-
Handbook of Clinical Neurology 2011Polycythemia vera is a sporadic myeloproliferative disorder of increased red blood cell mass affecting multiple organ systems. Associated thrombosis, hemorrhaging, and... (Review)
Review
Polycythemia vera is a sporadic myeloproliferative disorder of increased red blood cell mass affecting multiple organ systems. Associated thrombosis, hemorrhaging, and hyperviscosity commonly result in neurological manifestations, sometimes in the form of chorea and ballism. Resultant choreiform movements have been mainly described as generalized with orofaciolingual and appendicular muscle involvement, hypotonia, and hyporeflexia. Chorea has also been uncommonly reported as arising from secondary causes of polycythemia; however, the underlying pathophysiology has not been clearly elucidated. Proposed mechanisms for basal ganglia dysfunction include hypoperfusion due to venous stasis, receptor hypersensitivity in a setting of reduced catecholamine levels, and altered platelet dopamine metabolism. Magnetic resonance imaging and single-photon emission computed tomography perfusion studies have failed to reveal an anatomical or physiological basis for polycythemia vera-associated chorea, yet rare pathological examinations of deceased patients have shown signs of cerebral venous thrombosis and perivenous demyelination. Administration of neuroleptics may suppress abnormal choreiform movement; however, effective management of polycythemia vera requires serial venesections in conjunction with chemotherapy. Appropriate treatment may prolong survival to more than 10 years, although chorea may spontaneously remit, re-emerge with resurgence of disease, or continue indefinitely despite maintenance therapy.
Topics: Chorea; Humans; Polycythemia; Risk Factors
PubMed: 21496586
DOI: 10.1016/B978-0-444-52014-2.00019-7 -
Blood Reviews Mar 1989The approach to diagnosis and classification of patients with polycythemia is reviewed with presentation of general and specific guidelines for the management of... (Review)
Review
The approach to diagnosis and classification of patients with polycythemia is reviewed with presentation of general and specific guidelines for the management of patients with polycythemia vera, secondary polycythemia and relative polycythemia.
Topics: Adult; Aged; Bloodletting; Humans; Hydroxyurea; Middle Aged; Polycythemia; Polycythemia Vera
PubMed: 2650777
DOI: 10.1016/0268-960x(89)90026-x -
Pathologie-biologie Jun 2004Polycythemias can be differentiated based on the responsiveness of erythroid progenitors to circulating cytokines. Primary polycythemias are characterized by an... (Review)
Review
Polycythemias can be differentiated based on the responsiveness of erythroid progenitors to circulating cytokines. Primary polycythemias are characterized by an augmented response due to acquired somatic or inherited germ-line mutations that are expressed within hematopoietic progenitors causing increased proliferation or decreased apoptosis and resulting in accumulation of red blood cells. In terms of oxygen requirements, primary polycythemias can be viewed as the production of hemoglobin fully dissociated from the tissue oxygen needs and from the oxygen sensing pathway. Polycythemia vera (PV) is the most common primary polycythemia. PV bone marrow progenitors cells can form erythroid colonies in the absence of exogenous erythropoietin in vitro. These endogenous erythroid colonies (EEC) are useful in differentiating PV and secondary polycythemias. They also can differentiate PV where this feature is independent of Epo signalling from primary familial and congenital polycythemia. In this autosomal dominant primary polycythemia, at variance with PV, EEC formation is abolished by anti-Epo and anti-Epo receptor neutralising antibodies. Mutations of the EPOR have been described and resulted in nine cases in truncated EPORs lacking the cytoplasmic carboxy-terminal of the receptor which possesses a negative growth regulatory domain. However, recent data suggest that different mutations may cause PFCP in most cases. Secondary polycythemia can be viewed as either physiological response to satisfy the oxygen needs of the tissues, resulting for instance from high affinity hemoglobins or BPG mutase deficiency, or as the result of germ-line or somatic mutations disturbing the oxygen sensing pathway or its target: Epo. Chuvash polycythemia is a frequently symptomatic disorder with an autosomal recessive inheritance and inappropriately high Epo levels. The erythroid progenitors are hypersensitive to Epo linking this condition to both primary and secondary polycythemia. A germline missense mutation at nucleotide 598 in both alleles of the von Hippel-Lindau gene results in increased hypoxia inducible factor-1 (HIF-1) expression in normoxic conditions. HIF-1 controls the expression of many genes including Epo. Identifying causal defects in other situations like post-renal transplant erythrocytosis and cases of autosomal dominant polycythemia with high Epo levels will help further understanding of the regulation of erythropoiesis.
Topics: Erythrocytes; Hematopoietic Stem Cells; Humans; Oxygen; Oxygen Consumption; Polycythemia
PubMed: 15217714
DOI: 10.1016/j.patbio.2004.02.006 -
Current Opinion in Hematology Mar 2005Diagnosis and therapy of polycythemia vera are controversial since the molecular basis of polycythemia vera remains unknown. Distinguishing between polycythemia vera and... (Review)
Review
PURPOSE OF REVIEW
Diagnosis and therapy of polycythemia vera are controversial since the molecular basis of polycythemia vera remains unknown. Distinguishing between polycythemia vera and other polycythemic disorders can be very challenging. The purpose of this review is to discuss the recent progress in this area and critically review the published data in context of our knowledge of other polycythemic disorders.
RECENT FINDINGS
Erythropoietin is the principal regulator of regulator of erythropoiesis; its production is regulated by the degree of hypoxia. Our knowledge of cellular responses to hypoxia has recently exploded and led to the elucidation of the molecular basis of a polycythemia caused by augmentation of hypoxic sensing, Chuvash polycythemia. Similar progress in understanding the molecular basis of polycythemia vera has been elusive. A simple, readily available laboratory test to establish a diagnosis of polycythemia vera would be highly desirable; however, none exists. The value of quantization of neutrophil PRV-1 mRNA, platelet c-mpl expression, in vitro assays of erythroid progenitor cells, serum erythropoietin levels, establishing clonality in female subjects using assays employing X-chromosome-based polymorphism assays, and the progress in the chromosomal location of the gene is discussed. Integration of this information underlies the complexity of the molecular biology of polycythemia vera and indicates likely interaction of multiple genetic events in the genesis of polycythemia vera.
SUMMARY
The existence of family clustering of PV may facilitate the search for PV molecular basis. Only collaborative interaction of clinical researchers and laboratory scientists will lead to meaningful progress in determining the molecular basis of PV.
Topics: Diagnosis, Differential; Humans; Hypoxia; Mutation; Polycythemia; Polycythemia Vera
PubMed: 15725900
DOI: 10.1097/01.moh.0000154029.05396.d2 -
Expert Review of Hematology Apr 2023Erythrocytosis is associated with an elevation of the hemoglobin level above 16.5 g/dL in men and above 16 g/dL in women and an elevation of the hematocrit level above... (Review)
Review
INTRODUCTION
Erythrocytosis is associated with an elevation of the hemoglobin level above 16.5 g/dL in men and above 16 g/dL in women and an elevation of the hematocrit level above 49% in men and > 48% in women. In primary erythrocytosis, the defect is a clonal disorder in the myeloid compartment of the bone marrow, leading to an increased red cell production. Secondary erythrocytosis is the result of external stimuli to the bone marrow, leading to the production of red cells in excess. Secondary erythrocytosis is more common than primary erythrocytosis and has a broad differential diagnosis.
AREAS COVERED
This review will discuss secondary erythrocytosis, its causes, clinical presentation, and both diagnostic and therapeutic approaches.
EXPERT OPINION
Although secondary erythrocytosis is more common than PV, there are still challenges and difficulties associated with the distinction between these two conditions. Moreover, there is a paucity of data and guidance when it comes to the management of certain congenital and acquired conditions. A pragmatic approach is recommended in order to identify the cause for this condition. Treatment should be directed at the management of the underlying cause.
Topics: Male; Humans; Female; Polycythemia; Bone Marrow; Erythrocytes; Diagnosis, Differential; Erythropoietin
PubMed: 36927204
DOI: 10.1080/17474086.2023.2192475 -
Seminars in Fetal & Neonatal Medicine Aug 2008Neonatal polycythemia and hyperviscosity are defined as a hematocrit > or =65% and a viscosity value >2 standard deviations greater than the norm. Although polycythemia... (Review)
Review
Neonatal polycythemia and hyperviscosity are defined as a hematocrit > or =65% and a viscosity value >2 standard deviations greater than the norm. Although polycythemia can reflect normal fetal adaptation, it has been thought to be responsible for abnormalities in the neonate. Polycythemia and hyperviscosity are associated with blood-flow changes in some organs, which alter their function. Partial exchange transfusion (PET) has been used to treat both symptomatic and asymptomatic patients. At present, no data support the use of PET in asymptomatic infants; the potential benefit in symptomatic infants depends on the symptoms. Studies of long-term neurodevelopmental status do not show any clear long-term benefits for PET. Crystalloids are as effective as colloids in PET and have the advantage of being cheaper and more readily available; also, they do not confer any risk of infection or anaphylaxis.
Topics: Blood Viscosity; Colloids; Exchange Transfusion, Whole Blood; Humans; Infant, Newborn; Isotonic Solutions; Polycythemia
PubMed: 18424246
DOI: 10.1016/j.siny.2008.02.003 -
Indian Journal of Pediatrics Jan 2002Polycythemia is defined as a venous hematocrit above 65%. The relationship between viscosity and hematocrit is almost linear till 65% and exponential thereafter.... (Review)
Review
Polycythemia is defined as a venous hematocrit above 65%. The relationship between viscosity and hematocrit is almost linear till 65% and exponential thereafter. Increased viscosity of blood is associated with symptoms of hypo-perfusion. The hematocrit in a newborn peaks at 2 hours of age and decreases gradually after that. The etiology of polycythemia is related either to intra-uterine hypoxia or secondary to fetal transfusion. Clinical features related to hyperviscosity may affect all organ systems and this entity should be screened for in high-risk infants. Polycythemia maybe symptomatic or asymptomatic and guidelines for management of both types are provided in the protocol.
Topics: Blood Viscosity; Hematocrit; Humans; Incidence; Infant, Newborn; Polycythemia
PubMed: 11876126
DOI: 10.1007/BF02723782 -
Current Opinion in Hematology Mar 1999This overview concentrates on familial and congenital polycythemias in the context of other polycythemic disorders, with emphasis on those with established molecular... (Review)
Review
This overview concentrates on familial and congenital polycythemias in the context of other polycythemic disorders, with emphasis on those with established molecular lesions. Recent advances in the regulation of erythropoiesis, as they may relate to polycythemic states, are discussed as a background for those well-defined polycythemic states wherein the molecular defect has not yet been elucidated. Primary familial congenital polycythemias and congenital and familial secondary polycythemias, including hemoglobin mutants, methemoglobinemias and congenital 2,3-bisphosphoglycerate deficiency, are discussed. The most common primary polycythemia, polycythemia vera, as well as the only likely endemic congenital secondary polycythemia, known as Chuvash polycythemia, are discussed.
Topics: Animals; Biosensing Techniques; Erythropoiesis; Erythropoietin; Humans; Insulin-Like Growth Factor I; Oxygen; Polycythemia; Receptors, Angiotensin; Receptors, Erythropoietin
PubMed: 10088640
DOI: 10.1097/00062752-199903000-00008 -
Pediatrics in Review Jan 2007
Review
Topics: Anemia, Neonatal; Blood Transfusion; Erythropoiesis; Hematologic Tests; Hemorrhage; Humans; Infant, Newborn; Polycythemia
PubMed: 17197458
DOI: 10.1542/pir.28-1-33 -
La Revue de Medecine Interne Jul 2016Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities... (Review)
Review
Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia.
Topics: Algorithms; Diagnosis, Differential; Erythrocytes; Hemoglobins; Humans; Polycythemia
PubMed: 26827274
DOI: 10.1016/j.revmed.2015.12.022