What conditions are associated with elevated white blood cell (WBC) and red blood cell (RBC) counts?

Conditions with Concurrent Elevation of WBC and RBC

Polycythemia vera (PV) is the primary condition that presents with both elevated red blood cell counts and elevated white blood cell counts, representing a clonal myeloproliferative neoplasm with trilineage proliferation. 1

Primary Myeloproliferative Neoplasm: Polycythemia Vera

Polycythemia vera characteristically demonstrates:

• Elevated hemoglobin >18.5 g/dL (men) or >16.5 g/dL (women) with concurrent WBC elevation 1
• Bone marrow trilineage myeloproliferation affecting red cells, white cells, and platelets 1
• JAK2V617F mutation present in >95% of cases, serving as a major diagnostic criterion 1
• WBC counts frequently >10 × 10⁹/L, with elevated WBC >11 × 10⁹/L significantly associated with increased thrombotic risk (HR 2.35) 2

Diagnostic Criteria for PV

The WHO diagnostic criteria require meeting either both major criteria plus one minor criterion, or the first major criterion plus two minor criteria 1:

Major criteria:

• Hemoglobin elevation as above or documented increased red cell mass 1
• Presence of JAK2V617F or JAK2 exon 12 mutation 1

Minor criteria:

• Bone marrow trilineage myeloproliferation (affecting erythroid, granulocytic, and megakaryocytic lineages) 1
• Subnormal serum erythropoietin level 1
• Endogenous erythroid colony growth 1

Critical Diagnostic Pitfall: Masked Polycythemia Vera

Iron deficiency can mask the erythrocytosis in PV, particularly in menstruating women with blood loss, resulting in normal hemoglobin/hematocrit despite active disease. 3 Key features suggesting masked PV include:

• Splenomegaly with unexplained iron deficiency 3
• Low serum erythropoietin despite normal hemoglobin 3
• Unveiling of erythrocytosis after iron repletion 3
• Presence of JAK2V617F mutation with normal blood counts 3

Secondary Polycythemia with Reactive Leukocytosis

Cyanotic congenital heart disease produces compensatory erythrocytosis (hemoglobin >20 g/dL, hematocrit >65%) that can occur with concurrent reactive leukocytosis from chronic hypoxemia and inflammation. 1

• The white blood cell count is usually normal in isolated secondary polycythemia, but concurrent infection or inflammation can elevate WBC 1
• Platelet count may be normal or reduced 1
• Distinguished from PV by normal or elevated erythropoietin levels and absence of JAK2 mutation 1

Leukemoid Reaction vs. Chronic Myeloid Leukemia

When evaluating extreme leukocytosis with left shift, distinguish leukemoid reaction from chronic myeloid leukemia (CML):

Leukemoid reaction characteristics:

• Mature neutrophils predominate with immature forms (metamyelocytes, mielocytes) 4
• Blasts absent or <5% 4
• Occurs with severe bacterial infections or inflammatory conditions like Adult-Onset Still's Disease 5, 4
• Philadelphia chromosome and BCR-ABL negative 4

CML characteristics:

• Philadelphia chromosome t(9;22) and BCR-ABL transcripts present 4
• Characteristic basophilia 4
• Bone marrow hypercellularity with granulocytic proliferation 4
• Can have concurrent erythrocytosis, though less prominent than in PV 4

Management Approach for Concurrent Elevations

For confirmed polycythemia vera with elevated WBC:

• Maintain hematocrit <45% through phlebotomy to reduce thrombotic risk (HR 1.84 when >45%) 2
• Control WBC count, as levels >11 × 10⁹/L independently increase thrombotic risk even when hematocrit is controlled 2, 6
• Consider cytoreductive therapy (hydroxyurea) when WBC >12 × 10⁹/L with controlled hematocrit, given persistent thrombotic risk 2
• Monitor for disease progression to post-PV myelofibrosis, indicated by worsening cytopenias or splenomegaly 1

For suspected secondary causes:

• Evaluate for chronic hypoxemia (pulse oximetry, arterial blood gas) in cyanotic heart disease 1
• Assess for infection with fever, localizing symptoms requiring bacterial workup 5, 7
• Review medications causing leukocytosis (corticosteroids, lithium) 5, 7
• Exclude smoking, obesity, and chronic inflammatory conditions as causes of mild concurrent elevations 5, 7

Critical warning: Hyperviscosity symptoms (headache, poor concentration) with hemoglobin >20 g/dL and hematocrit >65% require therapeutic phlebotomy with equal volume replacement, but avoid repeated routine phlebotomies due to iron depletion risk and increased stroke risk. 1