Underdiagnosing of antibody-mediated transfusion-related acute lung injury: evaluation of cellular-based versus bead-based techniques.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To support the diagnosis of antibody-mediated TRALI, HLA and HNA antibodies are tested in involved blood donors. Identification of antibody positive donors is important as exclusion of these donors is part of preventative strategies against TRALI. We compared cellular-based versus bead-based techniques for diagnosis of antibody-mediated TRALI. MATERIALS AND METHODS: All reported TRALI cases in the Netherlands during a 5-year period were evaluated. Donors were screened for the presence of HLA class I and class II antibodies using both cellular-based and bead-based techniques. RESULTS: In total, 100 TRALI cases were reported of which 91 were fully tested. In 113 donors, HLA antibodies were detected of which 84 were only detected by bead-based techniques, 12 only by cellular-based tests and 17 by both assays. Antibody-mediated TRALI was diagnosed in 44 of 91 reported cases. Twenty-one (48%) of these cases would not have been identified using only cellular-based assays. CONCLUSION: Bead-based techniques show a higher sensitivity for detecting incompatible donors in TRALI cases than cellular-based assays. These results suggest that the use of bead-based assays will result in a significant reduction of future TRALI reactions as more antibody positive donors will be excluded from future donations.

Prediction of escape red blood cell transfusion in expectantly managed women with acute anaemia after postpartum haemorrhage.

OBJECTIVE: To determine clinical predictors of escape red blood cell (RBC) transfusion in postpartum anaemic women, initially managed expectantly, and the additional predictive value of health-related quality of life (HRQoL) measures. DESIGN: Secondary analysis of women after postpartum haemorrhage, either randomly allocated to, or opting for expectant management. SETTING: Thirty-seven hospitals in the Netherlands. POPULATION: A total of 261 randomised and 362 nonrandomised women. METHODS: We developed prediction models to assess the need for RBC transfusion: one using clinical variables (model 1), and one extended with scores on the HRQoL-measures Multidimensional Fatigue Inventory (MFI) and EuroQol-5D (model 2). Model performance was assessed by discrimination and calibration. Models were internally validated with bootstrapping techniques to correct for overfitting. MAIN OUTCOME MEASURES: Escape RBC transfusion. RESULTS: Seventy-five women (12%) received escape RBC transfusion. Independent predictors of escape RBC transfusion (model 1) were primiparity, multiple pregnancy, total blood loss during delivery and haemoglobin concentration postpartum. Maternal age, body mass index, ethnicity, education, medical indication of pregnancy, mode of delivery, preterm delivery, placental removal, perineal laceration, Apgar score and breastfeeding intention had no predictive value. Addition of HRQoL-scores (model 2), significantly improved the model's discriminative ability: c-statistics of model 1 and 2 were 0.65 (95% CI 0.58-0.72) and 0.72 (95% CI 0.65-0.79), respectively. The calibration of both models was good. CONCLUSIONS: In postpartum anaemic women, several clinical variables predict the need for escape RBC transfusion. Adding HRQoL-scores improves model performance. After external validation, the extended model may be an important tool for counselling and decision making in clinical practice.

Cost-effectiveness of red blood cell transfusion vs. non-intervention in women with acute anaemia after postpartum haemorrhage.

BACKGROUND: Red blood cell (RBC) transfusion is frequently used to treat women with acute anaemia after postpartum haemorrhage. We aimed to assess the economic consequences of red blood cell transfusion compared to non-intervention in these women. METHODS: A trial-based cost-effectiveness analysis was performed alongside the Well-Being of Obstetric patients on Minimal Blood transfusions (WOMB) trial. Women with acute anaemia [Hb 4·8-7·9 g/dl (3·0-4·9 mm)] after postpartum haemorrhage, without severe anaemic symptoms, were randomly allocated to RBC transfusion or non-intervention. Primary outcome of the trial was physical fatigue (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Total costs per arm were calculated using a hospital perspective with a 6 weeks time horizon. RESULTS: Per woman, mean costs in the RBC transfusion arm (n = 258) were €1957 compared to €1708 in the non-intervention arm (n = 261; P = 0·024). The 13% difference in costs between study arms predominantly originated from costs of RBC units, as costs of RBC units were six times higher in the RBC transfusion arm. RBC transfusion led to a small improvement in physical fatigue of 0·58 points per day; thus, the costs to improve the physical fatigue score with one point would be €431. CONCLUSION: In women with acute anaemia after postpartum haemorrhage (PPH), RBC transfusion is on average €249 more expensive per woman than non-intervention, with only a small gain in HRQoL after RBC transfusion. Taking both clinical and economic consequences into account, implementation of a non-intervention policy seems justified.

Transfusion policy after severe postpartum haemorrhage: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage. DESIGN: Randomised non-inferiority trial. SETTING: Thirty-seven Dutch university and general hospitals. POPULATION: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities. METHODS: Women were allocated to RBC transfusion or non-intervention. MAIN OUTCOME MEASURES: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum. RESULTS: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable. CONCLUSIONS: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified.

[Multicentre clinical study into the optimal blood transfusion policy in patients with postpartum haemorrhage: the 'Wellbeing of obstetric patients on minimal blood transfusions' (WOMB) study]. / Een klinisch multicentrisch onderzoek naar het optimale bloedtransfusiebeleid bij patiënten met een fluxus post partum: de 'Wellbeing of obstetric patients on minimal blood transfusions' (WOMB)-studie.

Postpartum haemorrhage is a common and potentially serious complication of delivery. In clinical obstetrics, exact measurement of blood loss is often difficult. Red blood cell (RBC) transfusion is the most important intervention to treat the complications of this sustained blood loss. Despite the introduction of various new guidelines, the triggers for transfusion still vary widely between clinicians. Therefore, a prospective randomised multicentre trial, the 'Wellbeing of obstetric patients on minimal blood transfusions' (WOMB) study, was developed. This study assesses the effect of RBC transfusion on the health-related quality of life (HRQoL) of the mother after delivery. Patients with a haemoglobin (Hb) level between 3.0 and 4.9 mmol/l and a blood loss of at least 1000 ml or a decrease of > 1.2 mmol/l in the Hb level are randomly assigned to receive RBC transfusion or not. A total of 400 patients will be included. Primary outcome is physical fatigue. The total follow-up period is 6 weeks. Currently, the study is ongoing in 10 hospitals in the Netherlands. The goal of this study is to develop a new transfusion policy based on Hb-levels as well as HRQoL criteria.

Postpartum hemorrhage and transfusion of blood and blood components.

UNLABELLED: Postpartum hemorrhage (PPH) is one of the top 5 causes of maternal mortality in developed and developing countries. The incidence of PPH is 40% after vaginal delivery and 30% after cesarean section. Criteria for PPH are based on the amount of blood loss. In clinical obstetrics, exact measurement of blood loss is often difficult. The most important treatment of PPH is red blood cell (RBC) transfusion. In the past few years, increasing concern has arisen about this treatment. Despite the introduction of several new guidelines, transfusion criteria still vary widely between clinicians. The decision whether to prescribe RBC transfusion is mostly based on postpartum hemoglobin (Hb) values. RBC transfusion should be aimed to reduce morbidity and especially to improve health-related quality of life (HRQoL). In this review, etiology, epidemiology, treatment, and prevention of postpartum hemorrhage are described. Special attention is given to the role of RBC transfusion in the treatment of PPH and the effects of RBC transfusion on HRQoL. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the new guidelines related to transfusion criteria, explain the importance of reducing morbidity related to improving quality of life issues, and list infectious and noninfectious complications of a red blood cell transfusion.

Clinical significance of bacteriologic screening in platelet concentrates.

BACKGROUND: Despite routine bacterial screening with a bacterial culturing system (BacT/ALERT, bioMerieux) of platelet (PLT) concentrates, two cases of life-threatening sepsis attributed to transfused PLT products contaminated with Bacillus cereus were reported to the regional hemovigilance office in the southwest region of the Netherlands. These reports necessitated a retrospective evaluation of the currently applied bacteriologic screening program. STUDY DESIGN AND METHODS: Bacteriologic screening of all PLT concentrates on production was introduced in October 2001. Aliquots (5-10 mL) of pooled PLT concentrates in additive solution were taken for cultures with the BacT/ALERT system 14 to 24 hours after donation. The total culturing period was 7 days and in case of positive signals, identification cultures were taken from the culture bottles. The results of the bacterial screening, identification, and clinical significance of possibly contaminated pooled PLT concentrates were evaluated retrospectively over a 2-year period. RESULTS: In this period, a total of 28,104 pooled PLT concentrates were produced. Positive bacterial screening was found in 0.72 percent (n = 203). Of these, in 184 pooled PLT concentrates bacteria were cultured and identified, and in the remaining 19 (9.4%) identification cultures were negative. Before a positive screening was found, 113 PLT concentrates had already been transfused without the occurrence of clinical significant transfusion reactions. CONCLUSION: Bacterial contamination of pooled PLT concentrates was not related to clinically significant transfusion reactions. Despite negative screening for bacterial contamination, life-threatening transfusion-transmitted infections by contaminated PLT products can still occur. Other strategies should be applied to guarantee a higher degree of bacteriologic safety.

Therapeutic efficacy of pooled buffy-coat platelet components prepared and stored with a platelet additive solution.

Despite the introduction of platelet additive solutions for the preparation of pooled platelet components, only a few studies of limited scope have evaluated the clinical efficacy of platelets stored in these solutions. The current report presents an analysis of data to evaluate the response to the transfusion of pooled buffy-coat components suspended in storage solution with reduced (35%) plasma content in comparison with 100% plasma products. During the euroSPRITE clinical trial of platelet components treated with a pathogen inactivation process, control treatment group platelet components were prepared in 100% allogeneic donor plasma (plasma control) or in platelet additive solution (T-Sol) mixed with plasma (T-Sol control). Control group thrombocytopenic patients received either plasma control or T-Sol control platelet components. One-hour and 24-h platelet count increments (CIs) and corrected count increments (CCIs) were analysed for these two types of preparation. In addition, haemostatic assessments were conducted for each transfusion. One-hour and 24-h mean platelet CIs and post-transfusion haemostatic scores were not significantly different for patients receiving platelet components suspended in 100% plasma and T-Sol plasma mixtures. Pooled buffy-coat platelet components prepared in reduced plasma content mixtures provided therapeutic platelet CIs with effective haemostasis.

Feasibility of a restrictive red-cell transfusion policy for patients treated with intensive chemotherapy for acute myeloid leukaemia.

Red-cell transfusions are required for symptomatic treatment of severe anaemia caused by intensive chemotherapy. Concerns about the transfusion-related complications, such as infections (e.g. the very low risk of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) transmission and the risk of postoperative infections), haemolytic transfusion reaction, immunological effects and the costs, prompt a reevaluation of the transfusion practice. Retrospective analysis of prospectively collected data on 84 patients with acute myeloid leukaemia (AML), who were treated with combination chemotherapy between June 1, 1997 and December 7, 2001, was performed. The use of red-cell transfusions with a restrictive transfusion policy (haemoglobin = 7.2-8.8 g dL(-1), dependent on age and symptoms, n = 38) was compared with a more liberal transfusion trigger (haemoglobin = 9.6 g dL(-1), n = 46). The number of units transfused was recorded. Signs and symptoms of anaemia, chemotherapy-related effects and complications were investigated for both transfusion policies. The more restrictive transfusion policy led to a significant decrease of 11% of red blood cell (RBC) transfusions in patients with AML. No significant differences were found in the incidence of infections, number of platelet units transfused, bleeding complications, cardiac symptoms or response to chemotherapy. The more restrictive transfusion policy was feasible in this clinical setting, and it might be concluded that a restrictive transfusion policy is safe in supporting clinical patients treated with intensive chemotherapy for AML.

[Reports of transfusion incidents: experiences from the first year of hemovigilance in the region of the former ZWN (South West Netherlands) blood bank in Rotterdam]. / Meldingen over transfusie-incidenten: ervaringen in het eerste jaar van hemovigilantie in de regio van de voormalige Bloedbank ZWN Rotterdam.

OBJECTIVE: Itemize blood transfusion incidents in the South-West Netherlands region (about 3.5 million inhabitants), where a regional reporting system for transfusion incidents was introduced in January 2001. DESIGN: Prospective, descriptive. METHOD: In the period 1 January 2001-31 December 2001, 22 hospitals voluntarily reported transfusion incidents in patients to the blood bank. All incidents were anonymously recorded in a standardised report and registered in 14 categories. RESULTS: A total of 119 transfusion incidents were reported and categorised as: incorrect blood component transfused (n = 8), mild fever 1-2 degrees C (n = 14), non-haemolytic fever > 2 degrees C (n = 36), acute haemolytic transfusion reactions (n = 3). delayed haemolytic transfusion reactions (n = 18), allergic reactions (n = 11), bacterial contamination (n = 3), transfusion-related acute lung injury (n = 1), near accidents (n = 6) and product recalls (n = 19). There were no reports in the categories anaphylactic shock, post-transfusion purpura, transfusion-acquired viral infection, and transfusion-related graft versus host disease. In the same year of haemovigilance, the blood bank issued a total of 158,000 blood products. A complication rate of 1:700 blood products was calculated. It is estimated that 53% of all incidents were reported. CONCLUSION: Despite all of the safety measures taken, severe adverse events still occurred. A well-run system for haemovigilance can contribute to the knowledge of transfusion incidents. The safety and quality of blood transfusions can be improved if this knowledge is incorporated into ongoing education about blood transfusions and in the prevention and treatment of transfusion reactions.

Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are clonal disorders characterized by dysplasia in at least two myeloid cell lines. Fatigue is one of the most significant symptoms. MDS patients are treated with blood transfusions to improve their health-related quality of life (HRQoL). A cross-sectional pilot study was performed for psychometric evaluation of three internationally established HRQoL measures in MDS patients, and for investigation of the association between the severity of chronic anaemia and HRQoL. Fifty consecutive MDS patients completed the Short Form 36, the Multidimensional Fatigue Inventory and the EuroQoL-5D Visual Analogue Scale. Hb level was measured during the same visit. Psychometric analysis focused on feasibility, construct validity and reliability. The questionnaires showed a high feasibility, reliability and validity. MDS patients had worse HRQoL scores than the age- and sex-matched general population. We found a positive correlation between haemoglobin (Hb) level and HRQoL. This study provides insights into the suitability of established HRQoL measures for the evaluation of interventions in MDS patients. Hb value and HRQoL are complementary variables for evaluation of the severity of chronic anaemia in patients with MDS.

Partial expression of RHc on the RHD polypeptide.

BACKGROUND: In the human Rh blood group system, c is, after D, the most immunogenic antigen. STUDY DESIGN AND METHODS: The background of a new partial c phenotype (D(c)), identified on the RBCs of two unrelated white persons, was studied. This was done by analyzing the reactivity of the RBCs from the donors with anti-c reagents, by performing sequence analysis, and by carrying out transduction studies. RESULTS: Serologic results suggested the existence of a new partial c phenotype. Genomic DNA and cDNA analysis revealed a normal RHCe allele, a normal RHD allele, and an RHD allele that carried two point mutations: 307T>C and 329T>C (the latter known to be associated with the DVII, Tar-positive phenotype). No normal RHc allele was found. Thus, it was most likely that c is encoded by the mutated RHD allele (phenotype DD(c)CCee). Indeed, subsequent transduction of K562 erythroleukemic cells with an RHD cDNA carrying the 307T>C point mutation (leading to S103P) resulted in the expression of c. CONCLUSION: In the human Rh system, P103 is involved in the expression of c. Moreover, c can be expressed in vivo on the D polypeptide.

Intravascular hemolysis by IgA red cell autoantibodies.

A 66-year-old male patient with severe intravascular hemolysis is presented. Laboratory investigation revealed initially a negative direct antiglobulin test (DAT), suggesting a Coombs-negative hemolytic anemia. Additional testing with monospecific anti-IgA was strongly positive. IgA autoantibodies with anti-e specificity and nonspecific IgA autoantibodies were identified. A diagnosis of IgA-only-associated warm AIHA was made. Treatment included transfusion of multiple e-negative typed red cell concentrates and administration of high-dose prednisone. The pathophysiologic mechanism of the rare IgA-induced warm AIHA is discussed.

Variable leukocyte composition of red blood cell concentrates prepared in top-bottom systems: possible implications for pre-transplant blood transfusion.

BACKGROUND AND OBJECTIVES: The beneficial effect of blood transfusion on kidney graft survival requires the presence of leukocytes in the transfusate, but a minimal dose has not been defined, nor has the role of individual leukocyte subsets been investigated. In the Netherlands, a standard pre-transplant blood transfusion consists of a buffy coat (BC)-depleted red blood cell concentrate (RBCC) containing a maximum of 1.2x10(9) residual leukocytes per unit. However, leukocyte subset composition is not standardized. MATERIALS AND METHODS: Using FACS analysis, this study compared the residual leukocyte composition of RBCCs produced by Compomat((R)) and Optipress((R)), two currently used top-bottom systems. RESULTS: While the total leukocyte content of the RBCCs was equivalent in both press types (0.5x10(9)), the percentage of mononuclear cells (lymphocytes and monocytes) was significantly higher in the Compomat as compared with the Optipress system (p < 0. 0001), resulting in significantly higher numbers of transfused T cells, B cells, HLA-DR-positive cells, NK cells and stem cells. CONCLUSIONS: The leukocyte composition of a pre-transplant blood transfusion depends on the BC depletion method used; this might differentially affect the tolerizing or immunizing potential of a pre-transplant blood transfusion.

DAR, a new RhD variant involving exons 4, 5, and 7, often in linkage with ceAR, a new Rhce variant frequently found in African blacks.

The highly polymorphic Rh system is encoded by 2 homologous genes RHD and RHCE. Gene rearrangements, deletions, or point mutations may cause partial D and CE antigens. In this study, a new RHD variant, DAR, and a new RHCE variant, ceAR, are described in 4 Dutch African Blacks. Serologically, DAR showed weaker reactions with a monoclonal antibody and polyclonal antiserum against D. The DAR phenotype was characterized by complete loss of at least 9 of 37 Rh D epitopes. Erythrocytes expressing ceAR were all typed as VS(-), V(+). DNA analysis showed a partial D allele with only 3 mutations: C602G (exon 4), T667G (exon 5), and T1025C (exon 7). The ceAR allele carried G48C (exon 1), a hybrid exon 5 (A712G, C733G, A787G, and T800A), and A916G (exon 6). To study the frequency of these variants, 326 South-African Blacks was screened genomically. Of the 326 donors, 16 (4.9%) carried the DAR allele, 20 (6.1%) the ceAR allele, and 14 (4.3%) both mutated alleles. Five of these donors (1.5%) had the DAR phenotype, indicating that they carried the DAR allele homozygously or next to a D-negative allele. Immunogenicity of the D antigen for individuals with the DAR phenotype was proven, because 1 of the 4 Dutch individuals produced allo-antibodies against D after multiple transfusions with D-positive blood. In a multiethnic society, the prevalence of this D phenotype will increase and is therefore relevant in transfusion practice and in prevention of hemolytic disease of the newborn.

Genotyping of RHD by multiplex polymerase chain reaction analysis of six RHD-specific exons.

BACKGROUND: Qualitative RHD variants are the result of the replacement of RHD exons by their RHCE counterparts or of point mutations in RHD causing amino acid substitutions. For RHD typing, the use of at least two RHD typing polymerase chain reaction (PCR) assays directed at different regions of RHD is advised to prevent discrepancies between phenotyping and genotyping results, but even then discrepancies occur. A multiplex RHD PCR based on amplification of six RHD-specific exons in one reaction mixture is described. STUDY DESIGN AND METHODS: Six RHD-specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7, and 9. DNA from 119 donors (87 D+, 14 D- and 18 with known D variants; whites and nonwhites) with known Rh phenotypes was analyzed. RESULTS: All six RHD-specific exons from 85 D+ individuals were amplified, whereas none of the RHD exons from 13 D- individuals were amplified. Multiplex PCR analysis showed that the genotypes of two donors typed as D+ were DIVa and DVa. Red cell typing confirmed these findings. From all D variants tested (DIIIc, DIVa, DIVb, DVa, DVI, DDFR, DDBT) and from RoHar, RHD-specific exons were amplified as expected from the proposed genotypes. CONCLUSION: The multiplex PCR assay is reliable in determining genotypes in people who have the D+ and partial D phenotypes as well as in discovering people with new D variants. Because the multiplex PCR is directed at six regions of RHD, the chance of discrepancies is markedly reduced. The entire analysis can be performed in one reaction mixture, which results in higher speed, higher accuracy, and the need for smaller samples. This technique might be of great value in prenatal RHD genotyping.

Quality and standardization in blood component preparation with an automated blood processing technique.

The use of automated blood processors in combination with bottom and top blood containers has been found to improve the standardization and quality of blood components. A study was performed to validate a new type of processor (Optipress II) and compare its performance with a first generation processor (Optipress I). Primary separation on the Optipress II was investigated on 570 mL (+/- 10%) of anticoagulated blood in a nonpaired study. In addition, the quality of the products in routine production was compared between the results of the Optipress I and Optipress II. The whole blood units were kept overnight at room temperature (20 +/- 2 degrees C). Separation was performed under conditions to obtain 55 mL buffy coats with a 50% haematocrit (ht). Platelet concentrate preparation was investigated in a paired study and compared to the routine manual method using PAS II additive solution. Parameters studied were volume, red cell, white cell and platelet counts, ht, haemoglobin (hb, total and free). Primary separation was more efficient in the Optipress II because the platelet count was lower in the erythrocyte concentrates (P < 0.0001), platelets were lower in plasma (P < 0.0001) and platelet counts were higher in buffy coats (P < 0.0001). Buffy coat volume showed less variation (Optipress II VC = 4%, Optipress I VC = 7.4%). Secondary separation did not show differences between the Optipress II and manual method but was advantageous because of the automatic termination of the procedure. Further improvement of standardization in blood component preparation is possible with an automated blood processor, leading to improvement of the quality of blood products for patient care.