ABSTRACT
BACKGROUND: Trauma-induced coagulopathy includes thrombocytopenia and platelet dysfunction that impact patient outcome. Nevertheless, the role of platelet transfusion remains poorly defined. The aim of the study was 1/ to evaluate the impact of early platelet transfusion on 24-h all-cause mortality and 2/ to describe platelet count at admission (PCA) and its relationship with trauma severity and outcome. METHODS: Observational study carried out on a multicentre prospective trauma registry. All adult trauma patients directly admitted in participating trauma centres between May 2011 and June 2019 were included. Severe haemorrhage was defined as ≥ 4 red blood cell units within 6 h and/or death from exsanguination. The impact of PCA and early platelet transfusion (i.e. within the first 6 h) on 24-h all-cause mortality was assessed using uni- and multivariate logistic regression. RESULTS: Among the 19,596 included patients, PCA (229 G/L [189,271]) was associated with coagulopathy, traumatic burden, shock and bleeding severity. In a logistic regression model, 24-h all-cause mortality increased by 37% for every 50 G/L decrease in platelet count (OR 0.63 95% CI 0.57-0.70; p < 0.001). Regarding patients with severe hemorrhage, platelets were transfused early for 36% of patients. Early platelet transfusion was associated with a decrease in 24-h all-cause mortality (versus no or late platelets): OR 0.52 (95% CI 0.34-0.79; p < 0.05). CONCLUSIONS: PCA, although mainly in normal range, was associated with trauma severity and coagulopathy and was predictive of bleeding intensity and outcome. Early platelet transfusion within 6 h was associated with a decrease in mortality in patients with severe hemorrhage. Future studies are needed to determine which doses of platelet transfusion will improve outcomes after major trauma.
Subject(s)
Blood Coagulation Disorders , Thrombocytopenia , Blood Coagulation Disorders/etiology , Hemorrhage/etiology , Hemorrhage/therapy , Humans , Platelet Transfusion/adverse effects , Thrombocytopenia/etiology , Thrombocytopenia/therapy , Trauma CentersABSTRACT
The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.
Subject(s)
Hemorrhage/chemically induced , Hemorrhage/therapy , Hemostasis, Surgical/methods , Platelet Aggregation Inhibitors/adverse effects , Anesthesia , Critical Care , France , Hemostasis , Hemostatics/therapeutic use , Humans , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Function Tests , Platelet Transfusion , Prasugrel Hydrochloride/adverse effects , Prognosis , Societies, Medical , Ticagrelor/adverse effectsABSTRACT
Essentials An immediate supply of plasma in case of trauma-induced coagulopathy is required. The Traucc trial compared French Lyophilised Plasma (FLyP) and Fresh Frozen Plasma (FFP). FLyP achieved higher fibrinogen concentrations compared with FFP. FLyP led to a more rapid coagulopathy improvement than FFP. SUMMARY: Background Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy. Methods In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6 h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45 min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality. Results Forty-eight patients were randomized (FLyP, n = 24; FFP, n = 24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90] min). FLyP achieved a higher fibrinogen concentration 45 min after randomization compared with FFP (baseline-adjusted mean difference, 0.29 g L-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6 h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP. Conclusion FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.
Subject(s)
Blood Coagulation Disorders/therapy , Blood Transfusion/methods , Fibrinogen/chemistry , Plasma/chemistry , Wounds and Injuries/therapy , Adult , Blood Coagulation , Blood Coagulation Disorders/etiology , Emergency Medicine/methods , Female , Fibrinogen/biosynthesis , France , Freeze Drying , Hemostatics , Humans , Male , Middle Aged , Resuscitation , Wounds and Injuries/complicationsABSTRACT
Despite a stringent donor selection, human islet isolation remains frustratingly unpredictable. In this study, we measured acute insulin response to arginine (AIRarg), an in vivo surrogate measure of islet mass, in 29 human deceased donors before organ donation, and correlated values with the outcome of islet isolation. Thirteen isolations (45%) met the threshold for clinical islet transplantation. Among all measured donor characteristics, the only discriminating variable between successful or unsuccessful isolations was donor AIRarg (p < 0.01). Using a threshold of 55 microIU/mL (ROC curve AUC: 72%), isolation was successful in 12/19 donors with high AIRarg and in 1/10 donors with low AIRarg (p < 0.001). The negative and positive predictive values were 90 and 63%, respectively. If used to select donors in the entire cohort, AIRarg would have increased our success rate by 40% and avoided 56% of unsuccessful isolations while missing only 8% of successful preparations. Our results suggest that donor AIRarg is markedly superior to body mass index (BMI) and other criteria currently used to predict isolation outcome. If routinely performed in deceased donors, this simple test could significantly reduce the failure rate of human islet isolation.
Subject(s)
Arginine/pharmacology , Insulin/metabolism , Islets of Langerhans Transplantation/physiology , Islets of Langerhans , Tissue Donors , Tissue and Organ Harvesting/methods , Brain Death , Cadaver , Humans , Insulin Secretion , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Predictive Value of Tests , Treatment OutcomeABSTRACT
OBJECTIVE: The aim was to determine whether myofilament Ca2+ sensitivity is altered in skinned cardiac fibres from endotoxin-treated rabbits. METHODS: Endotoxin was injected i.v. in conscious New-Zealand White rabbits at a dose of 0.5 mg/kg (groups I, II, and III) or 1 mg/kg (group IV). A fifth group was used as control. Hearts were excised 4 h (groups I and IV), 24 h (group II), or 5 days (Group III) after injection. Skinned fibres were obtained with chemical (EGTA + Brij 58) treatment of bundles isolated from papillary muscles. RESULTS: The maximal Ca(2+)-activated force (F0) of skinned cardiac fibres was not different between groups. However, [Ca2+] required to evoke 50% of F0 (Ca50) was higher in the fibres from group I than in controls (1.78 +/- 0.05 vs. 1.53 +/- 0.03 microM; P < 0.05). This effect was dose-dependent (group IV: Ca50 = 2.08 +/- 0.12 microM; P < 0.05 vs. group I), larger after 24 h (group II: Ca50 = 2.12 +/- 0.05 microM; P < 0.05 vs. group I). By 5 days, myofilament Ca2+ sensitivity had returned to normal (group III: Ca50 = 1.54 +/- 0.05 microM). CONCLUSION: Myofilament Ca2+ sensitivity is decreased in skinned fibres taken from rabbit myocardium after i.v. endotoxin injection. This effect is dose- and time-dependent, and reversible with time.