Coagulopathic Patients Research Articles

Flow, Liver, Flow: A Retrospective Analysis of the Interplay of Liver Disease and Coagulopathy in Chronic Subdural Hematoma.

Chronic subdural hematoma (cSDH) is a common neurosurgical ailment, particularly in elderly patients. A recent study uncovered an association between liver disease and recurrence in patients with cSDH. Here, we explored that relationship to identify recurrence predictors in at-risk patients. We hypothesized that the association between liver disease and recurrence was attributable to coagulopathy secondary to liver disease. We retrospectively reviewed all patients with cSDH treated with burr-hole drainage by 2 surgeons between 2007 and 2015. Comorbidities and laboratory findings for each patient were examined by Pearson χ2 analysis or Mann-Whitney U tests. We identified 261 cSDH in 215 patients. Patients were a mean age of 65.6 years, and 72% were male. Sixteen patients with cSDH required repeat surgery (6.1%). There were 123 coagulopathic patients (47.1%), and 14 with liver disease (5.4%), all of whom were coagulopathic (P<0.001). Coagulopathic patients with liver disease were more likely to experience recurrence than patients with coagulopathy alone (relative risk= 4.09, P= 0.019). Patients with liver disease had significantly elevated prothrombin time (P= 0.013) and reduced platelet counts (P<0.001). Platelets also were reduced in coagulopathic patients with liver disease, as compared with those with coagulopathy alone (P= 0.002). Thrombocytopenia remained significant in a multivariate analysis (P < 0.001). Liver disease is significantly associated with the recurrence of cSDH. Although coagulopathy alone does not predict recurrence, patients with coagulopathy and liver disease are at greater risk for recurrence than those with coagulopathy alone. Liver disease effects are reflected in certain hematologic laboratory values.

Prevalence and Impact of Admission Acute Traumatic Coagulopathy on Treatment Intensity, Resource Use, and Mortality: An Evaluation of 956 Severely Injured Children and Adolescents

Acute coagulopathy of trauma in children is of potential importance to clinical outcomes, but knowledge is limited and has only been investigated using conventional coagulation testing. The purpose of this study was to assess the prevalence and impact of arrival coagulopathy, determined by viscoelastic hemostatic testing, in severely injured children. Pediatric patients (younger than 17 years of age) who were admitted January 2010 to May 2016 and met highest-level trauma activation were included. Patients were divided into 2 groups (coagulopathy and controls) based on arrival rapid thrombelastography values. Coagulopathy was defined as the presence of any of the following on rapid thrombelastography: activated clotting time ≥128 seconds, α-angle ≤65 degrees, maximum amplitude ≤55mm, and lysis at 30 minutes from 20-mm amplitude ≥3%. Logistic regression was used to adjust for age, sex, blood pressure, mechanism, and injury severity. Nine hundred and fifty-six patients met inclusion; 507 (57%) were coagulopathic and 449(43%) were not (noncoagulopathic and control cohort). Coagulopathic patients were younger (median 14 vs 15 years) and more likely to be male (68% vs 60%) and Hispanic (38% vs 31%) (all p < 0.05). Coagulopathic patients received more RBC and plasma transfusions and had fewer ICU and ventilator-free days and higher mortality (12% vs 3%; all p < 0.05). Of these 956, 197 (21%) sustained severe brain injury-123 (62%) were coagulopathic and 74 (38%) were noncoagulopathic. The mortality difference was even greater for coagulopathic head injuries (31% vs 10%; p= 0.002). Adjusting for confounders, admission coagulopathy was an independent predictor of death, with an odds ratio of 3.67(95% CI 1.768 to 7.632; p < 0.001). Almost 60% of severely injured children and adolescents arrive with evidence of acute traumatic coagulopathy. The presence of admission coagulopathy is associated with high mortality in children, especially among those with head injuries.

Early Coagulopathy is Associated With Increased Incidence of Ventilator-Associated Events Among Burn Patients.

Coagulopathy is known to be associated with burn injury. Our group has shown that, in spinal cord injury patients, coagulopathy is associated with an increase in ventilator-associated pneumonia (VAP). We hypothesized that the same association exists between coagulopathic burn patients and ventilator-associated events. Patients admitted for burn care between January 1, 2011 and December 31, 2015 who required mechanical ventilation were included in the study. Ventilator-associated events (VAEs) as defined by the Center for Disease Control were categorized as no event, ventilator-associated condition, infection-related ventilator-associated complication, and possible VAP. Demographic, injury characteristics were compared among four international normalized ratio (INR) categories using analysis of variance and chi-square tests. Four hundred four patients were admitted for burn care, of whom 263 met the inclusion criteria. One hundred eleven had normal INR, 59 had a slightly elevated INR (1.2-1.4), 33 had a moderately elevated INR (1.4-1.6), and 60 had a severely elevated INR (>1.6). Those with moderately and severely elevated INR were ventilated for a longer period (P = 0.0034), had more days in the ICU (P = 0.0010), and had longer hospital stay (P = 0.0016). After adjusting for inhalation injury and total body surface area, patients with severely elevated INR were over four times as likely to have any VAE (OR: 4.16, 95% CI: 1.33-13.05) and 4.5 times as likely to develop infection-related ventilator-associated complication or possible ventilator-associated pneumonia combined (OR: 4.59, 1.35-15.67). Early coagulopathy is associated with a significantly increased incidence of VAEs in burn patients. While additional studies need to be conducted to verify these findings, early recognition and treatment could decrease VAEs.

A hospital cost analysis of a fibrin sealant patch in soft tissue and hepatic surgical bleeding

BackgroundDespite hemostat use, uncontrolled surgical bleeding is prevalent. Drawbacks of current hemostats include limitations with efficacy on first attempt and suboptimal ease-of-use. Evarrest® is a novel fibrin sealant patch that has demonstrated high hemostatic efficacy compared with standard of care across bleeding severities. The objective of this study was to conduct a hospital cost analysis of the fibrin sealant patch versus standard of care in soft tissue and hepatic surgical bleeding.MethodsThe analysis quantified the 30-day costs of each comparator from a hospital perspective. Published US unit costs were applied to resource use (ie, initial treatment, retreatment, operating time, hospitalization, transfusion, and ventilator) reported in four trials. A “surgical” analysis included resources clinically related to the hemostatic benefit of the fibrin sealant patch, whereas a “hospital” analysis included all resources reported in the trials. An exploratory subgroup analysis focused solely on coagulopathic patients defined by abnormal blood test results.ResultsThe surgical analysis predicted cost savings of $54 per patient with the fibrin sealant patch compared with standard of care (net cost impact: −$54 per patient; sensitivity range: −$1,320 to $1,213). The hospital analysis predicted further cost savings with the fibrin sealant patch (net cost impact of −$2,846 per patient; sensitivity range: −$1,483 to −$5,575). Subgroup analyses suggest that the fibrin sealant patch may provide dramatic cost savings in the coagulopathic subgroup of $3,233 (surgical) and $9,287 (hospital) per patient. Results were most sensitive to operating time and product units.ConclusionIn soft tissue and hepatic problematic surgical bleeding, the fibrin sealant patch may result in important hospital cost savings.

Inserting central venous catheter in emergency conditions in coagulopathic patients in comparison to noncoagulopathic patients.

Background:The current study was designed to compare the complications and adverse effects of central venous catheter (CVC) insertion under ultrasound guidance in patients with and without coagulopathy.Materials and Methods:In this clinical trial, 59 patients who needed CVC for various reasons were enrolled. Patients were divided into two groups of those with and without coagulopathy based on complete blood count, prothrombin time, partial thromboplastin time, and international normalized ratio test results, and then, CVC was inserted with ultrasound guidance in both groups. The CVC inserting site was examined for hematoma and hemorrhage in four stages at different times.Results:There was no significant difference in the terms of demographic features, catheter lumen size (P = 0.43), and number of attempting for CVC placement (odds ratio [OR] =2.35, 95% confidence interval [CI] = 0.36–15.3, P = 0.39) between two groups. Seven out of 59 patients suffered from complications (11.9%) that the complications in coagulopathic patients were oozing (5.7%) and superficial hematoma (8.6%) while in noncoagulopathic patients were 4.2% for both complications (OR = 0.54, 95% CI = 0.09–3.07, P = 0.767).Conclusion:According to our results, it can be concluded that inserting CVC with ultrasound guidance under emergency conditions causes no serious and life-threatening complications in coagulopathic patients.

Platelet-like particles for wound-triggered hemostasis in patients at high risk for bleeding during cardiac surgery

Event Abstract Back to Event Platelet-like particles for wound-triggered hemostasis in patients at high risk for bleeding during cardiac surgery Riley Hannan1, Byungwook Ahn2, 3, 4, Wilbur Lam3, 4, Andrew Lyon5, Nina Guzzetta3, 4, Thomas H. Barker2, 4 and Ashley Brown6 1 University of Virginia, United States 2 Georgia Institute of Technology, Biomedical Engineering, United States 3 Children’s Healthcare of Atlanta, United States 4 Emory University, United States 5 Chapman University, Schmid College of Science and Technology, United States 6 North Carolina State University and University of North Carolina at Chapel Hill, Biomedical Engineering, United States Introduction: Neonates born with congenital cardiac defects often undergo complex corrective surgery requiring cardiopulmonary bypass (CPB) within a few days following birth. CPB is known to contribute significantly to surgery associated bleeding through induction of massive hemodilution, thrombocytopenia and platelet dysfunction; these bleeding risks are exacerbated in neonates due to preexisting platelet dysfunction and an immature coagulation system. CPB greatly hinders platelet function; therefore, materials that recapitulate platelet hemostatic functions could be utilized as an alternative to transfusion of adult blood products for augmentation of clotting in patients post-CPB. We have recently developed platelet-like-particles (PLPs) created from highly deformable microgels conjugated to molecularly evolved wound-targeting motifs which enable specific and high affinity binding to the provisional matrix protein fibrin[1]. These PLPs are capable of recapitulating a number of functions of natural platelets, including augmentation of clotting of adult plasma in vitro, decreased bleeding times in vivo in rodent models of traumatic injury, specific homing to injury sites and clot contraction. Here, we characterize the ability of PLPs to augment clotting in CPB-patient plasma samples in vitro and in vivo in a rat model of impaired platelet activity. Materials and Methods: Ultra-low crosslinked (ULC) poly(N-isopropylacrylamide) (pNIPAM) microgels containing 95% pNIPAM and 5% acrylic acid (AAc) were produced through precipitation polymerization. PLPs were produced by conjugating fibrin-specific single domain variable fragment antibodies to ULC microgels through EDC/NHS coupling. Clotting was assessed in vitro in patient platelet poor plasma (PPP) samples collected from neonatal cardiac surgery patients at baseline, post-CPB (+/- PLPs) and post transfusion through an endothelialized microfluidics device that mimics the microenvironment of microcirculation[2]. Fibrin microarchitecture was analyzed using confocal microscopy. Clotting was assessed in vivo in a rodent platelet deficiency model, which mimics the gross dysfunction of platelets in pediatric cardiac patients. To induce platelet hyporeactivity, male Sprague Dawley rats received a daily oral gavage of aspirin (5 mg/kg) for seven days. On the seventh day, bleeding times following induction of a femoral vein injury were assessed in animals receiving intravenous administration of PLPs or saline. Results and Discussion: In vitro clotting experiments in an endothelialized microfluidic device demonstrate minimal clotting in post-CPB PPP alone, while the addition of PLPs induces significant fibrin formation (Figure 1A). To determine the effect of PLPs on fibrin network microstructure, confocal microscopy was performed; incorporation of PLPs into post-CPB PPP results in a denser fibrin network compared to post-CBP PPP alone or samples collected post-transfusion (Figure 1B). In an in vivo model of platelet hyporeactivity, PLPs significantly decreased bleeding following injury compared to control animals (Figure 1C). Conclusions: PLPs enhance clot formation in neonatal patient samples in vitro and decrease bleeding times in vivo in a rodent model of platelet dysfunction. These results highlight the utility of PLPs for treatment of postsurgical bleeding in coagulopathic neonatal patients. 1R21EB019068, NIH/NIBIB

Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)-mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline. Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis. The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3-11.2; NS, 4.5; IQR, 4.1-14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7-27.8; NS, 22.4; IQR, 20.1-25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5-19.9) compared with PFP (-4.9%; IQR, -9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, -6.2 to 7.1 vs. PFP, 1.7; IQR, -5.2 to 6.8; p = 0.699). Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.

The impact of coagulopathy on traumatic splenic injuries

BackgroundPatients with pre-injury coagulopathy have worse outcomes than those without coagulopathy. This article investigated the risk-adjusted effect of pre-injury coagulopathy on outcomes after splenic injuries. MethodsReview of the National Trauma Data Bank from 2007 to 2010 comparing mortality and complications between splenic injury patients with and without a pre-injury bleeding disorder. ResultsOf 58,896 patients, 2% had a bleeding disorder. Coagulopathic patients had higher odds of mortality (odds ratio, 1.3), sepsis (odds ratio, 2.0), acute respiratory distress syndrome (odds ratio, 2.6), acute renal failure (odds ratio, 1.5), cardiac arrest (odds ratio, 1.5), and overall complications (odds ratio, 2.4). The higher odds of myocardial infarction did not achieve statistical significance (odds ratio, 1.6). ConclusionsPre-injury coagulopathy in patients with splenic injury has a negative impact on cardiac arrest, sepsis, acute respiratory distress syndrome, acute renal failure, and mortality. The higher likelihood of myocardial infarction did not reach statistical significance.

PMD16 - Economic analysis of Evarresttm compared with standard care in CHALLENGING Liver Surgical Bleeding Populations: a U.S. Hospital perspective

Bleeding in liver surgery can be difficult to control due to extreme vascularity and tissue fragility, including compromised liver (e.g., cancer). Blood loss may be minimized with hemostats that have rapid effect and may impact cost of care. This study estimated budget impact of using EVARREST vs. SoC in hepatic surgery based on two randomized trials. An economic analysis was developed to quantify 30-day cost impact of EVARREST from a U.S. hospital perspective. Key resources, from two randomized trials (n=180), included initial treatment, retreatment, operating time, transfusions, ventilator, and hospitalization. Transplant patients (n=6) where normal liver tissue was resected were excluded from analyses. SOC was composed mainly of manual compression alone or with hemostats. The surgical analysis included resources clinically related to significant hemostasis benefits of EVARREST (i.e. retreatment, operating time, transfusion). A hospital analysis included all resources collected. Economic analyses were completed for the following subgroups: abnormal liver, metastatic cancer, anatomic/non-anatomic liver (classifications using IHPBA definitions), cirrhotic/steatotic liver, and if patients were obese or coagulopathic. Published U.S. costs were applied to resource use. Analysis results were weighted based on trial size. The surgical analysis predicted that the EVARREST cost was offset vs. SoC with a trial-weighted cost impact of $719 per patient. The hospital analysis predicted further resource reduction with EVARREST with trial-weighted cost-savings of $868 per patient. Subgroup analyses demonstrated a range of results from cost impact to cost savings with EVARREST vs. SOC (i.e., $1,976 to -$5,430 per patient, hospital analysis). EVARREST use in coagulopathic patients was found to have the largest degree of cost savings with $1,859 and $5,176 per patient anticipated, surgical and hospital results respectively. In addition to meeting an important unmet need in controlling problematic bleeding in liver tissue, this analysis suggests that EVARREST can be a cost saving strategy.

579 Management of benign prostatic obstruction using bipolar plasma kinetic energy in coagulopathic patients: Initial series

579 Management of benign prostatic obstruction using bipolar plasma kinetic energy in coagulopathic patients: Initial series

Complications of transjugular biopsies.

Transvenous biopsy was first performed in 1964 by Charles Dotter. Now routinely performed in the liver and kidney by interventional radiologists, the transjugular approach to biopsy has assumed a central role in coagulopathic patients. Major arterial complications from transjugular liver and renal biopsy are rare. In this article, the authors describe such complications in both organs that necessitated selective endovascular coil embolization.

Evolving beyond the vicious triad: Differential mediation of traumatic coagulopathy by injury, shock, and resuscitation.

A subset of trauma patients with critical injury present with coagulopathy, portending markedly worse outcomes. Clinical practice is evolving to treat the classical risk factors of hypothermia, hemodilution, and acidosis; however, coagulopathy persists even in the absence of these factors. We sought to determine the relative importance of injury- and shock-specific factors compared with resuscitation-associated factors in coagulopathy after trauma. Comprehensive demographic data, laboratory data, and outcomes data were prospectively collected from seven trauma centers over 8 years (November 2003 to August 2011) as part of the Inflammation and the Host Response to Injury Large-Scale Collaborative Program. A total of 1,537 critically injured patients with blunt trauma and hemorrhagic shock were analyzed to evaluate predictors of admission coagulopathy (international normalized ratio [INR] ≥ 1.3), multiorgan failure, and mortality. Of 1,537 patients, 578 (37.6%) had admission INR of 1.3 or greater. Coagulopathic patients had more severe injury, more severe base deficit and lactate levels, as well as lower admission temperature, lower pH, and higher prehospital crystalloid volume (all p < 0.001). Coagulopathic patients required more blood products and mechanical ventilation and had higher rates of nosocomial infection, multiorgan failure, and mortality (all p < 0.02). Injury severity, temperature, and acidosis (all p < 0.02) independently predicted coagulopathy in multivariate analysis, with a significant interaction between lactate and prehospital crystalloid. In Cox regression models, however, coagulopathy itself remained an independent predictor of both multiorgan failure and mortality (p < 0.02) even when adjusted for injury severity, shock, and elements of the vicious triad. Most patients with coagulopathy after trauma have mixed risk factors; however, coagulopathy has deleterious effects independent of injury severity, shock, and the vicious triad. Better understanding of the biochemical mechanisms of acute traumatic coagulopathy may facilitate biochemically targeted resuscitation strategies and improve outcomes. Prognostic and epidemiologic study, level II.

Successful Ultrasound-Guided Femoral Nerve Blockade and Catheterization in a Patient with Von Willebrand Disease.

Peripheral nerve blockade (PNB) is superior to neuraxial anesthesia and/or opioid therapy for perioperative analgesia in total knee replacement (TKR). Evidence on the safety of PNB in patients with coagulopathy is lacking. We describe the first documented account of continuous femoral PNB for perioperative analgesia in a patient with Von Willebrand Disease (vWD). Given her history of opioid tolerance and after an informative discussion, a continuous femoral PNB was planned for in this 34-year-old female undergoing TKR. A Humate-P intravenous infusion was started and the patient was positioned supinely. Using sterile technique with ultrasound guidance, a Contiplex 18 Gauge Tuohy needle was advanced in plane through the fascia iliaca towards the femoral nerve. A nerve catheter was threaded through the needle and secured without complications. Postoperatively, a levobupivacaine femoral catheter infusion was maintained, and twice daily Humate-P intravenous infusions were administered for 48 hours; enoxaparin thromboprophylaxis was initiated thereafter. The patient was discharged uneventfully on postoperative day 4. Given documentation of delayed, unheralded bleeding from PNB in coagulopathic patients, we recommend individualized PNB in vWD patients. Multidisciplinary team involvement is required to guide factor supplementation and thromboprophylaxis, as is close follow-up to elicit signs of bleeding throughout the delayed postoperative period.

Coagulation support algorithm with rapid TEG and functional fibrinogen TEG in critical bleeding: more results and less time

Early coagulation support is essential in massively bleeding patients. A Coagulation Support Algorithm (CSA), integrating rapid TEG (r-TEG) and functional fibrinogen TEG (ff-TEG) could shorten the time to a tailored treatment (Figure ​(Figure11). Figure 1 Coagulation Support Algorithm. Methods A retrospective comparison of the time to available TEG and Standard Coagulation Tests (SCT: INR, aPTTr, fibrinogen level) results in two groups of bleeding and coagulopathic patients using citrate kaolin-TEG (k-TEG) or the CSA protocol (r-TEG/ff-TEG). Statistical analysis was performed with Student's t test for unpaired samples.

Fibrinogen concentrate for bleeding--a systematic review.

Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled trials (RCTs) and non-randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non-randomised studies included a total of 2825 patients, but only 11 of 23 studies included a control group. Three out of 11 found a reduction in transfusion requirements while mortality was reduced in two and bleeding in one. In the available RCTs, which all have substantial shortcomings, we found a significant reduction in bleeding and transfusions requirements. However, data on mortality were lacking. Weak evidence from RCTs supports the use of fibrinogen concentrate in bleeding patients, primarily in elective cardiac surgery, but a general use of fibrinogen across all settings is only supported by non-randomised studies with serious methodological shortcomings. It seems pre-mature to conclude whether fibrinogen concentrate has a routine role in the management of bleeding and coagulopathic patients. More RCTs are urgently warranted.

Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study: Correlation with coagulopathy

BackgroundTrauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. MethodsAs part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥35sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. Results21.7% of patients were coagulopathic with the median (IQR) APTT of 44sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001). ConclusionsCellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.

Fibrinogen replacement in trauma haemorrhage

Fibrinogen replacement in trauma haemorrhage

Early tranexamic acid use in trauma haemorrhage: Why do we give it and which patients benefit most?

Trauma is a major contributor to the global burden of disease (WHO, 2009). Haemorrhage following injury is the leading cause of preventable death (Gruen et al., 2012), with many patients dying in the first 24 hours following the traumatic event (Borgman et al., 2007). Early phase care in prehospital (PHC) and emergency department (ED) settings focuses on timely recognition and control of haemorrhage. Many trauma systems have introduced major haemorrhage protocols (MHP) to help with the rapid identification of bleeding trauma patients and ensure that appropriate blood products are delivered (Khan et al., 2013). Haemorrhage following injury is strongly associated with early coagulation system dysfunction, known as acute traumatic coagulopathy (ATC) (Davenport, 2013). Approximately one quarter of all severely injured patients are reported to be coagulopathic on arrival to hospital (Brohi et al., 2003). ATC is a complex system of changes to normal clotting responses, occurring early in the patients’ clinical course. It causes increased mortality, and for patients who survive the first hours following injury, ATC is a strong predictor of in-hospital morbidity such as organ failure or infection (Cole et al., 2013). Short scene to ED times, early haemorrhage control and considered use of blood and clotting products are essential interventions for the management of bleeding, potentially coagulopathic patients. Additionally, the antifibrinolytic drug Tranexamic acid (TXA) is reported to be beneficial in the management of bleeding and ATC (Cap et al., 2011). Many trauma systems have included TXA in major haemorrhage or ‘code red’ protocols as a result of recent evidence and European guidance (Spahn et al., 2013). This paper aims to describe ATC and discuss the use of TXA in its management. 2. Overview of acute traumatic coagulopathy

Gerinnungsmanagement bei Polytrauma mit Hilfe viskoelastischer Tests

Exsanguination represents the most common and potentially preventable cause of death in major trauma patients. Rapid surgical intervention coupled with an early and aggressive hemostatic therapy not only results in survival benefits of coagulopathic trauma patients, but also reduces the incidence of complications and costs. Standard coagulation tests are not suitable to adequately characterize the complexity of trauma-induced coagulopathy (TIC). This fact has led to a renaissance of viscoelastic tests, such as rotational thromboelastometry (ROTEM®) and thrombelastography (TEG®), which can be used as point-of-care monitors. In some trauma centers treatment algorithms have been developed, where hemostatic therapy is based on viscoelastic test results. Shock and tissue trauma activate profibrinolytic pathways which in turn result in premature dissolution of formed clots. Tranexamic acid rapidly and inexpensively blocks hyperfibrinolysis. ROTEM®/TEG® measurements revealed that diminished clot strength is associated with an increased bleeding tendency. Depending on the underlying cause, administration of fibrinogen concentrate and/or platelet concentrate administration improves clot firmness. Thrombin generation is initially less compromised and can be improved by the administration of plasma, prothrombin complex concentrate, or with restrictiveness by recombinant activated factorVII.

The off-label utilization of prothrombin complex concentrate with cryoprecipitate as an alternative to plasma transfusion in bleeding patients with acute right ventricular failure

To the Editor, The coagulopathic patient with right ventricular failure presents a conundrum to the perioperative clinician. Because these patients are preload dependent, hemorrhage may rapidly result in cardiogenic shock and end-organ ischemia. Acute coagulation factor replacement to correct factor deficiencies and reverse bleeding entails the transfusion of a large volume of plasma (10-15 mL kg), which will increase most coagulation factors by 20-30% so as to approach the 30-40% target levels considered adequate for hemostasis. In turn, however, such large transfusion volumes can potentially decrease left ventricular preload and cardiac output through ventricular interdependence. Furthermore, when the surgical setting is cardiothoracic, volume overload may promote catastrophic wound or graft dehiscence. When confronted with such complex coagulopathic patients, we have administered the combination of prothrombin complex concentrates (PCCs) with cryoprecipitate as a lower-volume alternative to plasma transfusion. The combination of 1,000 units of a four-factor prothrombin complex and 10 units of cryoprecipitate provides most coagulation factors in doses comparable with four units of plasma, but at less than 15% of the volume (Table). We acknowledge that neither Factor V nor Factor XI is present in significant quantities in either PCCs or cryoprecipitate but propose that these shortfalls are unlikely to be clinically meaningful. The platelet transfusions that many hemorrhaging patients require (particularly in the setting of the acquired thrombasthenia of cardiopulmonary bypass circuits) likely provide an alternative source of Factor V, as 20% of circulating Factor V is contained within platelet alpha granules. While Factor XI concentrates are available, they are not currently licensed in Canada and are therefore difficult to obtain. Furthermore, the significance of not replenishing Factor XI in a patient with global coagulopathy is unclear. In patients with congenital Factor XI deficiency, for example, there is a poor correlation between factor levels and bleeding tendency, possibly reflecting the ability of tissue-factor(TF)/Factor VII to activate Factor IX, Factor XI’s natural substrate. As one of the hemostatic mechanisms of Factor XI is the induction of thrombin activatable fibrinolysis inhibitor, the co-administration of antifibrinolytic medications, such as tranexamic acid (considered a standard of care in patients undergoing cardiopulmonary bypass surgery), may also provide some compensation for relative Factor XI deficiency in hemorrhaging patients. Given the above, with the long circulating half-life of Factor XI at 50 hr and its thrombogenicity when plasma levels exceed 70%, we do not endorse specific replacement in this setting. Our anecdotal experience regarding the hemostatic efficacy of PCCs when combined with cryoprecipitate suggests that the combination may be a useful alternative to plasma in patients with global coagulopathy who are unable to tolerate plasma transfusions, particularly if they are already being managed concurrently with platelet transfusions and A. Alam, MD (&) C. Cserti-Gazdewich, MD J. Pendergrast, MD Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada e-mail: asim.alam@sunnybrook.ca