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BACKGROUND Cytopenias have been reported in dogs treated with phenobarbital, but detailed descriptions of bone marrow findings and response to treatment are lacking. OBJECTIVES We aimed to characterize the hematologic findings and clinical outcomes of dogs that had been receiving phenobarbital at the time of marrow evaluation. METHODS Archived bone marrow slides and clinicopathologic data were reviewed in dogs undergoing marrow evaluation for any hematologic problems that developed while receiving phenobarbital (2008-2020). Dogs were excluded if marrow samples lacked diagnostic value, phenobarbital was withdrawn >1 day before marrow collection, a same-day complete blood count (CBC) was lacking, or dogs had concurrent illness or therapy known to cause cytopenias. RESULTS Thirteen dogs met inclusion criteria: eight pancytopenic, three anemic/thrombocytopenic, one neutropenic/thrombocytopenic, and one nearly neutropenic. Neutropenia was marked (

A healthy 14-year-old, male neutered, Miniature Poodle was found to have a persistent erythrocyte macrocytosis and reticulocytosis with a normal and stable HCT. The hematologic features of macrocytosis, increased Howell-Jolly bodies, and metarubricytosis, in the absence of anemia or other cytopenias, combined with the cytologic evidence of bone marrow erythroid dysplasia, including megaloblastosis, binuclearity, increased mitotic activity, and nuclear fragmentation, are consistent with previous reports of congenital dyserythropoiesis termed poodle macrocytosis. We speculate that the additional presence of persistent reticulocytosis in the absence of an identifiable stimulus for accelerated erythropoiesis may represent a phenotypic variation of this inherited condition, and the morphologic abnormalities of the dyserythropoiesis are described.

Myeloid neoplasms with ring sideroblasts are currently categorized within the myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the World Health Organization classification. Recent findings have identified that the presence of ring sideroblasts in these disorders has a unique molecular basis, i.e., the somatic mutation of SF3B1, a gene encoding a splicing factor. Mutations of SF3B1 occur in up to 90% of patients with refractory anaemia with unilineage dysplasia (RARS) and 70% of those with refractory cytopenia with multilineage dysplasia and ring sideroblasts or RARS associated with marked thrombocytosis. Experimental evidence has shown that mutant SF3B1 results in the abnormal splicing of several genes, primarily due to misrecognition of 3' splice sites. The resulting aberrant mRNAs undergo nonsense-mediated mRNA decay (NMD), resulting in haploinsufficiency of canonical transcripts and protein expression. In addition, it is also possible that NMD-insensitive aberrant transcripts are translated into proteins with altered function. Patients with MDS carrying the SF3B1 mutation show a homogeneous disease phenotype characterized by isolated erythroid dysplasia and mild dysplasia in granulocytic or megakaryocytic lineages, supporting the notion that the SF3B1 mutation identifies a distinct entity within MDS. The available evidence suggests that these findings may have relevant impact on the diagnosis, classification and management of patients with these neoplasms.

Background/Aim: Abnormal immunophenotypes of haematopoietic cells in myelodysplastic syndromes (MDS) have been identified by flow cytometry (FCM) as a typical characteristic of myeloid dysplasia. Considering that most MDS patients show varying degrees of erythroid dysplasia, we analysed the immunophenotypic feature of erythroblasts to evaluate its diagnostic application in MDS. Methods: Erythroid antigens CD71 and CD105 expression were analysed using FCM. The development index (DI) acquired by log transformation of the CD71/CD105 expression ratio was used to denote the erythroid maturation and distinguish patients with non-clonal cytopenias from low-risk MDS. The diagnostic quality of DI in distinguishing MDS from non-clonal cytopenia patients was evaluated using the receiver–operator characteristic (ROC) curve. Results: Under-expression of CD71 and over-expression of CD105 were detected in erythroblasts of MDS patients compared with non-clonal cytopenias. The diagnostic test showed good diagnostic power that the area under the ROC curve was greater than 0.9. The diagnostic sensitivity and specificity were 75.6% and 92.3%, respectively, according to the DI threshold defined by the ROC curve in low-risk MDS patients with normal karyotypes. Moreover, the DI showed a positive correlation with the haemoglobin level, and the MDS patients with lower DI usually showed frequent red cell transfusion. The patients with a lower DI generally had the HLA-DR15 allele or marrow hypocellularity. Conclusion: Developmental defects and immune-associated factors may contribute to the erythroid dysplasia. The DI derived from ratios of CD71 and CD105 expression is a useful marker to characterise dyserythropioiesis associated with MDS and can be helpful in distinguishing it from dyerythropoiesis associated with non-clonal disorders.

An 11-year-old female Dachshund was presented with depression, diarrhea, weight loss, and radiographic evidence of masses involving the liver, spleen, and cranial lobe of the right lung. Results of a CBC included severe nonregenerative anemia (HCT 14.2%, hemoglobin, 4.3 g/dL, reticulocytes 66,000/microL) with marked metarubricytosis (nucleated RBCs 6.39 x 10(3)/microL). Examination of the peripheral blood smear revealed marked erythroid dysplasia, including marked anisocytosis with a prevalence of macrocytes, Howell-Jolly bodies, diffuse basophilic stippling, and multinucleated and atypical nucleated RBCs. Neutrophil hypersegmentation and giant forms were also noted. Numerous erythrocytes, particularly polychromatophilic cells, contained inclusions consistent with Cabot rings, which appeared as delicate red-purple ellipsoid or figure 8 structures. Rarely, Cabot rings were observed extracellularly. The dog was treated symptomatically with blood transfusions, prednisone, erythropoietin, and vitamin supplementation, but the anemia progressively worsened. The dog was euthanized 2 months after presentation. Bone marrow aspirate and core biopsy specimens obtained at the time of euthanasia revealed marked dysplastic changes in all cell lines, especially dyserythropoiesis, along with infiltrating carcinoma cells. A necropsy was performed, and histologic examination revealed poorly differentiated adenocarcinoma of the lung with multiple metastases to the marrow, spleen, and liver. The final diagnosis was marked myelodysplasia secondary to metastatic adenocarcinoma. Cabot rings are found rarely in humans with myelodysplasia, but have not been described previously in dogs. Based on the findings in this case, Cabot rings may occur rarely in dogs with severe dyserythropoiesis.

Background : Autoantibodies with anti-U specificity, usually in combination with autoantibodies of other specificities, have occasionally been identified in association with autoimmune hemolytic anemia. A case of life-threatening autoimmune hemolytic anemia, characterized by several atypical features, including apparent intravascular hemolysis associated with an IgG2 anti-U, reticulocytopenia, and bone marrow dyserythropoiesis is described. Case Report : A 36-year-old man with a severe case of acute-onset autoimmune hemolytic anemia was admitted to another hospital ; he had a hematocrit of 15 percent, elevated bilirubin and lactate dehydrogenase, and positive direct and indirect antiglobulin tests. He received 7 units of incompatible red cells without improvement in hematocrit, and he was transferred to University Hospitals of Cleveland (OH). He was jaundiced and became syncopal in the sitting position. His serum was reddish pink ; he had a hematocrit of 11.8 percent and a reticulocyte count of 2.5 percent. No spherocytes were observed in the peripheral blood smear. Shortly after admission, the hematocrit fell to 6.9 percent. He was given 3 units of least-incompatible red cells and was started on prednisone, with little improvement. An IgG2 autoanti-U was detected in his serum. Seven units of U- red cells were transfused over the next 4 days. The hematocrit improved to 23 percent and continued to rise without further transfusion. A bone marrow examination, initially revealing erythroid hyperplasia accompanied by dyserythropoiesis, became morphologically normal. Drug studies failed to show evidence of drug-related hemolysis. He remains well 2 years after discharge without evidence of recurrent hemolysis. Conclusion : Severe life-threatening autoimmune hemolytic anemia, in this instance induced by an autoanti-U, may be associated with lgG2 autoantibody and characterized by apparent intravascular hemolysis and bone marrow dyserythropoiesis. Early treatment with U- blood, in addition to steroids, may be beneficial.

According to evidence- and consensus-based practice guidelines, the majority of patients with myelodysplastic syndrome (MDS) should receive supportive therapy at present. Once anemia is symptomatic, red cell transfusions are the mainstay of therapy. The life expectancy of patients with isolated erythroid dysplasia aged 70 years or older is not significantly shorter than that of the general population; avoiding disease complication is therefore very important in these individuals. Recently we demonstrated that the development of red cell transfusion-dependency significantly affects survival of MDS patients (Malcovati et al. J Clin Oncol 2005; 23: 7594–603). This partly reflects the severity of bone marrow failure; however, development of secondary iron overload significantly worsens survival of transfusion-dependent patients. Considering patients with transfusion needs, iron overload (defined as serum ferritin above 1000 ng mL−1) is developed after receiving a median number of 20–25 RBC units. The effect of iron overload is mainly noticeable among patients with refractory anemia, who have a longer survival and therefore are more prone to develop the adverse effects of iron overload. In contrast, secondary iron overload does not affect the survival of patients with refractory cytopenia, who have a median survival of about 50 months. The negative effect of iron overload is significantly associated with serum ferritin levels, with a 40% increase in hazard for every 500 ng mL-1 of increase in serum ferritin. According to the currently available therapeutic guidelines iron chelation should be considered once a patient has received 20–50 units of red cells, but only in patients for whom long-term transfusion therapy is likely, or when an allogeneic stem cell transplantation is planned. The target serum ferritin concentration should be