Severe Anemia Research Articles

Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.

The role of donor type and pre-transplant immunosuppression on outcomes of hematopoietic stem cell transplantation in children and young adults with severe aplastic anemia.

The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA). This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment. The median age at HSCT for all 52 patients was 15 years (range 1-25). The 3-year overall survival (OS) by donor type were as follows: 95% [95% CI 85.4-99] for matched related donors (MRD) (N = 24), 84% [95% CI 63.5-99] for haploidentical (N = 13), and 71% [95% CI 36-99] for matched unrelated donors (MUD) (N = 7). The 3-year OS was 81% [95% CI 69.7-99] for all patients, 90.5% [95% CI 79.5-99] for non-IST patients (N = 27), and 70% [95% CI 51-99] for IST patients (N = 24) (log-rank p = .04). Survival of haploidentical HSCT (haplo-HSCT) recipients with post-transplant cyclophosphamide (PTCy) (N = 13) was excellent for both groups: 100% for non-IST patients (N = 3) and 80% for IST patients (N = 10). The 3-year OS for patients with previous IST by donor type in groups where >5 patients were available was 78.8% [95% CI 52.3-99] for haplo-HSCT (N = 10) and 66.7% [95% CI 28.7-99] for MUD (N = 6). Although it appears that patients receiving HSCT ≥6 months after the start of IST had worse survival, the number of patients in each category was small and log-rank was not significant(p = .65). Patients receiving MUD and haplo-HSCT with PTCy had similar outcomes, suggesting that haplo-HSCT with PTCy could be included in randomized trials of upfront IST versus alternative donor HSCT.

Successful treatment of concurrent cold agglutinin disease and myelodysplastic syndrome

Herein, we describe a case of severe anemia presenting with myelodysplastic syndrome with cold agglutinin disease that was successfully treated by a moderate dose of steroids followed by cyclosporine. In patients with myelodysplastic syndrome, autoimmunity in erythroid cells is occasionally demonstrated, and autoimmune hemolytic anemia is seen in some patients. However, hemolytic anemia with cold agglutinin in patients with myelodysplastic syndrome is less common, and the effect of corticosteroids for autoimmune hemolytic anemia caused by cold agglutinin is thought to be limited. Although the elevated levels of reticulocytes and LDH are usually caused by ineffective hematopoiesis in myelodysplastic syndrome, clinicians should be aware of latent cold agglutinin disease. In the present case, in addition to the improvement of erythroid dysplasia, the corticosteroid-sparing effect on cold agglutinin disease may have played a role in the mechanism underlying the effectiveness of cyclosporine.

Clinical and biochemical characteristics, and outcome in 33 patients with ceftriaxone-induced liver injury.

To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.

Clinical and haematological parameters in malaria caused by different plasmodium species in children

Background: Malaria is a disease of global importance and affects more than ninety countries in both the tropical and subtropical regions. Clinical and haematological parameters vary with type of malaria, although data relating to different species of malaria in children is limited. This study aims to understand the clinical and haematological profile of malaria and to correlate these with different malarial species among children. Methods: This is a descriptive cross-sectional study involving 130 proven malaria cases done over 18 months from October 2014 to April 2016. A detailed history and clinical examination along with haematological parameters were analysed and correlated with different types of malaria. Results: Among 130 children, 97 children were vivax positive, 4 were falciparum and 27 were mixed malaria. Fever was present in all, whilst other symptoms were chills and rigors (86.15%), vomiting (39.52%), headache (19%), pain abdomen (6.84%), myalgia (4.56%) and convulsions (1.52%). Clinical signs were pallor (29.64%), icterus (0.76%), splenomegaly (65.36%), hepatomegaly (23.56%) and hepatosplenomegaly (21.28%).75% of children with falciparum malaria had splenomegaly and pallor whereas hepatomegaly was observed in 34% of mixed malaria cases. Haematological parameters observed were anaemia (47.6%), severe anaemia (2%), leucocytosis (11.5%), leukopenia (39.2%), thrombocytopenia (87%) and severe thrombocytopenia (30%). Severe thrombocytopenia was seen with vivax malaria (70%). No mortality was noted in the studied population. Conclusions: Fever and splenomegaly are important clinical features, whereas anaemia and thrombocytopenia are the most noted haematological parameters in malaria. The parameters vary with different species of malaria knowledge of clinical and haematological parameters aid us in early diagnosis and prompt initiation of treatment and prevention of associated complications.

Towards a Cure for Diamond–Blackfan Anemia: Views on Gene Therapy

Diamond–Blackfan anemia (DBA) is a rare genetic disorder affecting the bone marrow’s ability to produce red blood cells, leading to severe anemia and various physical abnormalities. Approximately 75% of DBA cases involve heterozygous mutations in ribosomal protein (RP) genes, classifying it as a ribosomopathy, with RPS19 being the most frequently mutated gene. Non-RP mutations, such as in GATA1, have also been identified. Current treatments include glucocorticosteroids, blood transfusions, and hematopoietic stem cell transplantation (HSCT), with HSCT being the only curative option, albeit with challenges like donor availability and immunological complications. Gene therapy, particularly using lentiviral vectors and CRISPR/Cas9 technology, emerges as a promising alternative. This review explores the potential of gene therapy, focusing on lentiviral vectors and CRISPR/Cas9 technology in combination with non-integrating lentiviral vectors, as a curative solution for DBA. It highlights the transformative advancements in the treatment landscape of DBA, offering hope for individuals affected by this condition.

Romiplostim for Treatment of Children and Young Adults With Severe Aplastic Anemia and Myelodysplastic Syndrome.

Thrombopoietin receptor agonists (TPO-RAs) induce trilineage hematopoiesis under conditions with acquired hematopoietic failure. We evaluated safety, tolerability, and preliminary efficacy of a TPO-RA, romiplostim (Nplate), with or without standard-of-care immunosuppressive therapy (±IST) for children (ages <21y) with newly diagnosed and relapsed/refractory severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS). Data were collected from an observational study and a single arm interventional pilot study. The safety outcome was treatment-related adverse events (AEs). Efficacy was evaluated by complete hematopoietic response (CHR) at week 24. Romiplostim was commenced at 5µg/kg/week, with dose escalation of 2.5µg/kg/week (maximum, 20µg/kg/dose) based on platelet response. Romiplostim was continued until CHR was observed. Ten subjects (SAA, 9 [IST, 4; without IST, 5]; MDS, 1) completed the study (median age: 9.2y). Median romiplostim dose was 10µg/kg/week (range: 5 to 17.5µg/kg/week). The cumulative incidence of CHR was 70.4% (95% CI, 20.2%-92.6%). Among 21 AEs (Grade 1 to 3), 3 were attributed to romiplostim. At a median posttherapy follow-up of 10.9 months (range: 0.7 to 77.5), no clonal evolution, bone marrow fibrosis or mortality was reported. This proof-of-concept study provides data about short-term safety, tolerability, and preliminary efficacy of romiplostim (±IST) for treatment of pediatric SAA/MDS.

#1533 The relationship between the severity of anemia, the level of inflammation markers and the dose of epoetin in patients in pre-dialysis stages of CKD

Abstract Background and Aims Inflammation is known to be an important factor associated with hemoglobin variability in patients with anemia of chronic disease. However, the question remains whether high levels of C-reactive protein, a widely used marker of inflammatory activity, and other inflammatory markers predict less stable anemia control in patients with CKD. The purpose of this study was to establish the relationship between the severity of anemia with the levels of inflammatory markers (C-reactive protein, IL-6) and the dose of epoetin in patients with pre-dialysis stages of CKD. The purpose of our study was to study the age-related characteristics of the nutritional status in patients with CKD of the dialysis stages who are on parenteral nutrition. Method 180 patients (96 men and 84 women) with CKD as a result of nephropathies of diabetic and non-diabetic etiology were examined. Chronic pyelonephritis was diagnosed in 96 patients, chronic glomerulonephritis - in 73, polycystic kidney disease - in 11 patients. Glomerular filtration rate was calculated based on serum creatinine concentration using the CKD-EPI formula (2011). The patients were divided into 2 groups, depending on the achievement of the target hemoglobin value. Thus, group 1 included patients with CKD C3, C4, whose hemoglobin concentration was above 110 g/l (n = 101). Group 2 included patients whose hemoglobin concentration was less than 110 g/l in at least one analysis (n = 79). Results In the examined patients, a significant correlation was found between the range of hemoglobin concentration and the range of CRP concentration (p &amp;lt; 0.05), as well as between the range of hemoglobin concentration and the variation in the percentage of hypochromic erythrocytes (p &amp;lt; 0.05), between the range of hemoglobin concentration and the variation of ferritin ( p &amp;lt; 0.05). The change in the percentage of hypochromic erythrocytes also correlated with the change in IL-6 (p &amp;lt; 0.05) and the change in CRP ( p &amp;lt; 0.05). We found an association between the average weekly dose of epoetin and the levels of CRP, IL-6 and TNF-α. Patients with TNF-α levels ≥2 ng/mL and IL-6 ≥40 ng/mL required a significantly higher dose of epoetin than patients with lower levels of these markers (128 U/kg per week versus 57 U/kg at week). Conclusion The establishment of a relationship between inflammatory markers and hemogram and iron parameters suggests that inflammation had an indirect effect on the increase in hemoglobin through its effect on iron metabolism. The results of the study indicate the presence of diabetic and non-diabetic etiology of systemic inflammation in CKD, more so in the group of patients with type 2 diabetes mellitus.

#511 Inadequate diagnostic investigations and low treatment rates in CKD anemia: an inertia that can only change with long-term follow-up

Abstract Background and Aims Anemia is observed from the early stages in the course of chronic kidney disease (CKD), and as the stage progresses, the severity of anemia and its impact on quality of life increase. Early diagnosis of anemia in chronic kidney disease, assessments related to its etiology, and treatment are therefore crucial. There is no comprehensive and long-term study in Turkey addressing the diagnostic and therapeutic management of anemia seen in the course of chronic kidney disease. The aim of this study is to investigate the frequency of anemia in different stages of CKD in patients diagnosed with Stage 3 and more advanced stages, to evaluate the effectiveness of diagnostic approaches, and management of iron parameters and anemia, and to investigate the effect of anemia on patient survival. We aim to present “real-life” data from this study to guide clinical practice and correct errors or deficiencies in anemia management. Method This study is a single-center, observational-descriptive retrospective study. 1321 outpatients with Stage 3A and advanced CKD and anemia who admitted to Hacettepe University Faculty of Medicine Nephrology Clinic between 2014 and 2018 were included in the study. Data for demographics, CKD etiologies and stages, anemia severities, comorbid diseases were collected from electronic health system (Table 1). Diagnostic investigations for anemia evaluation and therapeutic interventions such as administration of iron, folic acid, vitamin B12, erythropoiesis stimulating agents (ESA) were assessed. The long-term yield of diagnostic and therapeutic approaches and their effects on survival were also evaluated. The study investigated whether the severity of anemia and improvement in anemia had an effect on survival. Results Ferritin is the most commonly performed test for the etiology of anemia (76.4%). Request rates for tests such as B12, folic acid, transferrin saturation and reticulocyte are below 20%. More than half of the patients with anemia (59.4%) have not received any form of anemia treatment. Even among those whose ferritin test was checked and the value was &amp;lt;100 µg/dL, only 41.4% were given iron treatment. As the clinical follow-up period of the patients increased, it was observed that anemia treatment was applied better and target values were reached more frequently (p &amp;lt; 0.001). More than one third of the patients (34.8%) died during follow-up. The overall survival in patients whose anemia improved was 79.8%, and it was 62.8% in patients whose anemia did not improve the overall survival was (p = 0.002) (Fig. 1). When examining the relationship between survival status and anemia severity for the non-dialysis-dependent CKD Stage 3-5 group, there was a statistically significant survival difference between the Hb group of 10-11.9 g/dL to Hb group of &amp;lt;10 g/dL (p = 0.004). Conclusion This study has shown that diagnostic tests for etiology of anemia were insufficiently ordered. It was also found that a significant majority of anemic patients who underwent etiological evaluation were not even adequately treated. Long-term follow up improved anemia treatment, and patients with improved anemia had better survival. In conclusion, we recommend an optimal evaluation of CKD patients with anemia and initiating treatment as early as possible.

#1881 Association of circulating autoantibodies to erythropoietin receptor with anaemia in patients with type 2 diabetes and chronic kidney disease

Abstract Background and Aims Anaemia is a risk factor for cardiovascular and kidney prognosis in patients with type 2 diabetes and it is important to identify patients at high risk of anemia. We have previously reported that autoantibodies to erythropoietin receptor (anti-EPOR antibodies) may functionally neutralize the activity of erythropoietin and are associated with haemoglobin (Hb) in patients with lupus nephritis, and hypo responsiveness to erythropoiesis-stimulating agents (ESAs) in patients undergoing haemodialysis. This study assessed the association between anti-EPOR antibodies and anaemia in patients with type 2 diabetes and chronic kidney disease. Method This cohort study included patients with type 2 diabetes and chronic kidney disease who were diagnosed between 1989 and 2014 at our hospital. The presence of anti-EPOR antibodies at baseline were assessed by ELISA in stocked serum. To investigate the association between anti-EPOR antibodies and anaemia, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis adjusted for multiple covariates. We then estimated hazard ratios (HR) and 95% CIs using Cox regression models to investigate the association between anti-EPOR antibodies and the risk of iron deficiency, defined as transferrin saturation below 20% in those with follow-up measurements of iron metabolism. Results The mean age was 63 years, the mean eGFR was 42 ml/min/1.73 m2 and the median urinary protein to creatinine ratio (UPCR) was 1.8 g/gCr. Anti-EPOR antibodies were detected in 26 out of 110 patients (24%). At baseline, most patients with anti-EPOR antibodies had anaemia (n=24, 92%) and severe anaemia with Hb&amp;lt;10 g/dl (n=16, 62%) and used ESAs (n=16, 62%). The presence of anti-EPOR antibodies was independently associated with severe anaemia (OR 9.3; 1.2-70.1, p=0.03) after adjustment for baseline covariates including HbA1c, eGFR, UPCR, iron, and CRP. During a mean follow-up of 6.5 years, 6 of 10 patients (60%) developed iron deficiency in anti-EPOR antibodies positive patients, while 3 of 20 patients (15%) in negative patients. Patients with anti-EPOR antibodies were associated with an higher risk of iron deficiency compared to those without (HR 76.0; 95% CI 1.2-4721.7, p=0.04). Conclusion In patients with type 2 diabetes and chronic kidney disease, the presence of anti-EPOR antibodies was associated with a risk of severe anaemia and iron deficiency independently of kidney function. These results suggest that anti-EPOR antibodies may be useful in predicting the risk of anaemia and establishing therapeutic strategies of anaemia in people with type 2 diabetes.

#1986 Incidence of renal anemia among patients with atrial fibrillation and chronic kidney disease stage IIIb-V

Abstract Background and Aims According to the QICKD study, the prevalence of anemia in stage IIIb-V chronic kidney disease (CKD) is 22%. The incidence of renal anemia ranges from 8.4% in patients with stage I CKD to 83.7% in patients with stage V CKD. In patients on program hemodialysis, anemia develops in 94.5% of cases. The problem is associated with an increased risk of unfavorable outcome of CKD, therefore, the study of aspects of anemia among patients receiving anticoagulant therapy with atrial fibrillation (AF) and CKD remains the most relevant today. The purpose of the study is to study the prevalence of renal anemia among patients with AF and CKD stages IIIb-V. Method 794 patients were admitted to the cardiology department with a diagnosis of AF and late stages of CKD—IIIb (glomerular filtration rate (GFR) 45–30 ml/min/1.73 m2), IV (GFR 29–15 ml/min/1.73 m2), V (GFR &amp;lt;15 ml/min/1.73 m2), for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2. The classification of renal anemia was carried out according to the recommendations of the World Health Organization. Results Renal anemia was diagnosed in 505 (63%) patients with AF and GFR less than 45 ml/min/1.73 m2. In total, among patients with CKD stage IIIb, anemia was detected in 207 (59%) patients, with CKD stage IV—in 110 (89%), with CKD stage V—in 43 (97%), with FISD in GFR—in 145 (51%). A mild degree of anemia (hemoglobin (Hb) in men 110-129 g/l, in women 110-119 g/l) was diagnosed in 39% of patients, with CKD stage IIIb in 85 (24%) patients, with CKD stage IV in 28 (22%) patients, with CKD stage V in 9 (20%) patients, with FISD in GFR in 75 (26%) patients. A moderate degree of anemia (Hb 81-109 g/l) was detected in 47.3% of cases, with CKD stage IIIb in 86 (25%) patients, with CKD stage IV in 60 (48%) patients, with CKD stage V in 29 (66%) patients, with FISD in GFR in 64 (23%) patients. Severe anemia (Hb 81-109 g/l) was detected in 47.3% of patients, with CKD stage IIIb in 36 (10%) patients, with CKD stage IV in 22 (19%) patients, with CKD stage V in 5 (11%) patients, with FISD in GFR in 6 (2%) patients. Conclusion Every fourth patient in the cardiology department with AF and GFR &amp;lt;45 ml/min/1.73 m2 was diagnosed with renal anemia, and its prevalence increases with a decrease in GFR. The above results indicate that a more careful selection of anticoagulant therapy is recommended for this patient population due to the high risk of progression of renal anemia in this cohort of patients.

#2070 Associations of fecal and plasma levels of SCFAs with gut microbiota and clinical characteristics in non-dialysis renal anemia patients

Abstract Background and Aims Renal anemia is one of the most common complications of Chronic Kidney Disease (CKD). The gut-kidney axis hypothesis has led to numerous studies showing that patients with CKD have a distinct gut microbiota structure compared with controls and that changes in gut microbiota correlate with disease severity and progression. The short-chain fatty acids (SCFAs) are speculated to be pivotal in the gut-kidney crosstalk. However, the role of SCFAs in renal anemia has not been elucidated. This study aimed to explore and compare the fecal and plasma levels of SCFAs in non-dialysis renal anemia patients and healthy controls to reveal the potential interactions among SCFAs, gut microbiota, and clinical features of renal anemia, which may provide new light on further studies. Method A cohort of 30 non-dialysis renal anemia patients and 20 healthy controls were recruited from the First Affiliated Hospital of Zhengzhou University. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. Fecal and plasma concentrations of SCFAs were measured using GC-MS/MS platform. The clinical characteristics of patients with renal anemia and controls were evaluated. Results Renal anemia patients displayed altered microbiota composition compared to healthy subjects. The relative abundance of Enterobacterales, Enterobacteriaceae, Escherichia-Shigella, and Escherichia-coli were higher in patients with renal anemia, and the Lachnospiraceae family decreased in renal anemia patients. In contrast, the relative abundance of Lachnospirales, Lachnospiraceae, and Bacteroides vulgatus was higher in the control group. Patients with renal anemia had higher fecal and plasma concentrations of SCFAs compared to controls. The fecal and plasma concentrations of SCFAs were significantly different not only between the patients with renal anemia and controls but also in the different severity of renal anemia. Moreover, different types of SCFAs are intimately associated with clinical characteristics. The applications of medications may exert effects on the fecal and plasma SCFAs. A positive correlation was obtained between Lachnospirales and the plasma SCFAs. The levels of acetic acid and caproic acid in fecal and the levels of acetic acid, propionic acid, and butyric acid in plasma were all positively correlated with the abundance of Cyanobacteria. Conclusion The gut metabolites SCFAs are tightly linked to the alterations of gut microbiota and clinical characteristics of renal anemia. Further studies are warranted to elucidate the relationships more in-depth.

#3090 Parvovirus infection in renal transplant recipients: a systematic review of clinical profile and treatment strategies

Abstract Background and Aims Parvovirus B 19 (PVB-19) virus infection can cause severe, persistent and/or refractory anaemia in kidney transplant recipients (KTR). There is paucity of data on the clinical manifestations, diagnosis and management of this infection and limited to case reports and case series. Method We performed a literature search of kidney transplant recipients infected with PVB-19 in MEDLINE, EMBASE and Cochrane databases and 93 articles were identified as suitable for assessment. The review was conducted in accordance with PRISMA statement. Results A total of two hundred and eighty-two patients were included from the studies assessed in the review. The mean age of the cohort was 37.05 years. The infection was more common in males when compared to females. The median onset of PVB-19 infection post transplantation was at 5 weeks (2, 15 weeks). One fourth of the recipients had at least one episode of rejection prior to PVB-19 infection. Majority of the patients were on Tacrolimus, MMF and corticosteroids maintenance. One third of the patients had co-infections with other organisms (EBV, CMV, etc.). Anemia and fever were the most common manifestations among all the kidney transplant patients infected with PVB-19 while CNS manifestations and rash were least reported. Hemoglobin was low (&amp;lt;10 mg/dl) in ninety eight percent of the patients (n=151). The lowest hemoglobin reported in the due course of illness was 6 mg/dl (5, 7.2 mg/dl) and with corrected reticulocyte count being only 0.2% (0.1%, 0.6%). The most consistent finding on peripheral smear was normocytic, normochromic anemia while a few reported helmet cells too. Pure Erythroid hypoplasia alone (45.3%) combined with giant pronormoblasts and inclusion bodies (49%) were the most common findings on bone marrow aspirate. Majority of PVB-19 diagnosis was made with the help of multiple methods of detection like IgM assay, PCR—qualitative and quantitative (42.2%). The average PCR copies detected were 1.3*107 (4.28*105, 2.53*109). IVIG only (47.2%) and combined IVIG + immunosuppression reduction (41.2%) was the mainstay of the treatment in majority. The median time to recover was 8 weeks (3, 16 weeks). One fourth of the patients had recurrence after recovery. A majority of the patients (96.7%) recovered from reactivation of PVB-19. Conclusion Parvovirus infection is not uncommon in the early post-transplant period. Though data is insufficient, immunosuppression reduction with IVIG remains the treatment of choice for affected patients. Prospective studies to assess the hemoglobin cutoffs and dose of IVIG are needed to frame screening and treatment protocols.

#1912 Assessment of the dynamics of renal anemia in patients with atrial fibrillation and chronic kidney disease stage IIIb-V during anticoagulant therapy

Abstract Background and Aims Therapy with oral anticoagulants prevents the development of most ischemic strokes and systemic embolisms in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), and also helps to increase life expectancy, improving its quality. It should be emphasized that with CKD, the risk of hemorrhagic complications also increases, which in turn can lead to the progression of renal anemia and deterioration in the patient's general condition. The main complication of anticoagulants is an increased risk of major bleeding, including intracranial, life-threatening bleeding. The purpose of the study is to assess the benefits and risks of anticoagulant therapy in patients with renal anemia in AF and stage IIIb-V CKD. Method From February 2022 to July 2023, 2983 patients with AF were admitted to cardiology departments. The majority of patients with AF had hypertension (94%), chronic heart failure (71%), coronary heart disease (65%), and type 2 diabetes mellitus (23%). CKD was diagnosed according to KDIGO criteria, glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. Indications for anticoagulant therapy (ACT) were determined according to European guidelines for AF using the scales for assessing the risk of thromboembolic complications (TEC)—CHA2DS2-VASc and the risk of bleeding—HAS-BLED. Results GFR up to 45 ml/min/1.73 m2 was detected in 2189 (73%) patients with AF, GFR less than 45 ml/min/1.73 m2 in 794 (27%) patients with AF (CKD stages IIIb–V in 516 (65%) cases, for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2 was detected in 278 (35%) cases). Among patients with AF and CKD, renal anemia was diagnosed in 23% of cases, in 63% (n = 505) of cases with AF and GFR &amp;lt;45 ml/min/1.73 m2. With a GFR of 45-30 ml/min/1.73 m2, renal anemia was detected in 59%, with a GFR of 30-15 ml/min/1.73 m2—in 89%, with a GFR &amp;lt;15 ml/min/1.73 m2—in 97%, with FISD in GFR &amp;lt;45 ml/min/1.73 m2—in 51%. When stratifying thromboembolic risk according to the CHA2DS2-VASc scale in patients with AF and CKD stages IIIb–V, 0-1 points were scored by 1% (n = 11), 2-5 points by 53% (n = 420), ≥6 points by 46% (n = 363) patients. The results of the analysis of the risk of bleeding according to the HAS-BLED scale showed the following data: 0-1 point—8% (n = 64), 2 points—15% (n = 118), ≥3 points—77% (n = 612). When studying the frequency of ACT prescription, it was revealed that rivaroxaban was prescribed in 21%, apixaban—22%, dabigatran—10%, warfarin—25%, low molecular weight heparins—3%, ACT not recommended—9%, ACT of choice—10% of cases (Table 1). In mild renal anemia (in 39% of patients), taking ACT led to a reduction in the risk of developing TEC—RR 0.55 with 95% CI 0.38-0.79; in case of moderate renal anemia (in 47.3% of patients), the risk of TEC did not decrease RR 1.03 with 95% CI 0.69-1.58; with severe renal anemia (in 13.7% of patients), the risk of TEC was also not reduced—RR 1.6 with 95% CI 1.17-2.2). Conclusion Every fourth patient in the cardiology department with AF showed a decrease in GFR &amp;lt;45 ml/min/1.73 m2, while 1/3 of them had FISD in GFR &amp;lt;45 ml/min/1.73 m2, and it is in these patients that the most common the dose of the prescribed anticoagulant did not correspond to the GFR; 50% of patients with GFR &amp;lt;45 ml/min/1.73 m2 and 32% with GFR &amp;lt;30 ml/min/1.73 m2 are recommended to use direct oral anticoagulants. Patients with stage V CKD were not prescribed direct oral anticoagulants; in 50% of cases, none of the anticoagulants was recommended.

CAD-Related Disorder (EIEE-50) in an Infant With Cortical Visual Impairment.

To document the association of CAD-related disorder (EIEE-50) with cortical visual impairment. An 8-month-old Caucasian boy with whole genome sequencing confirming 2 variants in the gene CAD, who presented with severe seizures, microcephaly, hyperreflexia, hypotonia, anemia, and severe cortical visual impairment. Magnetic resonance imaging (MRI) of the brain noted thickened cortical gray matter along the right calcarine fissure as well as changes suggesting malformation of cortical development. Empiric uridine monophosphate supplementation has significantly improved seizure activity, hypotonia, and development and has led to resolution of anemia. CAD-related disorder is treatable and may affect visual cortical development causing severe secondary cortical visual impairment, a newly described clinical manifestation.

Relationship between anemia and pneumonia severity in children aged 29 days to 5 years

relationship between anemia and pneumonia severity in children aged 29 days to 5 years

Managing recurrent parvovirus B19-associated anemia after a pediatric kidney transplant.

A 13-year-old girl who had a kidney transplant four weeks prior presented with a 10-day history of fatigue, paleness, and headache. On physical examination, tachycardia and paleness were noted. Laboratory testing was notable for severe anemia and mild leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) test for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative and for parvovirus B19 (PVB19) was positive. Despite lower immunosuppression and administration of intravenous immunoglobulin (IVIG) it persisted for 15months, and frequent red blood cell transfusions were needed. PVB19 is a less common but significant complication. The patient's clinical course demonstrates the importance of this complication and the challenges in its management. A notable void exists in the literature regarding standardized treatment protocols for PVB19-induced recurrent anemia after kidney transplant. This case indicates the need for further research and consensus to guide effective clinical interventions in similar cases.

Jehovah’s Witness Needing Critical Care: A Narrative Review on the Expanding Arsenal

Present day Jehovah’s Witness (JW) religion accounts for 8.5 million followers. A tenant feature of the JW faith is religious objection to transfusions of blood and blood products. Interpatient variability, as it pertains to blood and blood products may occur; hence, a confidential interview will determine which products individual may consent to (Marsh and Bevan, 2002). This belief and practice place great restrictions on treating medical professionals in scenarios of life-threatening anaemia and active haemorrhage. The review to follow explores the physiological and pathophysiological consequences of severe anaemia. Non-blood transfusion practices are explored, many of which are potentially lifesaving. Particular attention is drawn to the evolving science involving artificial oxygen carriers and their use in emergency situations. A greater safety profile ensures its future use amongst religious objectors to be greatly beneficial. Intravenous iron supplementation has enjoyed a lively debate within the critical care community. A review of recent systematic and meta-analysis supports its use in the ICU; however, more investigation is needed into the complementary use of hepcidin.

Assessment of Hematopoietic Response to Total Body Irradiation in a Rat Experimental Model.

Exposure to high doses of total body irradiation (TBI) may lead to the development of acute radiation syndrome (ARS). This study was conducted to establish an experimental rat model of TBI to assess the impact of different doses of TBI on survival and the kinetics of changes within the hematopoietic system in ARS. In this study, 132 Lewis rats irradiated with a 5Gy or 7Gy dose served as experimental models to induce ARS and to evaluate the hematopoietic response of the bone marrow (BM) compartment. Animals were divided into 22 experimental groups (n = 6/group): groups 1-11 irradiated with 5Gy dose and groups 12-22 irradiated with 7Gy dose. The effects of TBI on the hematopoietic response were assessed at 2, 4, 6, 8 hours and 5, 10, 20, 30, 40, 60 and 90 days following TBI. Signs of ARS were evaluated by analyzing blood samples through complete blood count in addition to the clinical assessment. Groups irradiated with 5Gy TBI showed 100% survival, whereas after 7Gy dose, 1.6% mortality rate was observed. Assessment of the complete blood count revealed that lymphocytes were the first to be affected, regardless of the dose used, whereas an "abortive rise" of granulocytes was noted for both TBI doses. None of the animals exhibited signs of severe anemia or thrombocytopenia. All animals irradiated with 5Gy dose regained initial values for all blood cell subpopulations by the end of observation period. Body weight loss was reported to be dose-dependent and was more pronounced in the 7Gy groups. However, at the study end point at 90 days, all animals regained or exceeded the initial weight values. We have successfully established a rat experimental model of TBI. This study revealed a comparable hematopoietic response to the sublethal or potentially lethal doses of ionizing radiation. The experimental rat model of TBI may be used to assess different therapeutic approaches including BM-based cell therapies for long-term reconstitution of the hematopoietic and BM compartments allowing for comprehensive analysis of both the hematological and clinical symptoms associated with ARS.

The effect of dietary diversity on anemia levels among children 6-23 months in sub-Saharan Africa: A multilevel ordinal logistic regression model.

Anemia is the most common hematologic disorder of children worldwide. Since dietary diversity is a main requirement of children is to get all the essential nutrients, it can thus use as one of the basic indicator when assessing the child's anemia. Although dietary diversity plays a major role in anemia among children in sub-Saharan Africa, there is little evidence of an association between the dietary diversity and anemia level to identified potential strategies for prevention of anemia level in sub-Saharan Africa. To examine the association between dietary diversity and anemia levels among children aged 6-23 months in sub-Saharan Africa. The most recent Demographic and Health Surveys from 32 countries in SSA were considered for this study, which used pooled data from those surveys. In this study, a total weighted sample of 52,180 children aged 6-23 months was included. The diversity of the diet given to children was assessed using the minimum dietary diversity (MDD), which considers only four of the seven food groups. A multilevel ordinal logistic regression model was applied due to the DHS data's hierarchical structure and the ordinal nature of anemia. With a p-value of 0.08, the Brant test found that the proportional odds assumption was satisfied. In addition, model comparisons were done using deviance. In the bi-variable analysis, variables having a p-value ≤0.2 were taken into account for multivariable analysis. The Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was presented for potential determinants of levels of anemia in the multivariable multilevel proportional odds model. The overall prevalence of minimum dietary diversity and anemia among children aged 6-23 months were 43% [95% CI: 42.6%, 43.4%] and 72.0% [95% CI: 70.9%, 72.9%] respectively. Of which, 26.2% had mild anemia, 43.4% had moderate anemia, and 2.4% had severe anemia. MDD, being female child, being 18-23 months age, born from mothers aged ≥25, taking drugs for the intestinal parasite, higher level of maternal education, number of ANC visits, middle and richer household wealth status, distance of health facility and being born in Central and Southern Africa were significantly associated with the lower odds of levels of anemia. Contrarily, being 9-11- and 12-17-months age, size of child, having fever and diarrhea in the last two weeks, higher birth order, stunting, wasting, and underweight and being in West Africa were significantly associated with higher odds of levels of anemia. Anemia was a significant public health issue among children aged 6-23 months in sub-Saharan Africa. Minimum dietary diversity intake is associated with reduced anemia in children aged 6 to 23 months in sub-Saharan Africa. Children should be fed a variety of foods to improve their anemia status. Reducing anemia in children aged 6-23 months can be achieved by raising mother education levels, treating febrile illnesses, and improve the family's financial situation. Finally, iron fortification or vitamin supplementation could help to better reduce the risk of anemia and raise children's hemoglobin levels in order to treat anemia.