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Zalpuri S.,Center for Clinical Transfusion Research | Middelburg R.A.,Center for Clinical Transfusion Research | Schonewille H.,Center for Clinical Transfusion Research | De Vooght K.M.K.,Center for Clinical Transfusion Research | And 3 more authors.
Transfusion | Year: 2014

Background Exposure to allogenic red blood cells (RBCs) may lead to formation of antibodies against nonself-antigens in transfused patients. While alloimmunization rates are known to increase with the number of transfusions, the transfusion course in patients can vary from receiving multiple units during a single transfusion event or getting them dispersed over a long(er) period. In this study we compared the immunization risk between different transfusion intensities. Study Design and Methods An incident new-user cohort study was conducted among consecutive transfused patients at two university medical centers. All patients who received their first RBC transfusion within the study period from January 2005 to December 2011 were eligible. Intensive transfusions were defined as at least 5, at least 10, and at least 20 RBC units within 48 hours. Alloimmunization hazard ratios (HRs), comparing patients receiving intensive transfusions to patients never receiving intensive transfusions, were estimated. Results The study cohort was composed of 5812 patients who had received a median of 7 (interquartile range, 4-12) units. RBC alloantibodies were formed by 156 patients. The adjusted Cox regression HRs for alloimmunization, with number of units as the time covariate and adjusted for patient age, sex, and follow-up time after first transfusion, ranged from 0.8 to 1.2 (95% confidence interval, 0.4-2.6). Conclusion The occurrence of RBC alloimmunization in patients receiving intensive transfusions did not differ significantly from patients receiving nonintensive transfusions. © 2013 American Association of Blood Banks.

van der Bom J.G.,Center for Clinical Transfusion Research | van der Bom J.G.,Leiden University
British Journal of Haematology | Year: 2014

This systematic review was designed to summarize the reported valid quantitative evidence on the association between use of von Willebrand factor (VWF)-containing Factor VIII (FVIII) concentrates and successful immune tolerance induction (ITI) in patients with severe haemophilia A. The primary outcome was successful ITI; secondary outcomes were time to success, complications of the inhibitor or ITI and relapse of the inhibitor. A systematic literature search identified 26 randomized controlled trials, registries and cohort studies, evaluating a total of 1284 patients. For a pooled meta-analysis, 13 studies evaluating 382 patients were included. Due to incomplete data we were not able to assign pre-ITI risk categories to all patients for risk factor analysis. The meta-analysis did not demonstrate a difference in the proportion of patients with successful inhibitor eradication between those treated with VWF-containing products and those treated with FVIII concentrates devoid of VWF (relative risk [RR] 0·70 (95% confidence interval [CI] 0·52-0·89) and 0·84 (95% CI 0·75-0·93) respectively). Bleeding rate during ITI ranged from 0·00 to 0·85 bleeding episodes per year. The proportion of patients with a relapse of the inhibitor (range 0-20%) was mentioned in four studies that were included in the meta-analysis. The results of this systematic review do not support the idea of a positive effect of VWF-containing products in ITI. © 2014 John Wiley & Sons Ltd.

Middelburg R.A.,Center for Clinical Transfusion Research | Roest M.,Leiden University | Ham J.,Leiden University | Coccoris M.,Leiden University | And 2 more authors.
Transfusion | Year: 2013

Background Platelet (PLT) function in PLT concentrates declines during storage and is further affected by pathogen reduction treatment. Flow cytometric assessment of agonist-induced P-selectin expression can be used to assess PLT function in patients with thrombocytopenia. The aim of this study was to evaluate how this functional test relates to established in vitro measures of PLT function. Study Design and Methods Six units of PLTs in plasma and 6 units of riboflavin and ultraviolet (Mirasol, TerumoBCT)-treated PLTs in plasma were sampled on Days 2, 6, 8, and 10 after donation. PLT concentration, Annexin 5A staining, ThromboLUX (LightIntegra) thrombelastography, and P-selectin expression, both in unstimulated PLTs and in response to concentration series of adenosine diphosphate, collagen-related peptide, and thrombin receptor-activating peptide (TRAP), were measured. Results For PLTs in plasma Annexin 5A expression increased by 0.60% (95% confidence interval [CI], 0.40%-0.80%) and P-selectin expression increased by 1.2% (95% CI, 0.80%-1.6%) per day. Responsiveness to TRAP simultaneously decreased by 1.3% (95% CI, 0.80%-1.8%) per day. After Mirasol treatment ThromboLUX scores decreased 3.3 points (95% CI, 0.2-6.4 points) from 22 to 19 points, Annexin 5A expression increased by 4.8% (95% CI, 3.3%-6.2%), and P-selectin expression increased by 13% (95% CI, 10%-16%), all averaged over the entire storage period. Responsiveness to TRAP simultaneously decreased by 19% (95% CI, 17%-21%). Conclusions Our results suggest flow cytometric measurement of agonist-induced P-selectin expression can measure PLT quality decline over the entire range encountered during 10-day storage of both standard PLTs and Mirasol-treated PLTs in plasma. © 2012 American Association of Blood Banks.

Van De Watering L.M.G.,Center for Clinical Transfusion Research
Current Opinion in Hematology | Year: 2013

PURPOSE OF REVIEW: Possible adverse effects of prolonged storage of red blood cell concentrates (RBCs) are being formally assessed both by observational studies and in randomized controlled trials. New mechanisms have been put forth to explain earlier conflicting observations. This review summarizes ongoing investigations into clinical and basic science studies on RBC storage effects. RECENT FINDINGS: Research into possible deleterious clinical effects of prolonged storage of RBCs has explored the contribution of various RBC production aspects (e.g. overnight hold, centrifugation speed, storage solution), seldom previously reported. Other studies investigated putative underlying mechanisms like free iron, inflammation, cytokines, and so on. Many publications include multiple analyses, like different cut-off values for 'old', or taking into account both oldest and average RBC storage time. Also, more studies correct for possible confounding effects to get a better estimate of associations. An alarming and ironic observation is that several studies found higher risks with fresh RBCs after correction for confounding. The results from the first large randomized controlled trials show no differences between old and fresh RBCs. SUMMARY: We still do not know whether older red cells have adverse effects, and if so, what determines such clinical effects after transfusion of 'old' RBCs. RBC production factors, previously seldom reported, may play an important role and should be reported.© 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.

Schonewille H.,Center for Clinical Transfusion Research | Schonewille H.,Leiden University | Doxiadis I.I.N.,Leiden University | Levering W.H.B.M.,Laboratory for Histocompatibility and Immunogenetics | And 3 more authors.
Transfusion | Year: 2014

Background A minority of red blood cell (RBC) alloantigen-exposed persons form antibodies. Responders are at high risk of developing additional antibodies upon subsequent transfusions. Several studies showed an association between particular HLA-DRB1 phenotypes and the development of specific RBC antibodies. This study evaluates the presence of HLA-DRB1 antigens in individuals with single or multiple RBC antibody specificities to explore whether the response against RBC antigens is associated with a summation of particular HLA-DRB1 susceptibility antigens. Study Design and Methods Frequencies of HLA-DRB1 alleles in individuals with antibodies against clinically relevant antigens were compared to a large population cohort to calculate odds ratios (ORs) for alloimmunization to different RBC antigens. Results The study cohort consisted of 941 individuals (female-to-male ratio, 3.8) possessing 1462 antibody specificities elicited by transfusion, pregnancy, transplantation, or a combination of these. Besides confirmation of known associations, new associations were identified for anti-E with DRB109 and for anti-S with DRB107 (ORs, 3.7 and 8.7, respectively). Multiple antibody formation was in a minority of cases associated with the presence of multiple DRB1 susceptibility genes. In multiple responders DRB115 was present in almost 40% of cases compared to approximately 25% in single-antibody responders and in the control population. Conclusion This study suggests that HLA-DRB1 restriction plays an important role for a first RBC antibody response but multiple antibody formation seems less dependent on the presence of particular HLA restriction genes, while HLA-DRB115 may represent a susceptibility phenotype enhancing formation of multiple RBC antibody specificities. © 2014 AABB.

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