Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in... Show moreIntroduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin.Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model.Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R-2 7%-44% across cohorts).Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations. Show less
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch... Show moreBackground: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn's and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn's Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that-despite inconsistently measured iron parameters-is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. Show less
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch... Show moreBackground: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. Show less
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch... Show moreBackground: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. Show less
Haploinsufficiency for Endoglin (ENG) and activin A receptor type II-like I (ACVRL1/ALK1) lead to the formation of weak and abnormal vessels in hereditary hemorrhagic telangiectasia (HHT). These... Show moreHaploinsufficiency for Endoglin (ENG) and activin A receptor type II-like I (ACVRL1/ALK1) lead to the formation of weak and abnormal vessels in hereditary hemorrhagic telangiectasia (HHT). These cause epistaxis (nosebleeds) and/or gastrointestinal blood loss. In vitro in cultured endothelial cells, tacrolimus has been shown to increase ENG and ALK1 expression. It is, therefore, a potential treatment option. We report here a proof-of-concept study in patients with HHT and severe epistaxis and/or gastrointestinal bleeding who were treated daily with orally-administered tacrolimus for twenty weeks. Twenty-five patients with HHT (11 females (44%)) and median age of 59 years were enrolled. Five patients (20%) stopped the trial prematurely-four due to (serious) adverse events ((S)AE). Twenty patients were included in further analyses. Hemoglobin levels increased during tacrolimus treatment from 6.1 (IQR 5.2-6.9) mmol/L at baseline (9.8 g/dL) to 6.7 (6.5-7.1) mmol/L (10.8 g/dL), p = 0.003. The number of blood transfusions over the twenty weeks decreased from a mean of 5.0 (+/- 9.2) to 1.9 (+/- 3.5), p = 0.04. In 64% of the patients, at least one AE occurred. Oral tacrolimus, thus, significantly increased hemoglobin levels and decreased blood transfusion needs, epistaxis and/or gastrointestinal bleeding in patients with HHT. However, side-effects were common. Further investigation of the potential therapeutic benefit is justified by the outcome of the study. Show less
Kranenburg, F.J.; Arbous, S.M.; Caram-Deelder, C.; Putter, H.; Cessie, S. le; Bom, J.G. van der 2022
Background To develop a model for the prediction of the (most likely) effect of red blood cell (RBC) transfusion on subsequent organ functioning in nonbleeding critically ill patients with... Show moreBackground To develop a model for the prediction of the (most likely) effect of red blood cell (RBC) transfusion on subsequent organ functioning in nonbleeding critically ill patients with hemoglobin concentrations between 6 and 9 g/dL. Study Design and Methods We conducted a retrospective cohort study using electronic health care data of nonbleeding patients admitted between November 2004 and May 2016 at the intensive care unit (ICU) of the Leiden University Medical Center, The Netherlands. We analyzed the associations between transfusion (yes/no) and next-day SOFA scores (Sequential Organ Failure Assessment-as a measure for organ functioning) for all observed combinations of hemoglobin values (between 6 and 9 g/dL) and concurrent clinical variables. Results Data of 6425 ICU admission of 5756 critically ill patients with 28,702 hemoglobin values between 6 and 9 g/dL (transfusion decision moments) of which 22.1% were followed by a transfusion were analyzed. The adjusted average difference between the next-day SOFA score of transfused versus not-transfused patients was 0.08 (95% confidence interval [CI] -0.03 to 0.18). At singular transfusion decision moments, the score predicted a beneficial effect of transfusion on next-day SOFA score for some subgroups and medical conditions and a harmful effect in other occasions. Conclusions Among these critically ill patients with hemoglobin concentrations between 6 and 9 g/dL the population average effect of transfusion on the next SOFA score was negligible. Further, our results support caution in clinical decision-making regarding transfusion of critical ill, nonbleeding ICU patients. Show less
Spadaccio, C.; Nenna, A.; Candura, D.; Rose, D.; Moscarelli, M.; Al-Attar, N.; Sutherland, F. 2022
ObjectivesBlood transfusions after coronary artery bypass grafting (CABG) has been associated to adverse outcomes, especially in anemic patients. However, little is known about the influence of the... Show moreObjectivesBlood transfusions after coronary artery bypass grafting (CABG) has been associated to adverse outcomes, especially in anemic patients. However, little is known about the influence of the modality of revascularization. Total arterial revascularization (TAR) was shown to reduce postoperative transfusion when compared to saphenous vein-based (SV)-CABG (LIMA plus one/more SV grafts). We, therefore, aimed to investigate the impact of TAR-CABG versus SV-CABG on blood products use and perioperative outcomes in patients with preoperative anemia, normally at higher risk for postoperative transfusions.MethodsFrom a cohort of 936 patients with mild preoperative anemia undergoing primary elective on-pump CABG, 166 matched pairs of patients undergoing either TAR- or SV-CABG were obtained. Anemia was defined as hemoglobin level <13 g/dl for men and <12 g/dl for women. The primary endpoint was the evaluation of red packed cells (RPC) use over the entire hospital stay.ResultsTAR patients showed significantly reduced RPC usage compared with SV (mean difference 0.45 units). TAR patients had a reduced intubation time (mean difference 7.6 h) and were discharged 1.24 days earlier than SV patients. Pneumonia and acute kidney injury were doubled among SV patients. Adjusted regression showed that TAR technique is a predictor of reduced RPC unit use regardless of age and EuroSCORE II (odds ratio: 0.63, p < .01).ConclusionPatients with preoperative anemia might benefit from TAR regardless of age or calculated operative risk. TAR-CABG was associated to reduced postoperative use of blood products and postoperative length of stay in comparison with SV-CABG in this subset of patients. Show less
Puy, R.S. du; Poortvliet, R.K.E.; Mooijaart, S.P.; Stott, D.J.; Quinn, T.; Sattar, N.; ... ; Elzen, W.P.J. den 2022
Context Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age. Objective The aim of this study was to assess whether levothyroxine... Show moreContext Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age. Objective The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism. Methods This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months. Results Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 +/- 1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (-0.03 g/dL [95% CI, -0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (-0.33 g/dL [95% CI, -0.87 to 0.21]). Conclusion In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia. Show less
Vliet, N.A. van; Kamphuis, A.E.P.; Elzen, W.P.J. den; Blauw, G.J.; Gussekloo, J.; Noordam, R.; Heemst, D. van 2022
Context: Thyroid dysfunction is associated with higher anemia prevalence, although causality remains unclear.Objective: This study aimed to investigate the association between thyroid function and... Show moreContext: Thyroid dysfunction is associated with higher anemia prevalence, although causality remains unclear.Objective: This study aimed to investigate the association between thyroid function and anemia.Methods: This cross-sectional and Mendelian randomization study included 445 482 European participants from the UK Biobank (mean age 56.77 years (SD 8.0); and 54.2% women). Self-reported clinical diagnosis of hypothyroidism was stated by 21 860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3431 (0.8%). Anemia, defined as hemoglobin level of < 13 g/dL in men and < 12 g/dL in women, was present in 18 717 (4.2%) participants.Results: In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12; 95% CI, 1.05-1.19 and OR 1.09; 95% CI, 0.91-1.30), although with wide confidence intervals for hyperthyroidism. We did not observe an association of higher or lower genetically influenced thyrotropin (TSH) with anemia (vs middle tertile: OR for lowest tertile 0.98 [95% CI, 0.95-1.02]; highest tertile 1.02 [95% CI, 0.98-1.061), nor of genetically influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05; 95% CI, 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes.Conclusion: While self-reported clinical diagnosis of hypothyroidism was associated with higher anemia risk, we did not find evidence supporting a causal association with variation of thyroid function within the euthyroid range. However, intracellular regulation of thyroid hormones might play a role in developing anemia. Show less
We describe a first Dutch case of Hb M Saskatoon (HBB:c.190C > T p.His64Tyr) in a 47-year-old female Dutch patient who presented with cyanosis, hemolysis, and abnormal co-oximetry. A mean... Show moreWe describe a first Dutch case of Hb M Saskatoon (HBB:c.190C > T p.His64Tyr) in a 47-year-old female Dutch patient who presented with cyanosis, hemolysis, and abnormal co-oximetry. A mean corpuscular volume (MCV) of 105 fL caused by reticulocytosis (160 x 10(9)/L) and low red blood cell count (3.6 x 10(12)/L) suggested an increased erythrocyte turnover. An HPLC glyco-globin analysis revealed a decreased HbA1c fraction of 12.3 mmol/mmol, HbA0 of 93.3% and an additional unidentified fraction at 1.2 min. DNA sequencing revealed a missense mutation in the HBB gene, (HBB:c.190C > T p.His64Tyr), known as Hb M Saskatoon, a variant which has been previously identified as an unstable hemoglobin variant leading to methemoglobinemia and anemia. In this report, we describe the clinical and remarkable laboratory aspects of our patient with Hb M Saskatoon, and the consequences for treatment and drug use. Show less
Objective:To describe the management of anemia at PICU discharge by pediatric intensivists.Design:Self-administered, online, scenario-based survey.Setting:PICUs in Australia/New Zealand, Europe,... Show moreObjective:To describe the management of anemia at PICU discharge by pediatric intensivists.Design:Self-administered, online, scenario-based survey.Setting:PICUs in Australia/New Zealand, Europe, and North America.Subjects:Pediatric intensivists.Interventions:None.Measurements and Main Results:Respondents were asked to report their decisions regarding RBC transfusions, iron, and erythropoietin prescription to children ready to be discharged from PICU, who had been admitted for hemorrhagic shock, cardiac surgery, craniofacial surgery, and polytrauma. Clinical and biological variables were altered separately in order to assess their effect on the management of anemia. Two-hundred seventeen responses were analyzed. They reported that the mean (+/- sem) transfusion threshold was a hemoglobin level of 6.9 +/- 0.09 g/dL after hemorrhagic shock, 7.6 +/- 0.10 g/dL after cardiac surgery, 7.0 +/- 0.10 g/dL after craniofacial surgery, and 7.0 +/- 0.10 g/dL after polytrauma (p < 0.001). The most important increase in transfusion threshold was observed in the presence of a cyanotic heart disease (mean increase ranging from 1.80 to 2.30 g/dL when compared with baseline scenario) or left ventricular dysfunction (mean increase, 1.41-2.15 g/dL). One third of respondents stated that they would not prescribe iron at PICU discharge, regardless of the hemoglobin level or the baseline scenario. Most respondents (69.4-75.0%, depending on the scenario) did not prescribe erythropoietin.Conclusions:Pediatric intensivists state that they use restrictive transfusion strategies at PICU discharge similar to those they use during the acute phase of critical illness. Supplemental iron is less frequently prescribed than RBCs, and prescription of erythropoietin is uncommon. Optimal management of post-PICU anemia is currently unknown. Further studies are required to highlight the consequences of this anemia and to determine appropriate management. Show less
Objectives To evaluate the long-term neurodevelopmental and behavioral outcomes in surviving infants of pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS), to compare outcome... Show moreObjectives To evaluate the long-term neurodevelopmental and behavioral outcomes in surviving infants of pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS), to compare outcome between donors and recipients, and to investigate potential risk factors for neurodevelopmental impairment (NDI).Methods This was a retrospective study of a consecutive cohort of spontaneous-TAPS survivors delivered between 2005 and 2017 at the Leiden University Medical Center, The Netherlands. Neurological, motor, cognitive and behavioral development were assessed at a median age of 4 years. The primary outcome was NDI, which was a composite outcome of cerebral palsy, deafness, blindness and motor and/or cognitive delay. NDI was subdivided into two grades of severity: mild-to-moderate and severe NDI. Outcome was compared between surviving donor and recipient twins. Logistic regression analysis was used to assess risk factors for NDI.Results Forty-nine twin pregnancies complicated by spontaneous TAPS were eligible for inclusion. The perinatal survival rate was 83% (81/98) of twins. Neurodevelopmental assessment was performed in 91% (74/81) of surviving twins. NDI occurred in 30% (22/74) of TAPS survivors, and was found more often in donors (44%; 15/34) than in recipients (18%; 7/40) (odds ratio (OR), 4.1; 95% CI, 1.8-9.1; P = 0.001). Severe NDI was detected in 9% (7/74) of survivors and was higher in donors compared with recipients (18% (6/34) vs 3% (1/40)), although the difference did not reach statistical significance; P = 0.056). Donors demonstrated lower cognitive scores compared with recipients (P = 0.011). Bilateral deafness was identified in 15% (5/34) of donors compared with 0% (0/40) of recipients (P = 0.056). Parental concern regarding development was reported more often for donor than for recipient twins (P = 0.001). On multivariate analysis, independent risk factors for NDI were gestational age at delivery (OR, 0.7; 95% CI, 0.5-0.9; P = 0.003) and severe anemia (OR, 6.4; 95% CI, 2.4-17.0; P < 0.001).Conclusion Surviving donor twins of pregnancies complicated by spontaneous TAPS have four-fold higher odds of NDI compared with recipient cotwins, are at increased risk of cognitive delay and have a high rate of deafness. Copyright (C) 2019 ISUOG. Published by John Wiley & Sons Ltd. Show less
