Background and ObjectivesDonor characteristics have been implicated in transfusion-related adverse events. Uncertainty remains about whether sex, and specifically pregnancy history of the blood... Show moreBackground and ObjectivesDonor 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 MethodsWe 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.ResultsThe 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.ConclusionThese findings do not consistently support the notion that the observed association between ever-pregnant donor units and mortality is mediated by blood product storage. Show less
Oud, J.A.; Evers, D.; Haas, M. de; Vooght, K.M.K. de; Kerkhof, D. van de; Som, N.; ... ; Zwaginga, J.J. 2022
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... Show moreMaternal 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 center dot 6%) females and 49 of 2507 (2 center dot 0%) males. Comparing females and males, overall alloimmunisation incidences were comparable (3 center dot 1% [95% confidence interval (CI) 2 center dot 1-4 center dot 4] versus 3 center dot 5% (95% CI 2 center dot 4-4 center dot 9, P = 0 center dot 853) after 10 units transfused). However, cEK alloimmunisation incidences were significantly lower among females (0 center dot 6% (95% CI 0 center dot 3-1.5) versus 2 center dot 2% (95% CI 1 center dot 5-3 center dot 4, P = 0 center dot 001) after 10 units transfused). Yet, despite cEK-matching guidelines being in effect, 6 center dot 5%, 3 center dot 6% and 0 center dot 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%. Show less
Cornelissen, L.L.; Caram-Deelder, C.; Meier, R.T.; Zwaginga, J.J.; Evers, D.; Dutch Blood Transfusion Related R 2020
Objectives There is scarce evidence about the effectiveness of anti-bleeding measures in hematological outpatients experiencing persistent severe thrombocytopenia. We aim to describe clinical... Show moreObjectives There is scarce evidence about the effectiveness of anti-bleeding measures in hematological outpatients experiencing persistent severe thrombocytopenia. We aim to describe clinical practice and clinicians' considerations on the administration of prophylactic platelet transfusions and tranexamic acid (TXA) to outpatients with acute leukemia, myelodysplastic syndrome (MDS), or aplastic anemia (AA) in the Netherlands.Methods We conducted an online survey among members of the Dutch Society for Hematology.Results The survey was filled out by 73 respondents. Prophylactic platelet transfusions are widely used in acute leukemia and MDS outpatients receiving disease-modifying treatments (87%-98% of respondents). TXA is predominantly prescribed in case of bleeding (tendency) (71%-88% of respondents). Conditions potentially increasing bleeding risks highly variably influence clinicians' decision making on anti-bleeding regimens, which includes a wide range in adhered platelet thresholds.Conclusion Considering that both the contribution of prophylactic platelet transfusions as well as TXA to limiting bleeding is insufficiently evidence-based, there is an urgent need for trials on optimal anti-bleeding strategies in this outpatient population, which should encompass efficacy, logistic, financial, and quality-of-life aspects. Show less
Oud, J.A.; Evers, D.; Middelburg, R.A.; Vooght, K.M.K. de; Kerkhof, D. van de; Visser, O.; ... ; Zwaginga, J.J. 2020
Background Renal failure and renal replacement therapy (RRT) affect the immune system and could therefore modulate red blood cell (RBC) alloimmunization after transfusion.Study Design and Methods... Show moreBackground Renal failure and renal replacement therapy (RRT) affect the immune system and could therefore modulate red blood cell (RBC) alloimmunization after transfusion.Study Design and Methods We performed a nationwide multicenter case-control study within a source population of newly transfused patients between 2005 and 2015. Using conditional multivariate logistic regression, we compared first-time transfusion-induced RBC alloantibody formers (N = 505) with two nonalloimmunized recipients with similar transfusion burden (N = 1010).Results Renal failure was observed in 17% of the control and 13% of the case patients. A total of 41% of the control patients and 34% of case patients underwent acute RRT. Renal failure without RRT was associated with lower alloimmunization risks after blood transfusion (moderate renal failure: adjusted relative rate [RR], 0.82 [95% confidence interval (CI), 0.67-1.01]); severe renal failure, adjusted RR, 0.76 [95% CI, 0.55-1.05]). With severe renal failure patients mainly receiving RRT, the lowest alloimmunization risk was found in particularly these patients [adjusted RR 0.48 (95% CI 0.39-0.58)]. This was similar for patients receiving RRT for acute or chronic renal failure (adjusted RR, 0.59 [95% CI, 0.46-0.75]); and adjusted RR, 0.62 [95% CI 0.45-0.88], respectively).Conclusion These findings are indicative of a weakened humoral response in acute as well as chronic renal failure, which appeared to be most pronounced when treated with RRT. Future research should focus on how renal failure and RRT mechanistically modulate RBC alloimmunization. Show less
Hoeks, M.; Pol, M. van der; Middelburg, R.; Evers, D.; Kraaij, M. van; Zwaginga, J.J. 2018
Transfusion of red blood cells (RBCs) causes exposure to foreign antigens and, consequently, may induce alloimmunization. This research focused on identifying clinical determinants of RBC... Show moreTransfusion of red blood cells (RBCs) causes exposure to foreign antigens and, consequently, may induce alloimmunization. This research focused on identifying clinical determinants of RBC alloimmunization, eventually aiming to prevent alloimmunization by pre-emptively select extended matched blood for the predicted responder patient. Both RBC antigen intrinsic characteristics and patient-related factors were studied. Regarding antigen immunogenicity, K was confirmed to be the most potent antigen, followed by E, Cw, e, Jka and c. Of importance, anti-Jka is known to easily induce complement-mediated hemolysis. Inflammation due to severe bacterial and viral infections was associated to increased RBC alloimmunization incidences. Remarkably, although in line with murine models, Gram-negative bacteremia coincided with a twofold reduction of alloimmunization risk. In a non-hemoglobinopathy population, alloimmunization post-splenectomy was a highly unlikely event. Consequently, the Caucasian splenectomized patient does not benefit from RBC products matched beyond ABO/RhD. Patients with acute (either myeloid of lymphoblastic) leukemia, mature lymphomas, myelodysplastic syndrome, or patients post-autologous or -allogeneic stem cell transplantation demonstrated strongly reduced incidences of RBC alloimmunization, primarily explained by the intense immunosuppressive nature of treatments. Consequently, matching for the MDS population deserves renewed focus and should be based on the cumulative transfusion burden rather than on the diagnosis itself. Show less
