Red Blood Cell Requirements Research Articles

Outcomes of endovascular management of acute thoracic aortic emergencies in an academic level 1 trauma center

BackgroundThoracic aortic emergencies account for 10% of thoracic-related admissions in the United States and remain associated with high morbidity and mortality rates. Open repair has declined owing to the emergence of thoracic endovascular aortic repair (TEVAR), but data on emergency TEVAR use for acute aortic pathology remain limited. We therefore reviewed our experience. MethodsWe retrospectively evaluated emergency descending thoracic aortic endovascular interventions performed at a single academic level 1 trauma center between January 2005 and August 2013 including all cases of traumatic aortic injury, ruptured descending thoracic aneurysm, penetrating atherosclerotic ulcer, aortoenteric fistula, and acute complicated type B dissection. Demographics, clinical data, and outcomes were extracted. Stepwise logistic regression was used to identify independent risk factors for death. ResultsDuring the study period, 51 patients underwent TEVAR; 22 cases (43.1%) were performed emergently (11 patients [50.0%] traumatic aortic injury; 4 [18.2%] ruptured descending thoracic aneurysm; 4 [18.2%] complicated type B dissection; 2 [9.1%] penetrating aortic ulcer; and 1 [4.5%] aortoenteric fistula). Overall, 72.7% (n = 16) were male with a mean age of 54.8 ± 15.9 years. Nineteen patients (86.4%) required only a single TEVAR procedure, whereas 2 (9.1%) required additional endovascular therapy, and 1 (4.5%) open thoracotomy. Four traumatic aortic injury patients required exploratory laparotomy for concomitant intra-abdominal injuries. During a mean hospital length of stay of 18.9 days (range, 1 to 76 days), 3 patients (13.6%) developed major complications. In-hospital mortality was 27.2%, consisting of 6 deaths from traumatic brain injury (1); exsanguination in the operating room before repair could be achieved (2); bowel ischemia (1) and multisystem organ failure (1); and family withdrawal of care (1). A stepwise logistic regression model identified 24-hour packed red blood cell requirements ≥4 units, admission mean arterial pressure <60 mm Hg, and 24-hour fresh frozen plasma to packed red blood cell (pRBC) ratio <1:1.5 as independent risk factors for death in this cohort. During a mean follow-up of 369 days (range, 35 to 957 days), no subsequent major complications or deaths occurred. All patients underwent serial computed tomographic angiography surveillance, and no device-related problems were identified during intermediate follow-up. ConclusionsThoracic aortic emergencies remain challenging. Our experience in a moderate-volume center supports the utilization of TEVAR in the acute setting. Twenty-four-hour pRBC requirements ≥4 units, admission mean arterial pressure <60 mm Hg, and 24 hour fresh frozen plasma to pRBC ratio <1:1.5 were independently associated with death.

Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. To assess the effectiveness and safety of late initiation of erythropoietin (EPO) between eight and 28 days after birth, in reducing the use of red blood cell (RBC) transfusions in preterm and/or low birth weight infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL in July 2013. Additional searches included the Pediatric Academic Societies Annual Meetings from 2000 to 2013 (Abstracts2View™) and clinical trials registries (www.clinicaltrials.gov; www.controlled-trials.com; and who.int/ictrp/en). For this update we moved one study from the early EPO review to this late EPO review. Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at ≥ eight days of age) versus placebo or no intervention in preterm (< 37 weeks) and/or low birth weight (< 2500 g) neonates. We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We include 30 studies (31 comparisons) randomising 1591 preterm infants. Literature searches in 2013 did not identify any new study for inclusion. For this update we moved one study enrolling 230 infants from the early EPO review to this late EPO review.Most included trials were of small sample size. The meta-analysis showed a significant effect of the use of one or more RBC transfusions (20 studies (n = 1142); typical risk ratio (RR) 0.71, 95% confidence interval (CI) 0.64 to 0.79; typical risk difference (RD) -0.17, 95% CI -0.22 to -0.12; typical number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 5 to 8). There was moderate heterogeneity for this outcome (RR I² = 68%; RD I² = 60%). We obtained similar results in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. There was no significant reduction in the total volume (mL/kg) of blood transfused per infant [typical mean difference (MD) -1.6 mL/kg, 95% CI -5.8 to 2.6); 5 studies, 197 infants]. There was high heterogeneity for this outcome (I² = 92%). There was a significant reduction in the number of transfusions per infant (11 studies enrolling 817 infants; typical MD -0.22, 95% CI -0.38 to -0.06). There was high heterogeneity for this outcome (I² = 94%).Three studies including 404 infants reported on retinopathy of prematurity (ROP) (all stages or stage not reported), with a typical RR 1.27 (95% CI 0.99 to 1.64) and a typical RD of 0.09 (95% CI -0.00 to 0.18). There was high heterogeneity for this outcome for both RR (I² = 83%) and RD (I² = 82%). Three trials enrolling 442 infants reported on ROP (stage ≥ 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was minimal heterogeneity for this outcome for RR (I² = 18%) but high heterogeneity for RD (I² = 79%). There were no significant differences in other clinical outcomes. There was no reduction in necrotizing enterocolitis in spite of a reduction in the use of RBC transfusions. Long-term neurodevelopmental outcomes were not reported. Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (ml/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment to prevent donor exposure is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure.

Safety of endoscopic interventions in patients with thrombocytopenia

The risk of endoscopic interventions in thrombocytopenia has received little attention in the medical literature. The aim of this study was to assess the safety of endoscopic interventions including evaluation of GI bleeding (GIB) in patients with thrombocytopenia. Retrospective study, tertiary oncology center. Review of consecutive endoscopies with preprocedure platelet counts (PCs) of 75× 10(3)/μL or lower. Risk of bleeding with routine endoscopic interventions and transfusion requirement after evaluation of GIB. A total of 617 (351 upper, 266 lower [90 colonoscopies]) endoscopies were performed in 395 patients. Forceps-biopsy specimens were obtained in 398 endoscopies (mean ± standard deviation [SD] PC: 38.21 ± 11.7× 10(3)/μL) and 45 polypectomies were performed in 17 endoscopies (mean ± SD PC: 39.65 ± 8.53× 10(3)/μL). The risk of bleeding was 1.5% (6 of 398 endoscopies) at the biopsy site and 4% (2 of 45 polypectomies) at the polypectomy site. Active GIB (mean ± SD PC: 32.85 ± 4.0× 10(3)/μL) was observed in 68 (11% of 617) endoscopies and intervention (mean ± SD PC: 33.68 ± 4.6× 10(3)/μL) was performed in 41 procedures. Together, angiodysplasias and ulcers were the most common etiology (51.2% of 41). Hemostasis was achieved in 39 (95.1% of 41) procedures. Comparison of blood transfusions ± 3 days of successful therapy showed a 52% reduction (P< .001). By multivariate analysis, a higher aggregate blood transfusion 3 days preceding endoscopy (odds ratio 1.32; 95% confidence interval, 1.16-1.50; P< .001) predicted endoscopic findings of active GIB. Retrospective design, single center. In the largest endoscopic experience reported in thrombocytopenic patients (Common Terminology Criteria for Adverse Events grade 3 or lower), bleeding caused by standard forceps biopsy and polypectomy (≤10mm) was minor and easily controlled. Endoscopic therapy for GIB is safe and significantly reduces the packed red blood cell requirement and should be considered in patients with thrombocytopenia in the setting of an appropriate transfusion strategy.

Safety of endoscopic interventions in patients with thrombocytopenia

Background The risk of endoscopic interventions in thrombocytopenia has received little attention in the medical literature. Objective The aim of this study was to assess the safety of endoscopic interventions including evaluation of GI bleeding (GIB) in patients with thrombocytopenia. Design and Setting Retrospective study, tertiary oncology center. Patients and Intervention Review of consecutive endoscopies with preprocedure platelet counts (PCs) of 75 × 10 3 /μL or lower. Main Outcome Measurements Risk of bleeding with routine endoscopic interventions and transfusion requirement after evaluation of GIB. Results A total of 617 (351 upper, 266 lower [90 colonoscopies]) endoscopies were performed in 395 patients. Forceps-biopsy specimens were obtained in 398 endoscopies (mean ± standard deviation [SD] PC: 38.21 ± 11.7 × 10 3 /μL) and 45 polypectomies were performed in 17 endoscopies (mean ± SD PC: 39.65 ± 8.53 × 10 3 /μL). The risk of bleeding was 1.5% (6 of 398 endoscopies) at the biopsy site and 4% (2 of 45 polypectomies) at the polypectomy site. Active GIB (mean ± SD PC: 32.85 ± 4.0 × 10 3 /μL) was observed in 68 (11% of 617) endoscopies and intervention (mean ± SD PC: 33.68 ± 4.6 × 10 3 /μL) was performed in 41 procedures. Together, angiodysplasias and ulcers were the most common etiology (51.2% of 41). Hemostasis was achieved in 39 (95.1% of 41) procedures. Comparison of blood transfusions ± 3 days of successful therapy showed a 52% reduction ( P P Limitations Retrospective design, single center. Conclusions In the largest endoscopic experience reported in thrombocytopenic patients (Common Terminology Criteria for Adverse Events grade 3 or lower), bleeding caused by standard forceps biopsy and polypectomy (≤10 mm) was minor and easily controlled. Endoscopic therapy for GIB is safe and significantly reduces the packed red blood cell requirement and should be considered in patients with thrombocytopenia in the setting of an appropriate transfusion strategy.

Iron Chelation Therapy Could Rapidly Reduce Oxidative DNA Damage In CD34+ Hematopoietic Cells Before Decrease Of Serum Ferritin Level

IntroductionMyelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species (ROS) especially hydroxyl radical that cause oxidative DNA damage including formation of mutagenic 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA double strand breaks. However, it is unclear whether iron-mediated oxidative stress affects the pathophysiology of MDS. MethodsThis study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000 ng/mL or they required more than 20 RBC transfusions (or 100 mL/kg of RBC). We analyzed hemoglobin, SF level and chromosomal abnormality and 8-OHdG levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox administration. ResultsWe showed that reactive oxygen species (ROS) in hematopoietic cells was higher in MDS patients with high SF level. Furthermore, the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and the 8-OHdG levels were positively correlated with SF (p=0.003, r=0.495) and chromosomal abnormalities (p=0.019). Importantly, the 8-OHdG levels in PBMC and CD34+ cells of MDS patients dramatically decreased 3 month after deferasirox administration (the 8-OHdG levels in PBMC, 3.374±78, p<0.05) although SF level were not reduced within 3 month (Figure). However, SF level decreased to 500-600 ng/mL after 36 months of iron chelation therapy, 8-OHdG is a sensitive marker of cellular iron chelation therapy by deferasirox which readily passes through the plasma membrane. When patients were divided into the no Iron chelation group (n=10) and high Iron chelation group (n=13), the survival time was significantly longer in the latter group than the former group (P=0.046) although International prognostic scoring system (IPSS) was not significantly difference between both groups. Further, 50% of patients without iron chelation group developed into leukemia, while no patients did progress into leukemia during 36 month. [Display omitted] ConclusionThese results indicated that cellular excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients. Disclosures:No relevant conflicts of interest to declare.

Parenteral Glutamine Supplementation Has No Effect on Chemotherapy-induced Toxicity in Children With Non-Hodgkin Lymphoma

Protecting patients from the acute and/or chronic toxicity of antineoplastic therapy has become a major concern of oncology centers around the world. Glutamine has been used as a multisystemic protective agent to minimize the side effects arising from the treatment of childhood cancers. In this study, the effect of intravenous glutamine supplementation was investigated in children receiving chemotherapy for non-Hodgkin lymphoma. Twelve children, of 48 to 120 months of age, and who had non-Hodgkin lymphoma were enrolled in the study. Thirty chemotherapy courses were given in combination with glutamine, and 31 chemotherapy courses were given without glutamine. Glutamine was given intravenously for 7 days, at a dose of 0.4 g/kg/d. Patients were evaluated in each course with regard to gastrointestinal, mucosal, and hematological toxicities. There were no significant differences in the hematological parameters between the 2 groups. The requirements for red blood cells and platelets during the chemotherapy courses were similar in both groups (P=0.64 and 0.40, respectively). Patients supplemented with glutamine developed mucositis in 21 of 30 courses (70%) and patients without glutamine supplements developed mucositis in 23 of 31 courses (74%). The mean duration of mucositis and the mean mucositis score in each course were similar between the 2 groups. In addition, gastrointestinal system and hepatic toxicity did not differ between groups. The mean duration of febrile neutropenia and the length of hospitalization were also similar in both groups (P=0.09 and 0.13, respectively). Parenteral glutamine supplementation has no effect on mucositis, fever and febrile neutropenia, length of hospitalization, red blood cell, and platelet requirements, and hematological, gastrointestinal, and hepatic toxicities in children receiving severe chemotherapy.

Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin

A population pharmacokinetics/pharmacodynamic (PK/PD) model was developed to describe changes in erythropoiesis as a function of plasma erythropoietin (EPO) concentration over the first 30 days of life in preterm infants who developed severe anemia requiring red blood cell (RBC) transfusion. Several covariates were tested as possible factors influencing the responsiveness to EPO. Discarded blood samples in 27 ventilated preterm infants born at 24-29 wk of gestation were used to construct plasma EPO, hemoglobin (Hb), and RBC concentration-time profiles. The amount of Hb removed for laboratory testing and that transfused throughout the study period were recorded. A population PK/PD model accounting for the dynamic Hb changes experienced by these infants was simultaneously fitted to plasma EPO, Hb, and RBC concentrations. A covariate analysis suggested that the erythropoietic efficacy of EPO is increased for preterm infants at later gestational ages. The PD analysis showed a sevenfold difference in maximum Hb production rate dependent on gestational age and indicated that preterm infants, when stimulated by EPO, have the capacity to produce additional Hb that may result in a decrease in RBC transfusions. The present model has utility in clinical trial simulations investigating the treatment potential of erythropoietic stimulating agents in the treatment of anemia of prematurity.

Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury

To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured. Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality. A Role 3 Combat Surgical Hospital in southern Afghanistan. A total of 1332 patients were identified from prospectively collected U.K. and U.S. trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). In-hospital mortality. Injury severity scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs. neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21). Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock.

Intraoperative cell salvage is associated with reduced postoperative blood loss and transfusion requirements in cardiac surgery: a cohort study

This study investigated whether implementation of cell salvage of shed mediastinal and residual blood in all patients undergoing low-to-moderate-risk cardiac surgery reduces the need for allogeneic red blood cell (RBC) transfusion compared to patients not subjected to cell salvage. This retrospective cohort study included patients undergoing low-to-moderate-risk cardiac surgery with cardiopulmonary bypass without (control; n = 531) or with cell salvage (n = 433; Autolog, Medtronic). Study endpoints, including 24-hour blood loss and RBC requirements, were evaluated using adjusted logistic regression. Baseline characteristics were similar between groups. The cell saver group received 568 ± 267 mL of autologous blood. Median number of allogeneic RBC transfusions was higher in the control group (2 [1-5]) compared with the cell salvage group (1 [0-3]; p < 0.001). There were no clinically relevant differences in postoperative coagulation test results between groups. The relative risk (RR) for postoperative RBC transfusion was reduced to 0.76 (95% confidence interval [CI], 0.70-0.83; p < 0.0001) in the cell salvage group. Moreover, patients in the cell salvage group had a lower chance for myocardial infarction (RR, 0.26; 95% CI, 0.08-0.91; p = 0.035), whereas the cell salvage group was associated with a higher probability for intensive care discharge within 24 hours after surgery (RR, 1.08; 95% CI, 1.02-1.14; p = 0.009). The use of cell salvage throughout the entire procedure reduces postoperative blood loss and allogeneic RBC transfusion. These findings advocate implementation of cell salvage in all patients undergoing on-pump cardiac surgery, irrespective of anticipated surgery-related blood loss.

Incidence of Hepatic Artery Variations in Liver Transplantation: Does It Really Influence Short- and Long-Term Results?

BackgroundSome variations of hepatic artery, which show 30% incidence, must be taken into account to avoid damage to the liver transplant during harvesting, we analyzed the incidence of variations and their influence on postoperative results. Patients and methodsWe performed a retrospective study of 325 liver transplantation between 2001 and December 2011. ResultsVariations in the hepatic artery were detected in 91 transplantations (32%) including 29 donors (8.9%), 57 recipients (17.5%), and 5 both (1.5%). The main variation among donors was a right hepatic artery originating from the mesenteric artery (38.2%), and a left hepatic artery from the left gastric artery (35.3%). Recipients showed the same distribution: RHA-UMA (right hepatic artery from upper mesenteric artery) (38.7%) and LHA-LGA (left hepatic artery from left gastric artery) (12.9%). 48.5% of donor hepatic variations did not need bench reconstruction, but all RHA-UMA required it mainly due to the donor gastroduodenal artery (7; 58%) We did not observe significant difference in cold or warm ischemia time, surgical time, red blood cell requirement, postoperative mortality, or overall survival when there was or was not an arterial anomaly. But arterial complications were more frequent in cases where there were recipient anomalies or both versus without anomalies or with donor anomalies (20%, 7,8%, 0%, 5,6%; P = .06). Donor RHA-UMA was associated with worse overall survival (69, 2%; P = .07) and longer cold ischemia time and red blood requirement. Bench reconstruction held to longer cold ischemia time and blood cell requirements (P = .01) and shorter overall survival (82.4%). RHA-UMA was associated (P = .08) with worse actuarial survival and a needed for bench reconstruction (P = .01). ConclusionOne must be careful during liver harvest to detect hepatic artery variations to avoid damage. Hepatic artery anomalies do not influence liver transplant results except for the presence of an RHA from the UMA with a need for bench reconstruction.

Analysis of Liver Transplant without Blood Transfusion in Adult Patients

Introduction: Liver transplantation (LT) is closely associated with blood transfusion practices since the first transplants. Requirement of blood has been reduced by advance and refinements in patient selection, transfusion methods, and surgical technique. LT without any blood product became real clinical practice in patient with stable preoperative condition. The aim of this study was to analyze the pre-operative, intra-operative, post-operative factors associated with LT without intraoperative red blood cell (RBC) transfusion. Methods: Four hundreds forty four adult patients were selected from our database due to the less than 5 units of RBC transfusion. Out of 444, 51 patients were selected as study group due to no RBC transfusion and 389 patients were selected as control group due to the 1-5 units of RBC transfusion during LT surgery. Coagulations were monitored intraoperatively and corrected if clinically indicated. Aprotinin was not used. Auto transfusion of blood salvaged was used routinely following our protocol. Independent factors were analyzed to find a link with no RBC transfusion. Survival curve was generated by Kaplan Meier methods and compared with log rank test. Results: Factors of study group vs. control group were as follows: MELD score was 20 vs. 20. Calculated MELD score was 12 vs. 12. Cold ischemic time was 429 vs. 425 min. Warm ischemic time was 37.0 vs. 37.1 min. Donor age was 41 vs. 39 yrs. Use of piggyback technique (PB) was 94% (n=48) vs. 92% (n=363). Use of Conventional cava reconstruction was 6% (n=3) vs. 8% (n=30). There were no statistically significant differences in demographic factors including donor age, recipient age, primary liver diagnosis, MELD score, CIT, WIT, INR, Cr, bilirubin, and amounts of auto-transfusion, cava reconstruction methods between the groups. Amount of fresh frozen plasma is significantly less in study group (P< 0.05). One, 3, 5 years' patient and graft survival were 92%, 88% 79% and 92%, 88%, 79% in study group and 89%, 82%, 76% and 84%, 78%, 71% in control group respectively. There was no statistical difference in patient and graft survival between the groups. Conclusion: Preoperative factor have limited predictive power for no intra-operative RBC transfusion in patient with stable condition. No transfusion could be achieved by LT. LT without transfusion did not show survival benefit. Surgical technique and auto transfusion of blood salvaged may play roles to decrease the intra-operative RBC requirements.[Figure 1]

Anemia hemolítica grave causada por hemoglobina Southampton. Presentación de caso clínico

Variant hemoglobins are the result of different types of mutations that occur in the globin genes. In many cases, these hemoglobinopathies are harmless, while in others they determine alterations in the physical and chemical properties raising clinical manifestations of variable severity. In the unstable hemoglobinopathies, the changes reduce solubility, inducing the formation of precipitates of denaturated hemoglobin (Heinz bodies), which damage the membrane and finally destroy the red blood cells prematurely. Up to now, more than 142 different unstable hemoglobins have been described, most of them cause chronic hemolysis, increased by infections or drugs. We report the clinical presentation of an unstable hemoglobin (hemoglobin Southampton) in a girl with severe hemolytic anemia, splenomegaly and red blood cell requirement.

Coagulopathy Management in Liver Transplantation

Risk of bleeding and transfusion in liver transplantation is determined by age, severity of liver disease, as well as hemoglobin and plasma fibrinogen values. During the hepatectomy and the anhepatic phase, the coagulopathy is related to a decrease in clotting factors caused by surgical bleeding, facilitated by the increased portal hypertension and esophageal-gastric venous distension. Corrections of hematologic disturbances by administration of large volumes of crystalloid, colloid, or blood products may worsen the coagulopathy. Also, impaired clearance of fibrinolytic enzymes released from damaged cells can lead to primary fibrinolysis. At time of graft reperfusion further deterioration may occur as characterized by global reduction among all coagulation factors, decreased plasminogen activator inhibitor factors, and simultaneous generation of tissue plasminogen activator. In situations with inherent risk of bleeding, hypofibrinogenemia must be corrected. Concern about unwanted events is a major limitation of preventive therapy. There is some evidence for the efficacy of antifibrinolytic drugs to reduce red blood cell requirements. A guide for antifibrinolytic therapy are clot firmness in trhomboelastometry or alternatively, diffuse bleeding associated to a fibrinogen value less than 1 g/L. Because thrombin generation is limited in severe thrombocytopenia, platelet administration is recommended when active bleeding coexists with a platelet count below 50,000/mm3. When the administration of hemoderivates and antifibrinolytic drugs does not correct severe bleeding, consumption coagulopathy and secondary fibrinolysis should be suspected. Treatment of affected patients should be based upon correcting the underlying cause, mostly related to tissue hypoxia due to critical hypoperfusion.

Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox

Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias, and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. This study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000ng/mL or they required more than 20 RBC transfusions (or 100mL/kg of RBC). We prospectively analyzed 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.

Cardiopulmonary bypass strategy with low-dose heparin and nafamostat mesilate in cardiac surgery: A safe option for patients with acute stroke

From the Narayana Hrudayalaya Institute of Medical Sciences, Bangalore, India; and theDepartment ofCardiology, St. John’sMedicalCollegeHospital,Bangalore, India. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Dec 13, 2011; revisions received March 2, 2012; accepted for publication March 16, 2012; available ahead of print April 27, 2012. Address for reprints: Naoto Morimoto, MD, PhD, Department of Cardiovascular Surgery, Himeji Cardiovascular Center, 520, Saishoko, Himeji, Hyogo, 670-0981, Japan (E-mail: naotofrcs@gmail.com). J Thorac Cardiovasc Surg 2012;144:726-8 0022-5223/$36.00 Copyright 2012 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2012.03.030

Awareness of and Identifying Iron Overload in Transfusion-Dependent Patients Can Be Improved: A Retrospective Review At a Single Tertiary Care Centre

Abstract 5283Awareness of and Identifying Iron Overload in Transfusion-dependent Patients can be improved: A Retrospective Review at a Single Tertiary Care Centre Nicole Hugel, HBSc1 and Cyrus C. Hsia, HBSc, MD, FRCPC2. 1Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada, 2Schulich School of Medicine and Dentistry, University of Western Ontario, Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada. Introduction:Several patient populations, including those with thalassemia, sickle cell disease, and bone marrow failure syndromes, often require red blood cell (RBC) transfusions and are at risk of iron overload. Chronic RBC transfusions lead to an increase in morbidity and mortality, particularly as a result of iron overload, proven in patients with thalassemia major and implicated in certain bone marrow failure syndromes such as myelodysplasia. Guidelines currently recommend iron chelation in these various clinical settings, yet the true incidence of iron overload and physician awareness patterns remain unknown. Iron overload is likely under recognized and under managed. We aim to determine the incidence of iron overload in transfusion-dependent patients in a general tertiary care centre and to determine if physicians are adequately screening for and considering treatment for iron overload. Methods:All adult patients at a single tertiary care centre, London Health Sciences Centre (LHSC), who received at least one RBC transfusion between January 1, 2006 and December 31, 2008, were captured through the local Blood Transfusion Laboratory (BTL) database. Patients who were deemed transfusion-dependent, defined as having received a minimum of 12 units of RBCs in any 12 month period with at least one RBC transfusion every 8 weeks, were identified for further analysis. This was based on the World Health Organization (WHO) criteria for RBC transfusion dependency in patients with myelodysplastic syndrome (MDS), where RBC transfusion dependency was defined as having at least one RBC transfusion every 8 weeks over a period of 4 months. Full chart reviews for these patients from the beginning of the study period to up to 12 months after the last transfusion in the LHSC BTL database during the study period were performed. For these transfusion-dependent patients, the number who had ferritin levels checked was determined. Those who had a ferritin level >1000μg/L were considered to have iron overload. Finally, of these patients who were transfusion-dependent with iron overload, full chart reviews during the study period were undertaken to determine if treating physicians considered monitoring for and treating the iron overload. Results:The LHSC BTL database included a total of 67449 RBC transfusions administered to 12486 unique patients during the study period. 1200 patients (6.6%) received at least 12 units of RBCs during the study period and were evaluated further. 48 adult patients (0.4%) satisfied the criteria for RBC transfusion dependence.Of the 48 transfusion-dependent patients, 40 (83.3%) had a ferritin value measured during and/or up to 12 months following the end of the study period. 30 (75.0%) transfusion-dependent patients with a ferritin measurement were deemed to have iron overload, consisting of patients with MDS (n=13), myelofibrosis (n=4), beta thalassemia (n=3), red cell aplasia (n=3), aplastic anemia (n=1), and other diagnoses (n=6). In this smaller cohort of 30 patients, 24 patients (80.0%) had physicians that referred to the possibility of iron overload in the clinical notes and only 16 patients (53.3%) were treated with iron chelation at some point during the study period. Conclusions:In a general tertiary care centre the percentage of transfusion-dependent patients is low compared to the total number of patients who are transfused. The percentage of transfusion-dependent patients who treating physicians monitored for or identified iron overload and subsequently managed were slightly higher than previous published rates. However, awareness of and identifying iron overload in transfusion-dependent patients at a general tertiary care centre can be improved. Disclosures:Hugel:Novartis: Unspecified Educational Fund.

Sacral Tumor Resection

Single-institution retrospective study. To assess the effect surgical staging (i.e., sequencing) has on clinical and economic outcomes for patients undergoing sacropelvic tumor resection requiring lumbopelvic stabilization. Sacral corpectomy with lumbopelvic stabilization is an extensive surgical procedure that can be performed in either a single episode or multiple episodes of care on different days. The impact of varied sequencing of surgical episodes of care on patient, resource, and financial outcomes is unknown. This single-center retrospective case series identified all cases of sacropelvic tumor resection requiring lumbopelvic stabilization over an 8-year period. We assessed and compared clinical and economic outcomes for patients whose anterior exposure and posterior resection were separated into two distinct surgical episodes of care (staged) versus patients whose anterior exposure and posterior resection occurred in a single encounter (nonstaged procedures). Primary endpoints included procedural outcomes (operative and after-hours surgical time), resuscitative requirements, adverse perioperative events, mortality, and direct medical costs (hospital and physician) associated with the surgical episodes of interest. From January 1, 2000, to July 15, 2008, a total of 25 patients were identified. Eight patients had their procedure staged. Surgical staging was associated with a significant increase in intensive care unit free days (P = 0.03), ventilator free days (P < 0.01), and reduced morbidity (P < 0.01). Surgical staging significantly reduced postoperative red blood cell (P = 0.03), and after-hours red blood cell (P < 0.01) and component requirements (P = 0.04). Mean total inpatient costs were $89,132 lower for patients undergoing the staged procedure (95% confidence interval of mean cost difference = -$178,899 to -$4661). Separating the anterior exposure and posterior resection phases of complex sacral tumor resection into two separate surgical episodes of care is associated with improved clinical outcomes and reduced inpatient cost.

A Predictive Model for Mortality in Massively Transfused Trauma Patients

Improvements in trauma systems and resuscitation have increased survival in severely injured patients. Massive transfusion has been increasingly used in the civilian setting. Objective predictors of mortality have not been well described. This study examined data available in the early postinjury period to identify variables that are predictive of 24-hour- and 30-day mortality in massively transfused trauma patients. Massively transfused trauma patients from 23 Level I centers were studied. Variables available on patient arrival that were predictive of mortality at 24 hours were entered into a logistic regression model. A second model was created adding data available 6 hours after injury. A third model evaluated mortality at 30 days. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model quality. Seven hundred four massively transfused patients were analyzed. The model best able to predict 24-hour mortality included pH, Glasgow Coma Scale score, and heart rate, with an area under the receiver operating characteristic curve (AUROC) of 0.747. Addition of the 6-hour red blood cell requirement increased the AUROC to 0.769. The model best able to predict 30-day mortality included the above variables plus age and Injury Severity Score with an AUROC of 0.828. Glasgow Coma Scale score, pH, heart rate, age, Injury Severity Score, and 6-hour red blood cell transfusion requirement independently predict mortality in massively transfused trauma patients. Models incorporating these data have only a modest ability to predict mortality and should not be used to justify withholding massive transfusion in individual cases.

Early embolization without external fixation in pelvic trauma

PurposesIn this retrospective study, we reviewed our protocol consisting of early embolization without acute external fixation in patients with pelvic fracture. Patients and MethodsEighty-eight patients with pelvic fracture were identified by reviewing the records of the Fukui Prefectural Hospital from April 2005 through September 2009. We managed the patients with a treatment protocol consisting of hemodynamic resuscitation and early pelvic embolization. Patients with hemodynamic instability without nonpelvic hemorrhage or extravasation of contrast in the pelvis by computed tomography (CT) were indicated to angiography and embolization. External fixation of the pelvic ring was not used in our protocol. ResultsOf the 88 patients with pelvic fractures, 43 underwent angiography. Twenty-eight patients (65%) were hemodynamically unstable. Twenty-five patients (58%) had major ligamentous disruption. Computed tomography detected extravasation in 21 patients (48%). Of the 43 patients who underwent angiography, 29 (67%) were positive. The average time from hospital arrival to angiography was 76.3 ± 34.5 minutes. The packed red blood cell requirement in the initial 24 hours was 8.4 ± 8.2 U, required in the embolization group. There was no complication-related embolization. Repeat angiography was not required in all patients. The mortality rate of patients requiring angiography was 11%. ConclusionsEarly pelvic embolization without external fixation may be useful for the initial treatment for patients with hemodynamic instability without nonpelvic hemorrhage or with extravasation of contrast in the pelvis by CT.

Use of Blood Transfusions In Paroxysmal Nocturnal Hemoglobinuria Patients with and without Aplastic Anemia Enrolled In the Global PNH Registry

Abstract 2241 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis which can lead to life-threatening complications including thrombosis, kidney disease, pulmonary hypertension, pain, anemia, and severe fatigue. PNH clones occur in a number of patients with concomitant aplastic anemia (AA) and other bone marrow disorders (BMD). Some patients with PNH and/or BMD may require red blood cell (RBC) transfusions to treat anemia due to hemolysis or bone marrow hypoplasia. Aims: To characterize the use of RBC transfusions among PNH patients with and without underlying AA. Methods: Enrollment data from 117 clinical sites participating in the observational PNH Registry in 16 countries on 5 continents was analyzed. Patients are included in the Registry regardless of the proportion of cells with deficiency of glycosylphosphatidyl-inositol anchored proteins (GPI-AP), bone marrow pathology, symptoms, or treatments. Sites collect clinical history at enrollment and additional data every 6 months. Demographic data, use of transfusions and other treatments, lab results, and symptoms are summarized for PNH patients with and without AA. Results: As of June 30, 2010 there were 655 enrolled patients in the Registry (53% female, median age 43). At enrollment, 28% of patients had history of AA and 45% had no history of BMD. Patients with underlying AA had lower median GPI-AP deficient granulocytes than those without BMD (median = 53% vs. 86%, respectively, p Conclusions: A substantial proportion (56%) of patients with PNH, but not all, required at least one transfusion in the year prior to enrolling in the registry, independent of underlying AA. The proportion of patients who had at least one transfusion increased with clone size. Among patients who had at least one transfusion, there was a trend for patients with underlying AA to receive more RBC units than patients without BMD. PNH patients with AA have fewer GPI-AP deficient granulocytes but demonstrate elevated hemolysis similar to patients without history of BMD when patients with similar clone sizes were compared. This Global PNH Registry, which remains open to accrual (pnhregistry@iconplc.com), should help to redefine prospectively the long-term natural history of PNH, its treatments, and the outcomes of treatment. Disclosures: Schrezenmeier: Alexion Pharmaceuticals: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Brodsky: Alexion Pharmaceuticals, Inc.: Membership on an entity9s Board of Directors or advisory committees. Muus: Celgene: Membership on an entity9s Board of Directors or advisory committees; Alexion: Membership on an entity9s Board of Directors or advisory committees; Amgen: Membership on an entity9s Board of Directors or advisory committees; Novartis: Membership on an entity9s Board of Directors or advisory committees. Bessler: Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity9s Board of Directors or advisory committees; Taligen: Consultancy. Szer: Alexion Pharmaceuticals, Inc.: Membership on an entity9s Board of Directors or advisory committees. Maciejewski: Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Socie: Alexion: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Urbano-Ispizua: Alexion: Membership on an entity9s Board of Directors or advisory committees. Kanakura: Alexion: Membership on an entity9s Board of Directors or advisory committees. Hoechsmann: Alexion: Speakers Bureau. Rosse: Alexion: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Khursigara: Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Karnell: Alexion Pharma International: Employment, Equity Ownership. Bedrosian: Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen: Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding.