Red blood cell transfusion support and management of secondary iron overload in patients with haematological malignancies in the Netherlands: a survey.

BACKGROUND AND OBJECTIVES: Evidence-based guidelines on optimal triggers for red blood cell (RBC) transfusion in patients with haematological malignancies exist, but the evidence is weak. Secondary iron overload is an often overlooked chronic complication of RBC transfusions, and also here, guidelines are either lacking or lack international consensus. Our aim was to evaluate the triggers for RBC transfusion support and management of secondary iron overload among haematologists in the Netherlands. MATERIALS AND METHODS: For this cross-sectional study, all haematologists and haematologists in training in the Netherlands were sent a web-based, 25-question survey including three clinical scenarios. The survey distribution took place between 19 November 2015 and 26 January 2016. RESULTS: Seventy-seven responses were received (24%), well distributed among community and university hospitals. A wide variation in haemoglobin triggers existed: 5·6-9·5 g/dl (median: 8·0 g/dl). Personalization of this trigger was mostly based on (estimated) cardiopulmonary compensation capacity of patients. About 65% of respondents reported two RBC units per transfusion episode (range 1-3). For monitoring secondary iron overload, serum ferritin was most frequently measured (97%), while a value of 1000-1500 µg/l was the most common cut-off to initiate treatment (39%). For 81% of respondents, phlebotomies were the first choice of treatment, although often the haemoglobin level was considered a limiting factor. CONCLUSION: Our results confirm large reported variation in daily practice among haematologists in the Netherlands regarding RBC transfusion support and management of secondary iron overload. Future studies providing better evidence are needed to improve guidelines specific for patients with haematological malignancies.

Effect of storage time of platelet products on clinical outcomes after transfusion: a systematic review and meta-analyses.

BACKGROUND: Prolonged storage improves availability of platelet products but could also influence safety and efficacy. This systematic review and meta-analyses summarize and quantify the evidence of the effect of storage time of transfused platelets on clinical outcomes. METHODS: A systematic search in seven databases was performed up to February 2016. All studies reporting storage time of platelet products and clinical outcomes were included. To quantify heterogeneity, I² was calculated, and to assess publication bias, funnel plots were constructed. RESULTS: Twenty-three studies reported safety outcomes and fifteen efficacy outcomes. The relative risk of a transfusion reaction after old platelets compared to fresh platelets was 1·53 (95% confidence interval (CI): 1·04-2·25) (12 studies). This was 2·05 (CI:1·47-2·85) before and 1·05 (CI: 0·60-1·84) after implementation of universal leucoreduction. The relative risk of bleeding was 1·13 (CI: 0·97-1·32) for old platelets compared to fresh (five studies). The transfusion interval was 0·25 days (CI: 0·13; 0·38) shorter after transfusion of old platelets (four studies). Three studies reported use of platelet products: two for haematological patients and one for trauma patients. Selecting only studies in haematological patients, the difference was 4·51 units (CI: 1·92; 7·11). CONCLUSION: Old platelets increase the risk of transfusion reactions in the setting of non-leucoreduction, shorten platelet transfusion intervals, thereby increase the numbers of platelet transfusions in haematological patients, and may increase the risk of bleeding.

Negative experiences and pre-donation blood pressure: the role of attitude and anxiety.

BACKGROUND/OBJECTIVES: Negative experiences (NEs) have been shown to result in an increased stress response, as indicated by blood pressure, at the subsequent donation. This response might be influenced by how the donor rates the donation in terms of importance and pleasantness [affective attitude (AA)/cognitive attitude (CA)] or by anxiety about donating blood. We investigated the effect of AA/CA/anxiety on the impact of NEs on pre-donation blood pressure (pd-BP) in the subsequent donation. MATERIALS/METHODS: pd-BP at visit 3 was compared between donors with and without a history of NEs during or after their first two visits (visit 1: medical check, visit 2: first donation). The effect of AA/CA/anxiety (measured 1 month prior to visit 1 on a 7-point scale) on visit 3 pd-BP was explored using linear regression and interaction analyses. Analyses were stratified for gender, age and pd-BP at visit 1, which were taken into account as confounders. RESULTS: In 1106 first-time blood donors (70% female), 632 donors (57% of total) indicated an NE at their first donation. Mean scores for AA/CA/anxiety were 5·2/6·5/2·2 (men without NE), 4·8/6·3/3·0 (men with NE), 5·2/6·6/2·6 (women without NE) and 4·8/6·6/3·2 (women with NE). No significant associations were found for NE and pd-BP at visit 3 after adjusting for confounding. Of 48 interaction effects, four were significant, but effects were small and inconsistent. CONCLUSION: In donors who had had negative experiences during their first donation, anxiety and attitude to donation did not influence their pre-donation blood pressure at their subsequent visit.

Effect of platelet storage time on platelet measurements: a systematic review and meta-analyses.

BACKGROUND: The storage time of platelet products negatively affects bacterial safety and platelet function. However, low maximum storage time increases outdating of valuable products. Thus, to quantify the effect of platelet storage time on platelet measurements after platelet transfusion, a systematic review and meta-analyses were performed. METHODS: Reports and meeting abstracts of randomized trials and observational studies, performed in humans, reporting platelet measurements after transfusion of platelet products of different storage times, were selected until February 2016. Meta-analyses were performed for four different storage time contrasts, each answering a different question. Random-effects models were used to account for substantial heterogeneity and the weighted mean differences calculated. RESULTS: Our search strategy yielded 4234 studies of which 46 papers satisfied the inclusion criteria. As judged by the 1-h corrected count increment, transfusions of fresher platelets compared to stored platelets showed better increment. The weighed mean difference varied from 2·11 (95%CI: 1·51-2·71) to 2·68 (95%CI: 1·92-3·45). For the 24-h corrected count increment, the weighted mean difference varied from 1·36 (95%CI: 0·12-2·60) to 1·68 (95%CI: 1·07-2·28) depending on the contrast. Recovery and survival of old platelets as percentage of fresh platelets were 81% and 73% for the original definition contrast. For the extended storage contrast, recovery and survival were 75% and 68%. CONCLUSIONS: Fresh platelets were superior to old platelets for all platelet measurements and for all storage time contrasts meta-analysed.

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.

Clinical practice of platelet transfusions in haemato-oncology.

Platelets are prophylactically transfused to patients receiving myeloablative chemotherapy. The trigger can be adapted if a patient has risk factors for bleeding. We performed an international survey to quantify differences in transfusion policies. While platelet counts are most important, bleeding, fever, use of anticoagulants and invasive procedures also determine transfusion strategies. The largest variation of triggers was observed for lumbar punctures and removal of central venous catheters.

Measuring clinical bleeding using a standardized daily report form and a computer algorithm for adjudication of WHO bleeding grades.

INTRODUCTION: Bleeding is increasingly considered an important end point in clinical platelet transfusion studies. Accurate recording and adjudication into well-defined bleeding grades, however, remains a major challenge. METHODS: We developed a computer algorithm for automatic adjudication. The algorithm's results were compared to those of three independent adjudicators. RESULTS: For one of 1186 bleeding days, the clinical report form (CRF) was filled out incorrectly, and the algorithm therefore missed one grade-1 skin bleed. For two bleeding days, the adjudicators incorrectly classified a grade-2 skin bleed as grade-1 while the algorithm correctly classified these days. The algorithm saved approximately six person-hours of adjudication time for the adjudication of 1186 days from 60 patients. DISCUSSION: The algorithm can be an invaluable tool for adjudicating large amounts of bleeding data.

Allo-exposure status and leucocyte antibody positivity of blood donors show a similar relation with TRALI.

INTRODUCTION: The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. METHODS: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. RESULTS: Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8.3% (95% confidence interval (CI): 5.1-11.5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: -5.0 to 36%). CONCLUSIONS: These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.

The observation of bleeding complications in haemato-oncological patients: stringent watching, relevant reporting.

BACKGROUND: The reported percentage of haemato-oncological patients experiencing bleeding complications is highly variable, ranging from 5 to 70%, posing a major problem for comparison of clinical platelet transfusion trials using bleeding complications as a primary endpoint. In a pilot study we assessed the impact of the design of scoring of bleeding on the percentage of patients with WHO grade 2 or higher bleeding grades. STUDY DESIGN AND METHODS: We performed a prospective, observational study using a rigorous bleeding observation system in thrombocytopenic patients with haemato-oncological disorders. Endpoints of the study were the percentage of patients and days with bleeding WHO grade ≥ 2 comparing designs in which skin bleeding represent a continuation of a previous bleed or a new bleed. RESULTS: In four participating hospitals 64 patients suffering 870 evaluable thrombocytopenic days (platelet count < 80 × 10(9) L(-1)) were included. At least one episode of bleeding grade ≥ 2 occurred in 36 patients (56%). Most grade 2 bleeding complications occurred mucocutaneously. The percentage of days with bleeding of grade ≥ 2 was 16% but decreases to 8% when only newly developed skin bleeding was included. CONCLUSION: Rigorous daily observation results in a bleeding incidence that is comparable to recent reportings applying the same method. The results of this study show that censoring for stable skin bleeding has a profound effect on bleeding incidence per day. The clinical relevance of rigorous or clinically judged bleeding scores as an endpoint remains to be defined.

Prevalence of leucocyte antibodies in the Dutch donor population.

INTRODUCTION: Donor leucocyte antibodies have been associated with transfusion-related acute lung injury (TRALI) and can be present in allo-exposed donors. Donor deferral policies aiming at excluding allo-exposed donors are increasingly implemented worldwide. We aimed at assessing the prevalence of leucocyte antibodies in different subgroups of allo-exposed donors in the Dutch donor population. METHODS: Consecutive donors were enrolled during routine whole blood donation. Donors filled out a questionnaire on allo-exposure history. Blood samples were tested for human leucocyte antigens (HLA) (LifeScreen Deluxe and the Lifecodes LSA I/II assays) and granulocyte-reactive (GIFT, GAT, and MAIGA) antibodies. RESULTS: Six thousand and thirty-four consecutive donors (60% men) were included. A total of 2.5% reported a history of blood transfusions, and 51% (of female donors) reported a history of pregnancy. In never allo-exposed donors, the prevalence of granulocyte-reactive antibodies was 2.0% (95% CI: 1.6-2.4), and for HLA antibodies, it was 7.0% (95% CI: 6.3-7.8). In previously pregnant donors, the prevalence of granulocyte-reactive antibodies was increased to 3.0% (95% CI: 2.0-4.0), and for HLA antibodies, it was increased to 33% (95% CI: 30-36). Prevalence of leucocyte antibodies of all types depended on transfusion history, number of pregnancies, time since last pregnancy, and pregnancy outcome. CONCLUSIONS: Fourteen percent of Dutch blood donors are allo-immunized against HLA or granulocyte antigens. Deferral of all self-reported allo-exposed donors will decrease this prevalence to 9%. Deferral of all female donors and transfused male donors will result in a similar prevalence among remaining donors but approximately twice as many deferrals.

Mortality after transfusions, relation to donor sex.

INTRODUCTION: Blood products from female donors have been associated with worse outcome after blood transfusions. We aimed to quantify the association of overall mortality with transfusions from female blood donors. METHODS: We performed a cohort study of all transfusion recipients during a 5-year period at the Leiden University Medical Center. Analyses were performed in a sub-cohort of recipients with all transfusions from donors of the same sex. Effects in male and female recipients were analysed both separately and averaged, for an overall estimate. RESULTS: Overall, when averaged over both male and female recipients, transfusions from female donors were not associated with increased mortality. However, in male recipients transfusions from female donors were positively associated with mortality, while in female recipients the association was reversed. The hazard ratio for mortality after sex-mismatched transfusions was 1.2 (95% CI, 0.98-1.4). In recipients aged 1-55 it was 1.8 (95% CI, 1.2-2.7). In recipients over 55, with more other risk factors for mortality, it was 1.0 (95% CI, 0.83-1.2). CONCLUSIONS: Overall transfusions from female donors were not associated with increased mortality. However, male recipients of blood from female donors did have an increased risk of death. Female recipients of blood from male donors showed a weaker increase in mortality.

Impaired Geriatric 8 Score is Associated with Worse Survival after Radiotherapy in Older Patients with Cancer.

AIMS: To investigate whether the Geriatric 8 (G8) score and the Timed Get Up and Go Test (TGUGT), together with clinical and demographic patient characteristics, are associated with survival and late toxicity after (chemo)radiation therapy, administered with curative intent in older patients with cancer. MATERIALS AND METHODS: Four hundred and two patients aged ≥65 years (median age 72 years, range 65-96 years), diagnosed with either breast, non-small cell lung, prostate, head and neck, rectal or oesophageal cancer, and referred for curative (chemo)radiation therapy, took part in a multicentre prospective cohort study in eight radiotherapy centres in the Netherlands. The G8 and TGUGT scores were assessed before starting treatment. Other potential predictors and late toxicity were also recorded. Survival status and date of death, if applicable, were ascertained at the Dutch national death registry. RESULTS: After 2.5 years, the overall survival was 83%. Survival was 87% for patients with high G8 scores and 55% for patients with low G8 scores (Log-rank P value < 0.0001). Survival was 77% for patients with good TGUGT results and 50% for patients with poor TGUGT results (Log-rank P value < 0.001). In multivariable analysis, in addition to age and type of primary tumour, the association of the G8 score with overall survival remained, with a hazard ratio of 2.1 (95% confidence interval 1.2-3.8) for low versus high scores. CONCLUSIONS: G8 was associated with overall survival in older patients with cancer irradiated with curative intent. This association was independent of the predictive value of age and primary tumour.