Conditions with Concurrent Elevation of WBC and RBC

Primary Myeloproliferative Neoplasm: Polycythemia Vera

The American Society of Hematology recommends that polycythemia vera be diagnosed based on the presence of a JAK2V617F mutation, which is present in >95% of cases, and characteristic bone marrow trilineage myeloproliferation affecting red cells, white cells, and platelets 1, 2
The World Health Organization diagnostic criteria for polycythemia vera require meeting either both major criteria plus one minor criterion, or the first major criterion plus two minor criteria, including hemoglobin elevation, presence of JAK2V617F or JAK2 exon 12 mutation, bone marrow trilineage myeloproliferation, subnormal serum erythropoietin level, and endogenous erythroid colony growth 2
Elevated hemoglobin >18.5 g/dL (men) or >16.5 g/dL (women) with concurrent WBC elevation is a characteristic feature of polycythemia vera 2
The presence of JAK2V617F mutation is a major diagnostic criterion for polycythemia vera, and is associated with an increased risk of thrombotic events 2

The American Heart Association recommends that cyanotic congenital heart disease be evaluated for compensatory erythrocytosis, which can occur with concurrent reactive leukocytosis from chronic hypoxemia and inflammation 3
Secondary polycythemia can be distinguished from polycythemia vera by normal or elevated erythropoietin levels and absence of JAK2 mutation 3

The National Comprehensive Cancer Network recommends that leukemoid reaction be distinguished from chronic myeloid leukemia based on the presence of mature neutrophils, absence of blasts, and negative Philadelphia chromosome and BCR-ABL 4, 5
Chronic myeloid leukemia is characterized by the presence of Philadelphia chromosome t(9;22) and BCR-ABL transcripts, basophilia, and bone marrow hypercellularity with granulocytic proliferation 4

The European Society for Medical Oncology recommends that patients with confirmed polycythemia vera and elevated WBC be managed with phlebotomy to reduce thrombotic risk, and cytoreductive therapy (hydroxyurea) when WBC >12 × 10⁹/L with controlled hematocrit 1, 6
The American College of Cardiology recommends that patients with suspected secondary causes of concurrent elevations be evaluated for chronic hypoxemia, infection, and medications causing leukocytosis, and that therapeutic phlebotomy be performed with equal volume replacement in cases of hyperviscosity symptoms 3, 5, 7

The American Heart Association recommends evaluating cyanotic congenital heart disease for compensatory erythrocytosis with concurrent reactive leukocytosis 8
Obtain complete blood count with manual differential to assess all three cell lines (RBC, WBC, platelets) and identify trilineage proliferation 9
Review peripheral blood smear by a qualified hematologist to identify abnormalities inconsistent with polycythemia vera, such as schistocytes or leukocyte inclusion bodies 8

Moderate or massive splenomegaly suggests an alternative cause beyond simple polycythemia vera and requires urgent evaluation 8
If constitutional symptoms, splenomegaly, or lymphadenopathy are present: perform bone marrow examination with flow cytometry and cytogenetic testing 8