Need For Red Blood Cell Transfusion Research Articles

Erythropoietin use in the newborn

The first descriptions of blood transfusion in neonates date back to the nineteenth century. Time is past but uncertainties still remain considerable on optimal red blood cell (RBC) transfusion use in an era of evidence-based medicine. The need for RBC transfusion in critically ill neonates is differently judged among clinicians due to a lack of an agreement on measures of the need for transfusion. However some studies have shown an association between preterm infant morbidities, such as necrotizing enterocolitis and significant intracranial hemorrhage, with transfusions. The erythropoietin (EPO) use might prove clinically important. Physiologically in all newborns there is a progressive fall in hemoglobin concentrations to the nadir at about 8–12 weeks of life. The nadir is even lower and sooner in preterm neonates. This anemia of prematurity is the consequence of multiple factors, some are physiological processes as vulnerability of red cells to oxidative damage, reduced red cell lifespan when compared to the adult, lower erythropoietin (EPO) response to anemia than in older ages, increased requirements due to the postnatal growth; some are non-physiological processes as iatrogenic blood sampling, inter-current illnesses and sepsis. All these factors are responsible for low plasma EPO concentration in preterm newborns. This provides a rationale for the use of EPO in prophylaxis or treatment of the anemia. EPO has been used clinically for more than 20 years and many randomized clinical trials demonstrated that EPO successfully stimulate erythropoiesis and decrease the need of transfusion in anemic adults and children with end-stage renal disease or cancer. Differently in preterm newborns, the EPO treatment has demonstrated varied success in decreasing the total number and volume of transfusions. There are not clear evidences from high quality trials to define the absolute requirement and benefit for neonatal RBC transfusion. A recent Cochrane metanalysis performed by Ohlsson A. and Aher S.M. (1) to assess the effectiveness and safety of early initiation of EPO or darbepoetin in reducing RBC transfusions in preterm and/or low birth weight infants, concludes that the small reductions in RBC transfusion observed after EPO treatment are of limited clinical importance. In contrast the possibly increased risk of ROP, does not recommend the administration of EPO. Darbepoetin requires further study for definitive conclusions.

Radiofrequency ablation for the treatment of gastric antral vascular ectasia.

The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. A total of 24 patients underwent a mean of 1.8 ± 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 ± 12.1 during the 6 months prior to RFA, to a mean of 2.5 ± 5.9 during the 6 months after RFA treatment (P < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 ± 1.4 g/dL to 9.8 ± 1.8 g/dL; P < 0.001). RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series.

The Impact of Perioperative Iron on the Use of Red Blood Cell Transfusions in Gastrointestinal Surgery: A Systematic Review and Meta-Analysis

Perioperative anemia is common, yet detrimental, in surgical patients. However, red blood cell transfusions (RBCTs) used to treat anemia are associated with significant postoperative risks and worse oncologic outcomes. Perioperative iron has been suggested to mitigate perioperative anemia. This meta-analysis examined the impact of perioperative iron compared to no intervention on the need for RBCT in gastrointestinal surgery. We systematically searched Medline, Embase, Web of Science, Cochrane Central, and Scopus to identify relevant randomized controlled trials (RCTs) and nonrandomized studies (NRSs). We excluded studies investigating autologous RBCT or erythropoietin. Two independent reviewers selected the studies, extracted data, and assessed the risk of bias using the Cochrane tool and Newcastle-Ottawa scale. Primary outcomes were proportion of patients getting allogeneic RBCT and number of transfused patient. Secondary outcomes were hemoglobin change, 30-day postoperative morbidity and mortality, length of stay, and oncologic outcomes. A meta-analysis using random effects models was performed. The review was registered in PROSPERO (CRD42013004805). From 883 citations, we included 2 RCTs and 2 NRSs (n = 325 patients), all pertaining to colorectal cancer surgery. Randomized controlled trials were at high risk for bias and underpowered. One RCT and 1 NRS using preoperative oral iron reported a decreased proportion of patients needing RBCT. One RCT on preoperative intravenous iron and 1 NRS on postoperative PO iron did not observe a difference. Only 1 study revealed a difference in number of transfused patients. One RCT reported significantly increased postintervention hemoglobin. Among 3 studies reporting length of stay, none observed a difference. Other secondary outcomes were not reported. Meta-analysis revealed a trend toward fewer patients requiring RBCT with iron supplementation (risk ratio, 0.66 [0.42, 1.02]), but no benefit on the number of RBCT per patient (weighted mean difference, -0.91 [-1.61, -0.18]). Although preliminary evidence suggests that it may be a promising strategy, there is insufficient evidence to support the routine use of perioperative iron to decrease the need for RBCT in colorectal cancer surgery. Well-designed RCTs focusing on the need for RBCT and including long-term outcomes are warranted.

Haemoglobin levels in autoimmune haemolytic anaemias at diagnosis: relationship with immunoproteins on red blood cells

Previous investigations of the relationship between characteristics of immunoproteins on red blood cells (RBCs) and the occurrence of autoimmune haemolysis yielded divergent results. Here, we studied these characteristics in autoimmune haemolytic anaemias (AIHAs) to determine their relationship with the degree of anaemia at diagnosis. We studied at diagnosis 52 cases of warm AIHA with positive direct antiglobulin test. Immunohaematological testing and determination of immunoglobulin class, complement, and immunoglobulin G (IgG) were performed using gel technology (GCT). Median haemoglobin (Hb) levels significantly differed between cases with IgG1 only or negative for IgG subclasses (7.4g/dl), those with IgG3 or IgG1+IgG3 (6.5g/dl), and those with multiple immunoglobulins (5g/dl). Logistic regression indicated that IgG3 detection was the only variable significantly related to the occurrence of RBC transfusion in AIHA (odds ratio 4.05, 95% CI 1.1-14.7). In our study, the type of immunoprotein(s) on the RBC surface was associated with different Hb levels at AIHA diagnosis. IgG3 and multiple immunoglobulins were associated with lower Hb levels; IgG3 was also associated with a higher percentage of patient transfusions in the first week after diagnosis. Thus, qualitative differences in these immunoproteins may lead to deeper and more prolonged anaemia levels, influencing the need for RBC transfusion.

Management and prevention of neonatal anemia: current evidence and guidelines

Neonatal anemia is a common disorder, particularly in (very) preterm neonates. Management of neonatal anemia is based principally on red blood cell (RBC) transfusion. Although the use of blood products is nowadays widespread in neonatal medicine, evidence on the potential benefit is extremely limited. Recent studies suggest that RBC transfusions in newborns may be associated with an increased risk for necrotizing enterocolitis, transfer of infectious agents and negative effects on neurodevelopmental outcome. Whether the benefits of RBC transfusions outweigh the risks is controversial and requires further studies. In this review, we summarize the current evidence on the management of neonatal anemia and compare the various international guidelines. In addition, we discuss the various strategies to prevent neonatal anemia and reduce the need for RBC transfusions and discuss important trials currently enrolling patients to improve the management in neonatal anemia.

Is best transfusion practice alone best clinical practice?

Is best transfusion practice alone best clinical practice?

Anemia in Patients with Chronic Hepatitis C Infection during Triple Therapy with Telaprevir or Boceprevir - A Controlled Study

Introduction: Triple therapy with protease inhibitors, telaprevir and boceprevir, is the new standard of treatment for hepatitis C virus (HCV) genotype 1 infection. In this study, we investigated the natural history of anemia in patients treated with triple therapy compared to those treated with pegylated-interferon and ribavirin (PEG/RBV) in the real-life setting. Methods: Anemia was monitored in 72 consecutive patients treated with telaprevir- (46) or boceprevir-based triple therapy (26) for 16 weeks. These patients were statistically matched to 72 controls with respect to age, sex, race, and fibrosis that were treated previously with PEG/RBV. Anemia was treated by dose RBV dose reduction, red blood cell (RBC) transfusions, or epoetin alfa injections (EPO). Results: The mean age for the study population was 52.1 years, 58.3% were male, 41.4% were treatment naive, and 30.3% were cirrhotic. The control group was similar in terms of age, sex, race, and fibrosis. The mean baseline hemoglobin was 14.8 ± 1.3 g/dL. Incidence of grade 2-4 anemia (hemoglobin<10g/dL) in patients was 50% for those treated with telaprevir, 50% for those treated with boceprevir, and 27.5% treated with PEG/RBV (p<0.005). Lowest mean hemoglobin was 10.3 ± 1.8 g/dL, 10.4 ± 1.8 g/dL, and 11.0 ± 1.8 g/dL for telaprevir, boceprevir, and controls respectively (p<0.061). Hemoglobin nadir was reached between treatment weeks 6-10 in all treatment arms. Anemia required RBV dose reduction in 60% of those on telaprevir, 57.1% of those on boceprevir and 17.9% of the controls (p<0.001). PEG dose reduction, use of EPO, and/or RBC transfusion was not significantly different between the three groups. None of the patients had to discontinue HCV therapy due to anemia. Conclusion: Using protease inhibitors such as telaprevir or boceprevir to treat patients with hepatitis C results in more significant anemia when compared to treatment with PEG/RBV alone. Ribavirin dose reduction was used more frequently in patients treated with protease inhibitors compared to controls; however, the need for RBC transfusions, EPO injections, and PEG dose reduction was similar in both groups.

Prognostic Interactions Between SRSF2, ASXL1, and IDH Mutations in Primary Myelofibrosis and Determination of Added Value to Cytogenetic Risk Stratification and DIPSS-Plus

AbstractAbstract ▪430▪This icon denotes a clinically relevant abstract Background:The Dynamic International Prognostic Scoring System (DIPSS-plus) uses eight risk factors to predict overall survival (OS) in primary myelofibrosis (PMF): unfavorable karyotype, peripheral blood (PB) blast count ≥1%, platelet count <100 × 109/L, white blood cell count (WBC) >25 × 109/L, hemoglobin level <10 g/dL, red blood cell transfusion need, constitutional symptoms, and age >65 years (JCO 2011;29:392). Among these risk factors, karyotype holds a dominant role in predicting both overall (OS) and leukemia-free (LFS) survival (Blood 2011;118:4595). More recently, certain PMF-associated somatic mutations (IDH, EZH2, ASXL1, SRSF2) have been reported (in print or at recent meetings) to carry prognostic relevance for OS or LFS in PMF while other mutations (JAK2, MPL, TET2, SF3B1) did not. The purpose of the current study was to examine the individual and combined prognostic relevance of the former in the context of cytogenetic risk stratification and DIPSS-plus. Methods:An updated Mayo Clinic database of 1008 karyotypically- and DIPSS-plus-annotated patients with PMF was used to identify study patients in whom DNA at time of referral was available for mutation analysis. OS and LFS were calculated from the time of referral, which was also the time of study sample collection. Results:In an ongoing project, a total of 397 PMF patients have so far been studied for IDH1/2 (n=367), SRSF2 (n=355), ASXL1 (n=260) and EZH2 (n=43) mutations. The corresponding mutational frequencies were 5.4% (20/367), 14.4% (51/355), 31.2% (81/260) and 7% (3/43). These mutations were not exclusive of either each other or JAK2 or MPL mutations and a significant clustering was noted between SRSF2 and IDH mutations; IDH mutational frequency was 21% (10/48) in SRSF2-mutated versus 3% (9/279) in unmutated cases (P<0.0001). Mutational hotspots were P95 in exon 1 for SRSF2 and exons 1, 2 and 5 for ASXL1.OS and LFS effect have so far been examined for ASXL1, SRSF2 and IDH 1/2 mutations; in univariate analysis, all three mutations significantly affected OS (ASXL1 RR 1.9, 95% CI 1.4–2.7; SRSF2 RR 1.7, 95% CI 1.2–2.5; IDH 1/2 RR 1.8, 95% CI 1.1–3.1) whereas only IDH 1/2 (RR 5.5, 95% CI 2.5–11.8) and SRSF2 (RR 3.5, 95% CI 1.7–7.0) but not ASXL1 (p=0.29) mutations affected LFS. The observed prognostic relevance for OS was sustained during multivariable analysis that included ASXL1 with either SRSF2 or IDH mutations, as co-variates, whereas both IDH and SRSF2 mutations remained significant for LFS.Based on the above observations, study patients were classified into two groups: i) unmutated for ASXL1, SRSF2 and IDH1/2 (all unmutated; n=146) and ii) mutated for at least one of the three mutations (one or more mutated; n=130); the latter group constituted 62%, 52%, 18% and 27% of DIPSS-plus high, intermediate-2, intermediate-1and low risk patients, respectively (p<0.0001). The corresponding rates for patients with favorable and unfavorable karyotype were 47% and 43% (p=0.7) and for normal vs. abnormal karyotype were 53% and 36% (p=0.008). The “all unmutated group”, compared to the “one or more mutated group” enjoyed a significantly superior OS (RR 0.5, 95% CI 0.4–0.7) and LFS (RR 0.3, 95% CI 0.2–0.7) that was DIPSS-plus-independent for OS (p=0.03) and karyotype-independent for LFS (p=0.004). The prognostic value of distinguishing “all unmutated” from “one or more mutated” patient groups was most evident for DIPSS-plus intermediate-2 or lower risk groups (p=0.002) and its added value for high-risk group was limited (p=0.23) (Figure). Conclusions:A concomitant analysis strategy reveals that SRSF2, ASXL1 and IDH mutations carry inter-independent prognostic relevance for overall or leukemia-free survival in PMF. Any one of these three mutations is more likely to occur in patients with normal karyotype and such an event predicts shortened survival that is not accounted for by DIPSS-plus and a higher risk of leukemic transformation that is independent of karyotype. The current study suggests that such information might be useful in treatment decisions involving intermediate-2 or lower risk patients. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Red Blood Cell Transfusion Risks in Patients with End‐Stage Renal Disease

Prior to the introduction of recombinant human erythropoietin (EPO), red blood cell (RBC) transfusions were frequently required when iron and anabolic steroids failed to improve the clinical symptoms of anemia associated with hemoglobin (Hb) levels that were commonly less than 7 g/dl. After the approval of EPO in the United States in 1989, the Hb levels of patients on hemodialysis dramatically improved and the need for RBC transfusions decreased significantly. The need for RBC transfusion remains for patients who require an immediate increase in their RBC mass due to symptomatic anemia and is likely to increase due to changes in the management of anemia in dialysis patients resulting from clinical trials data, regulatory changes, and new reimbursement policies for EPO. The safety of the blood supply has greatly improved over the last few decades, and the risk of transfusion-transmitted diseases has now been dramatically reduced. Noninfectious complications of transfusion currently cause the majority of morbidity and mortality associated with transfusion in the United States. Transfusion also brings a risk of alloimmunization, a particular concern for dialysis patients waiting for kidney transplantation. Knowledge of the risks of RBC transfusions will help clinicians better assess the risks and benefits of transfusing patients with ESRD. This article reviews the modern day infectious and noninfectious risks of allogeneic RBC transfusions.

Classification of Myeloproliferative Neoplasms and Prognostic Factors

Myeloproliferative neoplasms (MPNs) are currently diagnosed according to the World Health Organization (WHO) criteria. Molecular profiling should include the analysis of JAK2 V617F (first, exon 12 only in V617F-negative polycythemia vera [PV]) and MPL mutations (in V617F-negative essential thrombocythemia [ET] and myelofibrosis [MF]). For patients with PV and ET, the risk stratification of low- and high-risk disease requires only two parameters: older than age 60 and prior history of thrombosis. Additionally, it might be important to monitor leukocyte count and know the mutational profile. Survival of patients with MF is defined by the International Prognostic Scoring System (IPSS) model at diagnosis and the Dynamic IPSS (DIPSS) anytime during the course of the disease. The IPSS and the DIPSS are based on patient age older than age 65, presence of constitutional symptoms, hemoglobin level less than 10 g/dL, leukocyte count greater than 25 × 10(9)/L, and circulating blast cells 1% or greater. The DIPSS-plus adds critical prognostic information and suggests also considering cytogenetic categories, platelet count, and red blood cell transfusion need.

Predictors of Greater Than 80% Two-Year Mortality in Primary Myelofibrosis: A Mayo Clinic Study of 884 Karyotypically-Annotated Cases

Abstract▪2806▪This icon denotes a clinically relevant abstract Background:A high degree of prognostic certainty is required to recommend or discourage high risk treatment procedures in primary myelofibrosis (PMF). The Dynamic International Prognostic Scoring System (DIPSS-plus) uses eight risk factors to predict overall survival (OS) in PMF: unfavorable karyotype, peripheral blood (PB) blast count ≥1%, platelet count <100 × 109/L, white blood cell count (WBC) >25 × 109/L, hemoglobin level <10 g/dL, red blood cell transfusion need, constitutional symptoms, and age >65 years (Gangat et al. JCO 2011;29 :392). The presence of four or more of these risk factors defines high-risk disease. purpose:The purpose of the current study was to enhance the prognostic weight of some of the DIPSS-plus risk factors with the intent to identify one or two parameters that can reliably predict death in the first two years of disease. Methods:An updated Mayo Clinic database of 884 karyotypically-annotated patients with PMF was used. Calculations of 2-year mortality rates and variables considered for prognostic value were from time of referral to the Mayo Clinic. Cytogenetic risk categorization per DIPSS-plus was further refined to capture additional prognostic information from monosomal karyotype (MK) (Vaidya et al. Blood 2011;117 :5612) and inv(3)/i(17q) abnormalities (Caramazza et al. Leukemia 2011;25 :82). Receiver operating characteristic (ROC) analysis was employed to define best discriminant levels. Results:To date, 564 (64%) deaths have been documented. Each one of the aforementioned DIPSS-plus risk factors was associated with a 2-year mortality rate that ranged from 42% (PB blast count ≥1%) to 60% (unfavorable karyotype). High-risk disease per DIPSS-plus was associated with 57% two-year mortality. The only risk factors that were associated with >80% two-year mortality were MK (n =19) and inv(3)/i(17q) abnormalities (n =8) and both were associated with significantly worse survival, compared to other unfavorable karyotype (n =102): HR (95% CI) of 5.1 (3.1−8.4) and 3.9 (1.7−8.8), respectively. ROC analysis identified PB blast counts of 2% and 9% (AUC 0.62) and WBC of 43 × 109/L (AUC 0.66) as best discriminant levels for predicting 2-year mortality; OS was significantly worse in the presence of PB blast >9% (HR 4.1, 95% CI 2.8–6.1) vs. 2% to 9% (HR 1.8, 95% CI 1.5–2.2) vs. <2%; the corresponding 2-year mortality rates were 73%, 46% and 25%. OS was also significantly worse in the presence of WBC ≥40 × 109/L (HR 2.8, 95% CI 2.2–3.6) vs. 26–39 × 109/L (HR 1.6, 95% CI, 1.2–2.1) vs. <26 × 109/L; the corresponding 2-year mortality rates were 63%, 42% and 28%. Two-year mortality rates exceeded 80% in the presence of any two of the following: PB blast count >9%, WBC ≥40 × 109/L or unfavorable karyotype other than MK or inv(3)/i(17q). Conclusions:A greater than 80% 2-year mortality in PMF is predicted by the presence of MK, inv(3)/i(17q) abnormalities, or any two of the following: PB blast >9%, WBC ≥40 × 109/L, other unfavorable karyotype. Such patients and those with high DIPSS-plus risk should be referred to allogenic stem cell transplantation earlier than later. Disclosures:No relevant conflicts of interest to declare.

Leukemia Risk Models in Primary Myelofibrosis: An International Working Group Study,

Abstract 3833▪▪This icon denotes a clinically relevant abstract Background:Survival in primary myelofibrosis (PMF) is assessed by the Dynamic International Prognostic Scoring System (DIPSS) (Blood 2010;115:1703) and DIPSS-plus (JCO 2011;29:392). The latter is based on eight risk factors including age>65 years, constitutional symptoms, hemoglobin <10 g/dL, red blood cell transfusion need, leukocyte count >25 × 109/L, platelet count <100 × 109/L, peripheral blood (PB) blasts ≥1% and unfavorable karyotype. Recent studies have highlighted the prognostic significance of monosomal karyotype (MK) (Blood 2011;117:5612), unfavorable karyotype (Leukemia 2011;25:82) and platelet count <100 × 109/L ((JCO 2011;29:392), for leukemic transformation (LT) in PMF. Methods:A combination of multivariable and receiver operating characteristic (ROC) analyses were applied to a Mayo Clinic database of 884 karyotypically-annotated patients with PMF, in order to define karyotype-dependent and karyotype-independent risk models for LT. The karyotype-independent model was further validated in a separate cohort of 525 PMF patients from an international database (Blood 2010;115:1703). Patients in the Mayo cohort were evaluated at time of referral and those of the international database at time of initial diagnosis. Results I:Sixty cases of LT were documented. Karyotype (categorized into MK, inv(3)/i(17q) abnormalities, other unfavorable, and favorable), PB blast percentage (as a continuous variable), and platelet count (as a continuous variable) were the most reliable (p<0.01) in predicting leukemia-free survival (LFS). The best discriminant levels for inferior LFS were MK (HR 6.2, 95% CI 2.2–17.1), inv(3)/i(17q) abnormalities (HR 7.6, 95% CI 1.8–33.3), PB blast ≥2% (HR 2.4, 95% CI 1.4–4.2) and platelet count ≤41 × 109/L (HR 2.6, 95% CI 1.3–5.1). MK and inv(3)/i(17q) abnormalities were subsequently consolidated into one “very high risk” cytogenetic category (n =27), with a corresponding HR of 6.6 (95% CI 2.7–16.0). HR-based risk scores were assigned to “very high risk” karyotype (2 points), PB blast ≥2% (one point) and platelet count ≤50 × 109/L (one point) to classify patients into low (no adverse points; n =522), intermediate (one adverse point; n =290) and high risk (two or more adverse points; n =72) groups; the corresponding 3-year LT rates were 3%, 10% (HR 2.6; 95% CI 1.4–4.6) and 35% (HR 9.4, 95% CI 4.7–18.7) (Figure 1). [Display omitted] Results II:The karyotype-independent model was based on PB blast percentage and platelet count only; low-risk (no adverse points; n =525), intermediate-risk (one adverse point; n =311) and high-risk (two adverse points; n =48); the corresponding 3-year LT rates were 3%, 12% (HR 3.1, 95% CI 1.8–5.4; p<0.0001) and 25% (HR 6.0, 95% CI 2.6–14.1). The karyotype-independent model was validated in a separate cohort of 525 PMF patients with 70 documented cases of LT, from an international database (Blood 2010;115:1703). Conclusions:The current leukemia risk models are applicable at diagnosis or during follow-up, in the presence or absence of cytogenetic information, and complement DIPSS-plus in the comprehensive prognostication of patients with PMF. Disclosures:Vannucchi:Novartis: Honoraria.

Losing control over adenosine 5′-triphosphate release: Implications for the red blood cell storage lesion*

Losing control over adenosine 5′-triphosphate release: Implications for the red blood cell storage lesion*

498 Optimal Approach to Red Blood Cell Transfusions in Children Awaiting Heart Transplantation

Anemia is common among children awaiting heart transplantation (tx). The benefits of red blood cell (RBC) transfusion, such as improved oxygen delivery, must be weighed against the potential risks of allosensitizaiton. We sought to determine the use of RBC transfusion in this population as well as its impact on allosensitization. Lastly, we examined whether erythropoietin (Epo) administration impacted the need for RBC transfusion.

Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.

Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery, and previous reviews have found them to be effective in reducing blood loss, the need for transfusion, and the need for re-operation due to continued or recurrent bleeding. In the last few years questions have been raised regarding the comparative performance of the drugs. The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death. To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. We searched: the Cochrane Injuries Group's Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2010. Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. Two authors independently assessed trial quality and extracted data. This version of the review includes a sensitivity analysis excluding trials authored by Prof. Joachim Boldt. This review summarises data from 252 RCTs that recruited over 25,000 participants. Data from the head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of reducing perioperative blood loss, but the differences were small. Compared to control, aprotinin reduced the probability of requiring RBC transfusion by a relative 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.60 to 0.72). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.53 to 0.70) and was 0.81 (95% CI 0.67 to 0.99) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared more effective in reducing the need for RBC transfusion (RR 0.90; 95% CI 0.81 to 0.99).Aprotinin reduced the need for re-operation due to bleeding by a relative 54% (RR 0.46, 95% CI 0.34 to 0.62). This translates into an absolute risk reduction of 2% and a number needed-to-treat (NNT) of 50 (95% CI 33 to 100). A similar trend was seen with EACA (RR 0.32, 95% CI 0.11 to 0.99) but not TXA (RR 0.80, 95% CI 0.55 to 1.17). The blood transfusion data were heterogeneous and funnel plots indicate that trials of aprotinin and the lysine analogues may be subject to publication bias.When compared with no treatment aprotinin did not increase the risk of myocardial infarction (RR 0.87, 95% CI 0.69 to 1.11), stroke (RR 0.82, 95% CI 0.44 to 1.52), renal dysfunction (RR 1.10, 95% CI 0.79 to 1.54) or overall mortality (RR 0.81, 95% CI 0.63 to 1.06). Similar trends were seen with the lysine analogues, but data were sparse. These data conflict with the results of recently published non-randomised studies, which found increased risk of cardiovascular complications and death with aprotinin. There are concerns about the adequacy of reporting of uncommon events in the small clinical trials included in this review.When aprotinin was compared directly with either, or both, of the two lysine analogues it resulted in a significant increase in the risk of death (RR 1.39, 95% CI 1.02, 1.89), and a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects.

Prognostic relevance of anemia and transfusion dependency in myelodysplastic syndromes and primary myelofibrosis

Prognostic relevance of anemia and transfusion dependency in myelodysplastic syndromes and primary myelofibrosis

Benefits and risks of red blood cell transfusion in pediatric patients undergoing cardiac surgery

As the number of neonates and young infants undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) increases, red blood cell (RBC) transfusion will continue to be an integral part of the practice of pediatric cardiac anesthesiology. The decision of when to transfuse RBCs to these patients is complex and influenced by multiple factors such as size, presence of cyanotic heart disease, complexity of the surgical procedure, and the hemostatic alterations induced by CPB. The known benefits of RBC transfusion include an increase in the oxygen-carrying capacity of blood, improved tissue oxygenation, and improved hemostasis. Unfortunately, there is no minimum hemoglobin level that serves as a transfusion trigger for all pediatric patients undergoing cardiac surgery. Physiologic signs such as tachycardia, hypotension, low mixed venous oxygen saturation and increased oxygen extraction ratios can provide objective evidence of the need to augment a given hemoglobin level. Nevertheless, the benefits of RBC transfusion must be balanced against its risks and, in recent years, RBC transfusion has been subjected to intense scrutiny. The adverse consequences of RBC transfusion include the transmission of infectious diseases and immune-mediated and nonimmune-mediated complications. Advances in donor selection, infectious disease testing of donated blood, use of leukocyte reduction and irradiation of blood in defined situations have improved the safety of the blood supply in terms of infection transmission. However, a growing number of prospective randomized clinical trials are finding an association between RBC transfusion and an increased risk of morbidity and mortality even with the use of leuko-reduced blood. Thus, it is becoming increasingly important that the decision to transfuse RBCs be made with a thorough understanding of the benefit-to-risk ratio. This review addresses the benefits and risks of RBC transfusion, pertinent data acquired in the setting of congenital cardiac surgery and techniques designed to minimize the need for RBC transfusion.

Erythropoiesis stimulating agents, blood transfusion, and the practice of medicine

Erythropoiesis stimulating agents, blood transfusion, and the practice of medicine

Transfusion‐dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype

The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients ( approximately 24%) required transfusions at diagnosis whereas 22 ( approximately 9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotype-independent prognostic weight of transfusion status. Among IPSS intermediate-1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes.

Early massive transfusion in trauma patients: Canadian single-centre retrospective cohort study

To determine associations between red blood cell (RBC) transfusion and early and late clinical outcomes in massively transfused adult trauma patients. A retrospective cohort study (1992-2001) including 260 patients receiving >or=10 RBC units <or=24 hr after admission to a university-affiliated trauma centre. We extracted demographic and clinical data and used multivariable regression to determine independent effects of RBC transfusion on clinical outcomes. Patients had a high (mean [standard deviation]) injury severity score (ISS) (42.5 [15.1]), a high admission sequential organ failure assessment (SOFA) score (8.4 [3.8]), and a high hospital mortality (58.5%). They received 38 (25-64) (median [interquartile range]) blood components within 48 hr, including 19 (14-28) RBC units. For 143 patients surviving >or=48 hr, the maximum SOFA score was associated with RBC units transfused before 48 hr (linear regression beta coefficient 0.075, P < 0.0001), lower nadir hemoglobin before 48 hr (0.034, P = 0.03), age (0.032, P = 0.015), and admission SOFA (0.59, P < 0.0001). The RBC units transfused by 48 hr were not associated with either hospital mortality (n = 35) among patients surviving >or=48 hr (independent predictors, age [logistic regression odds ratio (OR) 1.06, 95% confidence interval 1.03-1.10], ISS [OR 1.07, 1.02-1.13], and maximum SOFA score [OR 1.56, 1.27-1.93]) or 48-hr mortality (n = 117) (independent predictors, admission SOFA [1.65, 1.45-1.88] and later year of hospital admission [OR 1.15, 1.02-1.29]). Hospital mortality is high among massively transfused trauma patients. Among early survivors, 48-hr RBC transfusion volume is associated with increased organ dysfunction, but not hospital mortality. Also, it is not associated with 48-hr mortality. Future research should continue to explore methods to improve hemostasis and minimize the need for RBC transfusion.