Erythrocytosis due to presumed polycythemia vera

Rushad Patell; Karl Theil; Alan Lichtin

doi:10.3949/ccjm.83a.15154

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FIGURE 1
Hemoglobin oxygen dissociation curve (venous sample), demonstrating a shift to the left (red) compared with normal (green), pointing to the presence of a hemoglobinopathy with increased oxygen affinity.
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FIGURE 2
Structure of the hemoglobin molecule. More than 200 variants that have greater than normal affinity for oxygen have been reported.

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TABLE 1

Causes of erythrocytosis

Primary erythrocytosis

Increased sensitivity of erythroid progenitors to erythropoietin
Polycythemia vera
Primary familial congenital polycythemia
Activating mutations of the erythropoietin receptor

Rare; due to altered hypoxia sensing
von Hippel-Lindau mutations, eg, homozygous R200W mutation (Chuvash polycythemia)
EGLN1 mutations (proline hydroxylase domain protein 2)
EPAS1 mutations (hypoxia-inducible factor 2 alpha)

Secondary erythrocytosis

Physiologically appropriate with increased erythropoietin
High-altitude erythrocytosis
Cardiac and pulmonary disease characterized by hypoxia
Hypoventilation syndromes
Chronic carbon monoxide poisoning
Congenital methemoglobinemia
Secondary familial congenital polycythemia
HBA1, HBA2, HBB mutations (high-oxygen-affinity hemoglobin)
Mutations of the BPGM (bisphosphoglycerate) gene

Physiologically inappropriate with increased erythropoietin
Androgen abuse
Erythropoietin abuse
Postrenal transplant erythrocytosis
Ectopic secretion of erythropoietin by neoplasms such as renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma, pheochromocytoma, uterine leiomyomata

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TABLE 2

Polycythemia vera: 2016 revision to the 2008 World Health Organization diagnostic criteria

Major criteria

Hemoglobin > 16.5 g/dL in men, > 16.0 g/dL in women; or hematocrit > 49% in men, > 48% in women; or increased red cell mass (> 25% above mean normal predicted value)
Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
JAK2 V617F or JAK2 exon 12 mutation

Minor criterion
Subnormal serum erythropoietin level

Diagnosis requires all three major criteria, or the first two major criteria and the minor criterion^a

↵a Criterion 2 (bone marrow biopsy) may not be required in cases with sustained absolute erythrocytosis: hemoglobin levels > 18.5 g/dL in men (hematocrit 55.5%) or > 16.5 g/dL in women (hematocrit 49.5%) if major criterion 3 and the minor criterion are present. However, initial myelofibrosis (present in up to 20% of patients) can only be detected by performing a bone marrow biopsy. This finding may predict a more rapid progression to overt myelofibrosis (post-polycythemia vera myelofibrosis).
Republished with permission of the American Society of Hematology, from Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127:2391–2405.