| Relative polycythemia |
| Volume contraction (eg, diuretics, vomiting, diarrhea, smoking) |
| Absolute polycythemia |
| Primary polycythemia |
Inherited (germline mutations): - Primary familial and congenital polycythemia (eg, EPOR mutation)
- Chuvash polycythemia/VHL mutation, some features of primary but more features of secondary erythrocytosis
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Acquired (somatic mutations; clonal): - Polycythemia vera (JAK2 mutations)
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| Secondary polycythemia (elevated or inappropriately normal serum erythropoietin [EPO]) |
Inherited (germline mutations): - VHL – Chuvash polycythemia also has some features of primary erythrocytosis/and some other VHL mutations.
- EGLN1 – Loss-of-function mutations of EGLN1 (encoding proline hydroxylase 2 [PHD2])
- EPAS1 – Gain-of-function mutations of EPAS1 (encoding HIF-2 alpha)
- CYB5R3 – Cytochrome b5 reductase deficiency causing congenital methemoglobinemia*
- BPGM – Bisphosphoglyceromutase loss-of-function mutations
- HBA1/2, HBB – Variants affecting globin chains can cause high oxygen affinity
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| Acquired (appropriate and inappropriate) |
Hypoxia: - Pulmonary disease; associated with arterial oxygen desaturation cyanosis and clubbing.
- Alveolar hypoventilation; Central form may be a result of cerebral vascular accident, Parkinsonism, encephalitis. Peripheral form may be a result of myotonic dystrophy, poliomyelitis, spondylitis, or severe obesity
- Sleep apnea; only <5% of subjects develop erythrocytosis, and those tend also to be hypoxic during day or take androgens.
- Cardiovascular (Eisenmenger syndrome)
- High-altitude acclimatization
- Renal causes:
- Following renal transplantation
- Others (eg, renal artery stenosis, cysts, hydronephrosis)
- Endocrine disorders: Pheochromocytoma, aldosterone-producing adenomas, Bartter syndrome
- Cerebellar hemangiomas (approximately 15% of patients have erythrocytosis) and other tumors (uterine myoma and hepatoma)
- Neonatal erythrocytosis
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Autonomous EPO production: - EPO-producing tumors (eg, hepatocellular carcinoma, renal cell carcinoma, hemangioblastoma, pheochromocytoma, uterine leiomyomata)
- TEMPI syndrome. Patients with erythrocytosis, elevated EPO and monoclonal gammopathy have been described as TEMPI syndrome. It consists of (1) telangiectasias; (2) elevated EPO and erythrocytosis; (3) monoclonal gammopathy; (4) perinephric fluid collections; and (5) intrapulmonary shunting.
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| Other causes |
| SGLT2 (sodium-glucose co-transporter-2) inhibitors |
| Athletic performance-enhancing agents (eg, recombinant erythropoiesis-stimulating agents, autologous transplantation ["blood doping"], androgens or anabolic steroids) |
| Cobalt toxicity |
