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Background The identification of blood donors at risk of developing low hemoglobin (Hb) and subsequent intervention is expected to reduce donation-induced iron deficiency and low Hb among blood donors. This study explores the effects of ferritin-guided iron supplementation for female first-time donors implemented in four of five administrative regions in Denmark. Study Design and Methods We included 45,919 female first-time donors in this study. Hb values were determined in donations of included donors during a 2-year follow-up period. For each region, an intervention group (after implementation) and a control group (before implementation) were defined. The primary outcome was Hb below the donation threshold (7.8 mmol/L ~ 12.5 g/dL) at the time of donation, in the control group, and the intervention group, using logistic regression. The secondary outcome was the number of donations per donor given during the follow-up period. Results We observed a statistically significant decrease in the risk of female first-time donors experiencing a donation with low Hb after ferritin-guided iron supplementation was introduced: Odds ratio, 0.82; 95% confidence interval (CI), 0.71–0.95. We found a statistically significant increase in the number of donations per donor during the follow-up period after intervention; rate ratio: 1.05, 95% CI: 1.02–1.08. Discussion Ferritin-guided iron supplementation led to a significant reduction in the occurrence of low hemoglobin (Hb) levels among Danish female first-time blood donors. The intervention was additionally associated with an increase in the number of donations per donor., Background The identification of blood donors at risk of developing low hemoglobin (Hb) and subsequent intervention is expected to reduce donation-induced iron deficiency and low Hb among blood donors. This study explores the effects of ferritin-guided iron supplementation for female first-time donors implemented in four of five administrative regions in Denmark. Study Design and Methods We included 45,919 female first-time donors in this study. Hb values were determined in donations of included donors during a 2-year follow-up period. For each region, an intervention group (after implementation) and a control group (before implementation) were defined. The primary outcome was Hb below the donation threshold (7.8 mmol/L ~ 12.5 g/dL) at the time of donation, in the control group, and the intervention group, using logistic regression. The secondary outcome was the number of donations per donor given during the follow-up period. Results We observed a statistically significant decrease in the risk of female first-time donors experiencing a donation with low Hb after ferritin-guided iron supplementation was introduced: Odds ratio, 0.82; 95% confidence interval (CI), 0.71–0.95. We found a statistically significant increase in the number of donations per donor during the follow-up period after intervention; rate ratio: 1.05, 95% CI: 1.02–1.08. Discussion Ferritin-guided iron supplementation led to a significant reduction in the occurrence of low hemoglobin (Hb) levels among Danish female first-time blood donors. The intervention was additionally associated with an increase in the number of donations per donor.

Background: The classic Bernard-Soulier syndrome (BSS) is a rare inherited thrombocytopenia (IT) associated with severe thrombocytopenia, giant platelets, and bleeding tendency caused by homozygous or compound heterozygous variants in GP1BA, GP1BB, or GP9. Monoallelic BSS (mBSS) associated with mild asymptomatic macrothrombocytopenia caused by heterozygous variants in GP1BA or GP1BB may be a frequent cause of mild IT. Objective: We aimed to examine the frequency of mBSS in a consecutive cohort of patients with IT and to characterize the geno- and phenotype of mBSS probands and their family members. Additionally, we set out to examine if thrombopoietin (TPO) levels differ in mBSS patients. Patients/Methods: We screened 106 patients suspected of IT using whole exome- or whole genome sequencing and performed co-segregation analyses of mBSS families. All probands and family members were phenotypically characterized. Founder mutation analysis was carried out by certifying that the probands were unrelated and the region around the variant was shared by all patients. TPO was measured by solid phase sandwich ELISA. Results: We diagnosed 14 patients (13%) with mBSS associated with heterozygous variants in GP1BA and GP1BB. Six unrelated probands carried a heterozygous variant in GP1BA (c.58T>G, p.Cys20Gly) and shared a 2.0 Mb region on chromosome 17, confirming that it is a founder variant. No discrepancy of TPO levels between mBSS patients and wild-type family members (P >.05) were identified. Conclusion: We conclude that the most frequent form of IT in Denmark is mBSS caused by the Copenhagen founder variant.

Inherited thrombocytopenia is a heterogeneous group of hereditary disorders with varying bleeding tendencies, not simply related to platelet count. Platelets transform into different subpopulations upon stimulation, including procoagulant platelets and platelet microparticles (PMPs), which are considered critical for haemostasis. We aimed to investigate whether abnormalities in PMP and procoagulant platelet function were associated with the bleeding phenotype of inherited thrombocytopenia patients. We enrolled 53 inherited thrombocytopenia patients. High-throughput sequencing of 36 inherited thrombocytopenia related genes was performed in all patients and enabled a molecular diagnosis in 57%. Bleeding phenotype was evaluated using the ISTH bleeding assessment tool, dividing patients into bleeding (n = 27) vs. nonbleeding (n = 26). Unstimulated and ADP, TRAP or collagen-stimulated PMP and procoagulant platelet functions were analysed by flow cytometry using antibodies against granulophysin (CD63), P-selectin (CD62P), activated GPIIb/IIIa (PAC-1) and a marker for phosphatidylserine expression (lactadherin). Procoagulant platelets were measured in response to collagen stimulation. An in-house healthy reference level was available. Overall, higher levels of activated platelets, PMPs and procoagulant platelets were found in nonbleeding patients compared with the reference level. Nonbleeding patients had higher proportions of phosphatidylserine and PMPs compared with bleeding patients and the reference level, in response to different stimulations. Interestingly, this finding of high proportions of phosphatidylserine and PMPs was limited to PMPs, and not present in procoagulant platelets or platelets. Our findings indicate that nonbleeding inherited thrombocytopenia patients have compensatory mechanisms for improved platelet subpopulation activation and function, and that generation of phosphatidylserine expressing PMPs could be a factor determining bleeding phenotype i

Genetic variants in growth factor-independent 1B (GFI1B), encoding transcription factor GFI1B, are causative of platelet-type bleeding disorder-17. Presently, 53 cases of GFI1B associated inherited thrombocytopenia (IT) have been published, however only three were homozygous. The bleeding- and platelet phenotypes of these patients depend on location and inheritance pattern of the GFI1B variant. We report a novel homozygous GFI1B (Thr174Ile) variant located in the first Zinc finger domain of GFI1B in two sisters of Palestinian ancestry born to consanguineous parents. They experienced severe bleeding tendency at moderately reduced platelet counts. Flow cytometry and immunofluorescent microscopy confirmed the diagnostic features of GFI1B associated IT: a reduced content of alpha granules and aberrant expression of the stem cell marker CD34 on platelets. Transcription factor GFI1B is differentially expressed during hemato- and lymphopoiesis. In addition, to platelet function investigations, we present results of lymphoid subgroup analyses and deformability of red cells measured by ektacytometry.

Purpose We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case–control study. Methods Cases were all women in Denmark diagnosed with endometrial cancer during 2000–2009. Age-matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated. Results We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated with use of low-dose aspirin (OR 0.97, 95 % CI 0.89–1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91–1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70–0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82–0.99). Conclusions We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some indications of risk reductions associated with low-dose aspirin use among nulliparous women and with non-aspirin NSAID use among women having used HRT., PURPOSE: We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study.METHODS: Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age-matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated.RESULTS: We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70-0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82-0.99).CONCLUSIONS: We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some indications of risk reductions associated with low-dose aspirin use among nulliparous women and with non-aspirin NSAID use among women having used HRT.