Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.

BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).

Effect of Donor Sex on Recipient Mortality in Transfusion.

BACKGROUND: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS: A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS: This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries.

Background: Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations. Methods: We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins. Results: Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p<0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p<0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p<0.001). Conclusion: Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia.

Serum Phosphate Levels Modify the Impact of FGF23 Levels on Hemoglobin in Chronic Kidney Disease.

Anemia is a complication of chronic kidney disease (CKD). Phosphate and fibroblast growth factor-23 (FGF23) have a close relationship, as both are related to the pathogenesis of anemia. However, the possible interplay between them regarding their effect on anemia has not been evaluated. This was a cross-sectional study of 896 participants from the NEFRONA study (273 CKD3, 246 CKD4-5, 282 dialysis and 95 controls). The levels of 25(OH) and 1,25(OH)2 vitamin D, intact FGF23 (iFGF23) and soluble Klotho were measured, together with standard blood biochemistries. Anemia was defined as hemoglobin levels < 13 g/dL in men and <12 g/dL in women. Patients with anemia (407, 45.4%) were younger, mostly men and diabetic; were in advanced CKD stages; had lower calcium, 1,25(OH)2 vitamin D and albumin levels; and had higher ferritin, phosphate, intact PTH, and iFGF23. An inverse correlation was observed between hemoglobin and both iFGF23 and phosphate. The multivariate logistic regression analyses showed that the adjusted risk of anemia was independently associated with higher serum phosphate and LogiFGF23 levels (ORs (95% CIs) of 4.33 (2.11−8.90) and 8.75 (3.17−24.2), respectively (p < 0.001)). A significant interaction between phosphate and iFGF23 (OR of 0.66 (0.53−0.83), p < 0.001) showed that the rise in the adjusted predicted risk of anemia with the increase in iFGF23 was steeper when phosphate levels were low. Phosphate levels acted as modifiers of the effect of iFGF23 concentration on anemia. Thus, the effect of the increase in iFGF23 levels was stronger when phosphate levels were low.

Erythrocyte indices and localized stage II/III periodontitis in military young men and women: CHIEF oral health study.

BACKGROUND: Prior studies have shown an association between generalized periodontitis and anemia in older or undernourished adults. The aim of the study was to examine the associations of erythrocyte indices with localized periodontitis in robust young adults, which has never been reported before. METHODS: The study included 1286 military participants, aged 19-40 years, with regular exercise training in Hualien, Taiwan. Localized periodontitis was grouped to healthy/stage I and stage II/III (n = 803 and 325) in men and (n = 130 and 28) in women according to the 2017 criteria of the world workshop. Systemic inflammation was evaluated by leukocyte counts. Multiple logistic regression analysis with adjustment for age, tobacco smoking status, betel nut chewing status, body mass index and leucocyte counts were used to determine the associations. RESULTS: Greater mean corpuscular volume in young men [odds ratio (OR) and 95% confidence intervals 1.03 (1.01-1.06)], and greater hematocrit and hemoglobin levels in young women were associated with a higher risk of localized stage II/III periodontitis [OR: 1.17 (1.02-1.34) and 1.60 (1.06-2.41), respectively]. However, there were no associations for erythrocyte counts. CONCLUSIONS: The localized stage II/III periodontitis risk increased with greater erythrocyte indices in robust young adults. This finding could be explained in part by that localized periodontitis may promote physical stress, possibly resulting in an increase of erythrocyte indices. On the other side, greater physical fitness associated with a lower risk of periodontitis may consume iron storage in the body, leading to exercise-induced anemia or smaller erythrocyte volume.

Erythropoietin and iron for anemia in HIV-infected patients undergoing maintenance hemodialysis in China: a cross-sectional study.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China. METHODS: This cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4 + T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann-Whitney U test, and chi-square statistics were applied in SPSS. RESULTS: The Hgb of HIV-HD and HD groups were 105.70 (95.93-112.08) g/L and 112.00 (93.00-126.00) g/L respectively (P = 0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55 ± 115.47 U/kg/week) compared to the HIV-negative HD group (161.86 ± 110.31 U/kg/week) (P = 0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P = 0.003). The ferritin levels were 316.50 (117.38-589.75) ng/ml and 272.70 (205.00-434.00) ng/ml in HIV-HD and HD groups respectively. CONCLUSIONS: A higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.

Characterization of acquired anemia in children by iron metabolism parameters.

Inflammatory states are associated with anemia of chronic disease and acute infection. Hepcidin, a regulator of iron metabolism, is involved in iron pathophysiology during inflammation. We investigated biochemical characteristics in children with anemia from different causes. Four patient groups (n = 38; mean age: 12.44 ± 4.35 years) were studied: (1) inflammatory bowel disease (IBD, 10 patients); (2) iron deficiency anemia (IDA, 12); (3) celiac disease (CD, 8); (4) acute infection (AI, 8). Laboratory measurements were evaluated at diagnosis: blood count, serum iron, transferrin, ferritin, vitamin B12, folic acid, CRP, erythropoietin, hepcidin and soluble transferrin receptor (sTfR). IDA patients had the lowest Hgb (6.9 ± 1.7 g/dL), MCV (63.2 ± 7.2 fL), iron (16.8 ± 13.5 µg/dL), ferritin (4.5 ± 4.5 ng/mL) and hepcidin (3.1 ± 0.8 ng/mL) values, and the highest transferrin and sTfR values. AI patients had the highest ferritin (156.2 ± 124.5 ng/mL), CRP (144.6 ± 94 mg/L) and hepcidin (74.67 ± 12.3 ng/ml) values. Overall, hepcidin levels correlated with CRP and with ferritin (r = 0.83 and 0.85, respectively). Elucidating specific etiology-related biochemical profiles in pediatric patients with anemia from different causes using a combination of laboratory biomarkers, including hepcidin, can help physicians treat the anemia.

'Bouncing Back' From Subclinical Malaria: Inflammation and Erythrocytosis After Resolution of P. falciparum Infection in Gambian Children.

Recent malaria is associated with an increased risk of systemic bacterial infection. The aetiology of this association is unclear but malaria-related haemolysis may be one contributory factor. To characterise the physiological consequences of persistent and recently resolved malaria infections and associated haemolysis, 1650 healthy Gambian children aged 8-15 years were screened for P. falciparum infection (by 18sRNA PCR) and/or anaemia (by haematocrit) at the end of the annual malaria transmission season (t1). P. falciparum-infected children and children with moderate or severe anaemia (haemoglobin concentration < 11g/dl) were age matched to healthy, uninfected, non-anaemic controls and screened again 2 months later (t2). Persistently infected children (PCR positive at t1 and t2) had stable parasite burdens and did not differ significantly haematologically or in terms of proinflammatory markers from healthy, uninfected children. However, among persistently infected children, IL-10 concentrations were positively correlated with parasite density suggesting a tolerogenic response to persistent infection. By contrast, children who naturally resolved their infections (positive at t1 and negative at t2) exhibited mild erythrocytosis and concentrations of pro-inflammatory markers were raised compared to other groups of children. These findings shed light on a 'resetting' and potential overshoot of the homeostatic haematological response following resolution of malaria infection. Interestingly, the majority of parameters tested were highly heterogeneous in uninfected children, suggesting that some may be harbouring cryptic malaria or other infections.

Prevalence and aetiologies of anaemia among first trimester pregnant women in Sri Lanka; the need for revisiting the current control strategies.

BACKGROUND: The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure. METHODS: All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing. RESULTS: Among 3127 participants, 14.4% (95%CI 13.2-15.7, n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /µl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4-59.2), 23.8% (95%CI 10.6-45.1) and 0.9% (95%CI 0.3-2.3%), respectively. Folate deficiency was not observed. CONCLUSION: Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.

Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study.

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10-11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

Preconception Hemoglobin Concentration and Risk of Low Birth Weight and Small-for-Gestational-Age: A Large Prospective Cohort Study in China.

Less is known about the impact of maternal preconception anemia on birth outcomes. We aimed to examine associations between preconception hemoglobin (Hb) concentrations with risk of low birth weight (LBW) and small-for-gestational-age (SGA). This study was from a large population-based prospective cohort in China and included 124,725 women with singleton live births delivered at gestational ages of 28-45 weeks who were registered before pregnancy. Maternal Hb concentrations were measured during registration, and other health-related information was recorded prospectively. Logistic regression was used to evaluate the associations between preconception Hb concentrations with risk of LBW and SGA, adjusting for potential confounders. The results showed women with preconception anemia accounted for 22.28%. The incidences of LBW/SGA were 2.37%/6.30% among anemic women, and 2.01%/5.48% among non-anemic women, respectively. Preconception mild anemia increased by 17% (95% confidence interval (CI): 1.06, 1.28) and 14% (95% CI: 1.07, 1.21) the risk for LBW and SGA, while moderate-to-severe anemia had no significant association with LBW and SGA. Compared with the 120-129 g/L group, a U-shaped association was observed between preconception Hb concentrations with LBW and SGA. In conclusion, not only maternal anemia but also elevated Hb concentrations before pregnancy contribute to an increased risk of LBW and SGA.

Development and Validation of a Nomogram for Predicting the Long-Term Survival in Patients With Chronic Thromboembolic Pulmonary Hypertension.

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

Bloodless Management of the Anemic Patient in the Emergency Department.

Anemia is a commonly encountered condition in emergency medicine; transfusion of packed red blood cells is commonly performed for anemic patients in the emergency department (ED), but some patients are unable to accept transfusion of blood products due to medical or religious concerns. The unique, acute, and time-sensitive nature of emergency medicine practice requires that physicians maintain an enhanced awareness of bloodless medicine treatment modalities. Identification of bloodless medicine patient preferences in the ED can help guide physicians in the recommendation of acceptable methods of treating anemia in this patient population. A focus on early hemostasis and resuscitation, instead of attempts to convince the patient to accept blood transfusion, can be lifesaving in patients with acute bleeding. Treatment strategies including the use of methods to reduce unnecessary blood loss, enhance red blood cell production, and increase the oxygen-carrying capacity of blood should also be considered early in patient presentation. Timely involvement of the Hospital Liaison Committee can help facilitate successful interpersonal communication and shared decisionmaking between emergency physicians and bloodless medicine patients. By embracing an understanding of bloodless medicine patient needs as well as available treatment strategies, ED physicians can contribute to optimal overall outcomes for anemic bloodless medicine patients.

Initial study of anaemia profile for primary care centres with automated laboratory algorithms reduces the demand for ferritin, iron, transferrin, vitamin B12 and folate tests.

AIM: To evaluate the influence of an algorithm designed to incorporate reflex testing according to haemogram results for analytical tests ordered to investigate anaemia. METHODS: In 2020, a new request for 'initial study of anaemia' was created in three primary care pilot centres for suspected anaemia or new anaemias. A haemogram was ordered and the remainder of the tests were created in a reflex manner according to an algorithm integrated in the laboratory information system that also generates a comment that is completed and validated by a haematologist. The demand for tests was evaluated over three time periods. RESULTS: Of 396 requests, anaemia was detected in 80 (20.2%), with 26 microcytic anaemias (6.57%), 20 iron deficiency anaemias, 41 (10.3%) normocytic anaemias and 13 macrocytic anaemias (3.28%); 4 with folate deficiency; and 1 haemolytic anaemia. No haematological diseases were detected. Twenty-four (6.06%) cases exhibited microcytosis/hypochromia without anaemia, 12 of which exhibited iron deficiency. Four young women exhibiting within-limit haemoglobin levels had iron deficiency. There were 56 (14.1%) cases of macrocytosis without anaemia.With the new profile of 'initial study of anaemia', the demand for tests was reduced and was significantly lower than in the remainder of primary centres for iron, transferrin, ferritin, vitamin B12 and folate. CONCLUSIONS: A new profile of 'initial study of anaemia' in the request form with algorithms integrated in the laboratory information system enabled submission of orders and decreased the demand for unnecessary iron, transferrin, ferritin, vitamin B12 and folate tests.

Impact of Perioperative Blood Transfusion in Anemic Patients Undergoing Infra Inguinal Bypass.

OBJECTIVE: Patients who present with lower extremity ischemia are frequently anemic and the optimal transfusion threshold for this cohort remains controversial. We sought to evaluate the impact of blood transfusion on postoperative major adverse cardiac events (MACE), including myocardial infarction, dysrhythmia, stroke, congestive heart failure, and 30-day mortality for these patients. METHODS: All consecutive patients who underwent infra-inguinal bypass at our institution from 2011 to 2020 were included. Perioperative red blood cell transfusion was the primary exposure, and the primary outcome was MACE. Univariate and multivariable analyses were performed to assess the impact of patient and procedural variables, including red blood cell transfusion, stratified by hemoglobin (Hgb) nadir: <7, 7-8, and >8 g/dL. RESULTS: Of the 287 patients reviewed for analysis, 146 (50.9%) had a perioperative transfusion (mean: 1.6 ± 3 units). Patients who received a transfusion had a mean nadir Hgb of 8.3 ± 1.0 g/dL, compared to 10.1 ± 1.7 g/dL without a transfusion. The overall incidence of MACE was 15.7% (45 of 287 patients). Univariate analysis demonstrated that MACE was associated with blood transfusion (P = 0.009), lower Hgb nadir (P = 0.02), and higher blood loss (P = 0.003). On multivariate analysis, transfusion was independently associated with MACE for patients with a Hgb nadir >8 g/dL (OR: 3.09; P = 0.006), but not for patients with Hgb nadir 7-8 g/dL (OR: 0.818; P = 0.77). Additionally, patients with MACE had significantly longer length of hospital stay than for patients without (13 vs. 7.7 days, P = 0.001). CONCLUSIONS: For patients undergoing infra-inguinal bypass, receiving a red blood cell transfusion with a Hgb nadir >8 g/dL was associated with a 3-fold increase in MACE, with nearly twice the length of stay. For patients with a Hgb 7-8 g/dL, transfusion did not increase or reduce the incidence of MACE. These findings suggest no benefit of blood transfusion for patients with Hgb nadir >7 g/dL and harm for Hgb >8 g/dL, however causation cannot be proven due to the retrospective nature of the study and randomized studies are needed to confirm or refute these findings.

The Impact of Anemia on One-Year Amputation-Free Survival in Patients Undergoing Revascularization for Chronic Limb-Threatening Ischemia: A Retrospective Cohort Study.

BACKGROUND: Anemia is potentially associated with increased morbidity and mortality following vascular surgery procedures. This study investigated whether peri-procedural anemia is associated with reduced 1-year amputation-free survival (AFS) in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI). METHODOLOGY: A retrospective analysis of patients diagnosed with CLTI between February 2018-February 2019, who subsequently underwent revascularization, was conducted. Hemoglobin concentration measured at index assessment was recorded and stratified by WHO criteria. Subsequent peri-procedural red blood cell transfusions (RBC) were also recorded. The primary outcome was 1-year AFS. Kaplan Meier survival analysis and Cox's proportional hazard modelling were conducted to assess the effect of anemia and peri-procedure transfusion on outcomes. RESULTS: 283 patients were analyzed, of which 148 (52.3%) were anemic. 53 patients (18.7%) underwent RBC transfusion. Patients with anemia had a significantly lower 1-year AFS (64.2% vs. 78.5%, P = 0.009). A significant difference in 1-year AFS was also observed based upon anemia severity (P = 0.008) and for patients who received RBC transfusion (45.3% vs 77.0%, P < 0.001). On multivariable analysis, moderately severe anemia was independently associated with increased risk of major amputation/death (aHR 1.90, 95% CI 1.06-3.38, P = 0.030). After adjusting for severity of baseline anemia, peri-procedural RBC transfusion was associated with a significant increase in the combined risk of major amputation/death (aHR 3.15, 95% CI 1.91-5.20, P < 0.001). CONCLUSION: Moderately severe peri-procedural anemia and subsequent RBC transfusion are independently associated with reduced 1-year AFS in patients undergoing revascularization for CLTI. Future work should focus on investigating alternative measures to managing anemia in this cohort.

Evaluation of recombinant human erythropoietin responsiveness by measuring erythrocyte creatine content in haemodialysis patients.

BACKGROUND: One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Eythropoiesis stimulating agent (ESA), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of ESA is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of ESA in haemodialysis patients by measuring the erythrocyte creatine content. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Erythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. RESULTS: ESA dose (152.4 ± 62.9 vs. 82.2 ± 45.5 units/kg/week, P = 0.0001) and erythrocyte creatine (2.07 ± 0.73 vs. 1.60 ± 0.41 µmol/gHb, p = 0.0003) were significantly higher in 27 patients with haemoglobin <10 g/dL compared to 56 patients with haemoglobin ≥10 g/dL. There was a fair correlation between ESA dose and the concentration of creatine in the erythrocytes (r = 0.55, P < 0.0001). Increase in haemoglobin (>0.1 g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine levels were significantly higher in those patients with an increase in haemoglobin compared to those without (2.04 ± 0.64 vs. 1.52 ± 0.39 µmol/gHb, p < 0.0001). When 8 variables (ESA dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, iron supplementation, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine levels emerged as the most important variable associated with increase in haemoglobin (Chi-square = 6.19, P = 0.01). CONCLUSION: Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of ESA in haemodialysis patients.

Mild Anemia May Affect Thyroid Function in Pregnant Chinese Women During the First Trimester.

Background: Pregnant women are often susceptible to anemia, which can damage the thyroid gland. However, compared with moderate and severe anemia, less attention has been paid to mild anemia. The purpose of this study was to evaluate the effect of mild anemia on the thyroid function in pregnant women during the first trimester. Methods: A total of 1,761 women in the first trimester of their pregnancy were enrolled from Shenyang, China, and divided into mild anemia and normal control groups based on their hemoglobin levels. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels were compared between the two groups. Results: The TSH levels of pregnant women with mild anemia were higher than those of pregnant women without mild anemia (p < 0.05). Normal control women were selected to set new reference intervals for TSH, FT3, and FT4 levels during the first trimester, which were 0.11-4.13 mIU/l, 3.45-5.47 pmol/l, and 7.96-16.54 pmol/l, respectively. The upper limit of TSH 4.13 mU/l is close to the upper limit 4.0 mU/l recommended in the 2017 American Thyroid Association (ATA) guidelines, indicating that exclusion of mild anemia may reduce the difference in reference values from different regions. Mild anemia was related to 4.40 times odds of abnormally TSH levels (95% CI: 2.84, 6.76) and 5.87 increased odds of abnormal FT3 (95% CI: 3.89, 8.85). The proportion of hypothyroidism and subclinical hypothyroidism in patients with mild anemia was higher than that in those without anemia (0.6% vs. 0, p = 0.009; 12.1% vs. 1.9%, p < 0.001). Mild anemia was related to 7.61 times increased odds of subclinical hypothyroidism (95% CI: 4.53, 12.90). Conclusions: Mild anemia may affect thyroid function during the first trimester, which highlights the importance of excluding mild anemia confounding when establishing a locally derived specific reference interval for early pregnancy.

Microfluidic Characterization of Red Blood Cells Microcirculation under Oxidative Stress.

Microcirculation is one of the basic functional processes where the main gas exchange between red blood cells (RBCs) and surrounding tissues occurs. It is greatly influenced by the shape and deformability of RBCs, which can be affected by oxidative stress induced by different drugs and diseases leading to anemia. Here we investigated how in vitro microfluidic characterization of RBCs transit velocity in microcapillaries can indicate cells damage and its correlation with clinical hematological analysis. For this purpose, we compared an SU-8 mold with an Si-etched mold for fabrication of PDMS microfluidic devices and quantitatively figured out that oxidative stress induced by tert-Butyl hydroperoxide splits all RBCs into two subpopulations of normal and slow cells according to their transit velocity. Obtained results agree with the hematological analysis showing that such changes in RBCs velocities are due to violations of shape, volume, and increased heterogeneity of the cells. These data show that characterization of RBCs transport in microfluidic devices can directly reveal violations of microcirculation caused by oxidative stress. Therefore, it can be used for characterization of the ability of RBCs to move in microcapillaries, estimating possible side effects of cancer chemotherapy, and predicting the risk of anemia.