Hemostatic Adjunct Research Articles

Resonant Acoustic Rheometry for Real Time Assessment of Plasma Coagulation in Bleeding Patients.

Disordered hemostasis associated with life-threatening hemorrhage commonly afflicts patients in the emergency room, critical care unit, and perioperative settings. Rapid and sensitive hemostasis phenotyping is needed to guide administration of blood components and hemostatic adjuncts to reverse aberrant coagulofibrinolysis. Here, resonant acoustic rheometry (RAR), a technique that quantifies the viscoelastic properties of soft biomaterials, was applied to assess plasma coagulation in a cohort of bleeding patients with concomitant clinical coagulation assays and whole blood thromboelastography (TEG) as part of their routine care. RAR captured the dynamic characteristics of plasma coagulation that were coagulation activators-dependent. RAR coagulation parameters correlated with TEG reaction time and TEG functional fibrinogen, especially when stratified by comorbidities. A quadratic classifier trained on RAR parameters predicted transfusion of fresh frozen plasma and cryoprecipitate with high overall accuracy. These results demonstrate the potential of RAR as a bedside hemostasis assessment to guide transfusion in bleeding patients.

Damage Control Resuscitation in Pediatric Trauma: What You Need to Know.

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Development of a national out-of-hospital transfusion protocol: a modified RAND Delphi study.

Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols. The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 ("Definitely should not include") to 7 ("Definitely should include"). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion. Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT. This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs.

Validation of VIBe bleeding scale amongst hepatopancreatobiliary surgeons: results from an IHPBA survey

BackgroundThe Validated Intraoperative Bleeding (VIBe) Scale could be used to aid assessment of intraoperative bleeding and guide the use of hemostatic products. The aim of this survey was to determine if the VIBe scale would serve as a generalizable and relevant tool for hepatopancreatobiliary(HPB) surgeons and trainees. MethodsA standardized online VIBe training module was conducted on 67 respondents from 25 countries, after which they used the VIBe scale to score videos depicting different severities of intraoperative bleeding. Interobserver agreement was assessed using Kendall’s coefficient of concordance. ResultsInterobserver agreement was excellent amongst all respondents with a Kendall’s W of 0.923. Sub-analyses showed a difference based on seniority and level of experience: Attendings/Consultants(0.947) vs Fellows/Residents(0.879); Increasing years of practice >10(0.952) vs <10 years practice(0.890). There was excellent concordance regardless of surgical volume, percentage of procedures performed minimally invasively, area of sub-specialty, and previous involvement with VIBe surveys. ConclusionThis international survey in the field of HPB surgery across surgeons of various levels of experience showed that the VIBe scale could serve as an excellent tool to assess the severity of bleeding. This scale would also be useful in guiding the use and choice of hemostatic adjuncts to achieve hemostasis.

SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock.

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function-including fibrinolysis-to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.

Activated 4-Factor Prothrombin Complex Concentrate as a Hemostatic Adjunct for Neonatal Cardiac Surgery: A Propensity Score-Matched Cohort Study.

Prothrombin complex concentrates are an emerging "off-label" therapy to augment hemostasis after cardiopulmonary bypass (CPB), but data supporting their use for neonatal cardiac surgery are limited. We retrospectively reviewed neonates undergoing open heart surgery with first-time sternotomy between May 2014 and December 2018 from a hospital electronic health record database. Neonates who received activated 4-factor prothrombin complex concentrate (a4FPCC) after CPB were propensity score matched (PSM) to neonates who did not receive a4FPCC (control group). The primary efficacy outcome was total volume (mL/kg) of blood products transfused after CPB, including the first 24 hours on the cardiovascular intensive care unit (CVICU). The primary safety outcome was the incidence of 7- and 30-day postoperative thromboembolism. Secondary outcomes included 24 hours postoperative chest tube output, time to extubation, duration of CVICU stay, duration of hospital stay, 30-day mortality, and incidence of acute kidney injury on postoperative day 3. We used linear regression modeling on PSM data for the primary efficacy outcome. For the primary safety outcome, we tested for differences using McNemar test on PSM data. For secondary outcomes, we used linear regression, Fisher exact test, or survival analyses as appropriate, with false discovery rate-adjusted P values. A total of 165 neonates were included in the final data analysis: 86 in the control group and 79 in the a4FPCC group. After PSM, there were 43 patients in the control group and 43 in the a4FPCC group. We found a statistically significant difference in mean total blood products transfused for the a4FPCC group (47.5 mL/kg) compared with the control group (63.7 mL/kg) for PSM patients (adjusted difference, 15.3; 95% CI, 29.4-1.3; P = .032). We did not find a statistically significant difference in 7- or 30-day thromboembolic rate, postoperative chest tube output, time to extubation, incidence of postoperative acute kidney injury (AKI), or 30-day mortality between the groups. The a4FPCC group had a significantly longer length of intensive care unit stay (32.9 vs 13.3 days; adjusted P = .049) and hospital stay (44.6 vs 24.1 days; adjusted P = .049) compared with the control group. We found that the use of a4FPCC as a hemostatic adjunct for post-CPB bleeding in neonatal cardiac surgery was associated with a decrease in mean total blood products transfused after CPB without an increased rate of 7- or 30-day postoperative thromboembolism. Our findings suggest that a4FPCCs can be considered as part of a hemostasis pathway for refractory bleeding in neonatal cardiac surgery.

Pediatric traumatic hemorrhagic shock consensus conference recommendations.

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

The National Blood Shortage-An Impetus for Change.

The National Blood Shortage-An Impetus for Change.

Pathogen Reduced Cryoprecipitate and Fibrinogen Concentrate Have Delayed Resuscitation of Simulated Dilutional Coagulopathy in a Microfluidic Model of Bleeding When Compared to Cryoprecipitate

Impaired fibrinogen function, one component of trauma-associated coagulopathy, is highly associated with increased mortality in patients with severe traumatic bleeding. Fibrinogen replacement is crucial for improving outcomes in bleeding patients. The two most common clinically-used hemostatic adjuncts for fibrinogen supplementation are fibrinogen concentrates (FibCon) and cryoprecipitate (Cryo), yet which of these products provides better hemostatic resuscitation remains controversial. Where FibCon is predominantly a source of fibrinogen, Cryo contains additional factors which may enhance hemostatic efficacy, such as FVIII and FXIII (inherent to clot strength and fibrin crosslinking) and von Willebrand factor (VWF, important for platelet adhesion and aggregation). Cryo poses more logistical challenges than FibCon, as Cryo is a frozen product that requires thawing (20 minutes) prior to use, and has a shelf life of 4-6 hours post thaw. FibCon is lyophilized, and can be reconstituted and used within 10 minutes, but with a cost roughly 3 times that of Cryo, use of FibCon can be cost-prohibitive. Ultimately, in the setting of hemostatic resuscitation, every minute matters and each minute delay in blood product transfusion is associated with a 5% increase in mortality. Moreover, Cryo is associated with an increased risk of transfusion transmitted infection (TTI).Thus, there is a need for an immediately available and safe fibrinogen source for use in hemostatic resuscitation.Pathogen reduction (PR) of blood products renders any nucleic acid-containing source replication incompetent via crosslinking using psoralens and ultraviolet light. PR was recently adapted for use with cryoprecipitate, yielding a novel hemostatic adjunct - pathogen reduced cryoprecipitated fibrinogen complex, or PR-Cryo FC. We have previously shown PR-Cryo FC stored out to 10 days performs similarly to Cryo and FibCon in current standard assays used to assess hemostatic function. However, as primary hemostasis is dictated by physiologically relevant flow conditions, we wanted to determine if PR of cryoprecipitate altered its hemostatic function during resuscitation of dilutional coagulopathy using a microfluidic model of hemorrhage.Healthy human whole blood (WB), Cryo, FibCon, and PR-Cryo FC were stained with fluorescent antibodies specific for VWF, CD41, fibrinogen, and FXIII. Stained WB was diluted 3:7 in 0.9% NaCl to induce dilutional coagulopathy (dWB). dWB was resuscitated 1:5 with stained adjuncts (Cryo:dWB, FibCon:dWB, or PR-Cryo FC:dWB) and perfused at three different shear rates (150, 500, 3500 1/s) through a microfluidic model of hemorrhage (a lumen that “bleeds” through an injury site into a collagen/tissue factor-coated extravascular space). Occlusion of the injury site was defined as the point at which clot formation sealed the injury site for > 3 minutes. The time from initial perfusion to occlusion was defined as the bleeding time (BT, seconds). If no seal was formed, the assay was stopped at 20 minutes, and the assay given a BT of 1200 seconds. Real-time phase and fluorescent images of the injury site were acquired. Data was extracted from real-time phase and fluorescent images using MATLAB.Both FibCon:dWB and PR-Cryo FC:dWB had significantly increased BT compared to Cryo:dWB at low shear (150 1/s). PR-Cryo FC:dWB had significantly increased BT compared to Cryo:dWB at medium shear (500 1/s), and at high shear (3500 1/s) there were no significant differences in BT between hemostatic adjuncts. However, kinetic analysis at high shear revealed there was a significant delay in clot formation and accumulation in the injury site, such that by 5 minutes, Cryo:dWB had filled 75% of the injury site and FibCon:dWB and PR-Cryo FC:dWB had only filled 50% of the injury site. Real-time fluorescent image analysis showed that both FibCon:dWB and PR-Cryo FC:dWB had reduced VWF deposition at the injury site compared to Cryo:dWB, and this led to a delays in platelet recruitment. FibCon has less VWF than Cryo, which would explain the delayed VWF deposition and platelet recruitment. In contrast, PR-Cryo FC and Cryo have similar amounts of VWF, suggesting that VWF from PR-Cryo FC has limited binding to the collagen-coated injury site, and as PR-Cryo FC:dWB phenocopies FibCon:dWB during clot formation at high shear, this suggests that pathogen reduction of Cryo may impair early VWF mediated capture of platelets at high shear. DisclosuresSpinella: Secure Transfusion Services: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cerus Corporation: Consultancy, Research Funding.

Pelvic fracture-related hypotension: A review of contemporary adjuncts for hemorrhage control.

Major pelvic hemorrhage remains a considerable challenge of modern trauma care associated with mortality in over a third of patients. Efforts to improve outcomes demand continued research into the optimal employment of both traditional and newer hemostatic adjuncts across the full spectrum of emergent care environments. The purpose of this review is to provide a concise description of the rationale for and effective use of currently available adjuncts for the control of pelvic hemorrhage. In addition, the challenges of defining the optimal order and algorithm for employment of these adjuncts will be outlined. Review, level IV.

Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro.

BackgroundFibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf‐stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction.Study Design and MethodsHemostatic adjunct study products were psoralen‐treated PR‐cryoprecipitated fibrinogen complex (PR‐Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR‐Cryo FC and Cryo were stored for 10 days at 20–24°C. Adjuncts were added to coagulopathies (dilutional, 3:7 whole blood [WB]:normal saline; or lytic, WB + 75 ng/ml tissue plasminogen activator), and hemostatic function was assessed by rotational thromboelastometry and thrombin generation.ResultsPR of cryoprecipitate did not reduce levels of FVIII, FXIII, or VWF. PR‐Cryo FC rescued dilutional coagulopathy similarly to Cryo, while generating significantly more thrombin than FibCon, which also rescued dilutional coagulopathy. Storage out to 10 days at 20–24°C did not diminish the hemostatic function of PR‐Cryo FC.DiscussionPR‐Cryo FC provides similar and/or improved hemostatic rescue compared to FibCon in dilutional coagulopathies, and this rescue ability is stable over 10 days of storage. In hemorrhaging patients, where every minute delay is associated with a 5% increase in mortality, the immediate availability of PR‐Cryo FC has the potential to improve outcomes.

Platelet Contributions to Trauma-Induced Coagulopathy: Updates in Post-injury Platelet Biology, Platelet Transfusions, and Emerging Platelet-Based Hemostatic Agents

The purpose of this review is to summarize the current understanding of the role of aberrant platelet biology in trauma-induced coagulopathy (TIC), discuss the evidence for platelet transfusions in the management of hemorrhaging trauma patients, and review emerging platelet-based hemostatic adjuncts. Advances in the study of post-injury platelet biology have led to the discovery of pathways associated with altered platelet activation and aggregation observed in the context of TIC. Impaired platelet aggregation after injury has recently been associated with histone driven modifications in platelet structureand function, alterations in calcium signaling, and alterations in von Willebrand factor (vWF) platelet interactions. Furthermore, studies have identified several soluble factors in plasma which may play a role in inhibiting platelets after injury. Lastly, loss of the normal regulatory and bidirectional relationships of platelets with the endothelium and with fibrinolytic pathways may additionally play key roles in TIC. Importantly, the use of platelet transfusions as a treatment for hemorrhage control is not “one size fits all”—the benefit in several circumstances may be outweighed by risks, and there is a lack of demonstrated effectiveness for certain populations. Therefore, current efforts are underway to develop platelet based and platelet mimetic hemostatic agents, and to improve the effectiveness of platelet transfusions while mitigating the risks. Our understanding of how injury leads to altered platelet behavior contributing to TIC has grown substantially but remains incomplete. Decoding the complex biologic interface of platelets with the endothelium, fibrinolysis, and inflammatory pathways will lead to a more complete understanding of platelets and of TIC. Platelet transfusions remain the mainstay of treatment as part of balanced and goal-directed resuscitation, but through advancing knowledge of the underlying biology, safer, targeted, and more effective therapies may emerge.

Massive transfusion in the pediatric population: A systematic review and summary of best-evidence practice strategies.

Pediatric patients require massive transfusion (MT) in a variety of settings. Multiple studies of adult MT support balanced ratio transfusion to improve outcomes; however, it is unclear if these findings can be extrapolated to pediatric populations. The use of balanced transfusion ratios, MT protocols, hemostatic adjuncts, and even the definition of a MT in children are all open questions. This review presents details of care from current practices in pediatric MT and summarizes practice strategies while providing insight from our single-center experience. PubMed, EMBASE, and Web of Science were searched using MeSH index and free-text terms for articles from 1946 to 2017. Articles were independently reviewed by two reviewers. Studies were assessed for definition of MT, factors predicting MT, MT complications, blood product ratios, hemostatic adjuncts, protocol logistics, and clinical outcomes. A heterogeneous composite of 29 articles was included in the analysis. Of these, 45% reported a formal transfusion protocol or adopted one during the study. Seven unique definitions of pediatric MT were reported; the most common was >1 total blood volume within 24 hours. A total of 18,369 patients were assessed, and 1,163 received MT (6.3%). Overall mortality for patients requiring MT in studies reporting mortality was high (range 14.7% to 51.2%). We identified 14 patients receiving MT at our center with an age range of 8 months to 18 years and average transfusion of 38.1 mL/kg red blood cells (range: 22.1 mL/kg to 156.7 mL/kg). Current practices of pediatric MT demonstrate a variety of site-specific interventions with a persistently high mortality rate. A national focus on improving techniques of MT in children has the potential to save the lives of these children. Systematic review, levels IV and V.

External Soft-Tissue Hemostatic Clamp Compared to a Compression Tourniquet as Primary Hemorrhage Control Device in Pilot Flow Model Study.

Acute blood loss represents a leading cause of death in both civilian and battlefield trauma, despite the prioritization of massive hemorrhage control by well-adopted trauma guidelines. Current Tactical Combat Casualty Care (TCCC) and Tactical Emergency Casualty Care (TECC) guidelines recommend the application of a tourniquet to treat life-threatening extremity hemorrhages. While extremely effective at controlling blood loss, the proper application of a tourniquet is associated with severe pain and could lead to transient loss of limb function impeding the ability to self-extricate or effectively employ weapons systems. As a potential alternative, Innovative Trauma Care (San Antonio, Texas USA) has developed an external soft-tissue hemostatic clamp that could potentially provide effective hemorrhage control without the aforementioned complications and loss of limb function. Thus, this study sought to investigate the effectiveness of blood loss control by an external soft-tissue hemostatic clamp versus a compression tourniquet. The external soft-tissue hemostatic clamp would be non-inferior at controlling intravascular fluid loss after damage to the femoral and popliteal arteries in a normotensive, coagulopathic, cadaveric lower-extremity flow model using an inert blood analogue, as compared to a compression tourniquet. Using a fresh cadaveric model with simulated vascular flow, this study sought to compare the effectiveness of the external soft-tissue hemostatic clamp versus the compression tourniquet to control fluid loss in simulated trauma resulting in femoral and posterior tibial artery lacerations using a coagulopathic, normotensive, cadaveric-extremity flow model. A sample of 16 fresh, un-embalmed, human cadaver lower extremities was used in this randomized, balanced two-treatment, two-period, two-sequence, crossover design. Statistical significance of the treatment comparisons was assessed with paired t-tests. Results were expressed as the mean and standard deviation (SD). Mean intravascular fluid loss was increased from simulated arterial wounds with the external soft-tissue hemostatic clamp as compared to the compression tourniquet at the lower leg (119.8mL versus 15.9mL; P &lt;.001) and in the thigh (103.1mL versus 5.2mL; P &lt;.001). In this hemorrhagic, coagulopathic, cadaveric-extremity experimental flow model, the use of the external soft-tissue hemostatic clamp as a hasty hemostatic adjunct was associated with statistically significant greater fluid loss than with the use of the compression tourniquet.Paquette R, Bierle R, Wampler D, Allen P, Cooley C, Ramos R, Michalek J, Gerhardt RT. External soft-tissue hemostatic clamp compared to a compression tourniquet as primary hemorrhage control device in pilot flow model study. Prehosp Disaster Med. 2019;34(2):175-181.

A prospective, single-blind, randomized, phase III study to evaluate the safety and efficacy of Fibrin Sealant Grifols as an adjunct to hemostasis compared with manual compression in vascular surgery

ObjectiveNew formulations and applications of hemostatic adjuncts such as fibrin sealant (FS) to support local hemostasis and sutures continue to be developed. In a pivotal, confirmatory, controlled, prospective, single-blinded, randomized, multicenter phase III clinical trial, the efficacy and safety of FS Grifols during vascular surgeries were evaluated. MethodsPatients undergoing a nonemergency, open, peripheral vascular surgical procedure with moderate arterial bleeding were recruited. In an initial preliminary part of the study, all patients were treated with FS Grifols. In a subsequent primary part, patients were randomized (2:1) to FS Grifols or manual compression (MC). The primary efficacy end point was the proportion of the primary part patients achieving hemostasis by 4 minutes after the start of treatment. Cumulative proportion and time to hemostasis were secondary efficacy end points. Safety end points (in pooled preliminary and primary parts) included adverse events (AEs), vital signs, physical assessments, clinical laboratory tests, viral markers, and immunogenicity. ResultsThe primary efficacy end point was met by 76.1% of patients (83/109) for the FS Grifols group versus 22.8% of patients (13/57) for the MC group (P < .001). The cumulative proportion of patients at 5, 7, and 10 minutes was 80.7%, 84.4%, and 88.1%, respectively, in the FS Grifols treatment group, and 28.1%, 35.1%, and 45.6% in the MC treatment group (P < .001). The median time to hemostasis was shorter in the FS Grifols group (4 minutes vs ≥10 minutes in the MC group; P < .001). The nature of AEs reported were those expected in the study patient profile. The percentage of patients experiencing treatment-emergent AEs were similar in both the FS Grifols (pooled n = 59 + 109) and MC groups (81.0% and 77.2%, respectively), most recurrent being procedural pain (34.5% and 36.8%, respectively) and pyrexia (11.3% and 10.5%, respectively). ConclusionsFS Grifols was superior in efficacy and similar in safety to MC as an adjunct local hemostatic agent in patients undergoing open vascular surgeries.

Hemorrhage Treatment Adjuncts in a Helicopter Emergency Medical Service

Hemorrhaging is the leading cause of preventable death after trauma. In our helicopter emergency medical service (HEMS), we introduced a bundle of 3 hemostatic adjuncts: 1) tourniquet, 2) hemostatic chitosan-based wound packings, and 3) tranexamic acid (TXA). The real-life frequency of applying these adjuncts in HEMS remains unclear. Therefore, we analyzed our electronic HEMS database regarding the use of these hemostatic adjuncts. We analyzed all subsequent dispatches of our HEMS “Lifeliner 1” within a searchable digital database (01.02.2013-22.05.2018). This HEMS operates 24/7, servicing ∼4.5 million inhabitants of the Netherlands. During the 75-month study period, we registered 15,759 dispatches, of which 8,658 were canceled, and 7,101 included on-site patient care, including 4,928 (69.4%) trauma cases. In total, we recorded 78 tourniquet applications (1.1% of patients), 104 hemostatic wound packings (1.5% of patients), and 1,379 cases with prehospital TXA administration (19.4% of patients). This difference in the use of hemostatics has several contributors, including a possible lack of awareness for tourniquets and procoagulant wound packing, a high proportion of blunt trauma with internal bleeding not accessible to tourniquet or wound packing, and a liberal use of TXA (eg, in patients with unproven hemorrhage). Besides creating awareness for those hemostatic adjuncts, the practical implications of our findings need further evaluation in future studies.

Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism.

Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE. This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality. Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12-27) and 14 (interquartile range, 8-22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3-9.1; p = 0.02). Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23-3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11-5.29; p = 0.03). Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms. Therapeutic, level III.

Blood transfusion management in the severely bleeding military patient.

Hemorrhage remains the primary cause of preventable death on the battlefield and in civilian trauma. Hemorrhage control is multifactorial and starts with point-of-injury care. Surgical hemorrhage control and time from injury to surgery is paramount; however, interventions in the prehospital environment and perioperative period affect outcomes. The purpose of this review is to understand concepts and strategies for successful management of the bleeding military patient. Understanding the life-threatening nature of coagulopathy of trauma and implementing strategies aimed at full spectrum hemorrhage management from point of injury to postoperative care will result in improved outcomes in patients with life-threatening bleeding. Timely and appropriate therapies impact survival. Blood product resuscitation for life-threatening hemorrhage should either be with whole blood or a component therapy strategy that recapitulates the functionality of whole blood. The US military has transfused over 10 000 units of whole blood since the beginning of the wars in Iraq and Afghanistan. The well recognized therapeutic benefits of whole blood have pushed this therapy far forward into prehospital care in both US and international military forces. Multiple hemostatic adjuncts are available that are likely beneficial to the bleeding military patient; and other products and techniques are under active investigation. Lessons learned in the treatment of combat casualties will likely continue to have positive impact and influence and the management of hemorrhage in the civilian trauma setting.

Research progress in hemorrhage control products of U. S. army

From Vietnam War to Operation Iraqi Freedom and Operation Enduring Freedom, hemorrhage remains the leading cause of combat death. The U. S. army has made great strides in research and development of hemorrhage control products and various tourniquets and hemostatic dressings have been fielded on the battlefield. This paper introduces current status of hemostatic products and hemorrhage control products. Currently, there are extremity tourniquets and junctional tourniquets. The hemostatic products include HemCon bandages, QuciClot granular and gauze, Celox gauze, XStat, etc. Meanwhile, the author summarizes three development trends of US military hemostatic products, ie, prehospital application of tourniquets, emphasis on hemorrhage control in junctional regions, and gauze hemostatic adjuncts preference. This review offers materials for fully understanding war wound treatment of U. S. army. Key words: Tourniquets; Hemostatic techniques; U. S. armed forces

Anticoagulation in extracorporeal membrane oxygenation

During extracorporeal membrane oxygenation (ECMO) support, the underlying disease process and contact between blood and non-biological surfaces cause alterations in haemostasis. This results in the activation of coagulation and platelet pathways and consumption of factors which can provoke haemorrhage, thrombosis or both. Currently, despite its limitations, unfractionated heparin (UFH) is the anticoagulant of choice in patients supported on ECMO. However, there is increasing experience with the use of new anticoagulants (bivalirudin, argatroban and lepirudin). Bleeding remains the most common complication and the use of haemostatic adjuncts in ECMO, including antifibrinolytic agents and desmopressin are supported by a weak body of evidence, although there is growing literature to support the cautious use of recombinant activated factor VII in certain situations. Bleeding bundles have been advocated to ensure step-by-step measures are taken to control bleeding. Similarly, advancements in monitoring of anticoagulation may lie in the development of anticoagulation laboratory protocols and algorithms. This review aims to furnish the ECMO provider with an update on advancements in anticoagulation in ECMO.