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.

Recombinant human erythropoietin in patients with myelodysplastic syndromes.

As anemia is frequently the main problem in myelodysplastic syndromes (MDS), we studied the efficacy of human erythropoietin (rhEpo) in stimulating the erythroid lineage in 14 patients, starting with 40 U/kg three times a week and doubling the dose every 6 weeks until a response was observed. The highest doses administered were 80 (n = 1), 160 (n = 4), 320 (n = 8) and 640 U/kg (n = 1). One patient (refractory anemia with an excess of blasts, RAEB) showed an increase of hemoglobin, white blood cells and platelets with 80 U/kg rhEpo. However, this patient developed acute leukemia while on therapy. Two other patients (RAEB and RAEB in transformation) also transformed to acute leukemia. In the other 11 patients no response was observed. There was no correlation between in vitro culture data and in vivo responsiveness. The treatment was well tolerated and no nonhematological side effects were observed. From this study we conclude that rhEpo, even when given at high doses, has a low response rate in patients with MDS. Further investigation is needed in order to clarify whether rhEpo increases the potential risk of transformation to acute leukemia.

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.

Changes in the surface marker pattern related to maturation in adult acute myeloid leukaemia.

Introduction of the maturation index (MI) as a measure for the degree of maturation improved the subtyping of acute myeloid leukemia (AML). A comparison is made here between the MI and the results of surface marker analysis with a panel of monoclonal antibodies (McAb) in the immunofluorescence technique. The McAb applied in 46 AML patients (greater than or equal to 15 years) were granulocyte specific (MI/N1, UJ 308, B4-3, B13-9), granulocyte-monocyte specific (OKM-1, B2-12) or had specificity for the Ia-like antigen (OKI-1), 'T-cells' (3A1), immature cells (OKT-10) or platelets (C17-28). In 32 of these patients more McAb could be investigated with specificities for granulocytes (VIM-D5), granulocytes-monocytes (RUPI-5), monocytes (MONO BRL, RUPI-4), erythrocytes (VIE-G4) and AML cells (VIM-S8). An increase in surface marker expression evident from the reaction with a number of McAb (UJ 308, B2-12, OKM-1 and OKI-1) paralleled the rise of the MI in FAB M5. A decrease of the expression of antigen detected by OKI-1 paralleled the rise of the MI in FAB M1-3. The granulocyte or monocyte specific McAb, as they are determined on normal human peripheral blood cells, did not distinguish between FAB M1-3 and M5. The maturation index seems to be a valuable tool in understanding the results of surface marker analysis.

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.

[Immunological effects of erythrocyte and leukocyte transfusion. Work Group Blood Group Serology of the Medical Advisory Commission of the College for Blood Transfusion of the Netherlands Red Cross]. / Immunologische effecten van transfusie van erytrocyten en leukocyten. Werkgroep Bloedgroepenserologie van de Medische Advies Commissie van het College voor de Bloedtransfusie van het Nederlandse Rode Kruis.

Immunological consequences of blood transfusion are less well-known than infectious complications although they occur more frequently. In many cases the effects in individual patients are hardly visible although fatal transfusion reactions may occur: Transfusion of red cells may induce acute or delayed haemolytic transfusion reactions. Transfusion of leukocytes may suppress the function of the immune system of the recipient (with consequences for immune tolerance in transplant patients, cancer surveillance and the occurrence of postoperative infections) but also may induce graft versus host disease.

[Revised definition of the concept rhesus-negative blood donor; practical experiences]. / Herziene omschrijving van het begrip rhesus-negative bloeddonor; de ervaringen in de praktijk.

In 1987 the Central Medical Blood-transfusion Committee of the Netherlands Red Cross decided to modify their definition of 'Rh-negative' as it applied to blood donors. Until then the term Rh-negative had been reserved for donations that grouped as C- and E-negative and failed to react with IgG anti-D by the indirect antiglobulin test (IAT). From June 1987, however, donations were considered to be Rh-negative if they failed to react with two strong anti-D sera. An evaluation is presented over the first one and a half years of working with the new definition, the problems that were encountered and the measures that are taken to guarantee the quality of Rh testing.

[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.