Mortality after red blood cell transfusions from previously pregnant donors: complexities in the interpretation of large data

Abstract

Red blood cell (RBC) transfusion is a common and potentially life-saving intervention. The requirement for RBC transfusions inherently reflects a degree of illness in the recipient, and healthy individuals do not generally require blood transfusions. In the recent past, restrictive blood transfusion policies have improved patient outcomes with the added benefit of driving down medical costs (1). Other policies and advances in cell preservation technology such as ABO and Rh matching, leukoreduction and limitations in the age of storage (to the age of RBC viability) of blood products have decreased recipient morbidity and mortality (1-3). However, the concept that RBC donor female gender and parity may influence recipient mortality has been a subject of much debate in the blood banking community and differing conclusions are reported in several large retrospective studies (4,5). Here we comment on the recent article by published inJAMA reporting increased mortality in male recipients of RBC units from female donors who had ever been pregnant compared with male recipients of RBC units from male donors.In this retrospective cohort study of first ever RBC transfusion recipients, the authors aimed to "quantify the association between RBC transfusion from female blood donors, with and without a history of pregnancy, and patient mortality in female and male transfusion recipients." They utilized three methodologies analyzing mortality results over a 10-year follow-up period in 42,132 recipients of RBC transfusions.The primary methodology, utilizing a "no-donor-mixture" cohort, was designed to prevent dilution effects by censoring or excluding recipient data when RBC products from more than one donor type were given. In these analyses, 31,118 recipients received 59,320 units from predominantly male (88%) donors. Never-pregnant female (NPF) and everpregnant female (EPF) RBC units comprised 6% each of the total donor pool. The second methodology utilized recipients who received only a single RBC unit (16,959 recipients). Finally, the third methodology utilized the full cohort, including recipients of multiple donor unit types. In the Netherlands, all transfusion information and mortality data are tracked within a national registry that includes age, gender, and dates of death but excludes information about ethnicity/race. All blood products were leukocyte-reduced by pre-storage filtration. Pregnancy status was obtained via self-reporting and due to an unknown pregnancy status, 44% of the donations from females were not used. All other transfused products were ignored in the primary analyses.There were 3,969 deaths over a 10-year follow-up period within the "no-mixture" cohort. Cox proportional hazards models were utilized and categorical variables were fit into the model to correct for potential confounding. These potential confounders included institution, ABORhD blood group, age of the donor, and cumulative number of transfusions. Resulting hazard ratios (HRs) were calculated for each of the two exposure groups (i.e., ...

Blood donor–recipient sex mismatch: outcomes impacted?

“…The availability of large data warehouses linking donors and their characteristics to recipients and their outcomes provides enormous scientific potential. However, questions asked of this data must be carefully analysed given the risk for subtle confounding [19,23]. The current evidence for increased mortality associated with sex-mismatching between red cell donors and recipients is conflicting.…”

“…This raises the question of case-mix. As pointed out by Kuldanek and Silliman, a young-male population may be enriched for trauma victims, who would be at increased risk for both massive transfusion and increased mortality by virtue of their underlying illness [19].…”

Perioperative Transfusion is Related to the Length of Hospital Stays in Primary Liver Cancer Patients

“… 3 Previous studies suggested that the storage time of red blood cells (RBCs) may lead to immunosuppression. 4 , 5 RBCs undergo morphologic and functional changes during the duration for storage 6 (what is called “storage lesions”), including imbalance of the cell membrane expression of CD47 and phosphatidylserine, which can contribute to activate the immune system. 7 Moreover, during storage, cytokines and other immunomodulatory substances accumulate in the supernatant and trigger the activation of immune cells.…”