Bleeding typically results as a consequence of derangements of primary hemostasis, secondary hemostasis, or both, and can be dramatically amplified by the presence of other predisposing conditions, especially inherited bleeding disorders. Life-threatening hemorrhages are, however, almost exclusively caused by penetrating wounds, blunt traumas of chest and abdomen, suicide attempts, amputations, bone fractures with concomitant injury to internal organs and blood vessels, and shearing forces from sudden rotation, violent flexion, extension, or deceleration injuries. The pathogenesis of posttraumatic bleeding is complex and multifaceted. The most dramatic phenomenon that always accompanies major hemorrhages is the abrupt and considerable loss of intravascular volume, that further leads to hypovolemic shock, also known as hemorrhagic shock, culminating with peripheral ischemia, especially in those tissues where oxygen delivery is more critical (i.e., central nervous system and myocardium). The mortality rate of severe posttraumatic bleeding can be as high as 50%, especially when an appropriate treatment is not established in a timely manner. The damage control sequence basically entails a four-step approach including damage control surgery, damage control resuscitation with fluid restoration, and hemocomponents administration, as well as correction of the coagulopathy with platelets, antifibrinolytic (e.g., tranexamic acid), and/or procoagulant agents such as fresh frozen plasma, prothrombin complex concentrate, or recombinant-activated Factor VII.

Massive posttraumatic bleeding: epidemiology, causes, clinical features, and therapeutic management.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/trf.15917

The impact of blood product ratio and procoagulant therapy on the development of thromboembolic events in severely injured hemorrhaging trauma patients.

BACKGROUND Rapid replacement of blood loss is critical in patients suffering from traumatic hemorrhage. When the availability of blood products is limited, certain interventions have shown promise in conserving blood supplies. Recombinant factor (rF) VIIa has been administered, as an off-label use, to assist in controlling hemorrhage in trauma patients. Although rFVIIa has a tendency to remain localized to areas of vascular insult, there may be an increase in thromboembolism formation when patients suffer multiple sites of injury as seen in blunt force trauma. OBJECTIVES This review aimed to synthesize the best available evidence regarding the incidence of thromboembolism formation after receiving rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of packed red blood cells [PRBCs], fresh frozen plasma [FFP], platelets and crystalloid solutions) in patients suffering from traumatic injuries (blunt force and penetrating trauma). INCLUSION CRITERIA TYPES OF PARTICIPANTS Civilian and combat trauma patients who were 15 years and older suffering from blunt force and penetrating traumatic injuries. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST Use of rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of PRBCs, FFP, platelets and crystalloid solutions). TYPES OF STUDIES This review considered both experimental and epidemiological study designs. TYPES OF OUTCOMES Confirmed formation of thromboembolism (confirmation based on specific diagnostic tests such as ultrasound, ventilation-perfusion scan or angiography). SEARCH STRATEGY The databases searched included CINAHL, Ovid MEDLINE, Web of Science, EMBASE and the Cochrane Control Register of Clinical Trials. Studies published after June 1986 were considered for inclusion in this review. Search for unpublished studies was performed. METHODOLOGICAL QUALITY Studies selected for inclusion were critically appraised by two independent reviewers using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI). DATA EXTRACTION Data was extracted from articles using standardized data extraction instruments from the JBI. DATA SYNTHESIS Quantitative results were pooled in statistical meta-analysis using the Joanna Briggs software for meta-analysis. RESULTS Two studies with a total of 831 participants were included. Both the studies were randomized, placebo-controlled, double-blind trials. No studies of combat trauma patients met the inclusion criteria for this review. A meta-analysis was performed. In blunt force trauma patients, the incidence of thromboembolism formation on administering rFVIIa revealed an overall relative risk of 1.17 with a 95% confidence interval (CI) from 0.77 to 1.79; results not statistically significant (P = 0.4594); large CI and imprecise estimate. In penetrating trauma patients, the incidence of thromboembolism formation on administering rFVIIa revealed an overall relative risk of 0.77 with a 95% CI from 0.27 to 2.20; results not statistically significant (P = 0.6242); very large CI and imprecise estimate. CONCLUSIONS The estimates of the effects are imprecise, results are compatible with effects in opposite directions, increase or decrease of thromboembolism formation, and an increase of thromboembolism formation cannot be excluded. IMPLICATIONS FOR PRACTICE When rFVIIa is administered to trauma patients, there does not appear to be an increased risk of thromboembolism formation favoring one type of injury over the other (blunt force versus penetrating trauma). Owing to large CIs and imprecise estimates, the overall risk of thromboembolism cannot be excluded. The use of rFVIIa does appear to decrease the overall need for blood products in trauma patients with no statistically significant improvement in survival rates. With the high cost of rFVIIa, its use is limited to those facilities that can afford it. In situations wherein blood supply is limited, rFVIIa could conserve limited supplies of blood products with no difference in thromboembolism risk between blunt force versus penetrating trauma, but the high cost will ultimately limit its use to facilities that can afford it. The use of rFVIIa in blunt force and penetrating trauma patients has a JBI Grade B Recommendation (Appendix I). IMPLICATIONS FOR RESEARCH This review excluded patients receiving pharmacologic anticoagulation such as warfarin sodium or heparin. The actions of these drugs will most likely counteract the desired coagulation effect of rFVIIa. Many studies do not account for the effects of rFVIIa in trauma patients receiving pharmacologic anticoagulation and this could be a future area of research.

The incidence of thromboembolism formation following the use of recombinant factor VIIa in patients suffering from blunt force trauma compared with penetrating trauma: a systematic review.

Introduction: Several series of patient studies have been published on the use of rFVIIa in traumatic haemorrhagic shock, although to date no international recommendations have been produced. France does not currently recognise traumatic haemorrhagic shock as an appropriate indication for the use of rFVIIa. Materials and methods: In this retrospective study, we present our experience in the use of rFVIIa in traumatic haemorrhagic shock. Results: Twenty-seven patients treated with rFVIIa after a traumatic injury between May 2005 and December 2008 were included. Average age was 46 years old. Eighty per cent of patients were polytransfused. Mortality rate was 33%. Adjusted mortality rate, using the Boffard study criteria, was 8.3%. We observed significant differences between the group of patients who died and the group of survivors in pH, PT, Hb, ionised calcaemia, temperature and platelet count. We observed significant differences between the successful rFVIIa group and the failed rFVIIa group in pH, Hb, platelet count and ionised calcaemia. Ten patients had an rFVIIa injection only and 17 patients had an rFVIIa injection combined with a mechanical procedure to stop the bleeding. Two patients presented with thromboembolic complications. We observed a tendency to recommend an rFVIIa injection before radical treatment is applied. Conclusion: It seems to us legitimate to recommend earlier use of rFVIIa in cases of traumatic haemorrhagic shock in the context of haematological damage control combined with the use of an algorithm to predict the risk involved in polytransfusion and a more aggressive transfusion strategy.

Jean-Christophe Bernard

Papers

Advantage of using a recombinant activated factor VII in traumatic haemorrhagic shock: The Bordeaux experience