58 Primary and Secondary Erythrocytosis/Polycythemia Flashcards
Primary polycythemic disorders that have erythroid progenitors hypersensitive to erythropoietin (EPO)
- Polycythemia vera
- Primary familial and congenital erythrocytosis/polycythemia (PFCP)
- Chuvash erythrocytosis
Chuvash erythrocytosis, have erythroid progenitors that are hypersensitive to EPO, but also may have normal or even increased EPO levels despite the increased red cell volume.
(Parang both primary and secondary)
Refers to those conditions in which only erythrocytes are increased in number and describes a group of disorders characterized by an increased red cell volume brought about by enhanced stimulation of red cell production by circulating physiologic mediators, most commonly EPO
Secondary erythrocytosis
Secondary erythrocytosis: Appropriate erythrocytosis
- Pulmonary disease
- Eisenmenger complex
- High-altitude erythrocytosis
- Hemoglobins (Hbs) with increased affinity for oxygen
Secondary erythrocytosis: Inappropriate erythrocytosis
- EPO-secreting tumors
- High levels of insulin growth factor 1
- Cobalt and manganese toxicities
- Self-administration of EPO
- High levels of androgens or adrenocorticotropic hormone
- Increased presence of other stimulators of erythropoiesis (as in post–renal transplant erythrocytosis)
Relative erythrocytosis
- Diuretic use
- Dehydration from excessive sweating
- Gaisbock syndrome
- Stress erythrocytosis
The term used to depict enhanced red cell count or blood Hb values that is caused by reduced plasma volume, not increased red cell mass
Relative erythrocytosis
Not a true erythrocytosis and is designated spurious, apparent, or relative erythrocytosis
Hypertensive patients had plethora and an elevated red cell count but no splenomegaly
Erythrocytosis hypertonica or Gaisbock syndrome
Publicized as Quebec beer-drinkers’ cardiomyopathy
Shown to increase erythropoiesis at least in part by increasing EPO
Also described in patients with hip replacement implanted with metal-on-polyethylene prostheses
Cobalt-Induced Erythrocytosis
Cognitive deterioration, cardiomyopathy, hypothyroidism, and neuropathy; all are the clinical manifestations of prosthetic cobaltism
About 1% to 3% of all patients with pheochromocytoma or paraganglioma have erythrocytosis.
Rare patients with congenital erythrocytosis develop pheochromocytoma or paraganglioma; these are most likely caused by genomic mosaicism for
Gain of function of EPAS1 (hypoxia-inducible factor [HIF] 2α)
Syndrome of erythrocytosis, elevated erythropoietin and monoclonal gammopathy
TEMPI syndrome
(1) telangiectasias;
(2) elevated erythropoietin and erythrocytosis;
(3) monoclonal gammopathy;
(4) perinephric fluid collections; and
(5) intrapulmonary shunting
Syndrome defined as a persistent elevation of Hct at over 51%, is a relatively common condition found in approximately 5% to 10% of renal allograft recipients
Post–Renal Transplant Erythrocytosis
Post–renal transplant erythrocytosis usually develops within_______months after transplantation, despite persistently good function of the allograft, and resolves spontaneously within_________ years in about 25% of patients.
8–24 months
2 years
Factors that increase the likelihood of Post–Renal Transplant Erythrocytosis
- Lack of EPO therapy before transplantation
- History of smoking
- Diabetes mellitus
- Renal artery stenosis
- Low serum ferritin levels
- Normal or higher pretransplant EPO levels
The only known endemic congenital erythrocytosis in the world
Chuvash Erythrocytosis
Russia
Caused by germline rather than acquired somatic mutations
It is congenital and manifests autosomal dominant inheritance
The defect changes intrinsic responses of erythroid progenitors, and EPO levels are low
Primary Familial and Congenital Polycythemia/Erythrocytosis
Gene mutation in Primary Familial and Congenital Polycythemia/Erythrocytosis
Eythropoietin receptor (EPOR)
The first signal is initiated by conformation change-induced activation of ________________ and its phosphorylation and activation of a transcription factor, _____________________, which regulates erythroid-specific genes.
“on” signals
JAK (Janus type tyrosine kinase) 2
Signal transducer and activator of transcription (STAT) 5
Enzyme used in dephosphorylation of EPOR
The “off ” signal
Hematopoietic phosphatase (HCP), also known as SHP1
Evidence of increased thrombotic risk in secondary erythrocytoses is lacking with the exception of secondary erythrocytoses resulting from ____________________
Augmented HIF signaling
Evidence for HIF-induced prothrombotic changes in leukocytes is emerging
In a subset of Andean high-altitude native dwellers, namely Quechuas and Aymaras, erythrocytosis becomes excessive and often results in _______________________ with its associated constitutional symptoms and pulmonary hypertension.
Monge’s disease or chronic mountain sickness
In the normovolemic state, viscosity increases in a log-linear fashion as Hct increases, and the effect is particularly pronounced when the Hct rises above ________%.
50%
Arterial hypoxemia with erythrocytosis
Andean “classic” erythrocytosis
Arterial hypoxemia with normal venous Hb concentration
Tibetan erythrocytosis
Genes affected in Tibetan adaptation
EPAS1 gene
EGLN1 gene
EPAS1 gene
EGLN1 gene
EPAS1 gene: α subunit of HIF2
EGLN1 gene: prolyl hydroxylase 2 (PHD2)
The principal negative regulator of both HIF1 and HIF2
PHD2
Cause of Peruvian mining community of Cerro de Pasco (altitude, 4280 m) with excessive erythrocytosis
Toxic serum cobalt levels
Erythrocytosis of Eisenmenger Syndrome
It may not be the microcytosis per se that is detrimental but the ____________________, which then directly causes pulmonary vasoconstriction and enhanced pulmonary vascular pressure
Induced iron deficiency that inhibits PHD2 and increases HIF
Erythrocytosis is characterized by its association with extreme obesity and somnolence.
Pickwickian syndrome
