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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite routine bacterial screening with a bacterial culturing system (BacT/ALERT, bioMérieux) of platelet (PLT) concentrates, two cases of life-threatening sepsis attributed to transfused PLT products contaminated withBacillus cereuswere 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.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.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.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. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor concerning the BacT/ALERT system used to screen platelet concentrates for bacteria.

Presents a case of a 54-year-old man with recurrent episodes of high fever, hypotension, and respiratory failure. Treatment for septic shock syndrome; Diagnosis of Graves' disease; Rarity of isolated deficiency of adrenocorticotropin hormone (ACTH)-deficiency as the cause of hypocortisolism; Autoimmunity as the probable cause of the deficiency in this patient.

In population pharmacokinetic (PK) models, interindividual variability is explained by implementation of covariates in the model. The widely used forward stepwise selection method is sensitive to bias, which may lead to an incorrect inclusion of covariates. Alternatives, such as the full fixed effects model, reduce this bias but are dependent on the chosen implementation of each covariate. As the correct functional forms are unknown, this may still lead to an inaccurate selection of covariates. Machine learning (ML) techniques can potentially be used to learn the optimal functional forms for implementing covariates directly from data. A recent study suggested that using ML resulted in an improved selection of influential covariates. However, how do we select the appropriate functional form for including these covariates? In this work, we use SHapley Additive exPlanations (SHAP) to infer the relationship between covariates and PK parameters from ML models. As a case‐study, we use data from 119 patients with hemophilia A receiving clotting factor VIII concentrate peri‐operatively. We fit both a random forest and a XGBoost model to predict empirical Bayes estimated clearance and central volume from a base nonlinear mixed effects model. Next, we show that SHAP reveals covariate relationships which match previous findings. In addition, we can reveal subtle effects arising from combinations of covariates difficult to obtain using other methods of covariate analysis. We conclude that the proposed method can be used to extend ML‐based covariate selection, and holds potential as a complete full model alternative to classical covariate analyses. [ABSTRACT FROM AUTHOR]

Nonlinear mixed effect (NLME) models are the gold standard for the analysis of patient response following drug exposure. However, these types of models are complex and time‐consuming to develop. There is great interest in the adoption of machine‐learning methods, but most implementations cannot be reliably extrapolated to treatment strategies outside of the training data. In order to solve this problem, we propose the deep compartment model (DCM), a combination of neural networks and ordinary differential equations. Using simulated datasets of different sizes, we show that our model remains accurate when training on small data sets. Furthermore, using a real‐world data set of patients with hemophilia A receiving factor VIII concentrate while undergoing surgery, we show that our model more accurately predicts a priori drug concentrations compared to a previous NLME model. In addition, we show that our model correctly describes the changing drug concentration over time. By adopting pharmacokinetic principles, the DCM allows for simulation of different treatment strategies and enables therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Summary: Congenital platelet disorders (CPDs) are rare bleeding disorders that are associated with mucocutaneous bleeds. However, data on vaginal bleeding in women with CPDs are scarce. A set of generic and bleeding‐specific questionnaires were used to evaluate the prevalence of vaginal bleeding, its impact on quality of life (QoL) and sexual functioning and the consequences for pregnancy, miscarriage and delivery in a cohort of women who were referred for diagnostic evaluation for CPDs. A total of 78 women included in the study were either diagnosed with a CPD (n = 35) or were clinically suspected of a CPD (n = 43). Heavy menstrual bleeding (HMB) was reported by a large proportion of women, which mainly started at menarche. In all, 76% of women received any kind of HMB treatment, often leading to surgical prodecures. HMB was shown to have a high impact on QoL, which improved upon treatment. Even though women reported that vaginal bleeding affects sexuality, this topic is not frequently discussed with physicians. Heavy blood loss frequently occurred after miscarriage/delivery, often requiring treatment. Women with (suspected) CPDs frequently encounter HMB, negatively impacting daily life and sexual functioning. Together with peripartum bleeding, these data highlight the burden of vaginal bleeding in CPDs and importance of adequate treatment. [ABSTRACT FROM AUTHOR]

Summary. 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. [ABSTRACT FROM AUTHOR]

SUMMARY: Objectives: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion‐associated circulatory overload ('TACO'). Background: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion. Methods: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B‐coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0‐ to 100‐point scale. Results: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [β 0·4(−0·1–1·0)], positive fluid balance [β 0·9(0·4–1·5)] and history of renal failure [β 0·6(0·1–1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [β 0·3(−0·2–0·7) resp. 0·5(−0·1–1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [β 0·3(−0·8–1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50–80) resp. 60 (IQR 50–80)]. No differences were observed between disciplines involved. Conclusion: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes. [ABSTRACT FROM AUTHOR]

Introduction: The bleeding assessment tool (BAT) has been developed to standardize and interpret bleeding history for mild bleeding disorders. However, a critical appraisal addressing the quality and results of validation studies is lacking. Aim: We performed a systematic review of diagnostic studies assessing the performance of the BAT in patients referred for evaluation of bleeding symptoms. Methods: The electronic database PubMed was searched from inception through July 27, 2017. Eligible publications were original studies that assessed and validated the diagnostic accuracy of bleeding questionnaires for identification of adults with mild bleeding disorders. For each study, sensitivity, specificity and diagnostic odds ratio (DOR) were calculated. Quality was assessed using the Quality Assessment of Diagnostic studies‐2 tool. To assess the influence of specific study characteristics on DOR, univariate meta‐regression analyses were performed. Results: Nine studies were included. Five studies investigating the ISTH‐BAT or other bleeding questionnaires had a moderate to low DOR. Four studies investigating Vicenza‐based BATs had a high DOR, with high specificity (>90%) and sensitivity of 59%‐85%. Study characteristics such as case‐control design, retrospective data collection and differences in reference standard were associated with optimistic estimates of diagnostic performance. Three of four studies with a high DOR had these study characteristics. Studies with good methodological quality mainly had a low DOR. Conclusion: The main advantage of the BAT is that it offers a complete and structured interview. However, the BAT is of limited diagnostic value to the workup of patients referred for bleeding evaluation in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objectives In this study, differences in levels of proteins involved in coagulation and fibrinolysis were compared between fresh frozen (quarantine plasma) and Omniplasma. Furthermore, thawing conditions and plasma stability after thawing were studied. Materials and Methods 10 Omniplasma and 10 quarantine plasma units were used to study different procoagulation, anticoagulation and fibrinolytic parameters. Analysis took place at different time-points during plasma storage at 2-6°C. Results At baseline, significant reduced levels of factor V, free protein S, α2-antiplasmin and tPA-induced ROTEM lysis time were observed in Omniplasma as compared to quarantine plasma. Moreover, thrombin generation, IXa- AT complex levels and factor XIa were significantly increased in Omniplasma. The majority of the parameters studied remained stable in Omniplasma 48 h after thawing, with the exception of factor VIII (decrease) and IXa- AT (increase). Conclusion Our results suggest an increased coagulation potential, presumingly as a result of contact activation during the production process and also, an increased fibrinolytic potential in Omniplasma. The stability of Omniplasma, based upon the different parameters studied, is comparable to Q-plasma. A maximum post-thawing time of 48 hfor Omniplasma can be suggested. [ABSTRACT FROM AUTHOR]