Bone marrow iron scoring in healthy and clinically ill dogs with and without evidence of iron-restricted erythropoiesis.

BACKGROUND: There are few reports in dogs that have evaluated the utility of semi-quantitative scoring of bone marrow iron stores in conjunction with reticulocyte hemoglobin (CHr) to identify iron-restricted erythropoiesis due to absolute iron deficiency or iron sequestration. OBJECTIVES: An established system for scoring iron stores in human bone marrow samples was applied to dogs. The objectives were to evaluate interobserver agreement (Κω ), determine marrow iron scores in dogs without detectable hematologic abnormalities, and assess combined interpretation of iron scores and CHr to evaluate for iron-restricted erythropoiesis. METHODS: Four blinded observers independently scored iron in 139 Prussian blue-stained canine marrow samples from 0 (none) to 6 (very heavy), including healthy controls (n = 12), clinically ill dogs with (n = 100) and without (n = 16) detectable hematologic abnormalities, and dogs with experimental nutritional iron deficiency (n = 11). Additional medical record data were available for 118 dogs to evaluate for other evidence of iron deficiency (abnormal CHr, RBC indices, serum iron variables, external blood loss, or nutritional deficiencies). RESULTS: Mean Κω was 0.69 (substantial agreement) for all samples but was 0.44 (moderate agreement) for samples with iron scores <3, indicating distinguishing scores 0-2 may not be reliable. Dogs without detectable hematologic abnormalities had scores from 3-5. Dogs with scores <3 and decreased CHr often had more indicators of iron deficiency vs dogs only having low iron scores or low CHr. CONCLUSIONS: Evaluation of dogs with marrow iron score <3 for external blood loss or nutritional deficiencies is likely clinically worthwhile, particularly if there is also decreased CHr.

Therapeutics of managing reduced red cell mass associated with chronic kidney disease - Is there a case for earlier intervention?

Reduced red cell mass is a poor prognostic indicator in chronic kidney disease (CKD) patients. Whilst overt anaemia impacts on the quality of life of patients with CKD, lowered red cell mass may also compromise oxygen delivery to proximal tubular cells and contribute to progressive kidney injury. Epidemiological data from cats with CKD support this hypothesis although controlled interventional studies involving drugs that raise red cell mass in trials designed to test this hypothesis are lacking in both human and veterinary medicine. Recombinant analogues of erythropoietin (EPO) are currently standard of care for human CKD patients where low red cell mass impacts on their quality of life. Resistance to EPO is encountered in 20% to 40% of patients treated, probably due to functional iron deficiency, reflecting the difficulties of managing iron deficiency associated with the chronic inflammation of CKD. Similar issues are likely faced in managing anaemia in feline CKD although published data on the use of human EPO analogues are limited as such treatment in cats risks antibody formation resulting in red cell aplasia and transfusion dependency and so is reserved for late stage cases only. This article reviews the recent alternative therapeutic approach to increase red cell mass using HIF-prolyl hydroxylase inhibitors and explains their mode of action and theoretical advantages over EPO analogues in the context of iron metabolism. The results of human clinical trials and the potential benefit of adopting this approach in feline CKD patients are discussed.

Intravenous iron sucrose is safe but does not prevent development of anemia or iron deficiency in healthy cats undergoing serial venipuncture.

OBJECTIVE: To evaluate IV iron sucrose safety and impact on hematologic and iron indices in healthy cats. ANIMALS: 5 healthy research cats. PROCEDURES: Cats were administered iron sucrose (0.5 mg/kg, IV) over 30 minutes. Monitoring for acute reactions (temperature, heart rate, respiratory rate, and blood pressure) was performed every 5 minutes during injection and every 15 minutes for an additional hour. Baseline, 24-hour, and 1-, 2-, and 3-week postinjection measurements of CBC with reticulocyte indices, iron panel (ferritin, total iron-binding capacity, and iron), calculated transferrin saturation (TSAT), and serum amyloid A (SAA) concentration were performed. RESULTS: No cat experienced an acute drug reaction. SAA concentration was increased at 24 hours versus baseline. TSAT and ferritin decreased over time, with 3 cats developing concurrent functional iron deficiency (FID) and anemia. Hct (Spearman correlation [rs] = 0.805), hemoglobin (rs = 0.770), and reticulocyte hemoglobin content (rs = 0.581) correlated with TSAT. CLINICAL RELEVANCE: IV iron sucrose was well tolerated in healthy cats but was associated with transient increase in the systemic inflammatory marker SAA. Efficacy evaluation of dose based on iron deficit is needed in sick cats. Despite cumulative blood draw volume below recommended limits, anemia and FID were observed, which has important implications for experimental designs and serial hematologic monitoring. Further evaluation of inflammatory response to IV iron sucrose administration is warranted.

Comparison of iron chelators used alone or in combination with phlebotomy in common mynahs (Acridotheres tristis) with experimental iron storage disease.

To compare the therapeutic effects of iron chelators used alone or in combination with phlebotomy on iron storage disease (ISD), 66 healthy common mynahs (Acridotheres tristis) were fed an iron-loading diet (3000 ppm) for 30 days. After confirmation of ISD, the birds were randomly divided into four treatment groups; DFO: deferoxamine (100 mg/kg SC q24 h), DFP: deferiprone (oral, 75 mg/kg), DFO + F: deferoxamine (100 mg/kg SC q24 h) with phlebotomy, and DFP + F: deferiprone (oral, 75 mg/kg) with phlebotomy. In phlebotomy-treated groups, blood sampling (1% BW) was performed weekly. At 1 and 2 months after treatments, seven birds from each group were euthanized and liver iron, copper, and zinc were analysed by ICP-OES assay. After 1 month, in all treatments, the liver amount of iron, copper, and zinc was reduced (P < 0.05) and there was no significant difference between groups. In the second month, the amount of liver iron, copper, and zinc decreased more in all groups, but this change was insignificant except in the DFP + F group (P < 0.05). These results suggest that all therapeutic protocols after 1 month effectively reduce the liver iron and there is no need to continue treatment. Otherwise, it may lead to iron deficiency, especially in birds treated with DFP + P. Since deferiprone, as an inexpensive oral chelator, effectively reduces liver iron levels without causing stress in the birds, it can be recommended as a more appropriate method for the treatment of mynahs with ISD. However, further clinical studies are needed to define the most effective treatment.RESEARCH HIGHLIGHTS Deferiprone is an optimized method for treating iron storage disease.The essential metals homeostasis is impaired in iron storage disease.