Administration Of Antifibrinolytics Research Articles

Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs). Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented. Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

Revolutionizing trauma care: advancing coagulation management and damage control anesthesia.

Despite advances in emergency transfer systems and trauma medicine, the incidence of preventable deaths due to massive hemorrhage remains high. Recent immunological research has elucidated key mechanisms underlying trauma-induced coagulopathy in the early stages of trauma, including sympathoadrenal stimulation, shedding of the glycocalyx, and endotheliopathy. Consequently, the condition progresses to fibrinogen depletion, hyperfibrinolysis, and platelet dysfunction. Coexisting factors such as uncorrected acidosis, hypothermia, excessive crystalloid administration, and a history of anticoagulant use exacerbate coagulopathy. This study introduces damage-control anesthetic management based on recent insights into damage-control resuscitation, emphasizing the importance of rapid transport, timely bleeding control, early administration of antifibrinolytics and fibrinogen concentrates, and maintenance of calcium levels and body temperature. Additionally, this study discusses brain-protective strategies for trauma patients with brain injuries and the utilization of cartridge-based viscoelastic assays for goal-directed coagulation management in trauma settings. This comprehensive approach may provide potential insights for anesthetic management in the fast-paced field of trauma medicine.

Anesthetic Management of a Jehovah's Witness Patient for Coronary Artery Bypass Grafting With Antiphospholipid Antibody Syndrome and Renal Transplant.

Anesthesia for cardiac surgical patients with antiphospholipid antibody syndrome (APLS) presents challenges with monitoring anticoagulation during cardiopulmonary bypass. Additionally, this condition is associated with other autoimmune diseases and comorbidities that need to be considered in caring for these patients, and there is minimal evidence for specific strategies during cardiac surgery. Separately, Jehovah's Witness (JW) patients typically do not consent to receiving blood products, presenting an additional challenge for resuscitation during cardiac surgery and especially in the context of APLS. We present our approach to the anesthetic management of a JW patient with systemic lupus erythematosus (SLE) complicated by APLS, thrombocytopenia, and renal failure with history of renal transplant who presented for coronary artery bypass surgery. Management strategies we recommend include administration of antifibrinolytics after heparinization to mitigate bleeding risk and interdisciplinary management with the perfusion, intensive care, surgical, and nephrology teams.

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V.

The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins and between fibrinolytic and antifibrinolytic ones. Coagulopathies are characterized by a mutation-induced alteration of the function of certain coagulation factors or by a disturbed balance between the mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement and nonreplacement treatments or in the administration of antifibrinolytic agents. Rebalancing products reestablish hemostasis by inhibiting natural anticoagulant pathways. These agents include monoclonal antibodies, such as concizumab and marstacimab, which target the tissue factor pathway inhibitor; interfering RNA therapies, such as fitusiran, which targets antithrombin III; and protease inhibitors, such as serpinPC, which targets active protein C. In cases of thrombophilia (deficiency of protein C, protein S, or factor V Leiden), treatment may consist in direct oral anticoagulants, replacement therapy (plasma or recombinant ADAMTS13) in cases of a congenital deficiency of ADAMTS13, or immunomodulators (prednisone) if the thrombophilia is autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) is used in the context of severe thrombophilia, regardless of the cause of the disorder. In cases of disseminated intravascular coagulation, the treatment of choice consists in administration of antifibrinolytics, all-trans-retinoic acid, and recombinant soluble human thrombomodulin.

Is Antifibrinolytic Therapy Effective for Preventing Hemorrhage in Patients with Hemophilia Undergoing Dental Extractions? A Systematic Review and Meta-Analysis

ObjectivesThis systematic review aims to analyze the systemic administration of antifibrinolytics (tranexamic acid and aminocaproic acid) to prevent postoperative bleeding in patients with hemophilia.MethodsThis systematic review was conducted adhering to PRISMA guidelines. Only randomized controlled trials that assessed human subjects of any age or gender with any severity of hemophilia undergoing dental extractions, and systemically administered antifibrinolytic therapy compared to placebo were included. Post-operative bleeding episodes and adverse events were presented. PubMed, Cochrane, Embase, CINAHL, Web of Science, and Scopus were searched through April 15, 2022. The risk ratio (RR) and odds ratio (OR) applying 95% confidence intervals (CI) were computed using RevMan 5.4.1 (Cochrane).ResultsTwo randomized, placebo-controlled trials pooling in a total of 59 patients were pooled in this analysis. Among patients administered antifibrinolytic therapy, 84% reduced risk of post-operative bleeding was reported (RR = 0.16, 95% CI = 0.05–0.47, P = 0.0009). The chances of post-operative bleeding were reduced by 95% among the antifibrotics group (OR = 0.05, 95% CI = 0.01–0.22, P < 0.0001).ConclusionThis review finds favorable outcomes for the routine use of antifibrinolytic therapy for dental extractions in hemophiliacs. Further trials are required to rationalize existing evidence.

To Tranexamic Acid or Not to Tranexamic Acid? Accuracy of Antifibrinolytic Administration at Altitude

ObjectiveTranexamic acid (TXA) has demonstrated a reduction in all-cause mortality in trauma patients with hemorrhage. Administering TXA in the prehospital setting presents unique challenges because the identification of bleeding is based on clinical suspicion without advanced imaging or diagnostic tools. The objective of this study was to examine whether prehospital suspicion of bleeding is validated by in-hospital computed tomographic imaging and examination and to determine if patients received TXA in the absence of hemorrhage. The study was conducted at a level 1 trauma center supported by air medical transport services. MethodsThis is a retrospective cohort study examining 88 trauma patients receiving prehospital TXA to treat suspected hemorrhage. Adult trauma patients who received TXA during the study period and were transported to our level 1 trauma center were included. A panel of trauma surgeons reviewed CT imaging and examination findings to retrospectively identify significant hemorrhage. ResultsForty-three percent of patients who received TXA during air medical transport did not have confirmed hemorrhage upon arrival. ConclusionTXA was given to a significant number of patients who did not have confirmed hemorrhage upon arrival. We recommend that institutions using TXA perform this internal validation to ensure they are accurately identifying hemorrhage in the prehospital setting.

Viscoelastic Testing in Traumatic Brain Injury: Key Research Insights.

The role of viscoelastic testing in the evaluation and management of traumatic brain injury (TBI) remains a subject of ongoing exploration. This review highlights four key publications that provide significant insights into this subject. Holcomb etal. provided early evidence of the relationship between thromboelastography (TEG) and conventional coagulation tests (CCTs). Later, Samuels etal. used TEG to identify a unique coagulopathy phenotype in TBI characterized by a notable absence of fibrinolytic abnormalities. Dixon etal. built upon these findings by exploring the application of TEG in the context of antifibrinolytic administration, noting a similar lack of effect on LY30. Finally, Guillotte etal. demonstrated the utility of TEG-PM in assessing platelet dysfunction in TBI. While these studies provide key early support for the utility of viscoelastic testing in the TBI, further exploration is needed to define evidence-based guidelines for clinical application.

Platelet Dysfunction and Persistent Fibrinolysis in Pediatric Scoliosis Surgery Patients Receiving Tranexamic Acid

High blood loss requiring transfusion is a common complication in pediatric scoliosis surgery. Bleeding in patients undergoing spinal surgery is exacerbated by the development of coagulopathy in response to extensive activation of the acute phase response (APR). Coagulopathy is characterized by consumption of coagulation factors, inflammation, and hyperfibrinolysis. Although the administration of antifibrinolytics (e.g. tranexamic acid, TXA) has significantly reduced transfusions, patients still experience high rates of blood loss, suggesting either that TXA dosing needs optimization or that plasmin-independent aspects of coagulopathy could be driving bleeding. Major orthopedic surgeries are characterized by a reduction in platelet counts indicating the coagulopathic conditions of surgery exert a tropism on the circulating platelet population. Indeed, platelet dysfunction concomitant with trauma-induced coagulopathy has been extensively described in literature. Platelet dysfunction during adult orthopedic surgery has been observed but has not been correlated with bleeding, and platelet function in pediatric spine surgery has yet to be assessed. To determine if pediatric patients also experience platelet dysfunction, we measured platelet activation by whole blood flow cytometry during the course of scoliosis surgery in 8 pediatric patients. In parallel, circulating markers of the APR (i.e. IL-6, IL-10, IL-8), products of fibrinolysis (D-dimer), and indicators of consumptive coagulopathy (Protein C) were measured by multiplex ELISA. Samples were collected preoperatively (Preop), intraoperatively (every 2 hours, Intraop 1 and Intraop 2), immediately after closure (Postop) and the following morning (POD1). Samples were stimulated with submaximal concentrations of thrombin, convulxin (GPVI agonist, collagen receptor), and ADP. Platelet integrin activation was measured by PAC1 binding (GPIIbIIIa activation) and platelet secretion was measured by CD62p binding (P-selectin surface expression). We observed a progressive and statistically significant reduction in the platelet response (GPIIbIIIa activation and P-selectin expression) to both thrombin and convulxin stimulation during the procedure but with distinct temporal patterns. The reduction in response to thrombin became significant at Postop, remaining down even at POD1 (PAC1 max reduction, Postop 1: 32.5%, p=0.0403; P-selectin max reduction, POD1: 33.9%, p=0.016). The reduction in response to convulxin, on the other hand developed almost immediately after the initiation of surgery, starting with Intraop1 and resolving by Postop (PAC1 max reduction, Intraop 1: 25.1%, p=0.0087; P-selectin max reduction, Intraop 1: 18.3%, p=0.0369). Intra-operative responses to thrombin (both PAC1 and CD62p binding) significantly correlated with estimates of blood loss based on red blood cell mass (Estimated Red Blood Cell Mass, ERCM def) and hemoglobin mass (Hg mass loss) (see Table I below). Although we observed a consistent and statistically significant reduction in platelet number it correlated with blood loss at POD1 only, suggesting platelet function is a better predictor of blood loss than platelet count. Despite all patients receiving a bolus of TXA with continuous low dose infusion, multiplex results indicated a progressive increase in circulating D-dimer, becoming statistically significant at Postop and persisting through POD 1. Elevations in D-dimer, the byproduct of plasmin degradation of fibrin, suggest elusive fibrinolysis despite administration of TXA. Significant intraoperative elevations in IL-6, IL-10, and IL-8 and consumption of Protein C were also noted that persisted through POD1, indicating the development of coagulopathy. In conclusion, pediatric scoliosis surgery is characterized by persistent fibrinolysis platelet dysfunction, activation of the APR, and coagulopathy despite administration of the anti-fibrinolytic TXA. Future studies will focus on altering the dose of TXA to determine if an optimal dosing can be achieved that effectively inhibits fibrinolysis and answer important questions about the dependence of the APR and platelet hypofunction on the persistent fibrinolysis seen in these patients. Figure Disclosures No relevant conflicts of interest to declare.

Thromboelastography in Evaluation of Hyperfibrinolysis: A Single Center Review

Background Hyperfibrinolysis is a pathologic state of fibrin(ogen) degradation which can be observed in disseminated intravascular cogulation (DIC), post-partum hemorrhage, trauma, or liver transplant settings. Hyperfibrinolysis is associated with bleeding, transfusion, and adverse patient outcomes (Pommerening et al. J Am Coll Surg 2014. 219: 1157). Rapid administration of antifibrinolytics has been demonstrated to significantly improve mortality (Ker et al. Cochrane Database of Systematic Reviews 2015, Issue 5). Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic testing methods which allow rapid assessment of many aspects of hemostasis including hyperfibrinolysis. TEG/ROTEM have largely replaced euglobulin clot lysis as laboratory methods of diagnosing hyperfibrinolysis. However, the sensitivity and specificity of TEG/ROTEM abnormalities for diagnosis of hyperfibrinolysis is not well-described. Methods TEG 5000 (CK alone, CK/CKH, or CK/CRT/CFF packages) were ordered by clinicians based on clinical need. TEG 6S (Global Hemostasis cartridge) is also performed at our institution but is not included due to lack of lysis data in the FDA-approved reportable parameters. All TEG testing performed over a 17.75 month span (March 2018 to October 2019) was reviewed for hyperfibrinolysis, defined as LY30 &amp;gt;5% based on locally validated reference range. Patient demography, other lab data, management including blood product use and antifibrinolytics, and survival were reviewed. Results 19532 test traces across 9952 sample accessions were performed from 2076 unique patients. Of these, 84 traces (0.85%) across 72 accessions (0.72%) from 56 patients (2.70%) exhibited LY30 &amp;gt;5%. Of TEG runs that showed abnormal lysis that were run with multiple reagents, 7.6% showed elevated lysis in 2+ traces, while 92.4% showed elevated lysis in just one trace. The most common clinical contexts for elevated LY30 were ECMO use (N=18), post-partum hemorrhage (N=15), and trauma (N=12). Four trauma patients demonstrated a distinct "black diamond" trace pattern with high LY30 and return of curve to baseline, all of whom died during admission. Patients on ECMO demonstrated a trace which scalloped after achievement of maximal amplitude ("secondary hyperfibrinolysis") and may not represent true fibrinolysis. Admission survival was decreased in patients with LY30 &amp;gt;10% (41.2%) as compared to LY30 5-10% (18.4%); this was not significant by Fisher's exact test (Table One). All deaths following within 36 hours of testing showed LY30 &amp;gt;10%. Positive predictive value of LY30&amp;gt;10% for admission mortality (relative to LY30 5-10%) was 41%, negative predictive was 82%. Survival was decreased in patients with LY &amp;gt;5% in multiple traces (40%) as compared to patients with LY &amp;gt;5% in only one trace (21.4%) (Table Two); this was also not significant by Fisher's exact test. Positive predictive value of multiple traces with LY30&amp;gt;5% for admission mortality (relative to single trace) was 60%, negative predictive value was 82%. Patients with LY30 &amp;gt;10% (as compared to LY30 between 5-10%) were more likely to undergo subsequent massive transfusion (41.2% vs 23.7%) or receive cryoprecipitate (17.4% vs 7.7%). Antifibrinolytics were only administered in 3 postpartum hemorrhage patients. Discussion In this retrospective study, we cannot comment on the analytical sensitivity or specificity of TEG hyperfibrinolysis detection relative to a different methodology. However, we have used the outcomes of patients with LY30 abnormalities to estimate clinical predictive vaules. LY30 &amp;gt;5% is a nonspecific cutoff for diagnosis of hyperfibrinolysis. Absent a gold-standard method, we suggest a cutoff of LY30 &amp;gt;10% or LY30 abnormality in multiple TEG traces as a more specific indicator of clinically significant hyperfibrinolysis. Absence of such degrees of LY30 abnormality has an 82% NPV for death during admission. Figure 1 Disclosures Wool: STAGO: Honoraria.

Combined Cardiothoracic Surgery and Liver Transplantation Versus Isolated Liver Transplantation

Combined cardiothoracic surgery and liver transplantation (cCSLT) recently increasingly has been used. Despite that, liver transplant immediately after cardiothoracic surgery has not been well-characterized. The authors aimed to compare perioperative management and postoperative outcomes between patients undergoing cCSLT and isolated liver transplantation (iLT). A retrospective study. University tertiary medical center. Twenty-five cCSLT patients and 1091 iLT patients at a single institution from 2010 to 2017. Twenty-five cCSLT patients were compared with 100 randomly selected and 100 propensity-matched iLT patients. All cCSLT patients underwent comprehensive preoperative evaluation by a multidisciplinary team. Of 25 cardiothoracic surgeries, heart transplant (n = 9) was most common, followed by coronary artery bypass grafting (n = 5) and lung transplant (n = 3). Intraoperative management of cCSLT was provided by 2 separate teams, one for cardiothoracic surgery and one for liver transplantation. Patients undergoing cCSLT often required cardiopulmonary bypass, an intra-aortic balloon pump, extracorporeal membrane oxygenation, or cardiac pharmacologic therapies and, additionally, needed more interventions including antifibrinolytic administration, venovenous bypass, massive blood transfusion, and platelet transfusions compared with iLT patients. Ninety-day survival rates were similar in the cCSLT (100%) and iLT groups (random iLT 87% and matched iLT 93%, log-rank test p = 0.089). Despite having end-stage liver disease and advanced cardiothoracic disorders and experiencing a complex intraoperative course, cCSLT patients had comparable 90-day survival to iLT patients. Comprehensive planning before transplant, optimal patient/donor selection, the multiple-team model, and meticulous intraoperative management are critical to the success of cCSLT.

Association between perioperative surgical home implementation and transfusion patterns in adolescents with idiopathic scoliosis undergoing spinal fusion.

Blood transfusions in patients with adolescent idiopathic scoliosis after fusion have been associated with increased morbidity, mortality, and cost. The aim of this study was to evaluate the association between implementation of blood-conservation strategies within the perioperative surgical home on transfusion rates for patients with adolescent idiopathic scoliosis undergoing spinal fusion. Two hundred and thirteen patients (44 preperioperative surgical home, 169 postperioperative surgical home) who underwent posterior spine fusion for adolescent idiopathic scoliosis between 23 June 2014, and 30 July 2017, were enrolled in this case control study. The perioperative surgical home implemented in March 2015 involved evidence-based perioperative interventions to create a standardized clinical pathway including judicious use of crystalloid management, restrictive transfusion strategy, routine use of cell saver, and standardized administration of anti-fibrinolytics. The primary outcome was odds of perioperative transfusion. Secondary outcomes included volumes of crystalloid, albumin, cell saver, packed red blood cells as well as calculated blood loss. Other variables that were documented included antibrinolytic total dose, mean arterial pressure, temperature, laboratory values, intrathecal morphine dosing, and surgical time. Statistical methods included t test and logistic regression. For the postperioperative surgical home, the odds of perioperative transfusion were 0.30 (95% CI 0.13-0.70), as compared to preperioperative surgical home. In terms of secondary outcomes, calculated blood loss was significantly lower in the postperioperative surgical home patients (27.0mL/kg preperioperative surgical home vs 22.8mL/kg postperioperative surgical home; mean difference=-0.24 [-0.44, -0.04]). Although no difference was noted in the amount of intraoperative cell saver or albumin administered, a reduction was noted in mean intraoperative crystalloid given postperioperative surgical home (41.4mL/kg±20.4mL/kg preperioperative surgical home vs 28.0mL/kg±13.7mL/kg postperioperative surgical home; log mean difference=0.37 [95% CI 0.21-0.53], P<0.001). Postperioperative surgical home patients also had a significantly higher temperature nadir (mean difference=-0.47 [95% CI -0.70 to -0.23]; P<0.001), received a significantly higher total anti-fibrinolytic dose (mean difference=-3939 [95% CI -5364 to -2495]; P<0.001), and were exposed to shorter surgical times (mean difference=0.72 [95% CI 0.36-1.09]; P<0.001). Implementation of blood-conservation strategies as part of a perioperative surgical home for patients with adolescent idiopathic scoliosis undergoing posterior spine fusion resulted in significant decrease in perioperative blood transfusions.

Predictors of transfusion outcomes in pediatric complex cranial vault reconstruction: a multicentre observational study from the Pediatric Craniofacial Collaborative Group.

Pediatric patients undergoing complex cranial vault reconstruction (CCVR) are at risk of significant perioperative blood loss requiring blood product transfusion. Minimizing allogeneic blood product transfusion is an important goal because of the associated risks and cost. The impact of patient and surgical variables on transfusion is unknown in this population. Our primary aim was to examine relationships between demographic and perioperative variables and blood product transfusion outcomes in CCVR. The multicentre Pediatric Surgery Perioperative Registry was checked for children undergoing CCVR between June 2012 and September 2016. Univariable and multivariable analyses were performed examining patient, procedure, and blood conservation variables and their relationship to three outcomes: intraoperative red blood cell-containing product (RBC-CP) transfusion, total perioperative blood donor exposures, and transfusion-free hospitalization. The registry search returned data from 1,814 cases. Age and surgical duration were the only variables significantly associated with all three outcomes studied. Predictors of reduced RBC-CP transfusion included lower American Society of Anesthesiologists (ASA) physical status and antifibrinolytic administration. Total cranial vault reconstruction, intraoperative vasoactive infusion, and presence of a tracheostomy predicted increased donor exposures. Increased body weight, higher preoperative hematocrit, and utilization of intraoperative cell saver and transfusion protocols were associated with transfusion-free hospitalization. Clinical factors associated with increased allogeneic blood product transfusion in pediatric CCVR include: age ≤ 24 months, ASA status ≥ III, preoperative anemia, prolonged surgical duration, lack of intraoperative antifibrinolytic use, lack of intraoperative cell saver use, and the lack of transfusion protocols.

Acquired factor XIII deficiency: A review

Acquired factor XIII (FXIII) deficiency is a rare bleeding disorder that can manifest with spontaneous or delayed life-threatening hemorrhage. Causes of acquired deficiency include immune-mediated inhibition, as well as non-immune FXIII hyperconsumption or hyposynthesis. The occurrence of acquired FXIII deficiency can be idiopathic or may be associated with comorbidities, such as malignancies or autoimmune disorders. Recognition of acquired FXIII deficiency and its underlying cause is imperative, as treatment options vary depending on the etiology. Diagnosis requires quantitative FXIII testing in addition to supplemental inhibitor studies if the clinical situation suggests an immune-mediated pathophysiology. Treatment may involve FXIII replacement, antifibrinolytic administration, and/or inhibitor eradication. However, treatment targets and thresholds are undefined in acquired FXIII deficiency. This review will focus on the clinical characteristics, diagnostic issues and therapeutic options for both immune and non-immune acquired FXIII deficiency. Cases are described to illustrate the clinical features of acquired FXIII deficiency.

Current practices in perioperative blood management for patients undergoing liver resection: a survey of surgeons and anesthesiologists

Objective: The development of new techniques and blood management strategies in liver resection, and the multidisciplinary nature of perioperative transfusion decision-making, creates an opportunity for practice variation. The aim of this study was to describe the current practices in perioperative blood management, and explore differences between surgeons and anesthesiologists. Methods: A survey was circulated to Canadian liver surgeons and anesthesiologists. The survey focused on management of pre-operative anemia, blood conservation strategies, estimation of blood loss, and transfusion decision-making in a multidisciplinary setting. Results: 198 physicians received the survey, with 117 responding (59.1%). Most responding surgeons (66.7%) perform over 20 liver resections per year, while most responding anesthesiologists (90%) take part in less than 20. The most common blood conservation strategy used is administration of anti-fibrinolytics (63% used them at least occasionally). The most important factor for anesthesiologists when deciding on an intraoperative transfusion was hemoglobin value (47.2%), for surgeons, it was patient hemodynamics (33.4%). Compared to when they started their career, 60.5% of respondents felt they were less likely to transfuse a patient now. Almost 40% of respondents replied that they had no specific management for preoperative anemia, or that someone else managed it. Conclusion: The results of our survey provide insights into current transfusion practice and decision making in liver resection, including a comparison between anesthesiologist and surgeon transfusion behaviour. The findings reflect trends toward restrictive transfusion strategies, and promote the development of improved blood conservation techniques and clinical practice guidelines.

Safety of antifibrinolytics in cranial vault reconstructive surgery: a report from the pediatric craniofacial collaborative group.

Antifibrinolytic therapy significantly decreases blood loss and transfusion in pediatric cranial vault reconstructive surgery; however, concern regarding the side effects profile limits clinical use. The aim was to utilize the Pediatric Craniofacial Surgery Perioperative Registry database to identify the safety profile of antifibrinolytic therapy for cranial vault reconstructive surgery by reporting the incidence of adverse events as they relate to exposure to tranexamic acid and aminocaproic acid compared to no exposure to antifibrinolytics. The database was queried for cases of open cranial vault reconstructive surgery. Less invasive procedures such as neuro-endoscopic and spring-mediated cranioplasties were excluded. The outcomes evaluated included any perioperative neurological adverse event including seizures or seizure-like movements and thromboembolic events. Thirty-one institutions reported a total of 1638 cases from 2010 to 2015. Total antifibrinolytic administration accounted for 59.5% (tranexamic acid, 36.1% and aminocaproic acid, 23.4%), with 40.5% not receiving any antifibrinolytic. The overall incidence of postoperative seizures or seizure-like movements was 0.6%. No significant difference was detected in the incidence of postoperative seizures between patients receiving tranexamic acid and those receiving aminocaproic acid [the odds ratio for seizures being 0.34 (95% confidence interval: 0.07-1.85) controlling for American Society of Anesthesia (ASA) physical class] nor in patients receiving antifibrinolytics compared to those not administered antifibrinolytics (the odds ratio for seizures being 1.02 (confidence interval 0.29-3.63) controlling for ASA physical class). One complicated patient in the antifibrinolytic group with a femoral venous catheter had a postoperative deep venous thrombosis. This is the first report of an incidence of postoperative seizures of 0.6% in pediatric cranial vault reconstructive surgery. There was no significant difference in postoperative seizures or seizure-like events in those patients who received the tranexamic acid or aminocaproic acid vs those that did not. This report provides evidence of the safety profile of antifibrinolytic in children having noncardiac major surgery. Caution should prevail however in using antifibrinolytic in high-risk patients. Antifibrinolytic dosage regimes should be based on pharmacokinetic data avoiding high doses.

Outcomes in Patients With Hemophilia and von Willebrand Disease Undergoing Invasive or Surgical Procedures

Adults with hemophilia A (HA), hemophilia B (HB), and von Willebrand disease (VWD) frequently require surgery and invasive procedures. However, there is variability in perioperative management guidelines. We describe our periprocedural outcomes in this setting. A retrospective chart review from January 2006 to December 2012 of patients with HA, HB, and VWD undergoing surgery or invasive procedures was conducted. Type of procedures, management including the use of continuous factor infusion, and administration of antifibrinolytics were reviewed. Adverse outcomes were defined as acute bleeding (<48 hours), delayed bleeding (≥48 hours), transfusion, inhibitor development, and thrombosis. We identified 59 patients with HA and HB. In all, 24 patients had severe hemophilia and 12 had mild/moderate hemophilia. Twelve patients had inhibitors. There were also 5 female carriers of HA and 6 patients with VWD. There were 34 major surgeries (26 orthopedic, 8 nonorthopedic) and 129 minor surgeries. Continuous infusion was used in 55.9% of major surgeries versus 8.5% of minor surgeries. Antifibrinolytics were administered in 14.7% of major surgeries versus 23.2% of minor surgeries. In all, 4 patients developed acute bleeding and 10 patients developed delayed bleeding. Delayed bleeding occurred in 28.6% of genitourinary procedures and in 16.1% of dental procedures. Five patients acquired an inhibitor and 2 had thrombosis. In conclusion, patients with HA, HB, or VWD had similar rates of adverse outcomes when undergoing minor surgeries or major surgeries. This finding underscores the importance of an interdisciplinary management and procedure-specific guidelines for patients with hemophilia and VWD prior to even minor invasive procedures.

The effectiveness of tranexamic acid at reducing postoperative blood loss following cesarean section: a systematic review of quantitative evidence protocol

The effectiveness of tranexamic acid at reducing postoperative blood loss following cesarean section: a systematic review of quantitative evidence protocol

Time intervals from subarachnoid hemorrhage to rebleed.

The most threatening early complication and predictor of poor outcome after an aneurysmal subarachnoid hemorrhage (aSAH) is a rebleed. To evaluate what proportion of rebleeds might be prevented by early treatment, we assessed the time interval from the initial hemorrhage to rebleed, and the location of the patient at the time of rebleed. Patient characteristics, World Federation of Neurological Surgeons grade on admission and modified Rankin Scale outcome scores, referring hospitals and time intervals from initial hemorrhage to treatment of 293 patients treated between 2008 and 2011 were evaluated. Time intervals to rebleeds and location of the patients at the time of rebleed were retrieved. Rebleeds were confirmed by CT in 12% of patients, and an additional 4% of patients was diagnosed as having a possible rebleed. Sixty percent of rebleeds occurred after admission to the treatment center. Almost all rebleeds occurred within 24 h, with a median time interval between initial hemorrhage and rebleed of 180 min. A significantly shorter time to treatment and a higher mortality were seen in the group of patients with a rebleed. Approximately, one in six patients with an aSAH had a rebleed, of which a majority might have been preventable because they occurred after admission to the treatment center. A reduction in the rebleed rate seems feasible by securing the aneurysm as soon as possible by improving in-hospital logistics for early aneurysm treatment. Alternative options, such as immediate administration of antifibrinolytics, are being explored in a multicenter trial.

Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial

BackgroundA frequent complication in patients with subarachnoid hemorrhage (SAH) is recurrent bleeding from the aneurysm. The risk is highest within the first 6 hours after the initial hemorrhage. Securing the aneurysm within this timeframe is difficult owing to logistical delays. The rate of recurrent bleeding can also be reduced by ultra-early administration of antifibrinolytics, which probably improves functional outcome. The aim of this study is to investigate whether ultra-early and short-term administration of the antifibrinolytic agent tranexamic acid (TXA), as add-on to standard SAH management, leads to better functional outcome.Methods/DesignThis is a multicenter, prospective, randomized, open-label trial with blinded endpoint (PROBE) assessment. Adult patients with the diagnosis of non-traumatic SAH, as proven by computed tomography (CT) within 24 hours after the onset of headache, will be randomly assigned to the treatment group or the control group. Patients in the treatment group will receive standard treatment with the addition of a bolus of TXA (1 g intravenously) immediately after randomization, followed by continuous infusion of 1 g per 8 hours until the start of aneurysm treatment, or a maximum of 24 hours after the start of medication. Patients in the control group will receive standard treatment without TXA. The primary outcome measure is favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin Scale (mRS), at 6 months after SAH. Primary outcome will be determined by a trial nurse blinded for treatment allocation. We aim to include 950 patients in 3 years.DiscussionThe strengths of this study are: 1. the ultra-early and short-term administration of TXA, resulting in a lower dose as compared to previous studies, which should reduce the risk for delayed cerebral ischemia (DCI), an important risk factor in the long-term treatment with antifibrinolytics; 2. the power calculation is based on functional outcome and calculated with use of recent study results of our own population, supported by data from prominent studies; and 3. the participation of several specialized SAH centers, and their referring hospitals, in the Netherlands with comparative treatment protocols.Trial registrationNederlands Trial Register (Dutch Trial Registry) number NTR3272

Haemostatic resuscitation

Recommendations for resuscitation of patients in early haemorrhagic shock, with active ongoing bleeding, have evolved in recent years. This review covers current theories of the pathophysiology of shock and recommended treatments, including damage control surgery, deliberate hypotensive management, administration of antifibrinolytics, early support of the coagulation system, and the possible role of deep anaesthesia. Future directions for resuscitation research are discussed.