Efficacy and Safety of Early Use PCC in Severe Trauma

Overview

Uncontrolled hemorrhage within 24 hours after severe trauma is the main cause of death in trauma patients. Hemorrhagic shock may be accompanied by traumatic coagulopathy in the early stages of severe trauma. Among them, the main pathogenesis of traumatic coagulation disorder is tissue injury, hypoperfusion, inflammatory response and , increased consumption of coagulation factor, loss of coagulation factor caused by massive bleeding, low temperature and other factors aggravate the disorder of coagulation function and cause hyperfibrinolysis. Studies have shown that the fatality rate of patients with severe traumatic coagulopathy is 4-8 times higher than that of patients without coagulopathy. Active and effective injury-controlled resuscitation and surgical treatment, target-oriented supplementation of coagulation substrate and correction of coagulation function are the main measures for high-quality treatment of patients with severe trauma. Therefore, early improvement of coagulation function is the key to improve the comprehensive treatment level of patients with severe trauma. At present, four-factor prothrombin complex (4F-PCC) is a compound preparation containing coagulation factors Ⅱ, VII, IX and X separated from fresh plasma of healthy people. However, large-scale, long-term observation of the efficacy and safety of the early application of 4F-PCC in traumatic massive hemorrhage has not been proven. In this study, it is to study the efficacy and safety of early use of 4F-PCC in patients with severe traumatic massive hemorrhage through a multi-center, randomized controlled and open-label clinical trial.

The treatment of severe traumatic hemorrhage, hemorrhagic shock and traumatic coagulopathy includes timely correction of massive hemorrhage, timely use of proportional transfusion of blood products to ensure effective fluid volume resuscitation and temperature maintenance, and achieve target-oriented correction of coagulopathy while taking into account thrombosis prevention and other comprehensive therapeutic strategies. Therefore, more and more European and American countries begin to apply Coagulation Factor Concentrates (Coagulation Factor Concentrates, CFCs) included Prothrombin Complex Concentrates (PCC) and Fibrinogen Concentrates (FC) for early resuscitation and target-directed coagulation management. Compared with FFP alone, the advantages of CFCs to correct coagulation dysfunction include: by providing standardized and high concentration of coagulation factors, reducing virus transmission and transfusion-related adverse reactions (such as acute respiratory distress syndrome, sepsis and multiple organ failure), immediate use without matching, and easy operation; The bolus use of PCC can effectively reduce the need for blood transfusion, achieve faster correction of coagulation function and reduce in-hospital mortality. A prospective, single-center, randomized controlled trial found that early use of fibrinogen concentrate (FC) may reduce blood transfusion volume and the incidence of multiple organ failure . However, at present, for patients with severe trauma and massive hemorrhage, the use of MTP and blood products can only be effectively implemented on the basis of the completion of coagulation function test, accurate thrombus elastogram (TEG) and dynamic evaluation of the body's coagulation function. However, the acquisition of TEG test results is often slow, which cannot timely and effectively guide clinicians to carry out target-oriented use of blood products and clinical mass transfusion in early stage. In addition, when hemorrhagic shock cannot be effectively corrected in patients with severe traumatic massive hemorrhage in the early stage, timely treatment of coagulopathy is delayed. In conclusion, timely and sufficient supplement of prothrombin complex PCC and other blood products may have certain application value for timely and effective correction of coagulation dysfunction. Prothrombin complex (PCC) is a kind of plasma protein concentrate containing coagulation factor which is isolated and prepared from healthy human mixed plasma. However, the efficacy and safety of 4F-PCC in early dosing and bunching of traumatic massive bleeding have not been demonstrated by prospective multicenter randomized controlled trials. In addition to the application of PCC in patients with traumatic hemorrhage complicated by anticoagulant drugs, the European Guidelines for Massive Hemorrhage 2023 Edition lacks clear guidelines for the treatment of patients with severe traumatic hemorrhage complicated with coagulopathy. Pharmacovigilance data suggest that the risk of thromboembolic complications in PCC may be low, but the primary source of these data is vitamin K antagonist reversal . Therefore, for the application of PCC in the management of traumatic coagulopathy, there is still a lack of scientific clinical practice guidance basis, and systematic prospective research is needed at the same time. Therefore, we can assume that early use of 4F-PCC in severe trauma with hemorrhagic shock can correct bleeding and coagulodysfunction as soon as possible, thereby preventing circulatory, respiratory and renal multiple organ failure and improving prognosis. In addition, the lack of blood products and the difficulty in the implementation of massive blood transfusion plan also put forward a higher demand for the early and efficient use of clotting substrates in the treatment of patients with massive traumatic hemorrhage. This has also become an important research content in this study, such as the early empirical use of 4-PCC to improve the clinical prognosis of patients with severe traumatic massive hemorrhage, reduce the need for blood products, quickly correct coagulation dysfunction, and reduce the risk of thrombosis events. Therefore, this study intends to conduct early empirical bunching of 4-PCC in patients with severe traumatic massive hemorrhage, and evaluate its effectiveness and safety in the early stage of severe traumatic massive hemorrhage through a multicenter, randomized controlled, open-label study. To further improve the treatment of traumatic massive hemorrhage to provide a certain reference basis; It also provides the theoretical basis and clinical practice for correcting coagulation dysfunction in the early stage of severe trauma treatment.