Histologic and cytologic bone marrow findings in dogs with suspected precursor‐targeted immune‐mediated anemia and associated phagocytosis of erythroid precursors

Abstract

Background: Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. Objectives: The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. Methods: Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. Results: Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4 th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immunemediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. Conclusions: Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis.

ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats

“…This discussion is restricted to immune‐mediated destruction of circulating erythrocytes (ie, precursor‐targeted immune‐mediated anemia or pure red cell aplasia are not discussed). Readers requiring additional information on immune‐mediated differentiation failure or destruction at the level of the bone marrow are referred elsewhere …”

The utility of diagnostic tests for immune‐mediated hemolytic anemia

“…While the majority of IMHA patients present with a regenerative anemia, this initial classification is not a certainty. IMHA can be nonregenerative or pre‐regenerative if there has been insufficient time for a clearly regenerative response to occur (anemia present < 5 – 7 days) or if immune‐mediated destruction of erythroid precursors is occurring (“precursor‐targeted immune‐mediated anemia”) …”

“…In another study of canine patients with nonregenerative anemia present for more than 5 days, 41 of 43 (95%) had erythroid hyperplasia in bone marrow samples, 23 of 43 (54%) had a spherocytosis, and 20 of 35 (57%) were positive by DAT . To determine if dogs with a nonregenerative anemia >5 days duration have precursor‐targeted immune‐mediated anemia, bone marrow should be evaluated for macrophage phagocytosis of erythroid precursors . Weiss (2008) also evaluated 57 cats with nonregenerative anemia in which bone marrow analysis was indicated.…”

Clinical and clinicopathological features and outcomes of Miniature Dachshunds with bone marrow disorders

“…Besides neoplastic diseases, bone marrow disorders that could cause non-regenerative anemia in dogs include aplastic anemia (AA), essential thrombocytosis (ET), myelofibrosis (MF), myelodysplastic syndrome (MDS), non-regenerative immune-mediated anemia (NRIMA), and pure red cell aplasia (PRCA) [5,6,14,17,21,22]. Recently, a concept of precursor-targeted immune-mediated anemia (PIMA) was also proposed as an immune-mediated disease that causes non-regenerative anemia [12]. PIMA is characterized by phagocytosis of intact erythroid precursors by intact macrophages in bone marrow or spleen [12].…”

“…Recently, a concept of precursor-targeted immune-mediated anemia (PIMA) was also proposed as an immune-mediated disease that causes non-regenerative anemia [12]. PIMA is characterized by phagocytosis of intact erythroid precursors by intact macrophages in bone marrow or spleen [12].…”