Polycythemia vera differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Overview

Polycythemia vera must be differentiated from chronic myelogenous leukemia, essential thrombocythemia, and primary myelofibrosis.

Differential Diagnosis

Polycythemia vera must be differentiated from a variety of other conditions.

Characteristic/Parameter	Etiology	Symptoms	Laboratory abnormalities	Physical examination	Treatment	Other associated abnormalities
Polycythemia vera	JAK2 mutation (V617F or exon 12 mutation) Autonomous erythrocyte production	Erythromelagia Headache Stroke-like symptoms	Elevated hemoglobin Elevated red blood cell mass Elevated white blood cell count and platelet count in some cases (panmyelosis)	Ruddy face Splenomegaly	Aspirin Ruxolitinib Hydroxyurea Phlebotomy Interferon-alpha	Extramedullary hematopoiesis Stroke Venous thrombosis
Chronic myeloid leukemia	Reciprocal translocation of chromosomes 9 and 22 Production of BCR-Abl kinase, which drives cell proliferation	Abdominal pain Infections Fever	Elevated total white blood cell count Elevated red blood cell count and platelet count occasionally Increased proportion of metamyelocytes and other white blood cells at various stages of maturation	Splenomegaly	Vaso-occlusion in peripheral vascular beds Jaundice from hemolysis Hepatomegaly Splenomegaly	Folate supplemention Hydroxyurea (to increase fetal hemoglobin production Oxygen supplemention Transfusion support Iron chelation Gene therapy if available Crizanlizumab (P-selectin inhibitor) Patient education and genetic counseling	Extramedullary hematopoiesis Pain crises Acute chest syndrome
Iron deficiency anemia	Loss of iron from occult bleeding Gastrointestinal blood loss Menstrual blood loss Dietary iron deficiency	Microcytic (<80 femtoliter)	Low serum iron Elevated transferrin Low transferrin saturation Low ferritin	Pallor Weakness Positive occult blood testing (if GI bleeding)	Intravenous or oral iron supplementation Blood transfusions	Chronic blood loss
Hemolytic anemia	Medication-induced Autoimmunity Red blood cell membrane defect Red blood cell enzyme defect Shear stress from mechanical valves	Normocytic (80-100 femtoliter)	Indirect hyperbilirubinemia Reticulocytosis Low haptoglobin Elevated LDH	Pallor Jaundice	Removal of offending agent causing hemolysis Steroids Alternative immunosuppression	HELLP syndrome TTP CLL
Sideroblastic anemia	Alcoholism Lead poisoning Vitamin B6 deficiency Isoniazid Chloramphenicol	Microcytic (<80 femtoliter) Or Normocytic (80-100 femtoliter)	Ringed sideroblasts in bone marrow Low vitamin B6 level High lead level	Pallor Weakness	Removal of offending medication High-dose vitamin B6 (up to 200mg daily) Avoidance of splenectomy Symptomatic transfusion support with iron chelation as needed	Myelodysplastic syndrome Myeloproliferative neoplasm Iron overload
Anemia of chronic disease	Chronic kidney disease Rheumatologic disease Cancer HIV Chronic infection; excess release of IL-1 and IL-6	Normocytic (80-100 femtoliter)	Elevated ESR and CRP Elevated hepcidin Low serum iron Low transferrin Elevated ferritin	Pallor Weakness	Treatment of the underlying cause; erythropoiesis-stimulating agents Supportive red blood cell transfusions	Inflammatory bowel disease
Erythropoietin deficiency	Chronic kidney disease or other renal dysfunction	Normocytic (80-100 femtoliter)	Low erythropoietin level	Pallor Weakness Signs of chronic kidney disease	Epoetin alfa 50-100 units/kg 3 times weekly Darbepoietin 0.45 mcg/kg weekly or 0.75 mcg/kg every 2 weeks	Dialysis dependence Myelodysplastic syndrome
Vitamin B12 or folate deficiency	Pernicious anemia Diphyllobothrium latum infection Nutritional deficiency Crohn's disease of terminal ileum	Macrocytic (>100 femtoliter)	Low vitamin B12 or folate level Megaloblastic anemia with hypersegmented neutrophils	Numbness Weakness Tingling Paresthesias	Vitamin B12 1000mcg daily Folate 1mg daily	Neuropathy

• Chronic myelogenous leukemia
• Essential thrombocythemia
• Primary myelofibrosis

References

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