Red Cell Transfusion Requirements Research Articles

Can the normobaric oxygen paradox (NOP) increase reticulocyte count after traumatic hip surgery?

Study ObjectiveTo determine if the normobaric oxygen paradox (NOP) was effective in increasing reticulocyte count and reducing postoperative requirements for allogeneic red blood cell transfusion after traumatic hip surgery. DesignProspective, randomized, double blinded, multi-center study. SettingSurgical wards of two academic hospitals. Patients85 ASA physical status 1 and 2 patients undergoing surgery for traumatic hip fracture. InterventionsPatients were randomly assigned to receive 30 minutes of air [air group (control); n = 40] or 30 minutes of 100% oxygen (O2 group; n = 14) at 15 L/min every day from the first postoperative day (POD 1) until discharge. MeasurementsVenous blood samples were taken at admission and after surgery on POD 1, POD 3, and POD 7. Hemoglobin (Hb), hematocrit (Hct), reticulocytes, hemodynamic variables, and transfusion requirements were recorded, as were hospital length of stay (LOS) and mortality. Main ResultsFull analysis was obtained for 80 patients. On hospital discharge, the mean increase in reticulocyte count was significantly higher in the O2 group than the air group. Percent variation also increased: 184.9% ± 41.4% vs 104.7% ± 32.6%, respectively; P < 0.001. No difference in Hb or Hct levels was noted at discharge. Allogeneic red blood cell transfusion was 7.5% in the O2 group versus 35% in the air group (P = 0.0052). Hospital LOS was significantly shorter in the O2 group than the air group (7.2 ± 0.7 days vs 7.8 ± 1.6 days, respectively; P < 0.05). ConclusionsTransient O2 administration increases reticulocyte count after traumatic hip surgery. Hospital LOS also was shorter in the O2 group than the control group. Allogeneic red blood cell transfusion was reduced in the O2 group but it was not due to the NOP mechanism.

Volume Replacement Therapy during Hip Arthroplasty using Hydroxyethyl Starch (130/0.4) Compared to Lactated Ringer Decreases Allogeneic Blood Transfusion and Postoperative Infection

Background and objectivesHydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. MethodsIn this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15mL.kg-1 of HES 130/0.4 and 24 patients received a preload of 30mL.kg-1 lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. ResultsRed blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. ConclusionsDuring hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer.

Volume Replacement Therapy during Hip Arthroplasty using Hydroxyethyl Starch (130/0.4) Compared to Lactated Ringer Decreases Allogeneic Blood Transfusion and Postoperative Infection

Background and objectivesHydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. MethodsIn this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15mL.kg−1 of HES 130/0.4 and 24 patients received a preload of 30mL.kg−1 lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. ResultsRed blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p=.029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p=.037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. ConclusionsDuring hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer.

Decreasing blood loss and the need for transfusion after CABG surgery: a double-blind randomized clinical trial of topical tranexamic acid

Reopening sternotomy to control bleeding after coronary artery bypass grafting surgery (CABG) has been reported in 2%-7% of cases. Platelet dysfunction and activation of fibrinolytic cascade are the common causes of bleeding after on-pump CABG. Different antifibrinolytic drugs have been used to reduce bleeding. In this study, we aimed to investigate the efficacy of topical tranexamic acid in reducing postoperative mediastinal bleeding after CABG. Materials and methods: This was a double-blind placebo-controlled randomized clinical trial on 40 patients as the control and another 40 patients as the study group. On completion of CABG before sternotomy wound closure, tranexamic acid (2 g/20 mL) or placebo (20 mL of saline) was diluted in 500 mL of warm saline (37 °C), poured into the pericardial cavity, and left for 5 min. Results: There was no significant difference in baseline demographic data and laboratory results between the 2 groups (P > 0.05). Mediastinal bleeding and packed red cell transfusion requirements were significantly lower in the study group (P =< 0.01). There were no complications related to topical tranexamic such as mortality, myocardial infarction, cerebrovascular accident, seizure, or renal failure. Conclusion: Topical tranexamic acid can reduce mediastinal bleeding and packed red cell transfusion requirements after CABG.

Selective Splenic Artery Embolization for the Treatment of Thrombocytopenia and Hypersplenism in Paroxysmal Nocturnal Hemoglobinuria (PNH)

Abstract 4408PNH is a hemolytic disorder resulting from dysregulation of complement on the rbc, and is associated with immune mediated marrow failure and marked hypercoagulability. Thrombosis can be prevented with anticoagulation or the complement inhibitor eculizumab, and it often involves the hepatic, portal, and splenic veins. This can result in an increase in portal pressure and complications that we term the “Thrombosis-Splenomegaly-Thrombocytopenia” syndrome (TST). TST is frequently associated with abdominal pain, and thrombocytopenia may be simultaneously exacerbated by marrow failure. Particularly, thrombocytopenia can complicate efforts at anticoagulation, leaving the patient exposed to the risk of further events. In some patients thromboses can reversed with tPA, but others will not be candidates because they have presented late after their thromboses. Ablating splenic function would be desirable: however, with a high risk of perioperative thrombosis, surgical splenectomy may be hazardous, particularly in patients who have already had thrombosis, and will confer a risk of sepsis. Here we report on 4 patients with PNH and late-presenting TST. We referred these 4 patients for selective splenic artery embolization (SSAE), which involves cannulating branches of the splenic artery– beyond the hilum– and introducing gelfoam and microcoils. We planned a multi-session stepwise approach: we started with the inferior branches of the splenic artery, to decrease the risk of pleural effusions. We planned to infarct no more than 1/3 of the spleen at any one time and to allow weeks to months for recovery. We routinely administered vaccinations and discontinued anticoagulation temporarily, and patients were given prophylactic antibiotics, fluids, analgesics, and antipyretics, and they were observed in the hospital with a back-up surgical team. Prior to the procedure, the median platelet count was 17 and the median spleen size was 22 cm. Patients 1–4 were treated with 3,2,1, and 3 procedures respectively, which resulted in a significant reduction in spleen volume in all 4 patients. The post procedure platelet counts were respectively 123, 12, 44, and 90, which represented a significant increase for all patients except patient 2, who remained thrombocytopenic; since there was evidence of bone marrow failure, she underwent a successful unrelated SCT. Patients 1,2, and 4 all had had abdominal pain before the procedure, which very significantly improved after recovery from the procedure, which we attribute to decreased venous return from the spleen into the portal circulation. Patients 1–3 were treated before eculizumab was available and patient 1, 3, and 4 are now on it. Patient 4 is a special case in that she had been on eculizumab for several months prior to the SSAE, but had had only a partial reduction in the red cell transfusion requirement; C3d deposition on rbcs was documented by flow cytometry, and it was thought that extravascular hemolysis was limiting her response to eculizumab, as has been described. Of note, her hemoglobin began to rise after the embolization procedure, concurrent with the increase in the platelet count, and a significant further reduction in the red cell transfusion requirement, suggesting that partially reducing splenic function markedly reduced C3-mediated extravascular hemolysis. Of the 9 procedures performed on these 4 patients, only one was complicated by a clinically significant left sided pleural effusion, which was drained by thorascope. All patients are doing well between 3.5 and 11 years after their procedures. We conclude that SSAE, when performed by an experienced interventional radiologist, is relatively safe in patients with PNH and TST, it produces sustained correction of hypersplenism without the risk associated with surgery or the asplenic state, and can be of benefit to patients on eculizumab who have hypersplenism.PtAge at diagnosisLowest plt count pre-SSAESpleen size (cm) pre-SSAEAbdominal pain pre-SSAEBone marrowPlt count post SSAESpleen size post SSAEAbdominal pain after recovery from SSAEComplications of SSAEFollow up (yrs)1304221+Hypercellular Megakaryocyte aggregates12312NoAbd pain and fever102181919+Hypocellular Megas reduced1212NoPain, pleural effusionSCT3271436–Erythroid hyperplasia Megas adequate44NANoAbd pain11426<1022+Normocellular Megas adequate9012NoNone3.5 Disclosures:No relevant conflicts of interest to declare.

Anemia Associated with Increased IL-6 and IL-8 Levels Predicts for Worse Progression-Free Survival in T-Cell and NK-Cell Large Granular Lymphocyte (LGL) Leukemia but Is Improved by Treatment with Cyclophosphamide

AbstractAbstract 1261LGL leukemia is a rare bone marrow failure disorder characterized by a clonal expansion of terminally differentiated T- or NK-cells with large cytoplasmic granules. Cytopenias of one or multiple lineages are the dominant phenotype, though lymphocytosis without cytopenias can also be present. Goals of therapy are minimizing cytopenias. Currently used immunosuppressive and chemotherapeutic agents have produced variable clinical responses. Predictors of response to therapy and overall outcomes have not been well studied. We reviewed 92 LGL patients (pts, T-LGL=79, NK-LGL=13) seen at Cleveland Clinic from January 2000 to July 2012 treated with various therapeutic agents.Overall (OS) and Progression-Free (PFS) Survival and Time to Next Treatment (TTNT) were estimated using the Kaplan-Meier method. The first three treatments for LGL pts were evaluated with TTNT; observation was not considered a treatment for this analysis. Risk factors for PFS and OS after initial treatment (including those who were never treated) were identified using Cox proportional hazard analysis. Clinical factors evaluated at time of diagnosis include age, sex, neutropenia (absolute neutrophil count ≤1000 per μL), anemia (hemoglobin ≤10gm/dL or transfusion requirement), lymphocytosis (absolute lymphocyte count >4000 per μL), lymphopenia (absolute lymphocyte count ≤1000 per μL), thrombocytopenia (platelet count ≤100 per μL), transfusion dependence (any red-cell transfusion requirement around time of diagnosis), history of B-cell dyscrasia and history of an autoimmune disease. Clinicopathologic risk factors included type of LGL leukemia (T- vs. NK-cell), detection of a monoclonal protein, number of Vβ clones measured by flow cytometry, and T-cell clonality by T-cell receptor (TCR)-γ rearrangement. P values of ≤0.05 were considered statistically significant. The median age of the cohort was 63 years (range: 16–85). 61% were male. Treatments (n=129) included cyclophosphamide (n=31), cyclosporine (n=33), methotrexate (n=25), alemtuzumab (n=12), chemotherapy (n=7), others (n=21), and supportive care or observation (n=28). Median TTNT was 18 months (range <1 to 122 months).Pts with neutropenia had worse PFS (6 vs 72 months; p≤0.0001) as did pts with anemia (17 vs 77 months; p=0.07) compared to pts without these cytopenias. Pts with a monoclonal T-cell population via TCR-γ rearrangement also had a worse PFS compared to those with biclonal or oligoclonal T-cell population (11 vs 46 months vs not reached [NR]; p=0.04). Multivariable analyses supported these findings for PFS (anemia: HR=2.2, CI 1.10–4.67, p=0.03; T cell clonality: HR= 2.43, CI 1.16–5.48, p=0.02; neutropenia: HR=3.92, CI 1.87–8.78, p=0.0002).To provide biologic insight into the pathogenesis of anemia and its associated prognostic outcome in LGL leukemia, we performed cytokine analysis on plasma samples using a Multi-Analyte ELISArray Kit for human inflammatory cytokines that interrogates a total of 12 cytokines including IL-1A, IL-1B, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17-A, IFN-γ, TNF-α, and GM-CSF. We found increased levels of IL-6 and IL-8 in LGL pts with isolated anemia compared to pts without cytopenias. Full analysis with available samples from our cohort is ongoing. IL-6 has been associated with poor outcomes in some bone marrow syndromes.Cyclophosphamide produced the most durable TTNT compared to other treatments (36 vs. 15 months, p=0.04), particularly in those with anemia, (36 vs. 8 months, p=0.007) though its effects were negligible in pts with neutropenia (9 vs. 11 months, p=0.38).In summary, LGL is an indolent disorder with a long natural history and frequent episodes of progression. We found that anemia associated with increased IL-6 and IL-8 levels and monoclonal T-cell population predicts for worse PFS together with neutropenia. Treatment with cyclophosphamide is associated with better TTNT particularly in the presence of anemia. Cyclophosphamide is a reasonable treatment option for pts with LGL leukemia presenting with anemia. Disclosures:Maciejewski:NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding.

The cost of post-operative shed blood salvage after total knee arthroplasty: an analysis of 1,093 consecutive procedures.

Requirements for allogeneic red cell transfusion after total knee arthroplasty are still high (20-50%), and salvage and reinfusion of unwashed, filtered post-operative shed blood is an established method for reducing transfusion requirements following this operation. We performed a cost analysis to ascertain whether this alternative is likely to be cost-effective. Data from 1,093 consecutive primary total knee arthroplasties, managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged blood (control group, n=330), were retrospectively reviewed. The costs of low-vacuum drains, shed blood collection canisters (Bellovac ABT, Wellspect HealthCare and ConstaVac CBC II, Stryker), shed blood reinfusion, acquisition and transfusion of allogeneic red cell concentrate, haemoglobin measurements, and prolonged length of hospital stay were used for the blood management cost analysis. Patients in the reinfusion group received 152±64 mL of red blood cells from postoperatively salvaged blood, without clinically relevant incidents, and showed a lower allogeneic transfusion rate (24.5% vs. 8.5%, for the control and reinfusion groups, respectively; p =0.001). There were no differences in post-operative infection rates. Patients receiving allogeneic transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate, both reinfusion systems may provide net savings in different cost scenarios (€ 4.6 to € 106/patient for Bellovac ABT, and € -51.9 to € 49.9/patient for ConstaVac CBCII). Return of unwashed salvaged blood after total knee arthroplasty seems to save costs in patients with pre-operative haemoglobin between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin <12 g/dL, although cost-saving, its efficacy could be increased by associating some other blood-saving method.

Pre-filling of the extracorporeal circuit with autologous blood is safe, but not effective in optimizing biocompatibility in high-risk patients

Haemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusions in high-risk cardiac surgery patients. We designed this study to evaluate the effects of antegrade autologous priming (AAP) on reducing perioperative blood transfusion and markers of the inflammatory response in older patients (>75 years). Seventy-two patients undergoing first-time coronary bypass and/or aortic valve replacement were prospectively randomised to a cardiopulmonary bypass (CPB) with or without AAP. AAP was performed by adding the patient's own blood to the prime solution (mean 280 ml). Perfusion and anaesthetic techniques were as usual. The haematocrit was maintained at a minimum of 21% during CPB. Patients were well matched for all preoperative variables, including established transfusion risk factors. The primary endpoint was the requirement of red cell transfusion. The surrogate endpoints were renal function, inflammatory response and ischaemic parameters. Blood samples were drawn pre- and intraoperatively and at intervals of 6 hours till POD 6. Current analysis shows no differences in patients receiving homologous packed red cell transfusions. Also, markers of the inflammatory response (IL6, IL8), renal function (cystatin C, creatinine) and myocardial ischaemia (troponin T, CK-MB) were comparable in both groups (p>0.05). Clinical outcomes were similar with respect to pulmonary, renal and hepatic function, length of ICU stay and hospital stay. These data suggest that antegrade autologous priming is a safe procedure, but an ineffective way for improving biocompatibility and reducing the need for blood transfusion in older patients.

The role of complement in the trafficking of hematopoietic stem/progenitor cells

Transplantation of hematopoietic stem/progenitor cells (HSPC) has become a well-established treatment for various malignant and non-malignant hematological disorders and certain solid tumors. Approximately 60,000 autologous and allogeneic HSPC transplants are performed annually worldwide. Characteristics of HSPC that make clinical transplantation feasible, apart from their regenerative potential, include their ability to be coaxed out of the bone marrow (BM), or “mobilize”, and their capacity to “home” back to the marrow space after intravenous infusion. In our investigations of HSPC mobilization and homing, the complement system has emerged as an important, yet underappreciated, modulator of this bidirectional trafficking of HSPC. Although many factors contribute to HSPC mobilization and homing, here, we focus on the role of complement cascade (CC) components C1q, C3a, C5a and C5b-C9 (membrane attack complex; MAC) and infer that their modulation in the future could have significance to improve outcomes of HSPC transplantation. After autologous and allogeneic transplantation the patient requirements for red blood cell transfusion are high (median 12; range: 8–16 units per patient),1 and despite variations in practice, there is also substantial need for platelet transfusions (median 5; range 0–110 units per patient).2 Hence, improving the strategies for HSPC collection based on better understanding of the mechanisms of mobilization and homing could also reduce the utilization of blood products.

Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia

Recombinant factor VIIa (rFVIIa) is licensed for use in patients with haemophilia and inhibitory allo-antibodies and for prophylaxis and treatment of patients with congenital factor VII deficiency. It is also used for off-license indications to prevent bleeding in operations where blood loss is likely to be high, and/or to stop bleeding that is proving difficult to control by other means. This is the third version of the 2007 Cochrane review on the use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia, and has been updated to incorporate recent trial data. To assess the effectiveness of rFVIIa when used therapeutically to control active bleeding or prophylactically to prevent (excessive) bleeding in patients without haemophilia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other medical databases up to 23 March 2011. Randomised controlled trials (RCTs) comparing rFVIIa with placebo, or one dose of rFVIIa with another, in any patient population (except haemophilia). Outcomes were mortality, blood loss or control of bleeding, red cell transfusion requirements, number of patients transfused and thromboembolic adverse events. Two authors independently assessed potentially relevant studies for inclusion, extracted data and examined risk of bias. We considered prophylactic and therapeutic rFVIIa studies separately. Twenty-nine RCTs were included: 28 were placebo-controlled, double-blind RCTs and one compared different doses of rFVIIa. In the 'Risk of bias' assessment, most studies were found to have some threats to validity although therapeutic RCTs were found to be less prone to bias than prophylactic RCTs.Sixteen trials involving 1361 participants examined the prophylactic use of rFVIIa; 729 received rFVIIa. There was no evidence of mortality benefit (risk ratio (RR) 1.04; 95% confidence interval (CI) 0.55 to 1.97). There was decreased blood loss (mean difference (MD) -297 mL; 95% CI -416 to -178) and decreased red cell transfusion requirements (MD -261 mL; 95% CI -367 to -154) with rFVIIa treatment; however, these values were likely overestimated due to the inability to incorporate data from trials (four RCTs in the outcome of blood loss and three RCTs in the outcome of transfusion requirements) showing no difference of rFVIIa treatment compared to placebo. There was a trend in favour of rFVIIa in the number of participants transfused (RR 0.85; 95% CI 0.72 to 1.01). However, there was a trend against rFVIIa with respect to thromboembolic adverse events (RR 1.35; 95% CI 0.82 to 2.25).Thirteen trials involving 2929 participants examined the therapeutic use of rFVIIa; 1878 received rFVIIa. There were no outcomes where any observed advantage or disadvantage of rFVIIa over placebo could not have been observed by chance alone. There was a trend in favour of rFVIIa for reducing mortality (RR 0.91; 95% CI 0.78 to 1.06). However, there was a trend against rFVIIa for increased thromboembolic adverse events (RR 1.14; 95% CI 0.89 to 1.47).When all trials were pooled together to examine the risk of thromboembolic events, a significant increase in total arterial events was observed (RR 1.45; 95% CI 1.02 to 2.05). The effectiveness of rFVIIa as a more general haemostatic drug, either prophylactically or therapeutically, remains unproven. The results indicate increased risk of arterial events in patients receiving rFVIIa. The use of rFVIIa outside its current licensed indications should be restricted to clinical trials.

Postliver Transplant Acute Renal Injury and Failure by the RIFLE Criteria in Patients With Normal Pretransplant Serum Creatinine Concentrations: A Matched Study

Acute renal injury (ARI) and acute renal failure (ARF) are serious complications after liver transplantation (LT). Few studies apply the risk, injury, function, loss, and end-stage criteria on the patients who have normal preoperative renal function. The aims of this study were to identify the incidence, risk factors, and impact of ARI and ARF in this patient population. After institutional review board approval, adult LT patients who had preoperative serum creatinine less than or equal to 1.5mmol/L were reviewed. Postoperative ARI and ARF were determined by the risk, injury, function, loss, and end-stage criteria. Risk factors were determined by multivariable regression. Postoperative outcomes were compared among patients with or without ARI or ARF. Among 334 patients included the study, 20.4% and 18.0% had ARI or ARF in the first week after LT, respectively. Then 118 ARI or ARF patients were matched with patients without post-LT renal injury by gender, creatinine, and body mass index. Multivariable analysis showed that increased requirement of red blood cell transfusion (odds ratio [OR] 2.7-8.8, P<0.05), vasopressors (OR 2.2, P=0.018), and pre-LT albumin less than or equal to 3.5 mg/dL (OR: 2.8, P=0.003) as risk factors for post-LT ARI or ARF. Both ARI and ARF were associated with longer hospital stay and higher reoperation rate. ARF, but not ARI, was associated with higher 30-day graft failure and mortality rates. Post-LT ARI or ARF occurred frequently in patients with normal preoperative renal function and was associated with both preoperative and intraoperative risk factors. Although both post-LT ARI and ARF are associated with significant post-LT morbidity, the impact of ARF is greater.

Influência do ácido épsilon aminocapróico no sangramento e na hemotransfusão pós-operatória em cirurgia valvar mitral

The epsilon aminocaproic acid is an antifibrinolytic used in cardiovascular surgery to inhibit the fibrinolysis and to reduce the bleeding after CPB. [corrected]To analyze the influence of the using of epsilon aminocaproic acid in the bleeding and in red-cell transfusion requirement in the first twenty-four hours postoperative of mitral valve surgery.Prospective studying, forty-two patients, randomized and divided in two equal groups: group #1 control and group #2--epsilon aminocaproic acid. In Group II were infused five grams of EACA in the induction of anesthesia, after full heparinization, CPB perfusate after reversal of heparin and one hour after the surgery, totaling 25 grams. In group I, saline solution was infused only in those moments.Group #1 showed average bleeding volume of 633.57 ± 305,7 ml, and Group #2, an average of 308.81 ± 210.1 ml, with significant statistic difference (P = 0.0003). Average volume of red-cell transfusion requirement in Groups 1 and 2 was, respectively, 942.86 ± 345.79 ml and 214.29 ± 330.58 ml, with significant difference (P < 0.0001).The epsilon aminocaproic acid was able to reduce the bleeding volume and the red-cell transfusion requirement in the immediate postoperative of patients submitted to mitral valve surgery.

Use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia: a systematic review and meta-analysis.

The benefits and risks of off-label use of recombinant factor VIIa in patients without hemophilia are contested. We performed a systematic review to assess the effectiveness and safety of such use. We searched electronic databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing recombinant factor VIIa with placebo in any patient population except those with hemophilia up to January 2010. Eligible articles were assessed for inclusion, data were extracted, and study quality was evaluated. Outcomes included mortality, blood loss, requirements for red blood cell transfusion, number of patients transfused and thromboembolic events. We identified 26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137) and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic use, we found no significant difference in mortality or thromboembolic events between the treatment and placebo groups. We found modest benefits favouring recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95% confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials, we found a nonsignificant decrease in mortality and a nonsignificant increase in thromboembolic events but no difference in control of bleeding or red blood cell transfusion. Clinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven. Given its potential risks, such use cannot be recommended, and in most cases, it should be restricted to clinical trials.

JAK/STAT Pathways in Cytokine Signaling and Myeloproliferative Disorders: Approaches for Targeted Therapies

Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases (JAKs) and their downstream transcription factors, termed STATs (signal transducers and activators of transcription). Aberrations in these pathways, such as those caused by the recently identified JAK2(V617F) mutation and translocations of the JAK2 gene, are underlying causes of leukemias and other myeloproliferative disorders. This review discusses the role of JAK/STAT signaling in normal hematopoiesis as well as genetic abnormalities associated with myeloproliferative and myelodisplastic syndromes. This review also summarizes the status of several small molecule JAK2 inhibitors that are currently at various stages of clinical development. Several of these compounds appear to improve the quality of life of patients with myeloproliferative disorders by palliation of disease-related symptoms. However, to date, these agents do not seem to significantly affect bone marrow fibrosis, alter marrow histopathology, reverse cytopenias, reduce red cell transfusion requirements, or significantly reduce allele burden. These results suggest the possibility that additional mutational events might be associated with the development of these neoplasms, and indicate the need for combination therapies as the nature and significance of these additional molecular events is better understood.

Treatment options for hydroxyurea‐refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt

Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension.

The effect of desmopressin on blood loss in patients with rheumatoid arthritis undergoing hip arthroplasty

Blood loss is an important issue for patients with rheumatoid arthritis undergoing hip surgery. We hypothesised that intraoperative desmopressin treatment would result in a reduction in blood loss in rheumatoid patients undergoing total hip arthroplasty. Seventy-five patients scheduled for elective total hip arthroplasty were randomised to three groups to receive 0.4 microg/kg desmopressin (D 0.4), 0.2 microg/kg desmopressin (D 0.2) or placebo intraoperatively in a double-blind fashion. Blood transfusions were based on calculated safe allowable blood loss and haemoglobin measurements (trigger 90 g/l, 5.59 mmol/l). The primary endpoint was the total blood loss measured till the end of the fourth post-operative day. Secondary endpoints included red cell transfusion requirements and haemoglobin. Total blood loss during the study period was not significantly different between the groups (D 0.4 1829 +/- 1068; D 0.2 2240 +/- 843 and placebo 2254 +/- 1040 ml; P= 0.50). The total amount of red cell transfusions was fewer in group D 0.4 (3.6 +/- 1.6 U) when compared with D 0.2 (4.4 +/- 1.7 U; P=0.009) and placebo (4.5 +/- 2.0 U; P= 0.011) groups. Haemoglobin concentration was lower in the placebo group in the first (5.42 +/- 1.16 vs. 5.98 +/- 0.47 mmol/l; P=0.033) and the second (6.28 +/- 0.66 vs. 6.69 +/- 0.47 mmol/l; P=0.033) post-operative mornings compared with group D 0.4. Despite a lack of difference in the primary outcome, total blood loss, intraoperative administration of 0.4 microg/kg desmopressin resulted in fewer total red cell transfusion requirements in rheumatoid patients undergoing total hip arthroplasty when compared with 0.2 microg/kg treatment and placebo.

Exchange Transfusion Before Cardiopulmonary Bypass in Sickle Cell Disease

Cardiac operations in patients with sickle cell disease present the surgical team with many challenges. We describe a method of complete intraoperative exchange transfusion in the operating room that reduces the hemoglobin S (Hb S) level to less than 5%, without preoperative exchange transfusions. Plasma and platelet fractions separated intraoperatively from the patient's native red cell mass were used, in addition to hemoconcentration while on cardiopulmonary bypass, to effectively reduce the red cell and clotting factor transfusion requirements after the procedure. The technique is useful in reducing transfusion requirements, avoiding cardiovascular stress associated with exchange transfusion before the operation, and can be used in urgent situations.

Preoperative transcatheter arterial embolization of hypervascular metastatic tumors of long bones

Complete resection of hypervascular metastatic tumors is often complicated by massive intraoperative blood loss. To assess the technical success and clinical effectiveness of transcatheter arterial embolization (TAE) of hypervascular metastatic tumors of long bones to reduce blood loss during orthopedic surgery. From January 2000 to September 2009, 25 patients (M:F=13:12; mean age 58.3 years) were treated with TAE of metastatic bone tumors before elective, orthopedic surgery. In all cases, the indication for TAE was preoperative devascularization. Technical success, defined as obliteration of tumor staining to 70% or more, requirement for red blood cell transfusion within 24 h following surgery, and hematologic parameters, i.e. the hemoglobin, hematocrit, and erythrocyte counts before and after surgery, were obtained. The technical success rate was 96% (24/25 patients). Gelatin sponge particles (n=21) or polyvinyl alcohol particles (n=4) were used as embolic materials. The mean amount of red blood cell transfusion within the 24 h following surgery was 1.91 units (range 0-6) in the 23 patients with technically successful TAE and who underwent surgery within 3 days after TAE. In 22 patients with technically successful TAE and available hematologic data, the mean gaps in the hemoglobin, hematocrit, and erythrocyte counts before and after operation were 1.22 g/dl, 4.07%, and 0.45 x 10(6)/mm(3), respectively. Preoperative TAE is technically successful and clinically effective to minimize intraoperative and postoperative bleeding in patients with hypervascular metastasis to long bones.

Analysis of Survival After Primary Liver Transplantation: Multivariate Analysis of 155 Cases in a Single Center

Liver transplantation is known as a highly complex procedure. Several variables can affect the outcome. The present study is a retrospective multivariate analysis of the outcomes of primary liver transplant recipients from deceased donors. From November 2006 through January 2009, 155 patients received first liver transplants from deceased donors. The data included the following: age of the recipient, gender of the recipient, ABO type, indication for the transplantation, model for end-stage liver disease (MELD) score, operative time, donor age, gender of the donor, cold ischemia time, and quantity of transfused blood products—red blood cells (PRBC), red blood cells recovered during the operation (cell saver), platelets, and fresh frozen plasma. Statistical analysis was done using SPSS 17 software. Cox regression analysis was performed to identify significant variables. ROC (receiver operating characteristic) curve was applied for those significant factors. Among all variables, only PRBC transfusion and MELD score showed statistical significance. For PRBC the increment of death risk was 17.08%, and for MELD score it was 3.83%. Patients that had to use PRBC and higher MELD scores had worse survivals. We concluded that the requirement for red blood cell transfusions and MELD showed the most significant influences on the outcomes of adult liver transplantations from deceased donors.

CHOICE, an international, observational study to examine current practice use of darbepoetin alfa in the management of chemotherapy-induced anaemia

Introduction In February 2008, the European product label for darbepoetin alfa (DA) in the treatment of chemotherapy-induced anaemia (CIA) was changed to stipulate target haemoglobin (Hb) values between 10 and 12 g/dL. EORTC guidelines on ESA use state similar Hb target levels. The primary aim of this study is to assess adherence to the recommended Hb target range in patients (pts) receiving DA in routine clinical practice. Methods This prospective, multicenter, observational study evaluated the routine clinical practice use of DA in 11 European countries in pts with various non-myeloid malignancies (breast, colorectal, ovarian and lung cancer) at any time during chemotherapy treatment. Key outcome measures were Hb levels and the requirement for red blood cell (RBC) transfusions. Results 336 (mean±SD age 61.8±10.9 years) out of 1300 pts were included in this interim analysis. 80 pts had breast, 57 colorectal, 131 lung (33 small cell lung and 98 non-small cell lung cancer) and 68 ovarian cancer. 25% and 61% of pts had stage 3 and 4 disease at baseline, respectively. At baseline, 60% of all pts (53% of breast cancer and 62% of lung cancer pts) had a baseline Hb value of At week 9, Hb values for 243 pts (72%) were available. Of these, 136 pts (56%) had Hb levels between 10 and 12 g/dL, 59 pts (24%) had a Hb value > 12 g/dL and for 48 pts (20%), a Hb value below 10 g/dL was reported. The Kaplan-Meier percentage of pts with Hb levels ⩾10 g/dL was 89% (see table). The Kaplan-Meier percentage of pts requiring RBC transfusions from week 5 to end of treatment period was 17% (see table). A median DA dose of 500 μg was administered 3 times (median). Additional efficacy outcomes are presented in the table below. A treatment related non-serious adverse drug reaction (back pain) was reported for one patient only. Table 1Efficacy outcomes Total Breast cancer Lung cancer n (%) 336 (100) 80 (24) 131 (39) Hb (g/dL )at baseline, mean (SD) 9.8 (0.8) 9.9 (0.7) 9.7 (0.9) Hb (g/dL)at EOTP, mean (SD) 10.8 (1.6) 11.2 (1.4) 10.5 (1.7) K-M Hb⩾10 (g/dL) from wk 1 to EOTP, % (95% CI), na 89 (84, 95), 202 91 (82,101), 42 94 (85,102), 81 K-M RBC transfusions from wk 1 to EOTP, % (95% CI), n 26 (20, 31), 336 19 (8, 29), 80 37 (27, 46), 131 K-M RBC transfusions from wk 5 to EOTP, % (95% CI), nb 17 (12, 23), 208 12 (2, 22), 50 24 (14, 35), 72 CI, confidence interval; Hb, haemoglobin; EOTP, end of treatment period; K-M, Kaplan-Meier; RBC, red blood cell; wk, week.aOnly patients with Hb Conclusions This interim analysis suggests that the majority of pts were treated according to the European product label for DA and EORTC guidelines and did not surpass Hb levels of 12 g/dL. Furthermore, only 17% needed RBC transfusions from week 5 to end of treatment period. These data further support the effectiveness of DA for the treatment of pts with CIA. Sponsored by Amgen GmbH.