Blood Product Transfusion Requirements Research Articles

Association Between Cannabis Use and Complications Related to Crohn's Disease: A Retrospective Cohort Study.

Crohn's disease is an idiopathic inflammatory process that is occasionally associated with complications, which cause significant morbidity and mortality. The anti-inflammatory effect of cannabis in intestinal inflammation has been shown in several experimental models; it is unknown whether this correlates with fewer complications in Crohn's disease patients. To compare the prevalence of Crohn's disease-related complications among cannabis users and non-users in patients admitted with a primary diagnosis of Crohn's disease or a primary diagnosis of Crohn's related complication and a secondary diagnosis of Crohn's disease between 2012 and 2014. We used data from the Healthcare Cost and Utilization Project-National Inpatient Sample. Cannabis users (615) were compared directly after propensity score match to non-users, in aspects of various complications and clinical end-points. Among matched cohorts, Cannabis users were less likely to have the following: active fistulizing disease and intra-abdominal abscess (11.5% vs. 15.9%; aOR 0.68 [0.49 to 0.94], p = 0.025), blood product transfusion (5.0% vs. 8.0%; aOR 0.48 [0.30 to 0.79], p = 0.037), colectomy (3.7% vs. 7.5%; aOR 0.48 [0.29-0.80], p = 0.004), and parenteral nutrition requirement (3.4% vs. 6.7%, aOR 0.39 [0.23 to 0.68], p = 0.009). Cannabis use may mitigate several of the well-described complications of Crohn's disease among hospital inpatients. These effects could possibly be through the effect of cannabis in the endocannabinoid system.

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.

Effect of Autotransfusion Using Intraoperative Predonated Autologous Blood on Coagulopathy during Thoracic Aortic Surgery: A Randomized Controlled Trial.

Background: Intraoperative predonated autologous blood transfusion is thought to replenish platelets and coagulation factors and ameliorate coagulopathy. This study aimed to evaluate whether intraoperative predonated autotransfusion improves coagulopathy during thoracic aortic surgery.Methods: Patients who underwent thoracic aortic surgery were randomized into two groups as follows: those who received intraoperative predonated blood (group A: n = 31) and those who did not receive (group N: n = 22). In group A, autologous blood was retransfused immediately after cessation of cardiopulmonary bypass (c-CPB).Results: The mean intraoperative allogenic blood or blood product transfusion requirements were significantly lesser in group A than in group N (packed red blood cells [RBCs]: 6.3 ± 5.1 vs. 9.1 ± 4.3 units, p = 0.04; fresh frozen plasma [FFP]: 3.0 ± 4.1 vs. 6.1 ± 5.7 units, p = 0.03). After c-CPB, hemoglobin (Hb) level, platelet count, and coagulopathy became significantly worse than those at the start of surgery in both the groups. However, the values significantly improved 30 min after c-CPB only in group A. Renal function was significantly worse in group N.Conclusions: Intraoperative predonated autotransfusion significantly improved coagulopathy, with reduced allogeneic blood transfusion volume during thoracic aortic surgery. Furthermore, reduction of allogeneic blood transfusion may reduce the adverse effects on renal function.

Heparin dose calculated according to lean body weight during on-pump heart surgery.

The aim of this study is to compare heparin dose regimen calculated based on the lean body weight with traditional heparin regimen in terms of ensuring adequate anticoagulation and complications associated with perioperative bleeding. This prospective, single-blind, randomized study included a total of 100 adult patients (42 males, 58 females; mean age 52.7 years; range, 22 to 84 years) undergoing elective valve surgery with cardiopulmonary bypass between June 2016 and January 2017. Prior to cardiopulmonary bypass, heparin dose was adjusted as 4 mg/kg, according to the actual body weight (n=50) and lean body weight (n=50). The minimal activated clotting time target value was accepted as 480 sec for cardiopulmonary bypass initiation. Demographic and hemodynamic data, post-heparin activated clotting time, additional heparin and perioperative transfusion, postoperative drainage volumes, reoperations, and mortality were recorded. Demographic data, cross-clamp and cardiopulmonary bypass times, and intraoperative transfusion requirement were not significantly different between the groups. The initial and total doses of heparin, as well as the total dose of protamine, were significantly higher in the actual body weight group. Postoperative transfusion rates were also higher in this group. None of the patients in the lean body weight group required reoperation, while three patients in the actual body weight group underwent reoperation. Our study results showed that adequate anticoagulation was achieved with the titration of heparin dose calculated according to the lean body weight during cardiopulmonary bypass and reduced total heparin and protamine doses decreased postoperative bleeding and blood product transfusion requirement.

Use of antifibrinolytics in pediatric cardiac surgery: Where are we now?

Fibrinolytic activation is a major and preventable source of bleeding in neonates and children undergoing cardiac surgery with cardiopulmonary bypass. Based on the existing literature (adult and pediatric; cardiac and noncardiac), prophylactic administration of antifibrinolytic agents can help reduce fibrinolytic activation, and consequently reduces perioperative bleeding and the requirement for blood product transfusion. Due to the increased risk of renal failure and mortality reported in adults undergoing cardiac surgery, aprotinin should not be considered as a safe option in neonates and children. Further well-designed studies would be required before the prophylactic administration of aprotinin could be considered in pediatric cardiac surgery. The lysine analogs, tranexamic acid and ϵ-aminocaproic acid,, should be considered as safe and effective antifibrinolytic agents. Although no major side effects have been reported following the administration of lysine analogs in children undergoing cardiac surgery, high-dose tranexamic acid should not be recommended in order to avoid the increased risk of clinical seizures. Despite the recent advances made in our understanding of the pharmacokinetics of tranexamic acid and ϵ-aminocaproic acid,, the optimal plasmatic concentration to be targeted remains unknown. Further studies are therefore urgently needed to better define the optimal dose regimen to be used in neonates and children. In the meantime, the dose regimen published in the most recent pharmacokinetic studies can be used. Although no studies have assessed the effect of massive bleeding and transfusion on the plasmatic concentrations of the lysine analogs, additional boluses might be considered in the presence of bleeding and/or when signs of fibrinolytic activations are observed on viscoelastic hemostatic assays.

Effect of Tranexamic Acid on Blood Loss, D-Dimer, and Fibrinogen Kinetics in Adult Spinal Deformity Surgery.

Antifibrinolytics such as tranexamic acid reduce operative blood loss and blood product transfusion requirements in patients undergoing surgical correction of scoliosis. The factors involved in the unrelenting coagulopathy seen in scoliosis surgery are not well understood. One potential contributor is activation of the fibrinolytic system during a surgical procedure, likely related to clot dissolution and consumption of fibrinogen. The addition of tranexamic acid during a surgical procedure may mitigate the coagulopathy by impeding the derangement in D-dimer and fibrinogen kinetics. We retrospectively studied consecutive patients who had undergone surgical correction of adult spinal deformity between January 2010 and July 2016 at our institution. Intraoperative hemostatic data, surgical time, estimated blood loss, and transfusion records were analyzed for patients before and after the addition of tranexamic acid to our protocol. Each patient who received tranexamic acid and met inclusion criteria was cohort-matched with a patient who underwent a surgical procedure without tranexamic acid administration. There were 17 patients in the tranexamic acid cohort, with a mean age of 60.7 years, and 17 patients in the control cohort, with a mean age of 60.9 years. Estimated blood loss (932 ± 539 mL compared with 1,800 ± 1,029 mL; p = 0.005) and packed red blood-cell transfusions (1.5 ± 1.6 units compared with 4.0 ± 2.1 units; p = 0.001) were significantly lower in the tranexamic acid cohort. In all single-stage surgical procedures that met inclusion criteria, the rise of D-dimer was attenuated from 8.3 ± 5.0 μg/mL in the control cohort to 3.3 ± 3.2 μg/mL for the tranexamic acid cohort (p < 0.001). The consumption of fibrinogen was 98.4 ± 42.6 mg/dL in the control cohort but was reduced in the tranexamic acid cohort to 60.6 ± 35.1 mg/dL (p = 0.004). In patients undergoing spinal surgery, intravenous administration of tranexamic acid is effective at reducing intraoperative blood loss. Monitoring of D-dimer and fibrinogen during spinal surgery suggests that tranexamic acid impedes the fibrinolytic pathway by decreasing consumption of fibrinogen and clot dissolution as evidenced by the reduced formation of D-dimer. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Blood Transfusions in Dogs and Cats Receiving Hemodialysis: 230 Cases (June 1997-September 2012).

BackgroundMultiple factors exist that contribute to anemia in dogs and cats receiving hemodialysis, can necessitate transfusion.ObjectivesTo describe blood product usage in dogs and cats with acute and chronic kidney disease that were treated with intermittent hemodialysis to determine risk factors associated with the requirement for blood product transfusion.Animals83 cats and 147 dogs undergoing renal replacement therapy at the Animal Medical Center for acute or chronic kidney disease.MethodsRetrospective medical record review of all dogs and cats receiving renal replacement therapy for kidney disease, from June 1997 through September 2012.ResultsBlood products (whole blood, packed RBCs, or stromal‐free hemoglobin) were administered to 87% of cats and 32% of dogs. The number of dialysis treatments was associated with the requirement for transfusion in cats (adjusted OR 2.21, 95% CI 1.13, 4.32), but not in dogs (adjusted OR 0.98, 95% CI 0.95, 1.03). Administration of a blood product was associated with a higher likelihood of death in dogs (OR 3.198, 95% CI 1.352, 7.565; P = .0098), but not in cats (OR 1.527, 95% CI 0.5404, 4.317, P = .2).Conclusions and Clinical ImportanceVeterinary hospitals with a hemodialysis unit should have reliable and rapid access to safe blood products in order to meet the needs of dogs and cats receiving dialysis.

Impact of Postoperative Hypothermia on Outcomes in Coronary Artery Bypass Surgery Patients

To determine the impact of postoperative hypothermia on outcomes in coronary artery bypass graft surgery (CABG) patients. A retrospective study was performed on patients who underwent isolated CABG between 2011 and 2014. Single-center study at a university hospital. All patients who underwent isolated CABG with cardiopulmonary bypass between 2011 and 2014. Patients underwent isolated CABG on cardiopulmonary bypass. Patients were propensity-score matched based on the likelihood of being hypothermic (<36ºC) or normothermic (≥36ºC) on arrival to the cardiac surgery intensive care unit (ICU) from the operating room. Total transfusion requirements, composite in-hospital morbidity and/or mortality endpoint, total hours in the ICU, and length of hospital stay were compared between the 2 groups. Of the 1,030 patients undergoing isolated CABG, 529 (51.3%) were hypothermic on arrival to the ICU. The hypothermic cohort were older, had more females, had lower body mass indices, had lower starting hematocrit values, were cooled to lower temperatures while on cardiopulmonary bypass, and had longer cardiopulmonary bypass runs compared with the normothermic group. Of the 748 patients who were propensity matched, there were no differences in blood and blood product transfusion requirements, mortality and complication rates, time on the ventilator, length of ICU stay, and length of hospital stay between hypothermic and normothermic patients. Hypothermia at ICU admission after CABG was not associated with increased adverse outcomes, possibly suggesting that complete rewarming before separation from cardiopulmonary bypass may not be essential in all patients.

Dengue fever may mislead the surgeons when it presents as an acute abdomen.

To review the management experience of a consecutive series of patients presenting as acute surgical abdomen whom were ultimately diagnosed to have DF (Dengue fever)/DHF (Dengue hemorrhagic fever). Clinical data of all cases of apparent acute abdomen (AA) which were later confirmed as having DF/DHF reviewed by two surgical units from December 2012 to December 2013 were analyzed. Initially confirmed patients with DF/DHF who developed abdominal symptoms were not considered. Out of the seventeen cases (7 males, age range 10-71 years) presented with fever and AA; appendicitis, cholecystitis, pancreatitis and non-specific peritonitis were suspected initially in 8, 5, 1 and 3 cases, respectively. Neutropenia or thrombocytopenia signifying DF/DHF occurred only in 11 patients at first evaluation thus six remained as surgical candidates beyond 24h. One patient underwent appendicectomy with a prolonged hospital stay. DF was confirmed by serology in all patients, latest by fourth day of admission. One required blood product transfusion, 4 needed critical care treatment and there was 1 death. DF/DHF misleads the clinicians when it presents as AA. Initial hematological and ultrasonographic findings may be equivocal creating a diagnostic and management dilemma. Vigilant clinical suspicion and early dengue serological assessment is advisable in equivocal cases of AAs with fever in dengue endemic areas, to confirm/exclude the infection in order to avoid unnecessary surgical morbidity in the presence of DF.

The use of angiography in pediatric blunt abdominal trauma patients.

Angiography is a common treatment used in adults with blunt abdominal trauma and/or severe pelvic fractures. The Committee on Trauma of the American College of Surgeons has recently advocated for this resource to be urgently available at pediatric trauma centers; however, its usefulness in the pediatric setting is unclear. The purpose of this study was to determine the incidence of angiography in the treatment of blunt abdominal trauma among injured children. An analysis was performed using an established public use data set of children (younger than 18 years) treated at 20 participating trauma centers for blunt torso trauma through the Pediatric Emergency Care Applied Research Network. Patients who underwent angiography of the abdomen or pelvis were identified and analyzed. Of the 12,044 children evaluated for blunt abdominal trauma included within the data set, 973 sustained abdominopelvic injuries. Of these, only 26 (3%) underwent angiography. The median age was 14 years, 65% were males, with a mortality rate of 19%. Overall, 29 angiographic procedures were performed: 21 abdominal, 8 pelvic, with 3 patients undergoing both abdominal and pelvic. Eleven patients underwent embolization of a bleeding vessel, all of which were related to the spleen. No hepatic, renal, or pelvic vessels required embolization. The median time to angiography from emergency department evaluation was 7.3 hours. In addition to angiography, 50% also required surgical intervention, of which 31% underwent a laparotomy. Thirty-five percent of these patients required blood product transfusion, and 42% were admitted to the intensive care unit. The emergent use of angiography with embolization is uncommon in pediatric patients with blunt abdominal injuries. The requirement that pediatric trauma centers have access to interventional radiology within 30 minutes may be unnecessary. Epidemiologic study, level III; therapeutic study, level IV.

Comparison of supramesenteric aortic cross-clamping with supraceliac aortic cross-clamping for aortic reconstruction

Supraceliac aortic cross-clamping (SCXC) is routinely used during open aortic reconstruction (OAR) of pararenal aortic disease when suprarenal control is not feasible. On occasion, however, aortic control may be obtained at the supramesenteric level by supramesenteric cross-clamping (SMXC) between the superior mesenteric artery and the celiac axis. The purpose of this study was to compare outcomes between patients who had SMXC vs SCXC during OAR for both aneurysmal and occlusive diseases. A retrospective chart review identified 69 patients who underwent elective OAR requiring SMXC (n= 18) or SCXC (n= 51). All patients with thoracoabdominal aneurysms and those who had inframesenteric (suprarenal and infrarenal) aortic control were excluded. Propensity score-based matching was performed to adjust for confounding factors in a 1:1 ratio to compare outcomes. Late survival was estimated by Kaplan-Meier methods. Propensity score-based matching was performed at a 1:1 ratio; 18 SMXC cases were matched with 18 SCXC cases. The average age was 66.7years, and men constituted 72%. Baseline characteristics were matched, except for the incidence of peripheral vascular occlusive disease (72.2% in the SMXC group vs 33.3% in the SCXC group; P= .04). A majority (80.6%) of patients underwent OAR for aneurysmal disease (72.2% in the SMXC group, 88.9% in the SCXC group). Intraoperatively, there were no differences in operative times (325minutes for SMXC vs 298minutes for SCXC; P=.48), but the SMXC group had a longer renal ischemia time (40minutes vs 28minutes; P= .03). There were no significant differences in intraoperative blood loss (2.4L vs 1.6L; P= .2) or blood product transfusion requirements (packed red blood cells, 2.2 units vs 1.6 units [P= .5]; Cell Saver, 1.3L vs 0.7L [P= .09]). Overall complication rates did not differ significantly (27.8% for SMXC vs 44.4% for SCXC; P= .24). Thirty-day mortality rates did not differ between the two groups (0% for SMXC vs 5.6% for SCXC; P= 1). In this study, there were no differences in early morbidity or mortality between SMXC and SCXC during aortic reconstruction. SMXC, however, can be performed safely and effectively in properly selected patients. A larger, multicenter prospective study would help elucidate the potential benefits.

Use of tranexamic acid in craniosynostosis surgery

Background Intraoperative tranexamic acid (TXA) administration has been used to abate blood loss in a variety of surgical procedures. Several recent studies have supported its efficacy in reducing transfusion requirements in pediatric cranial vault reconstruction (CVR). Objective To conduct a retrospective chart review to determine whether a significant reduction in packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions exists when TXA is used. Methods A retrospective cohort study of 28 patients who underwent CVR for sagittal craniosynostosis was performed. Transfusion requirements for 14 patients who did not receive TXA were compared with 14 patients who did. Predictors of increased blood product transfusion were also studied. Results Total volume of PRBC transfusion was reduced by 50% with the use of TXA (P=0.004) with a 34% reduction in intraoperative PRBC transfusion (P=0.017) and a 67% reduction in postoperative PRBC transfusion (P&lt;0.001). Total volume of FFP transfusion was reduced by 46% (P=0.002) and postoperative FFP transfusion was reduced by 100% (P=0.001). The use of TXA was associated with a lower total volume of PRBC (P=0.003) and FFP (P=0.003) transfusions. Older patient age was associated with lower total volume of PRBC transfused (P=0.046 and P=0.002), but not with FFP (P=0.183 and P=0.099) transfusion volumes. Increasing patient weight was associated with lower PRBC (P=0.010 and P=0.020) and FFP (P=0.045 and P=0.016) transfusion volumes. Conclusion TXA decreased blood product transfusion requirements in patients undergoing CVR for sagittal craniosynostosis, and should be a routine part of the strategy to reduce blood loss in these procedures.

The effectiveness of a 'Code Red' transfusion request policy initiated by pre-hospital physicians.

Major trauma is a leading cause of mortality and serious morbidity. Recent approaches to life-threatening traumatic haemorrhage have emphasized the importance of early blood product transfusion. We have implemented a pre-hospital transfusion request policy where a pre-hospital physician can request the presence of a major transfusion pack on arrival at the destination trauma centre. This study was performed to establish whether three simple criteria (1) suspicion or evidence of active haemorrhage (2) systolic BP<90 mmHg (3) failure of blood pressure to respond to an intravenous fluid bolus) which were used to activate a pre-hospital 'Code Red' transfusion request accurately identified seriously injured patients who required transfusion on arrival at hospital. Prospective evaluation of all pre-hospital 'Code Red' requests over a 30-month period (August 2008-May 2011) was performed for patients transported to a major trauma centre. Mechanism of injury, Injury Severity Score, hospital mortality, and use of blood products were recorded. Patients were followed up to hospital discharge. 176 'Code Red' activations were made in the study period. 129 patients were transported to the Trauma Centre. Mechanism of injury was penetrating trauma in 39 (30%) cases, road traffic collision in 58 (45%), falls in 18 (14%) and 'other' in 14 (10.8%). Complete data was available for 126 patients. Of the patients reaching hospital, 20 died in the emergency department or operating theatre, 22 died following admission and 84 survived to hospital discharge. Mean Injury Severity Score (ISS) was 29.1. (range 0-66). Overall, 115 (91%) of the patients declared 'Code Red' pre-hospital received blood product transfusion after arrival in hospital. Eleven patients did not receive any blood products following hospital admission. In patients declared 'Code Red' pre-hospital, mean packed red blood cell transfusion in the first 24-h was 10.4 unit (95% CI 8.4-12.3 unit). The use of simple pre-hospital criteria allowed physicians to successfully identify trauma patients with severe injury and a requirement for blood product transfusion. This allowed blood products to be ready on the patient's arrival in a major trauma centre with the potential for earlier transfusion.

Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries

BackgroundSevere injury often results in substantial bleeding and mortality. Injury provokes cellular activation and release of extracellular vesicles. Circulating microvesicles (MVs) are predominantly platelet-derived and highly procoagulant. They support hemostasis and vascular function. The roles of MVs in survival after severe injury are largely unknown. We hypothesized that altered MV phenotypes would be associated with transfusion requirements and poor outcomes.MethodsThis single-centre study was approved by the Institutional Review Board. The study cohort consisted of patients with major trauma requiring blood product transfusion and 26 healthy controls. Plasma samples for MVs were collected upon admission to the emergency department (n=169) and post-resuscitation (n=42), and analysed by flow cytometry for MV counts and cellular origin: platelet (PMV), erythrocyte (RMV), leukocyte (LMV), endothelial (EMV), tissue factor (TFMV), and annexin V (AVMV). Twenty-four hour mortality is the outcome measurement used to classify survivors versus non-survivors. Data were compared over time and analysed with demographic and clinical data.ResultsThe median age was 34 (IQR 23, 51), 72% were male, Injury Severity Score was 29 (IQR 19, 36), and 24 h mortality was 13%. MV levels and phenotypes differed between patients and controls. Elevated admission EMVs were found both in survivors (409/µL) and non-survivors (393/µL) compared to controls (23/µL, p<0.001) and persisted over time. Admission levels of PMV, AVMV, RMV, and TFMV were significantly lower in patients who died compared to survivors, but were not independently associated with the 24 h mortality rate. Patients with low MV levels at admission received the most blood products within the first 24 h. AVMV and PMV levels either increased over time or stabilized in survivors but decreased in non-survivors, resulting in significantly lower levels at intensive care unit admission in non-survivors (1,048 vs. 1,880 AVMV/µL, p<0.00004 and 1,245 PMP/µL vs. 1,866 PMP/µL, p=0.003).ConclusionSevere injury results in endothelial activation and altered MV phenotypes. Significant differences in specific MV phenotypes or changes over time were associated with blood product requirements and the 24 h mortality rate.

Use of tranexamic acid in craniosynostosis surgery.

Intraoperative tranexamic acid (TXA) administration has been used to abate blood loss in a variety of surgical procedures. Several recent studies have supported its efficacy in reducing transfusion requirements in pediatric cranial vault reconstruction (CVR). To conduct a retrospective chart review to determine whether a significant reduction in packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions exists when TXA is used. A retrospective cohort study of 28 patients who underwent CVR for sagittal craniosynostosis was performed. Transfusion requirements for 14 patients who did not receive TXA were compared with 14 patients who did. Predictors of increased blood product transfusion were also studied. Total volume of PRBC transfusion was reduced by 50% with the use of TXA (P=0.004) with a 34% reduction in intraoperative PRBC transfusion (P=0.017) and a 67% reduction in postoperative PRBC transfusion (P<0.001). Total volume of FFP transfusion was reduced by 46% (P=0.002) and postoperative FFP transfusion was reduced by 100% (P=0.001). The use of TXA was associated with a lower total volume of PRBC (P=0.003) and FFP (P=0.003) transfusions. Older patient age was associated with lower total volume of PRBC transfused (P=0.046 and P=0.002), but not with FFP (P=0.183 and P=0.099) transfusion volumes. Increasing patient weight was associated with lower PRBC (P=0.010 and P=0.020) and FFP (P=0.045 and P=0.016) transfusion volumes. TXA decreased blood product transfusion requirements in patients undergoing CVR for sagittal craniosynostosis, and should be a routine part of the strategy to reduce blood loss in these procedures.

Ventricular assist devices and increased blood product utilization for cardiac transplantation.

The purpose of this study was to examine whether blood product utilization, one-year cell-mediated rejection rates, and mid-term survival significantly differ for ventricular assist device (VAD patients compared to non-VAD (NVAD) patients following cardiac transplantation. From July 2004 to August 2011, 79 patients underwent cardiac transplantation at a single institution. Following exclusion of patients bridged to transplantation with VADs other than the HeartMate II® LVAD (n = 10), patients were stratified by VAD presence at transplantation: VAD patients (n = 35, age: 54.0 [48.0-59.0] years) vs. NVAD patients (n = 34, age: 52.5 [42.8-59.3] years). The primary outcomes of interest were blood product transfusion requirements, one-year cell-mediated rejection rates, and mid-term survival post-transplantation. Preoperative patient characteristics were similar for VAD and NVAD patients. NVAD patients presented with higher median preoperative creatinine levels compared to VAD patients (1.3 [1.1-1.6] vs. 1.1 [0.9-1.4], p = 0.004). VAD patients accrued higher intraoperative transfusion of all blood products (all p ≤ 0.001) compared to NVAD patients. The incidence of clinically significant cell-mediated rejection within the first posttransplant year was higher in VAD compared to NVAD patients (66.7% vs. 33.3%, p = 0.02). During a median follow-up period of 3.2 (2.0, 6.3) years, VAD patients demonstrated an increased postoperative mortality that did not reach statistical significance (20.0% vs. 8.8%, p = 0.20). During the initial era as a bridge to transplantation, the HeartMate II® LVAD significantly increased blood product utilization and one-year cell-mediated rejection rates for cardiac transplantation. Further study is warranted to optimize anticoagulation strategies and to define causal relationships between these factors for the current era of cardiac transplantation.

Contact Activation Inhibition and Platelet Rich Plasma Are Required in Order to Differentiate Bleeders from Non-Bleeders in FXI Deficiency Using the Thrombin Generation Assay

Introduction: FXI deficiency is characterised by a variable bleeding tendency. No clear correlation exists between bleeding and either FXI:C level or genotype. Some patients with major FXI deficiency (FXI:C <15 IU/dL) do not exhibit excessive bleeding, even after surgery or trauma, while others with partial deficiency (FXI:C 20-60 IU/dL) report significant haemorrhagic symptoms. The variation in bleeding tendency is observed between individuals with the same FXI:C level and also between individuals within families who share the same F11gene mutation. The thrombin generation (TG) assay quantifies the overall haemostatic potential of an individual through the measurement of thrombin production. While reduced TG has been observed in some FXI deficient individuals, there are conflicting reports about the ability of the TG assay to distinguish between patients with a history of bleeding (bleeders) and those without (non- bleeders).Aims: To identify the optimal TG assay conditions which discriminate between normal controls and individuals with different levels of FXI deficiency. To investigate which conditions allow the TG assay to differentiate between bleeders and non-bleeders.Methods: 97 adults with FXI deficiency were studied together with 50 controls. Bleeding histories were taken from each individual and citrated blood samples, both with addition of corn trypsin inhibitor (+ CTI) and without (- CTI). Platelet rich (PRP) and platelet poor plasmas (PPP) were prepared. TG was performed using the CAT method with tissue factor (TF) concentrations of 5pM, 1pM and 0.5pM in the following samples: PPP + CTI, PPP - CTI, PRP + CTI, PRP - CTI. TG results were compared between controls and 3 patient groups: partial FXI deficiency (FXI:C 20-60 IU/dL) (n=78), major low level FXI deficiency (FXI:C 3-15 IU/dL) (n=10) and major very low level FXI deficiency (FXI:C ≤2IU/dL) (n=9) using unpaired t-test or Mann Whitney U tests.A subgroup of 74 patients was divided into bleeders and non-bleeders based solely on their experience of tonsillectomy and /or dental extraction prior to diagnosis of FXI deficiency. Those with excessive bleeding (requiring blood product transfusion or return to theatre/dentist for re-suturing or packing) were classified as bleeders (n=24) and those without, as non-bleeders (n=50). The optimal TG assay conditions to differentiate between bleeders and non-bleeders groups were identified with Receiver Operator Curves (ROC) using Area Under Curve (AUC) values.Results: TG performed in PPP with CTI was unable to differentiate between controls and all of the 3 patient groups. In all other sample types the best discrimination between controls and FXI deficient patients was seen at low TF (0.5pM) with a sequential reduction in peak height and ETP measurements observed as FXI:C levels decreased across the 3 patient groups (see Figure 1).When TG results were compared between the bleeder (n=24) and non-bleeder (n=50) groups, peak height and ETP measured in PRP with CTI were best able to differentiate between the two groups (peak height ROC AUC = 0.9362, P<0.0001) (ETP ROC AUC=0.9362, P<0.0001). PPP samples and those without CTI were unable to segregate bleeders from non-bleeders as effectively.Conclusions: In the presence of contact activation inhibition, FXI:C levels have minimal impact on thrombin generation in PPP but do influence thrombin generation in the presence of platelets. TG measured at low TF in PPP and PRP samples without CTI (with in vitro contact activation of FXI possible) was able to differentiate between controls and individuals with different levels of FXI deficiency but not between bleeders and non-bleeders.TG performed at low TF in PRP with CTI samples demonstrated the greatest differentiation between bleeders and non-bleeders in FXI deficiency providing further support for the clinical importance of platelet interaction with FXI in this disorder and suggesting that these test conditions may best mimic those in vivo.Acknowledgments: This work is supported by a Fellowship Project Award (Bayer Hemophilia Awards Program), an unrestricted grant (LFB Biotechnologies) and a Wycherley Fellowship grant. [Display omitted] [Display omitted] [Display omitted] DisclosuresPike:Bayer: Honoraria, Research Funding; LFB Biotechnologies: Honoraria, Research Funding. Bolton-Maggs:Bio-Products Laboratory (U.K.): Consultancy; LFB Biotechnologies: Consultancy.

Outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass for lung transplantation

The study objective was to compare the outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung transplantation. We performed a retrospective cohort study from a prospective database of adult lung transplantations performed at the University of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases of extracorporeal membrane oxygenation (2012-2013) and 228 cases of cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal life support, underwent a concomitant cardiac procedure, received a combined liver or hearttransplant, were colonized with Burkholderia cenocepacia, or required emergency cannulation for cardiopulmonary support were excluded. Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases of cardiopulmonary bypass according to age (±10 years), lung transplantation indication, and procedure type (bilateral vs single lung transplantation). Recipient factors such as body mass index and gender were not different between extracorporeal membrane oxygenation and cardiopulmonary bypass groups. Furthermore, donor variables were similar, including age, body mass index, last PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain death and donation after cardiac death). Early outcomes, such as mechanical ventilation requirement, length of intensive care unit stay, and length of hospital stay, significantly favored extracorporeal membrane oxygenation (median 3 vs 7.5 days, P=.005; 5 vs 9.5 days, P=.026; 19 vs 27 days, P=.029, respectively). Perioperative blood product transfusion requirement was lower in the extracorporeal membrane oxygenation group. The 90-day mortality for the extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary bypass (P=.32). Extracorporeal membrane oxygenation may be considered as the first choice of intraoperative cardiorespiratory support for lung transplantation.

Prediction of Intraoperative Transfusion Requirements During Orthotopic Liver Transplantation and the Influence on Postoperative Patient Survival

Predicting blood product transfusion requirements during orthotopic liver transplantation (OLT) remains difficult. Our primary aim in this study was to determine which patient variables best predict recipient risk for large blood transfusion requirements during OLT. The secondary aim was to determine whether the amount of blood products transfused during OLT impacted patient survival. Eight hundred four primary adult OLTs performed during a 9-year period were retrospectively analyzed, and predictive models were developed for blood product usage, usage >20 and usage >30 units of red blood cells (RBCs) plus cell salvage (CS). For survival analysis, potential predictors included all blood products administered during OLT. For analyses of RBC + CS usage, we used several statistical techniques: regression analysis, logistic regression, and classification and regression tree analysis. Several preoperative factors were highly statistically significant predictors of intraoperative blood product usage in each of the analyses, namely lower platelet count and higher Model for End-Stage Liver Disease Score or one or more of its components (creatinine, total bilirubin, international normalized ratio). Despite these highly significant associations, the models were unable to predict reliably that patients might require the largest amount of blood products during OLT. For example, the classification and regression tree analyses were able to predict only 32% and 11% of patients requiring >20 and >30 units of RBC + CS, respectively. Survival analysis demonstrated poorer survival among patients receiving larger amounts of RBC + CS during OLT. Prediction of intraoperative blood product requirements based on preoperatively available variables is unreliable; however, there is a strong measurable association between transfusion and postoperative mortality.

Nilotinib Combined With Multi-Agent Chemotherapy For Adult Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Final Results Of Prospective Multicenter Phase 2 Study

We previously reported the interim analysis on the clinical outcome of nilotinib (Tasigna®, Novartis Pharma, Basel, Switzerland), when combined with multi-agent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) in adults. Herein, we reported the final results of the multicenter prospective phase2 trial of Adult Acute Lymphoblastic Leukemia Working Party, the Korean Society of Hematology. Newly diagnosed Ph+ALL patients aged 18 years old or more were eligible when they had adequate organ function. Diagnosis of Ph+ALL was performed via confirmation of the presence of Ph chromosome by conventional GTL-band technique, and/or positive molecular analysis with nested RT PCR for detection of BCR-ABL fusion transcripts. Written informed consent was obtained from all subjects. All patients received induction treatment consisting of vincristine, daunorubicin, oral or parenteral prednisolone, and nilotinib. After achieving complete remission (CR), subjects received either 5 courses of consolidation followed by 2-year maintenance with nilotinib, or allogeneic hematopoietic cell transplantation (alloHCT) depending on the donor availability, his/her tolerability, and patient's wish. Nilotinib was administered twice a day with a single dose of 400mg (800mg per day) from day8 of induction until the initiation of conditioning for alloHCT or the end of maintenance therapy. Minimal residual disease (MRD) monitoring was performed at the central lab with quantitative RT-PCR assays for peripheral blood BCR-ABL RNA using LightCycler® Technology in serial; at the time of diagnosis, at hematologic CR(HCR), and every 3 months thereafter. BCR-ABL quantification was expressed relative to the amount of glucose-6-phosphate dehydrogenase (G6PDH) mRNA. The molecular response was defined as complete (MCR, MRD-negative) if the BCR-ABL/G6PDH ratio was less than 1x10-6. Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (version 2.0). Subjects had been followed up for 2 years after alloHCT or during maintenance therapy. Data were frozen up in June, 2013. A total of 91 subjects (male: female = 45: 46) were enrolled onto the study between January 2009 and May 2012. The median age was 47 (range 18-71) years old. Type of BCR breakpoint was minor (e1a2) in 71% of patients. The median BCR-ABL/G6PDH ratio was 6.09 (bone marrow) and 3.28 (peripheral blood) at diagnosis. During induction, all subjects required blood product transfusion, and incidence of nonhematologic adverse events (AE) over grade 3 was 17% (jaundice), 18% (ALT elevation), 13% (lipase elevation), and 2% (pancreatitis). Neither QTc prolongation over 500ms nor significant arrhythmia happened among any subject and any cycle. HCR rate was 90% and median time to HCR was 27 days (range, 13-72); most of failure was due to death in aplasia (n=8). MCR rate at HCR was 55%, Cumulative MCR rate was 84%, and median time to MCR was 1.1 months (range, 0.6-15.8). Most common cause of dropout from study was treatment-related death (n=22; during induction/consolidation vs. after alloHCT = 12 vs. 10), and HREL (n=15). Nilotinib was interrupted 75 times among 64 subjects, reduced 14 times among 12 subjects, and discontinued permanently due to hematologic relapse (HREL, n=14), AE (n=6, over gr3:3), and other cause (n=2). Fifty nine patients underwent alloHCT, 34 with myeloablative and 25 with reduced-intensity conditioning. Incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were 41% and 29%, respectively. With a median follow-up of 20.7 months of surviving subjects, estimated hematologic relapse-free survival (RFS), and overall survival (OS) rate at 2 years were 74% and 70%, respectively. Among subject achieving MCR, 2-year molecular RFS rate was 56%. When events were defined as ‘dropout due to AE, isolated molecular / extramedullary relapse, HREL, and death from any cause', median event-free survival was 12.5 months. In this prospective study, nilotinib was shown to be effective for adult Ph+ALL, and concurrent administration of nilotinib with cytotoxic drug was well-tolerable, although death in aplasia during induction was the most common cause of failure of achieving HCR. In terms of MRD, potential of nilotinib to achieve and maintain MRD negativity were satisfactory (Clinicaltrials.gov NCT00844298). Disclosures:Off Label Use: Nilotinib for Ph+ALL-sientific and academic purpose.