Chronic Iron Deficiency Anemia Research Articles

6970 Severe Symptomatic Hypophosphatemia After Intravenous Iron Therapy: An Under-recognized Adverse Reaction

Abstract Disclosure: A. Morvant: None. O. Olajide: None. Introduction: Iron deficiency is a common condition that is often treated with intravenous preparations of iron supplementation. It has been documented in the literature that ferric carboxymaltose is the form of intravenous iron supplementation that is associated with the highest incidence of hypophosphatemia, when compared to other formulations of intravenous iron therapy. This case highlights a severe case of hypophosphatemia after ferric carboxymaltose therapy that led to multiple hospitalizations and required several months of oral and intravenous phosphorus repletion. Clinical Case A 36-year-old woman presented to the ED with severe diffuse arthralgias, generalized muscle weakness, and fatigue. Laboratory analysis revealed the following: phosphorus 1.2 mg/dL (2.3-4.7 mg/dL), 25-hydroxyvitamin D 13 ng/mL (25-80 ng/mL), parathyroid hormone 220 pg/mL (16-77 pg/mL), and calcium 8.5 mg/dL (8.4-10.5 mg/dL). She was admitted and started on intravenous and oral phosphorus repletion as well as oral ergocalciferol. She was subsequently discharged home on oral phosphorus and ergocalciferol supplementation, with a phosphorus level of 1.8 mg/dL. She was readmitted one day later with persistent arthralgias, myalgias, and severe fatigue, and found to have a phosphorus level of 1.1 mg/dL. Additional laboratory studies revealed the following: FGF23 41 pg/mL (<59 pg/mL) and 24-hour urine phosphorus 2191 mg/24hr (400-1300 mg/24hr). The patient notably had a history of chronic severe iron deficiency anemia due to menorrhagia and had been treated with intravenous iron sucrose infusions 7 months prior to her presentation. Due to adverse reactions to iron sucrose, this was switched to ferric carboxymaltose, and she had received two doses; one month and two weeks prior to her initial presentation. She was treated again with intravenous and oral phosphorus repletion and ergocalciferol and discharged after two weeks on oral phosphorus and ergocalciferol as well as thrice-weekly intravenous phosphorus infusions in the outpatient setting. She continued intravenous phosphorus infusions for about three months, and this was subsequently discontinued without recurrent hypophosphatemia. She is currently on low doses of oral phosphorus with normophosphatemia. Conclusion: Intravenous ferric carboxymaltose therapy can lead to severe and long-lasting, treatment-resistant hypophosphatemia due to increased urinary phosphate excretion. An increased awareness about this is needed by clinicians in treating patients who receive ferric carboxymaltose and monitoring phosphorous levels is crucial.

S2913 Chronic Left Lower Quadrant Pain and Iron Deficiency Anemia in a Young Lady Mimicking a Colonic Endometrioma: Consider Cavernous Hemangioma of the Sigmoid

S2913 Chronic Left Lower Quadrant Pain and Iron Deficiency Anemia in a Young Lady Mimicking a Colonic Endometrioma: Consider Cavernous Hemangioma of the Sigmoid

Periprosthetic joint infection after total knee arthroplasty. Lessons learned: a case report and literature review

Introduction. The increasing proportion of the aging population and overweight people with various joint problems leads to an increased demand for joint replacements. As the number of joint arthroplasty surgeries continues to rise, the persistent incidence of periprosthetic joint infections highlights the need for a comprehensive and evolving approach. In addition to the preoperative period, it is also necessary to consider the course of the intraoperative, and to a greater extent the postoperative period, when the development of periprosthetic infection occurs. This case is indicative of the fact that underestimation of the importance of the postoperative period and control of risk factors can lead to the recurrence of infection. This negatively affects the economy due to an increase in the number of disabilities.Case presentation. A 60-year-old female patient was diagnosed with a periprosthetic joint infection following total knee arthroplasty. The patient's premorbid background was aggravated by the presence of type 2 diabetes mellitus, arterial hypertension, secondary cardiomyopathy, and chronic iron-deficiency anemia. Single stage revision of knee arthroplasty, removal of prosthetic components, excision of degenerative tissue, prolonged antibiotic therapy as well as rehabilitation were ineffective, and the pain increased. Therefore, the patient is admitted for the two-stage revision surgery, removal of the endoprosthesis, and installation of a nonarticulating cement spacer of the left knee joint.Conclusion. Through a relevant literature search, we believe that uncorrected chronic iron-deficiency anemia in combination with uncontrolled diabetes mellitus, both in the preoperative and postoperative period for joint replacement, may increase the risk of the development of periprosthetic infection. Moreover, focusing patients' attention on the importance of the postoperative period and strict monitoring of health indicators will help reduce the likelihood of re-prosthetics.

Erythroferrone in focus: emerging perspectives in iron metabolism and hematopathologies.

Beyond its core role in iron metabolism, erythroferrone (ERFE) has emerged as a key player with far-reaching implications in various hematologic disorders. Its regulatory effect on hepcidin underlines its significance in conditions characterized by disrupted iron homeostasis. In β-thalassemia and myelodysplastic syndromes, its dysregulation intricately contributes to the clinical challenges of anemia and iron overload which highlights its potential as a therapeutic target. In anemia of chronic disease and iron deficiency anemia, ERFE presents a unique profile. In chronic kidney disease (CKD), the intricate interplay between ERFE, erythropoietin, and hepcidin undergoes dysregulation, contributing to the complex iron imbalance characteristic of this condition. Recent research suggests that ERFE plays a multifaceted role in restoring iron balance in CKD, beyond simply suppressing hepcidin production. The potential to modulate ERFE activity offers a novel approach to treating a spectrum of disorders associated with iron dysregulation. As our understanding of ERFE continues to evolve, it is poised to become a key focus in the development of targeted treatments, making it an exciting and dynamic area of ongoing research. Modulating ERFE activity presents a groundbreaking approach to treat iron dysregulation in conditions like iron deficiency anemia, thalassemia, and hemochromatosis. As new research unveils its intricate roles, ERFE has rapidly emerged as a key target for developing targeted therapies like ERFE agonists and antagonists. With promising studies underway, this dynamic field holds immense potential to improve patient outcomes, reduce complications, and offer personalized treatment options in hematology research. This comprehensive overview of ERFE's role across various conditions underscores its pivotal function in iron metabolism and associated pathologies.

МАТЕМАТИЧЕСКОЕ МОДЕЛИРОВАНИЕ В ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКЕ АНЕМИИ ХРОНИЧЕСКИХ ЗАБОЛЕВАНИЙ И ЖЕЛЕЗОДЕФИЦИТНОЙ АНЕМИИ У ПАЦИЕНТОВ С ВОСПАЛИТЕЛЬНЫМИ ЗАБОЛЕВАНИЯМИ СУСТАВОВ

Aim. To develop based on the indicators of clinical blood tests, some biochemical markers, iron metabolism and cytokines a mathematical model that allows with high sensitivity and specificity to conduct differential diagnosis of anemia of chronic diseases (AHD) and iron deficiency anemia (IDA) in patients with inflammatory joint diseases (rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS)). Material and methods. The study included 104 patients with inflammatory joint diseases and anemic syndrome (37 males/67 females, age 48.4±5.42 years old), of which 54 patients with RA, 27 patients with PSA and 23 patients with AS. The control group consisted of 22 patients with inflammatory diseases of the joints without anemia (13 males/9 females, age 47.8±3.55 years old), of which 7 patients with RA, 10 with PSA, 5 with AS. For all patients, in addition to hemogram parameters, the concentrations of interleukin-6, interleukin-10, interleukin-1β, interferon-gamma, tumor necrosis factor alpha, ferritin, C-reactive protein, hepcidin, transferrin, soluble transferrin receptor were determined. For quantitative indicators, the median, standard error of the mean, and interquartile range was calculated. The significance of differences between several unrelated groups was determined using the Kruskal-Wallis test. The calculation of a mathematical model for the differential diagnosis of ACD and IDA was carried out using discriminant analysis. Results. As a result of the study, a canonical linear discriminant function (CLDF) was obtained: CLDF = 1.612171-0.002725× Hepcidin -0.005429× Ferritin The coordinates of the centroids are calculated, for ACD it is -1.44222008, and for IDA it is 1.52705656. A patient whose CLDF value is determined based on ferritin and hepcidin concentrations should be classified into the ACD or IDA group based on the minimum distance to the corresponding centroid. The resulting mathematical model has 100% sensitivity and 80% specificity. Conclusions. The equation based on hepcidin and ferritin (obtained from the results of discriminant analysis) allows, with high sensitivity, specificity and information ability, to carry out differential diagnosis of ACD and IDA in patients with inflammatory joints diseases instantly at the stage of initial contact with the doctor. Using of the equation will make it possible to more effectively diagnose and correct these types of anemia in this pathology, including for the purpose of more effective treatment.

Endoscopically diagnosed hookworm infestation in an adult with chronic iron deficiency anaemia

Despite advances in hookworm control and prevention campaigns, the prevalence remains high in sub-Saharan Africa. Iron deficiency anaemia is a major complication in those with prolonged infection, a high hookworm burden, and undernutrition, though most infected people are asymptomatic. While infected patients are commonly diagnosed by the presence of ova or cysts in the stool, gastrointestinal (GI) endoscopy is required for those with negative stool tests and chronic iron deficiency anaemia. A 48-year-old female with symptoms of anaemia for nearly two years presented to Mbarara Regional Referral Hospital with worsening palpitations, easy fatigability, and dizziness over a period of one month. She was given blood transfusions on two occasions. She lives near the lake where she also gets water for drinking and domestic use. We advise GI endoscopy for all patients with chronic iron deficiency anaemia of unexplained aetiology on standard non-invasive testing. Hookworm’s mass empirical treatment policy in endemic areas should be further emphasised.

Ferric carboxymaltose-induced hypophosphatemia - a case series.

Hypophosphatemia may cause serious complications. Depending on its severity and duration, signs and symptoms range from fatigue to life-threatening events, like severe rhabdomyolysis and mental status changes. Long-term consequences include osteomalacia. Hypophosphatemia may be secondary to the use of parental iron, mostly associated with ferric carboxymaltose (FCM), with an incidence of around 45% to 70%. We describe three cases of hypophosphatemia in patients with chronic iron deficiency anemia, requiring repeated FCM infusions. The patients' presentation to the Rheumatology department included musculoskeletal symptoms of severe hypophosphatemia and long-term hypophosphatemic osteomalacia, with fractures. We aim to raise awareness for ferric carboxymaltose-induced hypophosphatemia, an entity increasingly described in the literature that can be responsible for severe disability or potentially life-threatening adverse events.

The Role of Hepcidin, sTfR, and sTfR/Log Ferritin Index for the Differential Diagnosis of Iron Deficiency Anemia and Anemia of Chronic Disease

Background: In chronic diseases characterized by persistent inflammation, anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are commonly encountered forms of anemia and can often co-occur. In such situations, the conventional iron status tests used for differential diagnosis are influenced by inflammation, reducing their diagnostic accuracy. The primary objective of this study was to assess the significance of hepcidin as a crucial diagnostic marker for ACD and to investigate the correlation between hepcidin and inflammation-related indicators. Furthermore, a significant secondary aim of this research was to ascertain the diagnostic role of novel biochemical markers, specifically soluble transferrin receptor (sTfR) and the derived sTfR/log ferritin index (sTfR-F index). Methods and Results: This study was conducted at the Laboratory Service of the University Hospital Center "Mother Teresa" and included a cohort of 187 subjects, comprising 156 patients (83 females and 73 males) who were admitted to and received treatment at the Rheumatology and Cardiology Departments of the "Mother Teresa" University Hospital Center in Tirana. Additionally, 31 individuals without anemia and inflammatory conditions were included as a control group. All subjects incorporated into the study were classified into five distinct groups based on a comprehensive analysis of their complete blood profiles, iron status, and inflammation-related biomarkers: IDA, ACD, ACD+IDA, RA/CHF patients without anemia, and the control group without anemia. The comparison between groups showed that the mean values of pro-hepcidin, TNFα, IL6, Hs-PCR, and ferritin are significantly decreased in IDA vs. ACD, while sTFR and sTfR-F index are significantly increased. In comparing ACD vs. ACD+IDA groups, ferritin increased significantly in the ACD group, while sTFR and sTfR-F index decreased significantly in ACD, compared to the ACD+IDA group. The ROC curves analysis of the biochemical parameters selected for the comparison of ACD vs IDA showed that the pro-hepcidin test is a perfect test for the differential diagnosis of ACD vs. IDA. The suggested cut-off value for pro-hepcidin was ≥153 ng/ml, yielding a sensitivity of 100% and a specificity of 100% for the diagnosis of ACD. As regards sTFR, the suggested cut-off value for the diagnosis of IDA vs. ACD was≥ 4.9 µg/ml resulting in 84% sensitivity and 100% specificity. The sTfR-F index was also very useful for the diagnosis of IDA vs. ACD: for a cut-off value of ≥2.06, the sensitivity was 90% and the specificity was 96%. sTfR resulted in a good test for the diagnosis of ACD+IDA vs. ACD: the cut-off value was ≥ 3.7µ/ml, the sensitivity was 92.3% and the specificity was 93.2%. Similarly, the parameter sTfR-F index resulted in a very good test for the diagnosis of ACD+IDA vs. ACD: for the suggested cut-off value of ≥2.3, the sensitivity was 92.3% and the specificity was 100%. Conclusion: As a result of the study, it was found that the pro-hepcidin test was a highly accurate test for distinguishing between ACD and IDA. Meanwhile, sTfR and the sTfR-F index proved to be excellent indicators for the differential diagnosis of IDA in chronic inflammatory conditions.

Endometrial hyperplasia and endometrial polyps: clinical and anamnestic characteristics of women

Aim. To study the clinical and anamnestic characteristics of patients with endometrial hyperplasia (EH) and endometrial polyps (PE).Material and Methods. a retrospective study was conducted, which included 267 sick women of reproductive and perimenopausal age who sought gynecological care at «Euromed» in 2022-23, who, before receiving the examination results, were diagnosed with N92 - heavy, frequent and irregular menstruation. Depending on the results of the pathomorphological examination, the patients were divided into 3 groups: group A included 89 patients with GE; group B – 99 women with PE; Group B (control) included 79 patients in whom endometrial pathology was excluded.Results. Among all women who came to the clinic with heavy menstrual bleeding, 33.3% had GE, 37.1% had PE, 29.6% had BUN-O ovulatory dysfunction. GE without atypia was detected in 72 (80.9%) cases of group A, GE with atypia – in 7 (19.1%), in group B PE was diagnosed in 91 (91.9%) cases, PE with atypia – in 28 (8.1%).In group B, in 22 (27.8%) cases, the endometrium was identified in the proliferation phase, in 57 (72.2%) cases, the endometrium was identified in the phase of incomplete secretion.Conclusion. Women with GE are characterized by early menarche, absence of pregnancies and childbirth during life associated with the woman’s choice, contraception, endocrine diseases, obesity, polycystic ovary syndrome, ovarian tumors, heavy bleeding with clots during menstruation, menstruation for more than 8 days, chronic iron deficiency anemia. Women with endometrial polyps are characterized by arterial hypertension, uterine fibroids, adenomyosis, infertility, dysmenorrhea, chronic endometritis, a history of cervicitis and vaginitis; clinical manifestations include intermenstrual bleeding.

Combined intervention strategy for reversing iron-deficiency anaemia and deficiency in psychomotor development in chronic malnutrition.

Background: chronic iron-deficiency anaemia in children has a negative impact on neuronal and cognitive development. Despite current knowledge on this subject, in Bolivia iron intake along the psychomotor development stimulation as part of a comprehensive rehabilitation process for children with severe chronic malnutrition is not yet used. Objective: to evaluate the effect of a neurorestorative diet, consisting of iron supplements and other micronutrients, along with psychomotor stimulation in preschool children with chronic malnutrition, iron-deficiency anaemia and severe psychomotor delay. Patients and methods: twenty-four children between 1 and 56 months of age admitted to the integral nutritional recovery centre (INRC), Paediatric Hospital of Cochabamba, Bolivia were included. A strategy of intervention was applied consisting of nutritional replenishment through the administration of elaborated meals prepared from local foods with high heme and non-heme iron concentration, added with vegetables plus the administration of micronutrient´s supplementation and the psychomotor stimulation. Anthropometric indices, psychomotor and biochemical parameters were measured at four times points, during the hospitalisation period. Results: at the beginning, the anthropometric and psychomotor parameters were decreased (between -2 and -3 z score and below 50 % respectively). Combined strategy intervention with iron and other micronutrients together photons produced significant changes between the evaluated time points, both in anthropometric and psychomotor parameters, although these changes were less than expected. Conclusions: the combined strategy used in this study allowed recovery from the anaemia and minimal growth due to the low birth weight or chronic malnutrition. However, the intervention was insufficient to achieve a complete recovery.

Koilonychia in a Patient with Severe Iron Deficiency Anemia

Koilonychia is a known sequela of chronic and severe iron deficiency anemia. The pathogenesis is not well understood, but is postulated to be attributed to weakening of the underlying nail connective tissue secondary to poor oxygenation of the distal extremities. Because of the lower prevalence of koilonychia in developed nations, its clinical presentation in the U.S. is of particular significance. In the following case, a female patient presented with angina and heart palpitations of four month duration as well as severe anemia of unknown origin. Physical exam was notable for koilonychia, most prominent in the 1st - 4th digits of the right hand as well as the 1st and 2nd digits of the right foot.

Association Between Iron Deficiency Anemia and Chronic Daily Headache

Background: Chronic daily headache (CDH) and iron deficiency anemia (IDA) are prevalent health issues with significant impact on individuals' quality of life. Understanding the relationship between these conditions is essential for developing effective treatment strategies. Objective: This study aims to investigate the association between iron deficiency anemia and chronic daily headache. Methods: A case-control study was conducted at Pak Emirates Military Hospital, Rawalpindi, Pakistan, from February to July 2023. The study included 140 patients diagnosed with CDH and 140 age- and sex-matched controls without a history of CDH. Demographic data (age, gender, location, education, marital status) were collected along with clinical characteristics (headache frequency, intensity, duration) and hematological parameters (hemoglobin level, serum ferritin level, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, hematocrit level, mean corpuscular hemoglobin concentration). Statistical analysis was performed using chi-square tests and ANOVA. Results: There were no significant differences in demographic characteristics between the CDH and control groups. CDH patients exhibited higher headache frequency (57.14% experienced headaches 10-15 times per month), intensity (64.43% reported NRS score of 5-8), and duration (87.15% reported headache duration of over 4 hours) compared to controls. Hematological analysis revealed significantly lower mean hemoglobin (9.85±2.13 g/dL) and serum ferritin levels (30.72±7.65 ng/mL) in CDH patients compared to controls (13.1±2.70 g/dL and 65.09±12.82 ng/mL, respectively). A significant association between IDA and CDH was established (p<0.05). Conclusion: The study demonstrates a significant association between iron deficiency anemia and chronic daily headache, highlighting the potential role of iron deficiency in the development of CDH.

Transferrin and Erythropoietin Increased Levels Correlate with Thrombosis at High Altitude

Living at high altitude involves great interest because of the challenging multiple adaptive responses to a hypoxic environment. Native Bolivian Andeans have lived at an altitude of 4000 m in The Andes mountains for about 14,000 years exposed to a low atmospheric pressure (453 mmHg) and low oxygen concentration (12,7%). It was described Andeans adaptation to high altitude is mainly related to cardiovascular issues (PMID: 29100088), with a low significantly genetic selection in HIF pathway components responsible of erythropoiesis regulation (PMID: 36980912), so that they have adapted to exist with increased hemoglobin concentrations. Thus, Andeans can be prevalent to undergone hematological and thromboembolic disorders. Thrombotic events have been reported to be increased at high altitude, and this recently associated to increased transferrin (Tf) (PMID: 36040436), likewise to increased erythropoietin (Epo) (Amaru, RevMed 2022). Increased Tf were described to be induced by both iron deficiency and hypoxia via HIF (PMID: 9242677). In addition, iron deficiency was postulated to inhibit the function of prolyl hydroxylase 2 (PHD2) in the hydroxylation of HIF-2, necessary for recognition and degradation by VHL (PMID:22304911). Under normal conditions, Tf is bound to fibrinogen at a molar ratio of 4:1, leading to plasma Tf sequestration by fibrinogen and leaving little Tf free in the circulation. While at hypoxia conditions, abnormally upregulated Tf potentiates thrombin, factor XIIa and inhibits antithrombin, inducing hypercoagulability (PMID:36040436). Similarly, increased HIF1a at high altitude increases Tf promoting the transferrin gene expression, which contains HIF-1α binding sites in its enhancer region (PMID:36844187). HIF is a DNA-binding transcription factor for activating expression of Epo gene (PMID:32561149). Epo, in turn, is increased due to the hyperegulation of HIF as expected at low atmospheric pressure environments. Epo activates the hypoxia-inducible factor that leads to Epo synthesis to stimulate red blood cell production, which also increases the demand for iron to synthesize hemoglobin (PMID:21078592). This, added to a decreased iron and increased HIF 1a, gives rise to a hyperregulation of Tf. Epo has been described to have prothrombotic properties and be related to thrombotic events (PMID:10779449; Amaru, RevMed 2022). In this sense, to further observe a correlation of transferrin and erythropoietin increased levels with the risk of thrombotic events at high altitude, we studied patients with erythrocytosis, anemia and polycythemia vera. We analyzed clinical, lab tests and epidemiological data of 920 patients with Chronic Mountain Sickness erythrocytosis (CMS-e) (n=560), anemia (n=372), and Polycythemia Vera (PV) (n=20), all Bolivian Andeans born and residing at 4000 m. Considering at this altitude normal hemoglobin concentrations vary from 14-17 g/dl in women and 15-18 g/dl in men, erythrocytosis condition comprises Hb levels >18 g/dl in women and >19 g/dl in men (Amaru et al, Rev Hematol Mex, 2016); similarly, it embraces Hb <12 g/dl for women and <13 g/dl for men in anemias (PMID: 23317073). Positive JAK F617V tests were corroborated in PV patients. Iron deficiency correlation considered serum ferritin <30 ug/L and MCV <80 fL (Clark et al, Nutrition, 2008). Eco-doppler study records confirmed the occurrence of thrombotic events. Data analysis was performed through Excel 16.29.1 and SPSS program, Chi-squared, Fishers and Pearson tests were done. We observed significative increased Tf levels in erythrocytosis, anemia, and PV patients mainly on those presenting iron levels deficiency. Epo was highly increased in erythrocytosis patients with iron deficiency. These results correlated with the incidence of thrombotic events in erythrocytosis (CMS-e) and anemia patients with iron deficiency. Age was also relevant in both groups. (Table 1). The increase of Epo levels correlated with thrombosis in erythrocytosis and PV patients with iron deficiency (Table 1). Transferrin and Erythropoietin increased levels at high altitude correlated with thrombosis in Chronic Mountain Sickness erythrocytosis and iron deficiency anemia patients. However, Increased Tf did not correlate with thrombosis in PV patients at high altitude. Our data confirm that increased Tf and Epo have prothrombogenic properties in CMS-e, iron deficiency anemia patients at high altitude.

Abstract 13670: Prevalence and Long-Term Outcomes of Intravenous Iron Sucrose Therapy in Heart Failure With Reduced Ejection Fraction: A Single Institution Retrospective Cohort Study

Background: Iron deficiency (ID) is prevalent in heart failure with reduced ejection fraction (HFrEF) defined as left ventricular ejection fraction (LVEF) ≤ 40%. Most trials used in the 2022 AHA/ACC guidelines studied iron carboxymaltose; most had a short follow-up and evaluated heart failure readmissions. We explored the prevalence of iron use, long-term therapeutic benefits, and impact on all-cause readmission for patients with HFrEF. Methods: In this retrospective cohort study, we analyzed electronic medical record data from a university hospital from 2016 to 2021 with an ICD-10 code of systolic heart failure (LVEF < 50%) and ID, or iron deficiency anemia (IDA) (n=619). Intravenous (IV) iron sucrose group was matched to a control group (n = 43) by propensity score matching for age and sex. Conditional logistic regression was utilized to estimate unadjusted odds ratios (uOR) with 95% confidence interval (CI), while Mann-Whitney test was utilized to compare median values of nonparametric estimates. Statistical analysis was done in SAS version 9.4. Results: 66.7% of the studied population were male and 61.1% were ≥ 65 years. The common comorbid conditions were ischemic cardiomyopathy (39.6%), chronic kidney disease (CKD) (26.2%), and gastrointestinal (GI) bleeding (12.3%). ID was present in 115 (18.6%); IDA in 95 (15.4%) and 43 (6.9%) received IV iron sucrose. IV iron administration was significantly associated with LVEF 41-49% (uOR = 2.65, 95% CI: 1.10 - 6.43), GI bleeding (uOR = 16.00, 95% CI: 2.12 - 120.65), chronic kidney disease (uOR = 3.67, 95% CI: 1.49 - 9.04), iron deficiency (uOR = 26.00, 95% CI: 3.53 - 191.60]) and iron deficiency anemia (uOR = 24.00, 95% CI: 3.23 - 177.41). LVEF ≤40% was non-significantly associated with all-cause mortality (uOR = 1.50, 95% CI: 0.61 - 3.67). The IV iron group had a higher median rate of 6-year readmissions (8 [IQR:8] vs.1 [2]; p<0.001), and blood transfusions (11 [24] vs. 3.5 [2]; p=0.05). Conclusions: Patients with HFrEF were less likely to receive IV iron sucrose and more likely to die. Those with frequent blood transfusions, GI hemorrhage, and CKD were more likely to receive IV iron. The study indicates the impact of disease severity and comorbidities on management. Larger studies are needed to investigate this postulation.

Bone Marrow Sinusoidal Endothelial Cells Are a Site of Fgf23 Upregulation in Murine ß-Thalassemia

Fibroblast growth factor-23 (FGF23) is a bone-derived hormonal regulator of mineral metabolism with emerging functions in the bone marrow. FGF23 has been reported to negatively regulate erythropoiesis [PMID:24509850] and promote hematopoietic progenitor mobilization from the bone marrow [PMID:33512467]. Elevated FGF23 levels in the circulation have been described in iron-deficient subjects and also in subjects with the iron-loading anemia β-thalassemia. Recently, we reported bone marrow sinusoidal endothelial cells (BM-SEC) as a novel site of Fgf23 upregulation in mice with chronic iron-deficiency anemia and acute, phlebotomy-induced anemia [PMID:37417950]. We and others have detected Fgf23 mRNA elevation in total bone marrow of Hbb th3/+ mice, a model of non-transfusion dependent β-thalassemia that exhibits systemic iron loading. In the present study, we sought to clarify sites of Fgf23 promoter activity in Hbb th3/+ bone marrow using a reporter allele in which the enhanced green fluorescent protein (eGFP) coding sequence is knocked into the endogenous Fgf23 locus ( Fgf23 eGFP). We generated Hbb +/+ and Hbb th3/+ female littermates that carried either one ( Fgf23 +/eGFP) or zero ( Fgf23 +/+) copies of the Fgf23 reporter allele, which were raised on a standard rodent diet (200 mg/kg iron, 1.0% calcium, 0.7% phosphorus). Fgf23 eGFP/eGFP homozygotes were not generated due to known early growth retardation and mortality in Fgf23 null mice. After blood and tissue collection at 8 weeks of age, phenotypes of the 4 Hbb-Fgf23 genotype combinations were compared by two-way ANOVA. Compared to mice with intact Hbb and Fgf23 alleles ( Hbb +/+ Fgf23 +/+), Hbb th3/+ Fgf23 +/+ mice showed markedly elevated plasma levels of “total” FGF23 (sum of intact, active hormone and C-terminal cleaved fragments). Plasma total FGF23 levels in Hbb th3/+ Fgf23 +/+ and Hbb th3/+ Fgf23 +/eGFP mice were similar, indicating utility of the latter genotype for interrogating sites of increased Fgf23 expression in murine b-thalassemia. We therefore used anti-GFP immunohistochemistry in formalin-fixed bone marrow sections to assess Fgf23 eGFP reporter allele expression in the context of tissue architecture. Hbb th3/+ Fgf23 +/eGFP mice showed GFP expression in BM-SEC throughout the bone marrow, which was more intense than in non-anemic Hbb +/+ Fgf23 +/eGFP mice; controls lacking the Fgf23 eGFP allele confirmed anti-GFP antibody specificity. Hbb th3/+ mice also showed Fgf23 eGFP reporter expression in the thymic vasculature but not vasculature of the liver, spleen, or kidney. In contrast to their marked elevation in plasma total FGF23, Hbb th3/+ Fgf23 +/+ mice showed plasma levels of the intact, biologically-active FGF23 hormone that overlapped with levels in Hbb +/+ Fgf23 +/+ controls. Interestingly, compared with Hbb th3/+ Fgf23 +/+ mice, Hbb th3/+ Fgf23 +/eGFP mice showed 45% lower plasma intact FGF23, suggesting an effect of Fgf23 gene dosage. Given prior reported effects of FGF23 on hematopoiesis, we assessed if Fgf23 gene dosage modulated the severity of ineffective erythropoiesis in Hbb th3/+ mice. Compared to Hbb +/+ Fgf23 +/+ controls, Hbb th3/+ Fgf23 +/+ mice showed reductions in RBC, hemoglobin, and mean corpuscular hemoglobin, as well as increases in RDW and in spleen weight (reflecting extramedullary hematopoiesis). However, the severity of these parameters was not modified by heterozygous Fgf23 disruption ( Hbb th3/+ Fgf23 +/eGFP).While FGF23 has been reported to induce left ventricular hypertrophy [PMID:21985788], Hbb th3/+ Fgf23 +/+ and Hbb th3/+ Fgf23 +/eGFP mice showed similarly increased heart-to-body weight ratios compared to Hbb +/+ Fgf23 +/+ controls. In non-thalassemic mice, heterozygous Fgf23 disruption ( Hbb +/+ Fgf23 +/eGFP) caused a trend ( P=0.10) towards lower plasma intact FGF23 while not impacting hematological parameters or spleen weight. In summary, by showing that Fgf23 gene dosage modulates plasma intact FGF23 levels in Hbb th3/+ mice without altering severity of anemia or splenomegaly, our data suggest that moderate reductions in circulating levels of the intact FGF23 hormone do not alter the severity of ineffective erythropoiesis in Hbb th3/+mice at 8 weeks of age. Our finding that β-thalassemic mice exhibit Fgf23 upregulation in BM-SEC lays the groundwork for future investigation of the functional effects of locally-produced FGF23 in the thalassemic hematopoietic stem cell niche.

A Curious Case of IgG4-Related Disease Masquerading As an Occult Abdominal Malignancy

Introduction IgG4-related disease is an autoimmune, fibroinflammatory disorder involving multiple organ systems in the body. Diagnosis is often suggested by strong IgG4-positive stain on tissue biopsy. Patients respond well to steroids; and in cases of relapse, steroid-sparing agents like rituximab, azathioprine or cyclosporine can be used. Case Presentation Here we present the case of a 77 year-old African-American female with a past medical history significant for cerebrovascular accident, chronic hepatitis C infection status post treatment with antivirals, left chronic dacryoadenitis and chronic iron-deficiency anemia. She presented to the hematology office for a follow-up visit for chronic anemia and complained of new onset right upper quadrant pain and unexplained weight loss. Subsequent abdominal and pelvic imaging showed hypoechoic lesion in pancreatic head along with multiple epigastric, omental and gastro-hepatic nodules/lymph nodes suspicious for malignancy. This was followed by esophagogastroduodenoscopy (EGD) with endoscopic ultrasound (EUS) which revealed gastric body/antral erosions along with multiple enlarged abdominal lymph nodes and heterogeneous, hypoechoic irregular mass in the pancreatic head/neck, all of which were biopsied. While awaiting biopsy results, due to high suspicion for malignancy, PET-FDG was performed which showed hypermetabolic lesions corresponding to the EUS findings and a FDG-avid right paravertebral mid thoracic soft tissue mass favored to represent a neurogenic tumor, unrelated to abdominal disease. Laboratory work-up was significant for elevated IgG levels with particularly high titres of IgG subclass 4. Biopsy results from EUS showed no evidence of malignant cells, no clonal proliferation on flow cytometry in either the lymph nodes or pancreatic tissue. Cytology of pancreatic tissue biopsy revealed lymphoid infiltration, extensive edema and fibrosis with no malignant cells. Immunohistochemistry studies revealed strong positive stain for IgG4 suggestive of IgG4-related disease. Of note, the patient had been following up with ophthalmology for a few years for chronic inflammatory dacryoadenitis of the left eye, which can likely be attributed to IgG4-related disease. After shared-decision making with the patient regarding treatment options, treatment was initiated with a plan of rituximab for 4 cycles along with corticosteroid. As of this abstract submission, the patient received one dose of rituximab, pending assessment of response to treatment. Discussion Heterogeneous pancreatic masses on abdominal imaging should be considered malignant until otherwise proven. In cases where these masses are associated with diffuse abdominal and pelvic lymphadenopathy, definitive diagnosis is made through obtaining biopsies from the easily accessible sites. A benign, auto-immune, fibroinflammatory condition which mimics this presentation is IgG4-related disease, whose treatment is far less complicated than a metastatic carcinoma. It often involves lacrimal glands. A high index of suspicion backed by the biopsy results showing strong stain affinity to IgG4 and elevated blood IgG4 levels are required. Treatment involves initiation of steroids followed by steroid-sparing agents like azathioprine, cyclosporine or rituximab in cases of relapse after steroid induction. However, as in our case, combination therapy of simultaneous use of steroids with rituximab can be used after shared decision making with patients.

Evaluation of pancytopenia based on bone marrow examination in adults in a tertiary care hospital in Islamabad.

Objective: To evaluate etiological spectrum of pancytopenia in adults using bone marrow aspiration biopsy. Study Design: Randomized Prospective study. Setting: Department of Pathology, Pakistan Institute of Medical Sciences, Islamabad. Period: October 2018-October 2020. Material & Methods: Eight hundred bone marrow biopsies were performed out of which 250 patients came with pancytopenia. 135 patients out of these were in adult age group which are included in this study. Results: Out of 250 patients adults were 135 that presented with pancytopenia. Male to female ratio came out to be 1.22:1. The most common disorder that results in pancytopenia came out to be megaloblastic anemia that was 29.6%, after that 26.6% were infection related changes, 10.3% aplasia, 9.6% reactive marrow, 5.9% acute leukemia, 3.7% chronic leukemia and iron deficiency anemia followed by 2.9% myelodysplastic syndromes and hypersplenism, 2.2% multiple myeloma, 1.4% mixed deficiency anemia and 0.74% myelofibrosis. We also analyzed patients on their presenting complaints as well. Most common complaint of presentation was fever (54.8%), (31.85%) with fatigue and malaise, (31.1%) pallor, vomiting and diarrhea (25.9%) followed by bleeding (14.8%). On clinical examination 12% cases presented with hepatomegaly and 16.6% with splenomegaly. Conclusion: Pancytopenia is a common hematological finding in our setup with megaloblastic anemia to be the most common cause of it. Therefore, it’s very important to diagnose it as this is a curable (reversible) deficiency and patients can easily be managed to prevent serious hematological and neurological abnormalities.

Anemia of chronic diseases: a verdict or a protective reaction of the body?

Anemia of chronic disease occurs in patients with infectious, autoimmune, kidney diseases, neoplasia, inflammatory bowel disease, obesity, diabetes mellitus, congestive heart failure, and chronic lung disease. This variant of anemia is characterized primarily by impaired iron homeostasis, the suppressive effect of pro-inflammatory cytokines on erythropoiesis, and changes in the erythrocyte membrane that worsen their survival. Anemia of chronic disease is micro- or normocytic anemia with low levels of reticulocytes. In anemia of chronic disease, serum iron and transferrin levels are usually reduced or normal, and serum ferritin levels are within reference values or elevated. The article provides a review of studies on epidemiology, including age aspects, provides information on the etiology and prognosis in patients with anemia of chronic diseases. The issues of the history of anemia of chronic diseases and its place in the structure of all anemias are also covered. Anemia of inflammation is recognized as a widespread pathology; it occupies 40% in the structure of all anemias. It is important to note that anemia of chronic diseases, while accompanying a number of dangerous diseases, actually serves as a natural defense mechanism. This is due to the occurrence of iron starvation for microorganisms, since inflammatory reactions increase the synthesis of iron proteins, which quickly extract extracellular and unbound iron. This mechanism allows a person to destroy the infection in time with the help of innate immunity. The article reveals the pathogenetic aspects of anemia of inflammation development and data on the role of iron in the functioning of macro- and microorganisms. Particular attention is paid to the differential diagnosis of anemia of chronic diseases and iron deficiency anemia, key diagnostic hematological markers of anemia, iron metabolism, inflammation and erythropoiesis are given. The pros and cons of therapy options, as well as possible new pathogenetic methods for the treatment of anemia of chronic diseases, are described.

Iron Deficiency Anemia and Ischemic Stroke in Premenopausal Women (P14-5.022)

<h3>Objective:</h3> We describe three young women with iron deficiency anemia who developed ischemic strokes in the absence of typical risk factors. <h3>Background:</h3> Ischemic stroke is the third leading cause of death in women. Women have unique risk factors for ischemic stroke. Iron deficiency anemia disproportionately affects premenopausal women and has previously been identified to be associated with ischemic stroke. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 39-year old woman with hypertension and menorrhagia presented with left leg weakness and dizziness. Labs revealed a hemoglobin of 5.9g/dL, a unremarkable hypercoagulable work up, transesophageal echo, urine toxicology, rheumatological evaluation, and MRA brain vessel wall imaging. An ultrasound of her uterus revealed a pelvic fibroid measuring 6.5cm and MRI brain revealed a small right anterior cerebral artery territory infarction. A 46-year-old woman with chronic iron deficiency anemia with a hemoglobin of 6.8g/dL who presented with left mild sided weakness and was found to have a right MCA M3 occlusion by CT angiography of the head. She received intravenous tenecteplase and underwent decompressive craniectomy for a right temporal infarct associated with cerebral edema seen on MRI brain. Investigations revealed a normal hemoglobin electrophoresis, urine toxicology, hypercoagulable evaluation, rheumatological evaluation and transesophageal echo. A 43 year old woman presented with diplopia secondary to a vertical gaze palsy. MRI brain revealed an infarct in the left thalamus, cerebral peduncle, and midbrain. Cerebral angiography, transesophageal echocardiogram, urine toxicology, rheumatological evaluation, and hypercoagulable work up were unremarkable. Hemoglobin was 7.2g/dL on presentation and an EGD revealed an antral and duodenal ulcer. All three patients received packed RBC transfusions, iron replacement therapy and discontinuation of aspirin until hemoglobin stabilized. <h3>Conclusions:</h3> Iron deficiency anemia may be an important yet under-recognized risk factor for acute ischemic stroke and should be treated aggressively in premenopausal women. Further studies are warranted. <b>Disclosure:</b> Dr. Imam has nothing to disclose. Dr. Salahuddin has nothing to disclose.

Anemias in ancient Egyptian child mummies: Computed tomography investigations in European museums

AbstractThe aim of this study was to investigate the prevalence of anemias in ancient Egyptian child mummies. Whole‐body computed tomography (CT) examinations of 21 ancient Egyptian child mummies from European museums were evaluated for estimation of sex and age at death. CT examinations were systematically assessed for skeletal effects of anemias using a clinical radiological approach as well as quantitative measurements of the thickness of the cranial vault and diploe. Additionally, the technical feasibility to assess porotic hyperostosis on the available CT data was examined. Twelve children were assessed as male and seven as female, and in two, the sex was indeterminate. The estimated age at death ranged from about 1 year to 12–14 years. One case showed radiological signs of thalassemia (β‐thalassemia major) at the cranial vault and postcranial skeleton. Additionally, this case had a macroglossia that probably indicated Beckwith–Wiedemann syndrome. Quantitative measurements confirmed a high variability of cranial vault thickness and diploe thickness. Compared with clinical reference values, seven out of the 21 (33%) child mummies had a pathological enlargement of the frontal cranial vault that represents a typical finding of chronic hemolytic anemia and iron deficiency anemia. Assessment of porotic hyperostosis was not feasible on the available CT examinations as the image quality was not sufficient for this examination. In conclusion, pathological enlargement of the frontal cranial vault as an indicator for chronic hemolytic anemia and iron deficiency anemia had a high prevalence, especially in the younger children. The mummy with radiological signs of thalassemia seems to be the first case with radiological evidence of skeletal effects of this anemia to the cranial vault and postcranial skeleton from ancient Egypt.