Differential Diagnoses of Regenerative & Nonregenerative Anemia

Following are differential diagnoses for patients presented with nonregenerative or regenerative anemia.

Nonregenerative Anemia*

• Anemia of inflammatory/chronic disease

• Chronic renal disease

• Endocrine disease

  • Hyperestrogenism (eg, Sertoli cell tumor)

  • Hypoadrenocorticism

  • Hypothyroidism

• Hemophagocytic syndrome (secondary to histiocytic sarcoma, lymphoma, or other neoplastic, infectious, or immune-mediated disease)

• Hospital-acquired anemia (secondary to repeated blood sampling, surgery, inflammation, or hemodilution)

• Iron deficiency anemia; can be regenerative initially (eg, secondary to GI bleeding, ectoparasites [eg, fleas], or lead toxicity)

• Primary bone marrow disease (often with other concurrent cytopenias and/or dysplasia, except in cases of precursor-targeted immune-mediated anemia/pure red cell aplasia)

  • Congenital dyserythropoiesis

  • Drug-induced effect (often multifactorial [eg, estrogen, phenobarbital, sulfonamides])

  • Infectious disease (eg, FeLV/FIV, Ehrlichia spp, feline panleukopenia, canine parvovirus)

  • Myelodysplastic syndrome

  • Myelophthisis

    • Bone marrow necrosis/inflammation (eg, disseminated intravascular coagulation (DIC), sepsis, endotoxemia, drugs, toxins)

    • Myelofibrosis

    • Neoplasia (eg, lymphoma, leukemias, metastatic neoplasia)

  • Precursor-targeted immune-mediated anemia/pure red cell aplasia

• Sideroblastic anemia

Regenerative Anemia

• Hemolysis

  • Cold agglutinin disease 

  • Fragmentation anemia (eg, DIC, neoplasia [eg, hemangiosarcoma], liver disease, vasculitis, bacterial endocarditis, heartworm disease)

  • Hereditary cause

    • Feline congenital porphyria

    • Increased erythrocyte osmotic fragility (cats)

    • Phosphofructokinase deficiency (English springer spaniels, American cocker spaniels, whippets, Deutscher Wachtelhunds)

    • Pyruvate kinase deficiency (West Highland white terriers, Basenjis, beagles, cairn terriers, pugs, Labrador retrievers, domestic shorthair cats, Abyssinians, Somalis)

    • Spectrin deficiency (Dutch golden retrievers)

  • Hypophosphatemia (eg, treatment for diabetic ketoacidosis or refeeding syndrome)

  • Immune-mediated hemolytic anemia

    • Primary (idiopathic)

    • Secondary to underlying cause (eg, neoplasia, infection [eg, hemotropic Mycoplasma spp, Babesia spp], drugs, incompatible blood transfusion, envenomation)

  • Infectious cause (eg, hemotropic Mycoplasma spp, Babesia spp, Cytauxzoon felis, Leptospira spp)

  • Oxidant or Heinz body anemia (eg, secondary to onion or garlic ingestion, zinc toxicity [from pennies minted after 1982], copper toxicity [eg, copper hepatopathy], drugs [eg, acetaminophen, vitamin K], naphthalene, propylene glycol, benzocaine, skunk musk)

• Hemorrhage

  • GI ulceration (eg, secondary to NSAID administration, neoplasia, hypoadrenocorticism)

  • Hemostatic disorders

    • Coagulation disorder (eg, rodenticide toxicity [vitamin K antagonists], inherited coagulation deficiency [eg, hemophilia A])

    • DIC

    • Thrombocytopathy (eg, secondary reaction to monoclonal gammopathy, drugs [eg, aspirin])

    • Thrombocytopenia (eg, immune-mediated thrombocytopenia)

    • Von Willebrand disease

  • Neoplasia (eg, splenic hemangiosarcoma)

  • Parasitic disease (eg, fleas, hookworms)

  • Trauma (eg, vehicular, bite wound)

  • Vessel wall disorder (eg, vasculitis, colonic vascular ectasia)

• Normal puppies and kittens <8 weeks of age

Re-evaluation is needed after 4 to 5 days to ensure anemia is not preregenerative.

Editor's note: This article was originally published in November 2020 as "Differential Diagnosis: Anemia"