Reticulocyte Research Articles

Comparison between standard hematological parameters and blood doping biomarkers in dried blood spots within the athlete population of Swiss Sport Integrity.

The study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context. The aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, "DBS OFF-score". Ten athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards. Most athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu. In this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

Vitamin B12 Deficiency in Thrombotic Thrombocytopenic Purpura-Like Cases.

Thrombotic microangiopathies (TMA) are characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage which occur in the setting of endothelial damage and platelet activation. Vitamin B12 (cobalamin) deficiency could lead to a picture that resembles TMA, termed metabolic mediated TMA (MM-TMA). A 60-year-old female was brought to the hospital after she was found unresponsive. On presentation, she was pale, lethargic, tachycardic, and febrile. Laboratory investigations revealed normocytic anemia, thrombocytopenia, and elevated bilirubin. Blood smear revealed schistocytes and tear drop cells. Given the presence of hemolytic anemia, thrombocytopenia, acute renal failure, and altered mental status, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made with a PLASMIC score of 7 indicating high risk. She received plasma exchange, caplacizumab, and intravenous methylprednisolone. Given the patient's low level of vitamin B12, she was initiated on intramuscular cyanocobalamin 1000 μg daily. The encephalopathy resolved and renal function improved. On day 6, ADAMTS13 activity was normal ruling out the diagnosis of TTP. Accordingly, plasmapheresis, steroids, and caplacizumab were discontinued. With continued aggressive B12 replacement, hemolysis resolved indicating severe vitamin B12 deficiency was the likely culprit of this patient's microangiopathic hemolytic anemia. This case serves to highlight the variable presentation of vitamin B12 deficiency. Severe vitamin B12 deficiency can even mimic TTP. If patients have markers of hemolysis, a low vitamin B12 level, and low reticulocyte count we should consider vitamin B12 deficiency as a likely cause of microangiopathic hemolytic anemia as early detection allows for early initiation of appropriate management. Vitamin B12 deficiency can be a cause of thrombotic microangiopathy.

Assessment of Reticulocyte Count as a Prognostic Indicator for Canine Ehrlichiosis: Implications for Diagnostic and Therapeutic Strategies

Canine ehrlichiosis is increasingly recognized in India, with significant implications for canine health. It is a tick-borne disease, caused by Ehrlichia canis. It is prevalent in various regions, particularly in areas with high tick populations. Anaemia is one of the most common and important manifestation of this disease. Anemia results from the destruction of red blood cells and bone marrow suppression. The prevalence of canine ehrlichiosis correlates with the density of tick vectors and can be exacerbated by environmental factors. Canine anemia can be classified as either regenerative or non-regenerative. Objective of the study was, investigating the prognostic value of reticulocyte counts in dogs with ehrlichiosis. The study involved 212 dogs screened between February 2023 and March 2024. Risk factors such as age, sex, breed, and season were recorded. Canine ehrlichiosis was diagnosed by finding morula stages in monocytes and neutrophils in thin blood smear examination. The pathogen was confirmed through PCR-based molecular examination. Reticulocyte count was performed through supravital stain new methylene blue (NMB). Reticulocytes contain ribosomal RNA, which is less condensed than in mature erythrocytes. NMB has a high affinity for ribosomal RNA, resulting in a blue coloration of these immature cells. This staining reaction makes reticulocytes clearly distinct compared to mature red blood cells under a microscope, facilitating their identification and quantification. The study found that the haematological parameters of infected dogs were significantly lower than healthy dogs. The mean ±SE values of Hb, TEC, PCV, and corrected reticulocyte were significantly lower (p<0.001) in infected dogs compared to healthy dogs. These findings suggest that significantly lower values of Hb, TEC, PCV, MCV, MCH, MCHC, and corrected reticulocyte indicate anaemia, normocytic, normochromic anaemia, and non-regenerative anaemia. It can be concluded than in canine ehrlichiosis, anemia is one of the most common finding accounting aprox 28% of total diagnosed cases. Accurate anemia characterization is key for diagnosing and treating ehrlichiosis.

Components of Iron Deficiency Anemia: Understanding Pathophysiology, Diagnosis, and Management

Iron deficiency anemia (IDA) is a prevalent global health concern, marked by a significant reduction in iron levels, leading to diminished hemoglobin production and compromised oxygen transport. This condition disproportionately affects vulnerable populations, including women of reproductive age, infants, and individuals in low-resource settings, resulting in a multitude of health complications. The pathophysiology of IDA involves complex interactions between dietary iron intake, increased physiological demands, chronic blood loss, and malabsorption syndromes. Clinically, IDA manifests through symptoms such as fatigue, pallor, and cognitive impairments, necessitating a thorough diagnostic approach that includes complete blood counts, iron studies, and reticulocyte counts. Effective management strategies encompass dietary modifications, iron supplementation, and treatment of underlying causes. Furthermore, preventive measures—such as public health initiatives and food fortification—are crucial in addressing the root causes of IDA. Emerging research suggests innovative approaches, including bioavailable iron sources and genetic studies, to enhance prevention and treatment efforts. This review comprehensively examines the components of IDA, providing insights into its pathophysiology, diagnosis, management, and future directions for research and intervention. Keywords Iron deficiency anemia (IDA), Pathophysiology, Diagnosis, Management, Dietary iron.

Performance of red blood cell indices for the detection of reticulocytosis in anemic and non-anemic dogs in Taiwan

Reticulocyte counts (RETIC) are considered the gold standard in detecting an erythroid bone marrow response (BMR) in anemic and non-anemic dogs. Reticulocytosis without anemia (RWA) is a potential indicator of disease. The prevalence of anemia or RWA, as well as the effectiveness of red blood cell (RBC) indices in identifying a BMR, may vary based on geographical locations and breed differences. The purpose of the study was to determine the prevalence of regenerative and nonregenerative anemia, and RWA in pet dogs of Taiwan, and to assess the sensitivity and specificity of combined increased mean cell volume and decreased mean cell hemoglobin concentration (iMCV+dMCHC) to detect reticulocytosis in this population.The final population analysis consisted of 149,076 dogs. A cross sectional, retrospective analysis of complete blood count (CBC) samples from a field of automated hematology analyzers in Taiwan from December 1, 2018 through December 31, 2020 was performed. Among 149,076 dogs, 11.8 % (n=17,600) had reticulocytosis (RETIC > 110K/µl) and 21.8 % (n=32,474) had anemia (HCT < 37.3 %). Of 32,474 anemic dogs, 17.8 % (n=5,789) had reticulocytosis. Of 116,602 dogs without anemia, 10.1 % (n=11,776) had reticulocytosis. Across all dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 4.3 % and 99.4 %, respectively compared to RETIC. Among anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 9.8 % and 99.2 %, respectively. Among non-anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 1.6 % and 99.5 %, respectively. Therefore, most regenerative anemias and cases of RWA did not have a combined iMCV+dMCHC. To avoid overlooking potential illness, RETIC should be evaluated regardless of whether patients have anemia or not.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Laboratory reference intervals influence referral patterns for hemoglobin abnormalities in the Ontario virtual care system.

This retrospective cross-sectional study investigates the impact of laboratory-specific hemoglobin reference intervals on electronic consultation (eConsult) referral patterns for suspected anemia and elevated hemoglobin at a tertiary care center in London, Ontario that serves Southwestern Ontario. The study analyzed referrals through the Ontario Telemedicine Network's eConsult platform for hemoglobin abnormalities, excluding patients under 18 years old, between July 1, 2019, and June 30, 2023.The main outcome measures were influence of hemoglobin reference intervals on the referral patterns for suspected anemia and elevated hemoglobin, as well as the extent of pre-referral laboratory testing. Of the 619 eConsults reviewed, 251 referrals for suspected anemia and 93 for elevated hemoglobin were analyzed. Referral patterns showed significant variance in hemoglobin levels based on different laboratory thresholds. Referrals for suspected anemia in females from laboratories whose lower limit was 120 g/L or greater had a hemoglobin concentration 7.5 g/L greater than referrals that used laboratories with a threshold lower than 120 g/L. The study also identified potential areas for improvement in pre-referral investigations; 44% of eConsults did not provide a ferritin level, 53% were missing a B12 level, and 81% were missing a reticulocyte count. In conclusion, laboratory reference intervals for hemoglobin significantly influence referral patterns for suspected hemoglobin abnormalities in Ontario's eConsult system. There is a need for standardized reference intervals and comprehensive pre-referral testing to avoid unnecessary medicalization and referrals. We propose an anemia management algorithm to guide primary care providers in the pre-referral investigation process.

Unveiling immunological signatures and predictors of response to immunosuppressive therapy in acquired aplastic anemia.

Acquired aplastic anemia (AA) often results from immune destruction of hematopoietic stem and progenitor cells. However, only 60%-70% of patients with AA respond to immunosuppressive therapy (IST). There is a lack of strong predictive markers for response to IST which can help therapy. Our study sought to pinpoint unique immune markers in AA patients and validate established predictors for response to IST. We enrolled 51 severe AA patients and analyzed 57 immunological parameters via flow cytometry. Additionally, we measured paroxysmal nocturnal hemoglobinuria (PNH) clone, telomere length, and thrombopoietin (TPO) levels prior to IST. After a 6-month follow-up, a response was observed. Patients with AA had a distinct immunological signature characterized by absolute lymphopenia, skewed CD4/CD8 ratio with expansion of CD8 T cells with activated and senescent phenotype. Treg counts were reduced, while the proportion of Treg A and B was comparable to controls. Treatment response was correlated with elevated absolute neutrophil count (ANC), absolute reticulocyte count (ARC), and reduced CD57+ CD8+ naive cells and B cell % before therapy. However, predictors like TPO, telomere length, and PNH did not emerge as indicators of treatment response. Identifying predictors for treatment response in AA is challenging due to abnormal hematopoiesis, genetic mutations, and treatment variables.

Assessing the Burden of Anemia in Non-Communicable Diseases at a Tertiary Care Center: A Cross-Sectional Study

Background: Anemia is a prevalent global health issue, significantly affecting patients with non-communicable diseases (NCDs) like Type 2 Diabetes Mellitus (Type 2 DM), Hypertension (HTN), and Coronary Artery Disease (CAD). This study assessed the burden of anemia in patients with Type 2 DM, HTN, and CAD, and to identify its prevalence, types, and association with these chronic diseases. Methods: A cross-sectional study was carried out, involving 250 patients diagnosed with Type 2 DM, HTN, and CAD. Patients were categorized as anemic based on WHO criteria: males with Hb &lt; 13 gm% and females with Hb &lt; 12 gm%. Data were collected through a structured questionnaire. Laboratory investigations included Hb, serum creatinine, MCV, MCHC, and reticulocyte count. Statistical analysis was accomplished using chi-square tests and logistic regression to examine associations between anemia and NCDs. Results: Anemia was prevalent in 80% of the study population, with normocytic anemia being the most common type (45%). Significant correlations were found between anemia and Type 2 DM (p=0.036), HTN (p=0.032), and CAD (p=0.013). Anemic patients had significantly lower Hb levels and MCHC, and higher serum creatinine and reticulocyte counts compared to non-anemic patients. Conclusion: The study highlights a high prevalence of anemia among patients with NCDs, indicating a critical need for routine screening and integrated management of anemia in this population. Addressing anemia could improve clinical outcomes and enhance the quality of life for individuals with chronic diseases. Recommendations: Healthcare providers should implement regular anemia screening for patients with NCDs and adopt integrated care approaches that address both chronic diseases and anemia. Further research is needed to explore the underlying mechanisms linking anemia and NCDs and to develop targeted interventions. Keywords: Anemia, Non-Communicable Diseases, Type 2 Diabetes Mellitus, Hypertension, Coronary Artery Disease..

Risk of low levels of blood group antibodies mediating hemolysis in ABO-incompatible neonates with negative three hemolysis tests.

To explore the risk of low-level blood group antibody-mediated hemolysis in ABO-incompatible newborns with negative three hemolysis tests, aiming to assist in the identification and management of neonatal jaundice. A retrospective case-control study was performed in 892 children with jaundice. The patients were divided into three groups: group I, ABO compatible, negative three hemolysis tests; group II, ABO incompatible, negative three hemolysis tests; and group III, ABO incompatible, positive three hemolysis tests. We analyzed the differences in clinical data, blood routine and biochemical laboratory results. (1) Patients in group II had higher levels of mean corpuscular volume (MCV), standard deviation of red blood cell volume distribution width (RDW-SD), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bile acid (BA) than those in group I (P < 0.05). However, there were no statistically significant differences in the MCV, ALT, ALP and BA levels between groups II and III (P > 0.05). (2) Mean corpuscular hemoglobin concentration (MCHC) >359.5 g/L, cell volume distribution width (RDW-CV) >15.95%, and reticulocyte count (RET) >4.235% were identified as independent predictors of positive hemolysis test results (P < 0.001). The combination of MCHC, RDW-CV, and RET% yielded an AUC of 0.841. Low-level blood group antibody-mediated hemolysis may occur in ABO-incompatible neonates even when three hemolysis tests are negative. Changes in liver function parameters must be monitored. The combination of MCHC, RDW-CV, and RET% can be used to improve the detection rate of HDN.

Prevalence of co-infections with Ehrlichia spp. or Theileria spp. in dogs naturally infected with babesiosis in the Eastern Cape province

BackgroundCanine babesiosis and ehrlichiosis are tick-borne infections of great significance in South Africa. Theileriosis in dogs in South Africa is still poorly understood. Co-infection with multiple tick-borne diseases has been documented and is perceived as a common occurrence in South Africa. ObjectivesThe main objective of this study was to determine the prevalence of co-infections with Ehrlichia canis or Theileria equi in dogs with babesiosis in the Eastern Cape province. There is a lack of data on canine tick-borne disease distribution in this region. Possible associations of population characteristics and haematological and biochemistry measures with a co-infection of E. canis or T. equi in these dogs were also investigated. MethodThe study population included 150 dogs naturally infected with babesiosis that presented to the Mdantsane State Veterinary Clinic between January 2021 and November 2021. Quantitative polymerase chain reaction was used to confirm the Babesia spp. that the dogs were infected with and to identify co-infections. Association with co-infection for the following parameters were evaluated: sex, breed, age, duration of illness, leukocyte count, band neutrophil count, monocyte count, platelet count, ARC, and serum globulin concentration. Positive and negative predictive values of monocytosis, leukopenia, band neutrophilia, thrombocytopenia, and non-regenerative absolute reticulocyte count for co-infection were also calculated. ResultsBabesia rossi was identified in 149/150 samples and B. vogeli in only 1/150 samples. A co-infection prevalence of 2.0% (3/149; 95% CI: 0.4–5.7) with B. rossi and E. canis was found. No other co-infections were reported. No investigated variables showed significant associations with co-infections. Monocytosis, in particular, was not associated with co-infection. ConclusionCo-infection with other tick-borne diseases in dogs with babesiosis is uncommon in the Eastern Cape province. These findings raise the possibility that B. rossi may have a protective effect against other tick-borne diseases.

Effects of Oral Nutritional Supplement with β-Hydroxy-β-methylbutyrate (HMB) on Biochemical and Hematological Indices in Community-Dwelling Older Adults at Risk of Malnutrition: Findings from the SHIELD Study.

Malnutrition may result in abnormal biochemical and hematological indices. This planned prespecified analysis investigated the effects of a specialized oral nutritional supplement (ONS) on biochemical and hematological indices in community-dwelling older adults at risk of malnutrition. In the Strengthening Health in ELDerly through nutrition (SHIELD) study, 811 older adults aged 65 years and above took part in this randomized, double-blind, placebo-controlled, multi-center study. Participants were randomly allocated to either a complete and balanced specialized ONS (each serving provides 262 kcal, 10.5 g protein, 7.75 µg vitamin D3, and 0.74 g calcium β-hydroxy-β-methylbutyrate) and dietary counselling (intervention group) or a placebo and dietary counselling (placebo group). Both groups consumed study products twice a day for 180 days. Data were collected at baseline, day 90, and day 180. Blood analysis results at follow-up visits were analyzed using repeated measures analysis of covariance with adjustments for confounders. Overall, when compared with the placebo group, the intervention group showed significantly greater urea (6.0 mmol/L vs. 5.4 mmol/L, p < 0.001), urea to creatinine ratio (4.39 vs. 4.26, p < 0.001), prealbumin (24.9 mg/dL vs. 24.0 mg/dL, p < 0.001), vitamin B12 (480.0 pmol/L vs. 420.1 pmol/L, p < 0.001), and globulin levels (26.8 g/L vs. 26.5 g/L, p = 0.032). The intervention group also had a significantly higher absolute reticulocyte count (62.0 × 103/µL vs. 58.2 × 103/µL, overall p < 0.001) and mean platelet volume (10.0 fL vs. 9.9 fL, overall p = 0.003). Furthermore, significant improvements were seen in total protein at day 90 (71.7 g/L vs. 71.1 g/L, p = 0.017) and in absolute monocyte count at day 90 (0.50 × 103/µL vs. 0.47 × 103/µL, p = 0.009) in the intervention group. In conclusion, daily consumption of a specialized ONS for six months led to significant improvements in biochemical and hematological indices in community-dwelling older adults at risk of malnutrition.

Feasibility of Delivering 5-Day Normobaric Hypoxia Breathing in a Hospital Setting.

Beneficial effects of breathing at [Formula: see text] < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with [Formula: see text] as low as 0.11 in 5 healthy volunteers. All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from [Formula: see text] of 0.16 on the first day to [Formula: see text] of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' [Formula: see text], heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments. Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased [Formula: see text] and increased heart rate. At [Formula: see text] of 0.14, the mean [Formula: see text] was 92%; at [Formula: see text] of 0.13, the mean [Formula: see text] was 93%; at [Formula: see text] of 0.12, the mean [Formula: see text] was 88%; at [Formula: see text] of 0.11, the mean [Formula: see text] was 85%; and, finally, at an [Formula: see text] of 0.21, the mean [Formula: see text] was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension. Results of the current physiologic study suggests that, within a hospital setting, delivering [Formula: see text] as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.

Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.

An Atlas on Multitudinous Risk Factors Associated with Incident Hypertension: Comprehensive Exposome-Wide Association and Wide-angled Genetic Analyses.

Despite numerous risk factors being associated with hypertension, the breadth of research remains constrained, with a notable absence of systematic, data-driven exploration into established and novel factors across a broad spectrum of exposures. This study aims to construct an atlas on known and emerging factors for hypertension through comprehensive epidemiological and genetic analyses. We conducted exposome-wide association studies (ExWAS) via Cox regression models on two equally sized datasets for discovery and replication in UK Biobank, a large prospective cohort study. A maximum of 10,806 exposome variables were included in ExWAS and were grouped into 13 categories: genomics, sociodemographic, lifestyle, physical measure, biomarkers, medical history, imaging markers, sex-specific factors, psychosocial factors, cognitive function indicators, local environment, family history, and early life factors. The credibility of epidemiological associations was assessed through meta-analyses. The genetic underpinnings were explored through linkage-disequilibrium score regression (LDSC), quantifying global genetic correlation. Two-sample Mendelian randomization (MR) studies were conducted to investigate the causal effects of each exposure on hypertension, with co-analyses undertaken to identify associations supported by both epidemiological and genetic evidence. This study included 214,957 UK Biobank participants, hypertension-free at baseline. In our ExWAS analyses, 964 significant exposome variables were replicated. In meta-analyses, 462 were backed by convincing and highly suggestive evidence. Among 10,765 exposures in LDSC, 1923 had global genetic correlations with hypertension. The MR analyses yielded robust evidence for a causal relationship with 125 phenotypes, probable evidence for 270 phenotypes, and suggestive evidence for 718 phenotypes. Co-analyses identified 146 associations supported by strong epidemiological and genetic evidence. These primarily encompassed traits like anthropometry, lung function, lipids, and factors such as urate and walking pace. This coverage further extended from well-studied factors (like BMI and physical activity) to less explored exposures (including high light scatter reticulocyte count and age at first live). All study results are compiled in a webserver for user-friendly exploration of exposure-hypertension associations. This study provides an atlas on established and novel risk factors for hypertension, underpinned by epidemiological and causal evidence. Our findings present a multiple perspective to prioritize hypertension prevention strategies, encompassing modifiable risk factors like television watching time and walking pace. The study also emphasized the roles of urate in hypertension pathogenesis. Consequently, our study may serve as a critical guide for hypertension prevention and bear significant clinical implications.

Clinico-mutational profile and the impact of splenectomy in children with glucose-6-phosphate isomerase deficiency

BackgroundThere is a lack of literature on the role of splenectomy in hemolytic anemias due to glucose-6-phosphate isomerase (GPI) deficiency. GPI deficiency is a rare red blood cell (RBC) enzymopathy of the glycolytic pathway. Most present with severe disease requiring frequent transfusions. In this study, we report the effect of splenectomy in the world's largest cohort of GPI deficiency patients. The study aimed to describe the clinical, mutational, and laboratory parameters of patients with GPI deficiency. A comparison of the transfusion requirement pre- and post-splenectomy is also included. Material and methodsThe ambispective study was performed from 2017 to 2023. Patients with congenital non-spherocytic hemolytic anemia (CNSHA) were screened for GPI deficiency. Detailed history, including demographic, clinical data, and transfusion details, were noted. Hematological parameters and RBC enzyme activity were estimated using spectrophotometry. The genetic study was done using restriction fragment length polymorphism, and confirmation was obtained through Sanger's sequencing. Patients were followed up after splenectomy. ResultsEighteen patients were diagnosed with GPI deficiency. About 3/4th (14/18; 77.7 %) had significant hepatosplenomegaly. Median serum ferritin levels were 890 ng/ml. Seven patients were on oral iron chelation. The nutritional status assessed as per the Indian Academy of Pediatrics growth charts revealed significant growth retardation. All the patients had severe anemia (mean Hb: 6.4 g/dl) and macrocytosis (mean MCV: 129.2 fl). Laboratory features of hemolysis were evident with reticulocytosis, raised serum lactate dehydrogenase, and indirect bilirubin. The mean GPI enzyme activity was 28.75 IU/g Hb.Ten (55.5 %) patients underwent splenectomy at a median age of 7 years. Five remain transfusion-free post-splenectomy at a median follow-up of 54 months. Other 5 had a significant reduction in transfusion requirement post-splenectomy (p < 0.05). Post-splenectomy, the mean hemoglobin levels increased from 6.2 to 8.1 gm%, and the mean reticulocyte counts reduced from 7.4 % to 4.8 %. Fifteen of 18 had the pathogenic c.1040G > A(p.Arg347His) homozygous mutation. ConclusionThe study demonstrates the benefit of splenectomy in patients with GPI deficiency.

Efficacy of sutimlimab for cold agglutinin disease in a patient on chronic hemodialysis.

Reports of cold agglutinin disease (CAD), an autoimmune hemolytic anemia, in dialysis patients are limited. Recently, sutimlimab for CAD was covered by insurance. Herein, we report a case in which sutimlimab was effective in the treatment of CAD in a patient undergoing hemodialysis (HD). The patient was a 73year-old Japanese man with an 11year history of HD for diabetic nephropathy. He was admitted to our hospital for examination and treatment of erythropoiesis-stimulating agent (ESA)-induced hyporesponsive anemia and fatigue, which was present in the previous year October to March when temperatures were cooler. The patient was diagnosed with hemolytic anemia based on decreased hemoglobin levels, elevated reticulocyte count, elevated lactate dehydrogenase levels, and decreased haptoglobin levels. Furthermore, he was diagnosed with CAD based on a positive direct antiglobulin test for C3 and cold agglutinin tests. The patient did not respond well to an elevated dialysate temperature or rituximab therapy. After initiating sutimlimab treatment, an increase in the hemoglobin level was observed despite a decrease in temperature, and his fatigue disappeared. Anemia in hemodialysis patients is generally renal; however, some ESA resistance exists, which may be due to hemolytic anemia. In this case, the use of sutimlimab was effective in controlling hemolytic anemia due to CAD.

Exploring the effects of post operative hyperoxic intermittent stimuli on reticulocyte levels in cancer patients: a randomized controlled study

BackgroundAnemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries.MethodsThis is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression.ResultsThe final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values.ConclusionsThis study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings.Trial registrationThe study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

Mixed Autoimmune Hemolytic Anemia - A Rare Case Report

Abstract Mixed autoimmune hemolytic anemia (MAIHA) is a rare clinical condition where both warm and cold antibodies cause red cell destruction, leading to anemia. MAIHA can present as a blood group discrepancy or crossmatch incompatibility, which can be very challenging for transfusion medicine services to diagnose and issuing of best-matched blood. Therefore, a comprehensive immunohematology workup, including a monospecific direct antiglobulin test, and indirect antiglobulin test is performed to determine the thermal amplitude and titer of autoantibodies. It is important to be aware of this phenomenon because, like warm AIHA and MAIHA should be treated immediately, with steroids. We hereby report a case of a 14-year-old girl presenting with a history of generalized weakness and dizziness; preliminary investigations revealed anemia, increased reticulocyte count, and antinuclear antibodies positive. Hence, further diagnosis of MAIHA associated with systemic lupus erythematosus was made. A high-dose steroid therapy was given to the patient, and significant improvement was seen clinically.

Anemia predictive indicator (API). how can we predict in three days the anemia that will develop in three months? case report

The Anemia Predictive Indicator (API) includes the analysis of the reticulocyte count, the reticulocyte hemoglobine content (HCr) and immature reticulocyte fraction (IRF). API reflects erythropoietic activity and allows immediate detection and correction of iron deficiency anemia, and the response can be observed on the second and third day after starting treatment. In this case report, a 79-year-old woman after a total knee replacement, API provided predictability at the onset of anemia, allowed the follow-up of anemia and its treatment, collaborated in clinical and medical decision, contributed to preventive actions and improve the patient's quality of life.