The Effect of Sex-Mismatched Red Blood Cell Transfusion on Endothelial Cell Activation in Critically Ill Patients

Alshalani, Abdulrahman; Manen, Lisa van; Boshuizen, Margit; Bruggen, Robin van; Acker, Jason P.; Juffermans, Nicole P.

doi:10.1159/000520651

Cited by 6 publications

(4 citation statements)

References 56 publications

(71 reference statements)

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“…Despite the patient receiving several platelet transfusions, although it is difficult to prove unequivocally that SDC-1 levels are unaffected by platelet concentrate transfusion, there is currently no clear evidence that they increased serum SDC-1 concentrations, and as such we believe that their effect on values is limited ( 30 , 31 ). With regards to erythrocyte transfusions however, a previous study demonstrated that transfusion of a single sex-mismatched RBC unit was associated with higher SDC-1 levels than transfusion of a sex-matched RBC unit ( 32 ). Finally, as the patient required intensive care and various medications were administered, it is likely that drugs affected the patient, and future studies are needed to delineate the specific impact.…”

Section: Discussionmentioning

confidence: 99%

Serum syndecan-1 concentration in hemolysis, elevated liver enzymes, and low platelets syndrome: A case report

et al. 2023

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BackgroundHemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome occurs in pregnant and postpartum individuals. We observed serum syndecan-1 (SDC-1) levels, which is a component of the glycocalyx, in a patient with HELLP syndrome from admission to the postpartum period and examined their association as reflecting the pathophysiology related to endothelial injury.Case presentationA 31-year-old primiparous female patient without a previous medical history at a gestational age of 37 weeks and 6 days was transferred to our hospital the morning after a visit to a previous hospital with headache and nausea. Elevated transaminase, platelet count, and proteinuria were noted. Head magnetic resonance imaging revealed a caudate nucleus hemorrhage and posterior reversible encephalopathy syndrome. After she delivered her newborn through an emergency cesarean section, she was admitted to the intensive care unit. On day 4 post-delivery, the patient’s D-dimer concentration was elevated, and contrast-enhanced computed tomography was performed. The results indicated pulmonary embolism, and heparin administration was initiated. The serum SDC-1 level was highest on day 1 post-delivery and quickly decreased subsequently; however, it remained elevated during the postpartum period. Her condition gradually improved, and she was extubated on day 6 and discharged from the ICU on day 7 post-delivery.ConclusionWe measured SDC-1 concentration in a patient with HELLP syndrome and found that the clinical course correlated with SDC-1 levels, indicating that SDC-1 is elevated immediately before and after pregnancy termination in patients with HELLP syndrome. Therefore, SDC-1 fluctuations, combined with the elevation of the D-dimer level, may be a potential marker for the early detection of HELLP syndrome and estimation of the syndrome’s severity in the future.

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Section: Discussionmentioning

confidence: 99%

Serum syndecan-1 concentration in hemolysis, elevated liver enzymes, and low platelets syndrome: A case report

et al. 2023

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“…Implicated cytokines and chemokines include IFN-γ, IL-6 and IL-8,32 33 which differed between the transfusion exposure groups in the current study. Donor sex-related immunomodulation, with increases in proinflammatory cytokines, also contributes to endothelial activation, a potential predictive marker for transfusion-associated adverse outcomes and recently shown to be increased with sex-mismatched PRBC exposure 34…”

Section: Discussionmentioning

confidence: 99%

Does donor sex influence the potential for transfusion with washed packed red blood cells to limit transfusion-related immune responses in preterm newborns?

Crawford

Andersen

Marks

et al. 2023

Arch Dis Child Fetal Neonatal Ed

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ObjectiveTo evaluate the association of donor sex with transfusion-associated recipient immune responses in preterm newborns receiving unwashed and washed blood.DesignA cohort study using data collected during the Effect of Washed versus Unwashed Packed Red Blood Cell Transfusion on Immune Responses in the Extremely Preterm Newborn randomised trial.SettingParticipants were recruited from two South Australian hospitals between September 2015 and December 2020.PatientsPreterm newborns (<29 weeks).InterventionsTransfusion with unwashed and washed packed red blood cells (PRBCs) from either exclusively male or any female donor for the first three transfusions.Main outcomes measuresThe primary outcome was the change from baseline in post-transfusion plasma cytokine concentrations, specifically interferon gamma, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, IL-17A and tumour necrosis factor (TNF).ResultsIn total, 153 newborns were evaluated. By the third transfusion, the magnitude of pretransfusion to post-transfusion change in cytokines between the groups differed for IL-6 (p=0.003), IL-12 (p=0.008), IL-17A (p=0.003) and TNF (p=0.007). On post hoc comparison, compared with the unwashed–any female donor group, IL-6 (p<0.05), IL-12 (p<0.05) and IL-17A (p<0.01) were lower in the washed–exclusively male donor group, and IL-6 (p<0.01), IL-12 (p<0.05) and TNF (p<0.01) were lower in the washed–any female donor group.ConclusionThese findings suggest that transfusion with unwashed PRBCs from female donors is associated with an increased recipient immune response, an effect that can be ameliorated with pretransfusion washing. Larger randomised controlled studies confirming this mechanistic link between donor sex and transfusion-associated morbidity are warranted.Trial registration numberACTRN12613000237785.

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“…Donor sex related immunomodulation, with increases in pro-inflammatory cytokines, also contributes to endothelial activation. This is a potential predictive marker for transfusion associated adverse outcomes and has recently been shown to be increased with sex mismatched RBC transfusion exposure [ 69 ]. In vitro data supports the release of markers of endothelial activation following the incubation of endothelial cells with blood product supernatant [ 70 , 71 ].…”

Section: How Might Donor Sex Influence Outcome?mentioning

confidence: 99%

“…The link between transfusion exposure and endothelial activation may be directly related to post-transfusion increases in pro-inflammatory cytokines [ 73 ], a response observed in the preterm newborn [ 43 , 44 ], or due to the presence of free heme and non-transferrin bound iron [ 74 , 75 ]. Recently, Alshalani and colleagues reported significantly greater post-transfusion concentrations of syndecan-1 and soluble thrombomodulin in adult intensive care patients who received a single sex-mismatched RBC transfusion compared to those who received sex-matched blood [ 69 ]. Critically, both syndecan-1 and soluble thrombomodulin are known predictors of in-hospital mortality [ 76 ].…”

Section: How Might Donor Sex Influence Outcome?mentioning

confidence: 99%

Red Blood Cell Donor Sex Associated Effects on Morbidity and Mortality in the Extremely Preterm Newborn

2022

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Transfusion exposure increases the risk of death in critically ill patients of all ages. This was thought to relate to co-morbidities in the transfusion recipient. However, donor characteristics are increasingly recognised as critical to transfusion recipient outcome with systematic reviews suggesting blood donor sex influences transfusion recipient health. Originally focusing on plasma and platelet transfusions, retrospective studies report greater risks of adverse outcomes such as transfusion related acute lung injury in those receiving products from female donors. There is increasing awareness that exposure to red blood cells (RBCs) poses a similar risk. Recent studies focusing on transfusion related outcomes in extremely preterm newborns report conflicting data on the association between blood donor sex and outcomes. Despite a renewed focus on lower versus higher transfusion thresholds in neonatal clinical practice, this group remain a heavily transfused population, receiving on average 3–5 RBC transfusions during their primary hospital admission. Therefore, evidence supporting a role for better donor selection could have a significant impact on clinical outcomes in this high-risk population. Here, we review the emerging evidence for an association between blood donor sex and clinical outcomes in extremely preterm newborns receiving one or more transfusions.

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The Effect of Sex-Mismatched Red Blood Cell Transfusion on Endothelial Cell Activation in Critically Ill Patients

Cited by 6 publications

References 56 publications

Serum syndecan-1 concentration in hemolysis, elevated liver enzymes, and low platelets syndrome: A case report

Serum syndecan-1 concentration in hemolysis, elevated liver enzymes, and low platelets syndrome: A case report

Does donor sex influence the potential for transfusion with washed packed red blood cells to limit transfusion-related immune responses in preterm newborns?

Red Blood Cell Donor Sex Associated Effects on Morbidity and Mortality in the Extremely Preterm Newborn

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