Why Does My Patient Have Erythrocytosis?
Section snippets
Regulation of erythropoiesis
The interaction of EPO with EPOR on erythroid progenitor cells leads to its homodimerization, which results in initiation of cell division, differentiation, and prevention of apoptosis of erythroid progenitors and precursors.4 The cytoplasmic portion of the EPOR contains a positive regulatory domain that interacts with JAK2.5 On EPO binding, JAK2 phosphorylates itself, EPOR, and other cytoplasmic molecules including STAT5.6 The JAK2/STAT5 signaling pathway plays an important role in
Relative polycythemias
Patients with moderately increased hematocrit levels that are not necessarily accompanied by an increase in red cell mass are often erroneously assumed to be polycythemic.18 Relative polycythemia is a term used to describe an increase of the hematocrit level due either to an acute transient state of hemoconcentration associated with intravascular volume depletion or a chronic, sustained, relative polycythemia caused by contraction of the plasma volume. Transient polycythemia may be a result of
Primary Familial and Congenital Polycythemias
Primary familial and congenital polycythemias (PFCP) is an autosomal dominant disorder.20 Unlike patients with PV, patients with PFCP lack splenomegaly and do not progress to myelofibrosis and acute leukemia. They often present with headaches, epistaxis, exertional dyspnea, and dizziness. An increased risk of cardiovascular events and resulting premature morbidity and mortality have been reported in these patients.21 Although clinical symptoms are resolved with reduction in red cell mass via
Summary
Polycythemia is defined as hematocrit of more than 48% in women and 52% in men.
- •
Relative polycythemia is an increase in hematocrit without an increase in red cell mass. It is usually caused by an acute state of hemoconcentration.
- •
Accurate history and careful physical examination are essential to determine the cause of erythrocytosis. Many causes of secondary erythrocytosis can be elucidated from history (drug use, pulmonary disease, living at high altitude, smoking, family history). Splenomegaly
References (104)
The erythropoietin-hematocrit relationship in normal and polycythemic man: implications of marrow regulation
Blood
(1968)- et al.
Regulation of the erythropoietin gene
Blood
(1999) - et al.
JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin
Cell
(1993) Erythropoietin
Blood
(1991)Why is erythropoietin made in the kidney? The kidney functions as a critmeter
Am J Kidney Dis
(2001)Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis
Blood
(2009)- et al.
Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1
J Biol Chem
(1996) The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing
Biochem Biophys Res Commun
(2005)- et al.
Primary familial and congenital polycythaemia
Lancet
(1993) - et al.
Clinical update: cyanotic adult congenital heart disease
Lancet
(2007)
Posttransplant erythrocytosis
Kidney Int
Paraneoplastic erythrocytosis associated with an inactivating point mutation of the von Hippel-Lindau gene in a renal cell carcinoma
Blood
Congenital polycythemia in Chuvashia
Blood
Endemic polycythemia in Russia: mutation in the VHL gene
Blood Cells Mol Dis
Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors
Blood
Chuvash-type congenital polycythemia in 4 families of Asian and western European ancestry
Blood
Epidemiology of the myeloproliferative disorders: essential thrombocythaemia, polycythaemia vera and idiopathic myelofibrosis
Pathol Biol (Paris)
Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24,577 first-degree relatives of 11,039 patients with myeloproliferative neoplasms in Sweden
Blood
Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
Cancer Cell
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
Lancet
Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders
Blood
Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia
Lancet
Inapparent polycythemia vera: an unrecognized diagnosis
Am J Med
Unexplained pulmonary hypertension in chronic myeloproliferative disorders
Chest
Bleeding and thrombosis in the myeloproliferative disorders
Blood
Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey
Blood
A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis
Blood
Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel
Blood
Primary familial polycythemia: a frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin
Blood
Serum erythropoietin values in erythrocytoses and in primary thrombocythaemia
Br J Haematol
Erythropoietin
Transfusion
The role of Janus kinases in haemopoiesis and haematological malignancy
Br J Haematol
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
Mol Cell Biol
Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
Nature
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Nature
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing
Science
Cellular oxygen sensing: crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)
Proc Natl Acad Sci U S A
Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2alpha gain-of-function mutation
FASEB J
Spurious polycythemia
Semin Hematol
Life-threatening thrombotic complications of relative polycythaemia
J Intern Med
Advances in understanding the pathogenesis of primary familial and congenital polycythaemia
Br J Haematol
“Benign erythrocytosis” and other familial and congenital polycythemias
Eur J Haematol
Hypoxemia in patients with COPD: cause, effects, and disease progression
Int J Chron Obstruct Pulmon Dis
Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease
J Appl Physiol
Management of polycythaemia in adults with cyanotic congenital heart disease
Heart
Therapeutic methods used in patients with Eisenmenger syndrome
Cardiol J
Blood is thicker than water: the management of hyperviscosity in adults with cyanotic heart disease
Cardiol Rev
Secondary polycythaemia associated with nocturnal apnoea–a relationship not mediated by erythropoietin?
J Intern Med
Intermittent hypoxia in patients with unexplained polycythaemia
Br Med J (Clin Res Ed)
Rev Pneumol Clin
Cited by (0)
Disclosures: None.