currently poorly defined. Although traditionally performed via administration of fresh frozen plasma or cryoprecipitate, the use of lyophilized fibrinogen (concentrate) is becoming more prevalent in some countries. Recent reports relating to the efficacy of fibrinogen concentrate suggest that it is a viable alternative to traditional hemostatic approaches, which should be considered. The prospective study of fibrinogen supplementation in acquired bleeding is needed to accurately assess the range of clinical settings in which this management strategy is appropriate, the most effective method of supplementation and a comprehensive safety profile of fibrinogen concentrate used for such an approach.
Clot retraction and fibrinolysis may present as a decrease in amplitude on thrombelastography (TEG). The former represents normal or hyperactive platelet function, and the latter represents a fibrinolytic state. It is important to distinguish clot retraction from fibrinolysis because the treatment of each condition is different. To distinguish between these phenomena, we performed TEG with platelet-poor plasma (PPP) and platelet-rich plasma (PRP) with an increasing platelet count (range, 50-1200 x 10(9)/L) with or without abciximab. Maximum amplitude (MA) and the percentage decrease of amplitude at 30 and 60 min after MA were examined for each sample. Blood samples to which tissue plasminogen activator (tPA) was added served as positive controls for fibrinolysis. Morphological changes of clots and D-dimer levels were also examined. With higher platelet counts, the percentage decrease of amplitude after MA increased significantly at 30 and 60 min, but not in the abciximab samples. Morphological changes of clots have shown clot retraction in PRP, but not in PPP or PRP pretreated with abciximab. D-dimer levels increased only in samples to which tPA was added, but not in native PPP or PRP samples. In conclusion, we have shown that the decrease in amplitude at 30 and 60 min can be due to platelet-mediated clot retraction and can be attenuated by sample pretreatment with abciximab, which interrupts platelet-fibrin(ogen) binding.
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