Impact of platelet transfusion on outcomes in trauma patients.

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.

Recomendaciones sencillas sobre el uso de agentes antiplaquetarios: por fin un documento ameno / User-friendly recommendations on antiplatelet agents: At last, a readable document

No disponible

Management of antiplatelet therapy for non elective invasive procedures of bleeding complications: proposals from the French working group on perioperative haemostasis (GIHP), in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR).

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.

French lyophilized plasma versus fresh frozen plasma for the initial management of trauma-induced coagulopathy: a randomized open-label trial.

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.

[State of the art: Direct oral anticoagulants and transfusion]. / État de l'art : nouveaux anticoagulants et transfusion.

Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements.

[Antiplatelet agents and transfusion]. / Antiplaquettaires et transfusion.

Antiplatelet agents are at risk for bleeding complications, the management of which differs depending on the clinical situation and on the antiplatelet agent itself. Neutralization of antiplatelets is sometimes necessary, most often leading to platelet transfusion, although the benefit of this strategy is poorly documented. In addition, if platelet transfusion corrects the platelet inhibition induced by aspirin and probably by clopidogrel and prasugrel, it does not neutralize ticagrelor, as a consequence of its pharmacological properties. The clinical benefit of platelet transfusion is limited, and the most recent studies are challenging it. However, it is indicated on a perioperative basis for surgeries with high hemorrhagic risk and is discussed in severe hemorrhages. The neutralization of ticagrelor is a concern and the antidote currently under development may be a solution. In all cases, other therapeutic solutions may be considered, such as administration of desmopressin, tranexamic acid or activated factor VII.

[Management of the bleeding risk associated with antiplatelet agents]. / Prise en charge du risque hémorragique associé aux agents antiplaquettaires.

Like all antithrombotic drugs, antiplatelet agents expose to a risk of bleeding complications. Clinical research has extensively focused on the efficacy of these drugs to reduce ischemic events. The bleeding risk associated with them was solely considered as an inevitable and acceptable complication. When two new potent P2Y12-receptor inhibitors, prasugrel and ticagrelor, were marketed, the risk of major bleeding increased. These new agents have modified the balance between the absolute risk reduction in ischemic events and the absolute risk increase in bleeding events. This paper is an update on the bleeding risk assessment associated with antiplatelet agents. It discusses the place of platelet function monitoring, and the optimal management of bleeding complications. It addresses the challenging issue of reversal of antiplatelet therapy, focusing especially on ticagrelor, which pharmacodynamics complicate bleeding management.

Compliance with evidence-based clinical management guidelines in bleeding trauma patients.

BACKGROUND: In 2007, the multidisciplinary European Task Force for Advanced Bleeding Care in Trauma published guidelines for the management of the bleeding trauma patient. The present study aimed to assess compliance with the European guidelines during the first 24 h in a level I trauma centre and to determine whether compliance impacts mortality. METHODS: This was a retrospective study of consecutive bleeding trauma patients referred to a university hospital in France between 2010 and 2014. A reference document was developed on the basis of the European guidelines to transform the guidelines pragmatically into 22 objectively measurable criteria. We measured per-patient and per-criterion compliance rates and assessed the impact of guideline compliance on mortality. RESULTS: A total of 121 bleeding trauma patients were included. The median (interquartile range) per-patient compliance rate was 75 (65-82)% and the per-criterion compliance rate 64 (57-81)%. Mortality rates were 18 and 32% at 24 h and 30 days, respectively. After adjusting for injury severity, per-patient compliance rates were associated with decreased mortality at 24 h (odds ratio per 10% increase in patient compliance score, 0.43; 95% confidence interval 0.26-0.71; P = 0.0001) and at 30 days (odds ratio per 10% increase in patient compliance score, 0.47; 95% confidence interval 0.31-0.72; P = 0.0004). CONCLUSIONS: We found that compliance with protocols based on European guidelines impacts trauma outcome, because patient compliance was associated with survival. Further work is needed to improve adherence to these guidelines, with ongoing monitoring to ensure best practice and optimal patient outcome.

[Direct oral anticoagulant associated bleeding]. / Hémorragie survenant chez un patient traité par un anticoagulant oral direct.

Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development. Other options include hemodialysis for the treatment of dabigatran-associated bleeding and administration of oral charcoal if recent DOAC ingestion. DOAC plasma concentration measurement is necessary to guide DOAC reversal. We propose an update on DOAC-associated bleeding, integrating the availability of dabigatran antidote and the critical place of DOAC concentration measurements.

[Management of direct oral anticoagulants for invasive procedures]. / Gestion des anticoagulants oraux directs pour un acte invasif.

Three new Direct Oral Anticoagulants (DOACs), rivaroxaban, apixaban and dabigatran etexilate are available on the French market. Management of DOAC-induced bleeding risk remains challenging. For elective procedures with high hemorrhagic risk, a last DOAC intake five days before procedure ensures complete elimination in all patients. Heparin bridging therapy should be proposed only to patients at high thrombotic risk. For elective procedures with low hemorrhagic risk, the DOAC intake of the night before procedure should be omitted. For urgent procedures with high bleeding risk, DOAC plasmatic concentration can be helpful: concentration lower than 30 ng/mL should enable performing the procedure; a high concentration is associated with a higher bleeding risk, especially if higher than 400 ng/mL. In case of massive bleeding, no antidote is approved yet; activated prothrombin concentrates or non-activated 4-factors prothrombin concentrates could be considered.

Multimodal assessment of non-specific hemostatic agents for apixaban reversal.

BACKGROUND: Non-specific hemostatic agents, namely activated prothrombin complex concentrate (aPCC), PCC and recombinant activated factor (F) VII (rFVIIa), can be used, off-label, to reverse the effects of FXa inhibitors in the rare cases of severe hemorrhages, as no approved specific antidote is available. We have evaluated the ability of aPCC, PCC and rFVIIa to reverse apixaban. METHODS: Healthy volunteer whole blood was spiked with therapeutic or supra-therapeutic apixaban concentrations and two doses of aPCC, PCC or rFVIIa. Tests performed included a turbidimetry assay for fibrin polymerization kinetics analysis, scanning electron microscopy for fibrin network structure observation, thrombin generation assay (TGA), thromboelastometry, prothrombin time and activated partial thromboplastin time. RESULTS: aPCC generated a dense clot constituting thin and branched fibers similar to those of a control without apixaban, increased fibrin polymerization velocity and improved quantitative (endogenous thrombin potential and peak height) as well as latency (clotting and lag times) parameters. Adding PCC also improved the fibrin and increased quantitative parameters, but fibrin polymerization kinetics and latency parameters were not corrected. Finally, rFVIIa improved latency parameters but failed to restore the fibrin network structure, fibrin polymerization velocity and quantitative parameters. CONCLUSION: aPCC was more effective than PCC or rFVIIa in reversing in vitro the effects of apixaban. aPCC rapidly triggered the development of an apparently normal fibrin network and corrected latency and quantitative parameters, whereas PCC or rFVIIa had only a partial effect.

[Argatroban, a new antithrombotic treatment for heparin-induced thrombocytopenia application in cardiac surgery and in intensive care]. / L'argatroban, nouvel antithrombotique pour la thrombopénie induite par l'héparine en chirurgie cardiaque de l'adulte: utilisation en chirurgie cardiaque et en réanimation.

OBJECTIVES: Although heparin-induced thrombocytopemia (HIT) is uncommon, its thromboembolic complications are potentially life-threatening. The low-molecular weight heparins are less responsible of HIT than unfractionated heparin (UFH) but this latter is still indicated in some circumstances such as cardiac surgery. Argatroban, a selective thrombin inhibitor, recently available, has been indicated in HIT treatment. This review presents the main pharmacological characteristics, its indications and uses in the context of cardiac surgery and in intensive care medicine. METHODS: Review of the literature in Medline database over the past 15 years using the following keywords: argatroban, cardiac surgery, circulatory assistance, cardiopulmonary bypass. RESULTS: Despite its short-acting pharmacokinetic, argatroban cannot be recommended during cardiopulmonary bypass. On the contrary, argatroban is indicated in many circumstances in postoperative period of various cardiac surgeries (on-pump, off-pump, circulatory assistance). Nevertheless, after cardiac surgery, doses have to be adapted according to coagulation laboratory testing (ACT), particularly in patients presenting acute organ failure (kidney injury, heart failure, liver failure). This compound has no antagonist and is excluded during severe hepatic failure. The continuous intravenous administration is a drawback. CONCLUSION: Argatroban is a new direct competitive thrombin inhibitor well evaluated as treatment of HIT after cardiac surgery. In HIT management, argatroban is an interesting alternative to lepirudin that is not anymore available and danaparoid because of supply disturbances.

[Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors. Proposals of the Working Group on Perioperative Haemostasis (GIHP) - March 2013]. / Prise en charge des complications hémorragiques graves et de la chirurgie en urgence chez les patients recevant un anticoagulant oral anti-IIa ou anti-Xa direct. Propositions du Groupe d'intérêt en Hémostase Périopératoire (GIHP) - mars 2013.

New direct oral anticoagulants (NOAC), inhibitors of factor IIa or Xa, are expected to be widely used for the treatment of venous thromboembolic disease, or in case of atrial fibrillation. Such anticoagulant treatments are known to be associated with haemorrhagic complications. Moreover, it is likely that such patients on long-term treatment with NOAC will be exposed to emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose management for optimal safety as regards the risk of bleeding in such emergency conditions. In this article, only dabigatran and rivaroxaban were discussed. For emergency surgery at risk of bleeding, we propose to dose the plasmatic concentration of drug. Levels inferior or equal to 30ng/mL for both dabigatran and rivaroxaban, should enable the realization of a high bleeding risk surgery. For higher concentration, it was proposed to postpone surgery by monitoring the evolution of the drug concentration. Action is then defined by the kind of NOAC and its concentration. If the dosage of the drug is not immediately available, proposals only based on the usual tests, PT and aPTT, also are presented. However, these tests do not really assess drug concentration or bleeding risk. In case of severe haemorrhage in a critical organ, it is proposed to reduce the effect of anticoagulant therapy using a nonspecific procoagulant drug (activated prothrombin concentrate, FEIBA, 30-50U/kg, or non-activated 4-factors prothrombin concentrates 50U/kg). For any other type of severe haemorrhage, the administration of such a procoagulant drug, potentially thrombogenic in these patients, will be discussed regarding concentration of NACO and possibilities for mechanical haemostasis.

Trauma-induced coagulopathy.

Hemorrhage is the leading cause of death in trauma patients who arrive alive at hospital. This type of hemorrhage has a "coagulopathic" component, specific to major trauma and associated with poor outcomes. Over the last decade, a better understanding of this trauma-induced coagulopathy lead to a new therapeutic approach requiring earlier and more aggressive management. This hemostatic resuscitation includes early activation of massive transfusion protocols with: 1) immediate delivery of blood packs with high ratios for RBC units: fresh frozen plasma: platelet-concentrates; 2) antifibrinolytics; 3) substitution of coagulation factors. However, early identification of coagulopathic patients requiring aggressive hemostatic resuscitation remains challenging, with an increasing role of point of care devices for hemostatic diagnosis and monitoring. Efforts have to be focused on the early diagnosis of coagulopathy for immediate delivery of blood products and coagulation factors to the right, accurately screened patients through pre-established protocols within the golden hour.