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Summary: Red blood cell autoimmunity and alloimmunity are potentially linked. Quantification of this association can tailor extensively matched red blood cell transfusions in patients with autoimmunity. Using an incident new‐user cohort comprising 47 285 previously non‐transfused, non‐alloimmunised patients, we compared transfusion‐induced red blood cell alloimmunisation incidences in direct antiglobulin test (DAT)‐positive and control patients. Additionally, we performed case–control analyses to handle potential confounding by clinical immunomodulators. Among (IgG and/or C3d) DAT‐positive patients (N = 380), cumulative red blood cell alloimmunisation incidences after 10 units transfused reached 4.5% (95% confidence interval [CI] 2.5–8.2) versus 4.2% (CI 3.9–4.5, p = 0.88) in controls. In case–control analyses, alloimmunisation relative risks among DAT‐positive patients increased to 1.7 (CI 1.1–2.8). Additional adjustments for pre‐DAT transfusion exposure or the extent of Rh/K mismatching did not impact results. In conclusion, while patients with DAT positivity show an intrinsically increased alloimmune red blood cell response, their absolute risk is comparable to control patients due to counteracting co‐existing immunosuppressive conditions. Consequently, isolated DAT positivity in patients lacking overt haemolysis or complicated alloantibody testing does not seem to warrant extended matching strategies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Donor characteristics have been implicated in transfusion‐related adverse events. Uncertainty remains about whether sex, and specifically pregnancy history of the blood donor, could affect patient outcomes. Whether storage duration of the blood product could be important for patient outcomes has also been investigated, and a small detrimental effect of fresh products remains a possibility. Here, we hypothesize that fresh red blood cell products donated by ever‐pregnant donors are associated with mortality in male patients. Materials and Methods: We used data from a cohort study of adult patients receiving a first transfusion between 2005 and 2015 in the Netherlands. The risk of death after receiving a transfusion from one of five exposure categories (female never‐pregnant stored ≤10 days, female never‐pregnant stored >10 days, female ever‐pregnant stored ≤10 days, female ever‐pregnant stored >10 days and male stored for ≤10 days), compared to receiving a unit donated by a male donor, which was stored for >10 days (reference), was calculated using a Cox proportional hazards model. Results: The study included 42,456 patients who contributed 88,538 person‐years in total, of whom 13,948 died during the follow‐up of the study (33%). Fresh units (stored for ≤10 days) from ever‐pregnant donors were associated with mortality in male patients, but the association was not statistically significant (hazard ratio 1.39, 95% confidence interval 0.97–1.99). Sensitivity analyses did not corroborate this finding. Conclusion: These findings do not consistently support the notion that the observed association between ever‐pregnant donor units and mortality is mediated by blood product storage. [ABSTRACT FROM AUTHOR]

Considering this finding, preventing transfusion-induced RBC alloimmunisation by antigen matching should be similarly pursued for immunocompetent young and elderly patients. Transfusion-induced red blood cell alloimmunisation is unhampered in elderly patients With advancing age, adaptive immune responses undergo significant deteriorating changes resulting in a gradual decline of protective responses to infections and long-term immune memory vaccination responses.1-4 Considering the pathophysiology of red blood cell (RBC) alloimmunisation shares several aspects with vaccination responses, primary transfusion-induced RBC alloimmunisation may similarly deteriorate with advancing age. [Extracted from the article]

Background: Intracranial hemorrhage is seen more frequently in acute leukemia patients compared to the general population. Besides leukemia‐related risk factors, also risk factors that are present in the general population might contribute to hemorrhagic complications in leukemia patients. Of those, cardiovascular risk factors leading to chronic vascular damage could modulate the occurrence of intracranial hemorrhage in these patients, as during their disease and treatment acute endothelial damage occurs due to factors like thrombocytopenia and inflammation. Objectives: Our aim was to explore if cardiovascular risk factors can predict intracranial hemorrhage in acute leukemia patients. Methods: In a case‐control study nested in a cohort of acute leukemia patients, including 17 cases with intracranial hemorrhage and 55 matched control patients without intracranial hemorrhage, data on cardiovascular risk factors were collected for all patients. Analyses were performed via conditional logistic regression. Results: Pre‐existing hypertension and ischemic heart disease in the medical history were associated with intracranial hemorrhage, with an incidence rate ratio of 12.9 (95% confidence interval [CI] 1.5 to 109.2) and 12.1 (95% CI 1.3 to110.7), respectively. Conclusion: Both pre‐existing hypertension and ischemic heart disease seem to be strong predictors of an increased risk for intracranial hemorrhage in leukemia patients. [ABSTRACT FROM AUTHOR]

Summary: Maternal alloantibodies directed against fetal red blood cell (RBC) antigens may cause potentially life‐threatening haemolytic disease of the fetus and newborn (HDFN). Dutch transfusion guidelines therefore prescribe preventive cEK matching for all (pre‐)fertile females. To quantify the impact of cEK matching, we compared overall and antigen‐specific cumulative RBC alloimmunisation incidences in females and males aged <45 years. Among a multicentre cohort comprised of patients who received their first and subsequent RBC unit between 2005 and 2019, first‐formed RBC alloantibodies were detected in 47 of 2998 (1·6%) females and 49 of 2507 (2·0%) males. Comparing females and males, overall alloimmunisation incidences were comparable (3·1% [95% confidence interval (CI) 2·1–4·4] versus 3·5% (95% CI 2·4–4·9, P = 0·853) after 10 units transfused). However, cEK alloimmunisation incidences were significantly lower among females (0·6% (95% CI 0·3–1.5) versus 2·2% (95% CI 1·5–3·4, P = 0·001) after 10 units transfused). Yet, despite cEK‐matching guidelines being in effect, 6·5%, 3·6% and 0·2% of all RBC units remained mismatched for c, E or K antigens respectively. Most of these mismatches were almost always due to emergency settings. Even though cEK alloimmunisation was not prevented completely, implementation of cEK matching resulted in an alloantigen‐exposure risk reduction of up to 98%. [ABSTRACT FROM AUTHOR]

Haematopoietic stem-cell transplantation (HSCT) is performed mainly in patients diagnosed with malignancies or some severe congenital diseases. Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation. Patients with PRCA can become RBC transfusion dependent for a long period, suffering an important long-term iron overload, alloimmunization and transfusion reactions [15]. [Extracted from the article]

- We systematically monitor the efficacy of platelet transfusions by a post-transfusion platelet count at 20 h after transfusion. The efficacy of platelet transfusions is not routinely measured by a post-platelet transfusion increment (PPI), however if there are any concerns regarding the daily platelet counts (e.g. persisting low counts after prior transfusion such that the patient is requiring very frequent transfusions), we would perform platelet increment testing at 30-60 min post-transfusion. We advise monitoring of post-transfusion platelet counts (15-60 min post) in "high-use alert cases" (three consecutive days with >=1 platelet transfusion per day), or in the evaluation of immune-selected single donor apheresis platelets (to assess the in vivo efficacy of products which had been selected to circumvent the last known array of HLA- and/or HPA-specific antibodies). We systematically monitor the efficacy of platelet transfusions in patients undergoing HSCT by a post-transfusion platelet count about an hour after finishing the transfusion. At our institution, if a patient is independent of RBC transfusion for 90 days and no incompatible isohemagglutinins against the new RBC phenotype are detected in two consecutive blood samples, then the patient's native blood type is switched to the donor type for future transfusion. [Extracted from the article]

We designed a study to describe the incidence of intracranial hemorrhage according to severity and duration of thrombocytopenia and to quantify the associations of platelet transfusions with intracranial hemorrhage in patients with acute leukemia. In this case-control study nested in a cohort of 859 leukemia patients, cases (n = 17) were patients diagnosed with intracranial hemorrhage who were matched with control patients (n = 55). We documented platelet counts and transfusions for seven days before the intracranial hemorrhage in cases and in a "matched" week for control patients. Three measures of platelet count exposure were assessed in four potentially important time periods before hemorrhage. Among these leukemia patients, we observed the cumulative incidence of intracranial hemorrhage of 3.5%. Low platelet counts were, especially in the three to seven days preceding intracranial hemorrhage, associated with the incidence of intracranial hemorrhage, although with wide confidence intervals. Platelet transfusions during the week preceding the hemorrhage were associated with higher incidences of intracranial hemorrhage; rate ratios (95% confidence interval) for one or two platelet transfusions and for more than two transfusions compared with none were 4.04 (0.73 to 22.27) and 8.91 (1.53 to 51.73) respectively. Thus, among acute leukemia patients, the risk of intracranial hemorrhage was higher among patients with low platelet counts and after receiving more platelet transfusions. Especially, the latter is likely due to clinical factors leading to increased transfusion needs. [ABSTRACT FROM AUTHOR]

Introduction: Electronic health care data offers the opportunity to study rare events, although detecting these events in large datasets remains difficult. We aimed to develop a model to identify leukemia patients with major hemorrhages within routinely recorded health records. Methods: The model was developed using routinely recorded health records of a cohort of leukemia patients admitted to an academic hospital in the Netherlands between June 2011 and December 2015. Major hemorrhage was assessed by chart review. The model comprised CT-brain, hemoglobin drop, and transfusion need within 24 hours for which the best discriminating cut off values were taken. External validation was performed within a cohort of two other academic hospitals. Results: The derivation cohort consisted of 255 patients, 10,638 hospitalization days, of which chart review was performed for 353 days. The incidence of major hemorrhage was 0.22 per 100 days in hospital. The model consisted of CT-brain (yes/no), hemoglobin drop of ≥0.8 g/dl and transfusion of ≥6 units. The C-statistic was 0.988 (CI 0.981–0.995). In the external validation cohort of 436 patients (19,188 days), the incidence of major hemorrhage was 0.46 per 100 hospitalization days and the C-statistic was 0.975 (CI 0.970–0.980). Presence of at least one indicator had a sensitivity of 100% (CI 95.8–100) and a specificity of 90.7% (CI 90.2–91.1). The number of days to screen to find one case decreased from 217.4 to 23.6. Interpretation: A model based on information on CT-brain, hemoglobin drop and need of transfusions can accurately identify cases of major hemorrhage within routinely recorded health records. [ABSTRACT FROM AUTHOR]

Background: Storage time of platelet (PLT) concentrates has been negatively associated with clinical efficacy outcomes. The aim of this study was to quantify the association between storage time of PLT concentrates and interval to the next PLT transfusion for different types of PLT components, stored for up to 7 days and transfused to transfusion-dependent hematooncology patients with thrombocytopenia.Study Design and Methods: From a cohort of patients from 10 major Dutch hospitals, patients were selected whose transfusion patterns were compatible with PLT transfusion dependency due to hematooncologic disease. Mean time to the next transfusion and mean differences in time to the next transfusion for different storage time categories (i.e., fresh, <4 days; intermediate, 4-5 days; and old, >5 days) were estimated, per component type, using multilevel mixed-effects linear models.Results: Among a cohort of 29,761 patients who received 140,896 PLT transfusions we selected 4441 hematooncology patients who had received 12,724 PLT transfusions during periods of PLT transfusion dependency. Transfusion of fresh, compared to old, buffy coat-derived PLTs in plasma was associated with a delay to the next transfusion of 6.2 hours (95% confidence interval [CI], 4.5-8.0 hr). For buffy coat-derived PLTs in PAS-B and -C this difference was 7.7 hours (95% CI, 2.2-13.3 hr) and 3.9 hours (95% CI, -2.1 to 9.9 hr) while for apheresis PLTs in plasma it was only 1.8 hours (95% CI, -3.5 to 7.1 hr).Conclusion: Our results indicate that the time to the next transfusion shortens with increasing age of transfused buffy coat-derived PLT concentrates. This association was not observed for apheresis PLTs. [ABSTRACT FROM AUTHOR]

Importance: Transfusion of red blood cells from female donors has been associated with increased mortality in male recipients.Objective: To quantify the association between red blood cell transfusion from female donors with and without a history of pregnancy and mortality of red blood cell recipients.Design, Setting, and Participants: Retrospective cohort study of first-time transfusion recipients at 6 major Dutch hospitals enrolled from May 30, 2005, to September 1, 2015; the final follow-up date was September 1, 2015. The primary analysis was the no-donor-mixture cohort (ie, either all red blood cell transfusions exclusively from male donors, or all exclusively from female donors without a history of pregnancy, or all exclusively from female donors with a history of pregnancy). The association between mortality and exposure to transfusions from ever-pregnant or never-pregnant female donors was analyzed using life tables and time-varying Cox proportional hazards models.Exposures: Red blood cell transfusions from ever-pregnant or never-pregnant female donors, compared with red blood cell transfusions from male donors.Main Outcomes and Measures: All-cause mortality during follow-up.Results: The cohort for the primary analyses consisted of 31 118 patients (median age, 65 [interquartile range, 42-77] years; 52% female) who received 59 320 red blood cell transfusions exclusively from 1 of 3 types of donors (88% male; 6% ever-pregnant female; and 6% never-pregnant female). The number of deaths in this cohort was 3969 (13% mortality). For male recipients of red blood cell transfusions, all-cause mortality rates after a red blood cell transfusion from an ever-pregnant female donor vs male donor were 101 vs 80 deaths per 1000 person-years (time-dependent "per transfusion" hazard ratio [HR] for death, 1.13 [95% CI, 1.01-1.26]). For receipt of transfusion from a never-pregnant female donor vs male donor, mortality rates were 78 vs 80 deaths per 1000 person-years (HR, 0.93 [95% CI, 0.81-1.06]). Among female recipients of red blood cell transfusions, mortality rates for an ever-pregnant female donor vs male donor were 74 vs 62 per 1000 person-years (HR, 0.99 [95% CI, 0.87 to 1.13]); for a never-pregnant female donor vs male donor, mortality rates were 74 vs 62 per 1000 person-years (HR, 1.01 [95% CI, 0.88-1.15]).Conclusions and Relevance: Among patients who received red blood cell transfusions, receipt of a transfusion from an ever-pregnant female donor, compared with a male donor, was associated with increased all-cause mortality among male recipients but not among female recipients. Transfusions from never-pregnant female donors were not associated with increased mortality among male or female recipients. Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Blood transfusion has health-related, economical and safety implications. In order to optimise the transfusion chain, comprehensive research data are needed. The Dutch Transfusion Data warehouse (DTD) project aims to establish a data warehouse where data from donors and transfusion recipients are linked. This paper describes the design of the data warehouse, challenges and illustrative applications. Study design and methods: Quantitative data on blood donors (eg, age, blood group, antibodies) and products (type of product, processing, storage time) are obtained from the national blood bank. These are linked to data on the transfusion recipients (eg, transfusions administered, patient diagnosis, surgical procedures, laboratory parameters), which are extracted from hospital electronic health records. Applications: Expected scientific contributions are illustrated for 4 applications: determine risk factors, predict blood use, benchmark blood use and optimise process efficiency. For each application, examples of research questions are given and analyses planned. Conclusions: The DTD project aims to build a national, continuously updated transfusion data warehouse. These data have a wide range of applications, on the donor/production side, recipient studies on blood usage and benchmarking and donor-recipient studies, which ultimately can contribute to the efficiency and safety of blood transfusion. [ABSTRACT FROM AUTHOR]

Background: In neonates, hypoglycemia is an emergency condition requiring urgent treatment. Therefore, rapid and reliable blood glucose measurements are necessary. However, this step has been proven difficult because of both analytical and preanalytical variables. In our children's hospital, we incidentally observed cases of hypoglycemia that were not in line with the clinical picture of the infants. Remarkably, most of these infants had a high hematocrit. Methods: Glucose concentrations were determined in blood samples from healthy participants that were collected in Li-heparin capillary and pediatric tubes. The effect of hematocrit on glucose consumption over time was studied by artificially increasing sample hematocrits. To study the effect of sample cooling, glucose concentrations were followed over time in samples stored at room temperature and on ice. Results: In all samples, glucose concentrations declined with time. This effect was most dramatic [up to 18 mg/dL (1 mmol/L) in the first 30 min] in samples with high hematocrits and collected in capillary tubes. Cooling of samples clearly reduced glucose consumption; however, this was not evident in the first 30 min. Conclusions: Overestimation of hypoglycemia in infants must be considered if samples are not centrifuged or are not analyzed immediately after sampling. The extent of overestimation is more pronounced in samples with a high hematocrit, collected in capillary tubes. Cooling of samples does not prevent glucose consumption in vitro during the first 30 min. These results emphasize that, for glucose analysis, prompt handling of samples of newborns with a high hematocrit is necessary. [ABSTRACT FROM AUTHOR]

Stored red blood cells undergo progressive structural and functional changes over time. Recently, concerns have been raised about the transfusion of older red blood cell (RBC) concentrates after cardiac surgery. The objective of the study was to test the hypothesis that longer storage time of RBCs increases the risk of adverse outcome after cardiac surgery. This is a retrospective cohort study which includes patients who underwent coronary artery bypass surgery and/or valve surgery. All patients were operated in the period from September 2006 to December 2010 and received 1 to 6 units of RBCs intraoperative or after surgery. Patients were divided into two groups according to the storage time of the RBCs. The “younger” group comprised patients who received RBCs ≤14 days old ( n = 111) and the “any older” group comprised patients who received RBCs >14 days old ( n = 710). Using univariable and multivariable regression analysis, we examined the effect of storage time on the primary composite endpoint of death, myocardial infarction, and stroke (major adverse cardiovascular events). Secondary outcomes were prolonged ICU and hospital stay. Data of 821 patients who received a total of 2,004 RBCs were analyzed. The median storage time for the younger group was 13 ± 2 days, the median storage time for the “any older” group was 21 ± 5 days. The incidence of the primary outcome was 8.6 % in the “any older” group and 4.5 % in the younger group (adjusted odds ratio (OR) 1.68; 95 % confidence interval (CI), 0.65–4.34). Prolonged ICU stay was 12.3 % in the “any older” group and 6.3 % in the younger group (adjusted OR 1.58; 95 % CI, 0.69–3.66). In patients undergoing cardiac surgery, transfusion of RBCs stored for more than 2 weeks was not associated with adverse outcomes. [ABSTRACT FROM AUTHOR]

Blood contains a mixture of extracellular vesicles from different cell types, primarily platelets, endothelial cells, leucocytes and erythrocytes. Erythrocytes are themost abundant cell type in blood and could, especially in certain pathologies, represent an important source of vesicles. Since erythrocytes contain the haemoglobin components iron and haem, which are potentially toxic, it is important to investigate the contribution of vesicle-associated haemoglobin to total cell-free haemoglobin levels. To our knowledge, this is the first time that cell-free plasma haemoglobin has been differentiated into vesicle-associated and molecular species. We investigated the contribution of vesicle-associated haemoglobin in residual patient material that was routinely analysed for total cell-free plasma haemoglobin. All patient samples included in the study were haemolytic with total cell-free haemoglobin concentration ranging from 80 to 2500 mg/l. In the majority of the samples, total cell-free haemoglobin concentration was between 100 and 200 mg/l. No haemoglobin could be detected in the vesicle fraction, indicating that the contribution of vesicle-associated haemoglobin to total cell free-haemoglobin levels in plasma is negligible. It is important to investigate whether erythrocyte vesicles are not formed in blood or that their production is not increased during pathologies associated with haemolysis or that the clearance rate of the vesicles surpasses the formation rate. [ABSTRACT FROM AUTHOR]

Introduction. This study aims to evaluate for the first time the value of visualizing veins by a prototype of a near-infrared (NIR) vascular imaging system for venipuncture in children. Methods. An observational feasibility study of venipunctures in children (0-6 years) attending the clinical laboratory of a pediatric university hospital during a period of 2 months without (n = 80) and subsequently during a period of 1 month with a prototype of an NIR vascular imaging system (n = 45) was conducted. Failure rate (ie, more than 1 puncture) and time of needle manipulation were determined. Results. With the NIR vascular imaging system, failure rate decreased from 10/80 to 1/45 (P = .05) and time decreased from 2 seconds (1-10) to 1 second (1-4, P = .07). Conclusion . This study showed promising results on the value of an NIR vascular imaging system in facilitating venipunctures. [ABSTRACT FROM PUBLISHER]

Objective. Macrophage activation syndrome (MAS) in systemic onset juvenile idiopathic arthritis (SoJIA) is considered to be an acquired form of familial haemophagocytic lymphohistiocytosis (fHLH). FHLH is an autosomal recessive disorder, characterized by diminished NK cell function and caused by mutations in the perforin gene (PRF1) in 20–50% of patients. Interestingly, SoJIA patients display decreased levels of perforin in NK cells and diminished NK cell function as well. Here, we analysed PRF1 and its putative promoter in SoJIA patients with or without a history of MAS. [ABSTRACT FROM PUBLISHER]

The article discusses a study which evaluated the effect of the gaming app Prik! on experienced pain and distress during venipuncture/fingerprick by comparing it to the use of a noninformative gaming app and no app. Topics include venipunctures and finger pricks are a major source of pain and distress in pediatric healthcare, main outcome of the study, and conclusion on playing a serious gaming app such as Prik! before blood sampling.

Background: Usually, laboratory diagnostics of hereditary hemoglobin disorders is fairly straightforward. Sometimes, however, correct diagnosis can be difficult. In this study, we describe a family with multiple mutations and sequence variations in the α- and β-globin gene clusters. Methods: Hemocytometry results were obtained using an automated cell counter. Hemoglobin variant analysis was performed by cation-exchange HPLC. PCR and DNA sequence analyses were used to identify mutations in the globin genes. Results: The proposita was referred to our laboratory for hematological evaluation [hemoglobin 145 g/L (119-155 g/L) mean corpuscular volume 72 fl (80-97 fl), mean corpuscular hemoglobin 26 pg (28-36 pg), erythrocytes 5.6 x 1012/L (3.7-5.0 1012/L)]. Characterization and quantification of hemoglobin variants showed 11.3% HbA1, 4.4% HbA2, 58.9% HbC and 23.0% HbF. Subsequent analysis revealed, in addition to a heterozygous HbC mutation, the presence of a β-thalassemia causing mutation (-90C > T), a heterozygous α-thalassemia (-α-3.7/αα) and three different γ-globin sequence variations. Additional molecular analysis was performed in all family members. Conclusions: In the family presented in this study, 10 different mutations were found in the globin genes. Molecular analysis was necessary to clarify hemoglobin variant analysis, in particular the low amount of HbA1 in the proposita. Knowledge of the molecular background facilitates in the understanding of the hematological parameters and proper counseling of the patient. [ABSTRACT FROM AUTHOR]