Effect of oral vitamin C on serum hepcidin level, iron status and inflammation among hemodialysis patients with functional iron deficiency anaemia

Introduction: Hepcidin is a key regulatory peptide in iron homeostasis, the pathogenesis of functional iron deficiency (FID) anemia and erythropoiesis-stimulating agent (ESA) resistance is contributed to the inflammatory mediated increase in the serum hepcidin levels among prevalent hemodialysis (HD) patients. Objectives: To test the reducing therapeutic effect of oral vitamin C supplements on hepcidin levels and iron status among HD patients with FID anemia. Patients and Methods: This study is an interventional prospective cohort study; 48 prevalent HD patients were enrolled. Group one: 31 patients who received the conventional treatment of erythropoietin stimulating agents together with oral supplementation of vitamin C 500 mg every other day dose for 3 months. Group two: 17 patients who received only the conventional therapy of erythropoietin stimulating agents. Patients with hemoglobin level <11 g/dL, ferritin level >200 ng/mL and transferrin saturation (TSAT) >20 % were included. Laboratory parameters: serum hepcidin, high-sensitivity C-reactive protein (hs-CRP) titre, CBC, and iron indices were measured at baseline and after 3 months. Results: On comparing the two groups, oral vitamin C in group 1 resulted in a statistically significant reduction in hepcidin levels [mean 2506.456 ± 1320.53 pg/mL to 1748.396 ± 1432.28 pg/mL (P = 0.03)], and a significant reduction in hs-CRP level [mean 8603.236 ± 2547.77 ng/mL to 5611.296 ± 2829.27 ng/mL] (P = 0.001) after three months of treatment in comparison to control group. A decrease of EPO requirement and elevation of hemoglobin level were observed in a study group with oral vitamin C. Conclusion: Oral vitamin C may be a promising therapy in decreasing serum hepcidin and inflammatory markers among prevalent HD patients with FID anemia.

CD34-Positive Blast Count and p53 Expression in Bone Marrow Biopsies of Patients with Low-Risk Myelodysplastic Syndromes: Potential Predictive Tools of Response to Erythropoietin Stimulating Agents

<b><i>Introduction:</i></b> The first-line therapy for patients with low-risk myelodysplastic syndromes (MDSs) commonly consists of erythropoietin stimulating agents (ESAs), with a response rate ranging from 34 to 62%. For nonresponder patients, outside clinical trials, blood transfusions are the most frequent therapeutic option, with detrimental effect on the quality of life and with risks of iron-overload. Since no studies have been yet conducted on this topic, we investigated the potential predictive role of bone marrow (BM) histological evaluation in patients treated with ESAs. <b><i>Materials and Methods:</i></b> We performed a morphological and immunohistochemical retrospective analysis of BM biopsies of 96 patients with low-risk MDSs subsequently treated with ESAs. <b><i>Results:</i></b> In our series, substantial morphological overlap was found between responder and nonresponder patients. On the contrary, patients with a percentage of CD34-positive blasts &#x3e;3% or with p53 protein expression &#x3c;1% responded with a significantly higher frequency to ESAs. <b><i>Conclusions:</i></b> Our study reinforces the role of BM biopsy as diagnostic tool in MDSs, being also able to supply information related to response to ESAs and to its loss over time.

Assessment of Platelet/ Lymphocyte Ratio as a Predictor of Erythropoietin Resistance in Hemodialysis Patients

Background: Platelet / lymphocyte ratio has recently been investigated in different clinical conditions associated with hemodialysis and its association with other diseases has been assessed. The purpose of the study was to assess platelet lymphocyte ratio as a predictor of erythropoietin resistance in hemodialysis patients. Methods: The study population consisted of 60 hemodialysis patients, who were subdivided into two groups according to the response to erythropoietin stimulating agents (ESAs) .treatment. Group 1 included 30 patients treated with ESAs with good response to it and group 2 included 30 patients treated with ESAs but with resistance to it. The platelet/ lymphocyte ratio was calculated for each patient and compared between both groups. Results: Platelet lymphocyte ratio of group 2 was significantly higher compared to that of group 1 (P=0.001). Conclusion: PLR is a useful parameter to predict erythropoietin resistance in hemodialysis patients.

Evaluation of Erythropoietin Stimulating Agents (ESA) and Their Effect on Blood Optimization for Cardiac Surgery

Background: Cardiovascular surgeries increase the risk of receiving blood transfusions. Erythropoietin stimulating agents (ESAs) have been used to decrease the transfusion rate. The objective of this study was to evaluate the administration of blood products post-cardiothoracic surgery after receiving ESAs. Methods: This is a single-center, retrospective cohort study. Results: Between May 2017 to May 2018, 52 adult patients underwent cardiac surgery and received ESAs pre-operatively and/or post-operatively. A total of 35 patients were included in the study and 21 (60%) patients did not require a blood transfusion while 14 (40%) patients required a blood transfusion ( p = 0.597). The change in hemoglobin (Hgb = 0.773 g/dL, 1.7 g/dL; p = 0.002) and hematocrit (Hct = 2.31%, 4.3%; p = 0.04) was significantly different in patients who received ESAs alone versus ESAs with blood transfusion. Adverse drug reactions showed no significant difference between groups. Conclusions: In patients undergoing cardiac surgery, ESAs did not significantly reduce the need for blood transfusion. Future and larger studies are necessary to evaluate the effect of ESAs on blood transfusion.

A Systematic Review and Meta-Analysis of Luspatercept for Anemia Treatment in Low Risk Myelodysplastic Syndrome with Ring Sideroblast Subtype in Phase II and Phase III Clinical Trials

Background: Low-risk Myelodysplastic Syndromes (MDS) patients commonly present with anemia and may become blood transfusions dependent upon progression. Luspatercept, a targeted drug for an activin receptor ligand has emerged as new anemia treatment in MDS for patients with ring sideroblasts and the patients with SF3B1 mutation. This systemic review highlights the efficacy of luspatercept in MDS patients whom erythropoietin stimulating agents (ESA) are not effective. Methods: We conducted a comprehensive literature search using PubMed, Clinical trial.gov, Embase, Cochrane, and Web of science. Our search strategy included MeSH (Medical Subject Headings) terms and keywords for MDS and luspatercept including trade names and generic names from inception to 29 April 2020. Studies were selected according to PRISMA guidelines. The initial screening revealed 240 articles. After excluding review articles, duplicates, and non-relevant articles, finally we included two clinical trials, which reported transfusion independence (TI), an erythroid response (HI-E) in MDS patients with luspatercept. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of luspatercept. We pooled the results of the experimental arms of the two trials using the inverse variance method and logit transformation. Between studies, variance was calculated using DerSimonian-Laird Estimator. Results: A total of 287 patients were enrolled and evaluated in two phases II/III trials. Platzbecker et al and Fenaux et al reported Erythropoietin stimulating agents (ESA) with one median prior line of therapy (n= 148, n=46). Fenaux et al. also reported iron chelation therapy (n=71) as a prior line of therapy. Patients having ring sideroblast positive &lt;15% (n=172) and SF3B mutation were present in 169 evaluable patients. Low-risk MDS (LR-MDS) patients are classified according to IPSS-R criteria, defined as being of very low (n=19), low (n=135), or intermediate-risk (n=44). Platzbecker et al. (2017) studied luspatercept in MDS patients (n=58) in the PACE phase II trial. Fenaux et al. (2020) studied the efficacy of luspatercept in MDS pts (n=219) in the MEDALIST phase III trial. The baseline Erythropoietin (EPO) levels were: levels &lt;200: n=191, level 200-500: n= 81, level &gt;500: n=57 for both studies. The baseline means hemoglobin (Hb) levels were eight before therapy. TI for more than eight weeks was observed in 38% of patients in both the MEDALIST trial and PACE trial. The erythroid response was 53% and 63% in both trials respectively. In a Phase II study, for LR-MDS patients, the overall erythroid response was higher among patients (n= 69%) having ringed sideroblast status (&gt;15% ring sideroblast) and SF3B mutation (n=77%). The mean increase of Hb was observed in 29 out of 46 and 32 out of 41 pts in MEDALIST and PACE trial, respectively. Luspatercept proved to be efficacious in the pooled analysis i.e transfusion independence (TI): 38%, 95% CI 0.31-0.45; p =0.98, I2 = 0%), and erythroid response (HI-E): 54%, 95% CI 0.48-0.62; p=0.22, I2 = 32%) with an increase in mean Hb of 70% 95%: CI 0.59-0.78; I2 = 56%) (Figure 1). CONCLUSION: In patients with low risk MDS positive ringed sideroblast or SF3B1 mutation status shows good responses with luspatercept treatment, with reduced transfusion dependence, and higher erythroid response. Disclosures Anwer: Incyte Pharmaceuticals: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Millennium Pharmaceuticals: Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Acetylon Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; AbbVie Pharmaceuticals: Research Funding.

Anaemia in chronic kidney disease pregnancy

Aim To review the incidence and management of anaemia and outcomes in pregnancies in a cohort of Australian women with chronic kidney disease. Methods A retrospective audit of 63 pregnancies in 52 women with chronic kidney disease. Results Sixty-eight percent of chronic kidney disease pregnancies were complicated by haemoglobin less than 100 g/L. Iron stores were measured in only 62% of all pregnancies. Serum ferritin was less than 100 ng/ml in 95% of those tested. Erythropoietin-stimulating agents were used in 24 pregnancies (38%). Intravenous iron was used in only nine non-dialysis pregnancies. Conclusion Greater awareness of the importance of regular measurement of iron stores and appropriate levels for repletion in chronic kidney disease pregnancies amongst health professionals involved in obstetric care may result in earlier detection and treatment of iron deficiency, and potentially improve maternal and fetal outcomes.