Test Catalog

Test Id : REVEI

Not Orderable

Erythrocytosis Interpretation

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Interpretation of Erythrocytosis Evaluation profile test

 

Definitive, comprehensive, and economical evaluation of an individual with JAK2-negative erythrocytosis associated with lifelong sustained increased hemoglobin or hematocrit

Method Name
A short description of the method used to perform the test

Only orderable as part of a profile. For more information see REVE2 / Erythrocytosis Evaluation, Blood.

 

Medical Interpretation

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Erythrocytosis Interpretation

Aliases
Lists additional common names for a test, as an aid in searching

BPGM

Chuvash Polycythemia

Congenital erythrocytosis

Congenital polycythemia

EGLN1

EPAS1

EPOR

Erythrocytosis

Familial erythrocytosis

Familial polycythemia

HBA1

HBA2

HBB

Hereditary erythrocytosis

Hereditary polycythemia

HIF2

High oxygen affinity hemoglobin

HOA hemoglobin

PHD2

Polycythaemia

Polycythemia

Primary familial erythrocytosis

Primary familial polycythemia

VHL

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole Blood EDTA Refrigerated 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Interpretation of Erythrocytosis Evaluation profile test

 

Definitive, comprehensive, and economical evaluation of an individual with JAK2-negative erythrocytosis associated with lifelong sustained increased hemoglobin or hematocrit

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Erythrocytosis (polycythemia) is identified by a sustained increase in hemoglobin or hematocrit. An isolated increase in red blood cell count (in the absence of chronic phlebotomy or coincident iron deficiency) may occur in thalassemia or other causes and does not indicate erythrocytosis. Erythrocytosis may occur as a primary disorder, due to an intrinsic defect of bone marrow stem cells, or secondary, in response to increased serum erythropoietin (EPO) levels. Secondary erythrocytosis is associated with a number of disorders, including chronic lung disease, chronic increase in carbon monoxide, cyanotic heart disease, high-altitude living, kidney cysts and tumors, hepatoma, and other EPO-secreting tumors. Rare plasma cell dyscrasia-associated syndromes such as POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) and TEMPI (telangiectasias, elevated EPO and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) can be associated with increased hemoglobin levels. When these causes of secondary erythrocytosis are excluded, a heritable cause involving hemoglobin or erythrocyte regulatory mechanisms may be present. It is important to differentiate polycythemia vera (PV) from heritable causes of erythrocytosis, the latter of which can be passed to progeny but does not carry the risks of clonal evolution or marrow fibrosis associated with PV.

 

The most common cause of hereditary erythrocytosis is the presence of a high-oxygen-affinity (HOA) hemoglobin variant. A subset of hemoglobins with increased oxygen (O2) affinity result in clinically evident erythrocytosis caused by decreased O2 unloading at the tissue level. Many are asymptomatic; however, some patients have recurrent headaches, dizziness, fatigue, and restless legs. A subset of patients experience thrombotic episodes. Affected individuals can be plethoric, and many are misclassified as polycythemia vera, particularly prior to more recent genetic testing availability. The O2-dissociation curve is left-shifted (p50 values are decreased) in HOA variants. Changes to the amino acid sequence of the hemoglobin molecule may distort the protein structure, affecting O2 transport or unloading and the binding of 2,3-bisphosphoglyceric acid (2,3-BPG). 2,3-BPG stabilizes the deoxygenated state of hemoglobin. Therefore, a decrease in the 2,3-BPG concentration results in greater O2 affinity of the normal hemoglobin molecule. Rare cases of erythrocytosis have been associated with a reduction in 2,3-BPG formation. This is due to variants in the converting enzyme, bisphosphoglycerate mutase (BPGM). Truncating variants in the erythropoietin receptor gene, EPOR, have been shown to be a cause of the autosomal dominant primary familial and congenital polycythemia (OMIM 133100).

 

In addition, O2-sensing pathway variants, EPAS1(HIF2A) (OMIM 611783); EGLN1(PHD2) (OMIM 609820), and VHL (OMIM 263400) cause hereditary erythrocytosis, and a subset are associated with pheochromocytoma and paragangliomas. All have shown an autosomal dominant pattern of inheritance, except VHL-associated erythrocytosis, which is an autosomal recessive disorder. Homozygous VHL R200W alterations have been shown to be causative of Chuvash polycythemia, an endemic heritable erythrocytic disorder first described in Russia but subsequently found in other ethnic groups. The prevalence of causative variants in EPOR and the O2-sensing pathway genes is unknown; however, in our experience, they are less prevalent than genetic variants that cause HOA hemoglobin variants and are much less prevalent than polycythemia vera. Because there are many causes of erythrocytosis, an algorithmic and reflexive testing strategy is useful for evaluating these disorders. Initial JAK2 V617F alteration testing and serum EPO levels are useful. Importantly, a significant subset of HOA hemoglobin variants can be electrophoretically silent on multiple routine screening platforms; however, most, and possibly all, HOA hemoglobin variants can be identified with addition of the intact mass spectrometry method. Our extensive experience with these disorders allows an economical, comprehensive evaluation with high sensitivity.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Only orderable as part of a profile. For more information see REVE2 / Erythrocytosis Evaluation, Blood.

 

Definitive results and an interpretative report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

The evaluation includes testing for a hemoglobinopathy. Reflex testing for EPOR, EGLN1 (PHD2), EPAS1 (HIF2a), VHL, and BPGM will be performed as needed.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

No significant cautionary statements

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Patnaik MM, Tefferi A. The complete evaluation of erythrocytosis: congenital and acquired. Leukemia. 2009;23(5):834-844

2. McMullin MF. The classification and diagnosis of erythrocytosis. Int J Lab Hematol. 2008;30(6):447-459

3. Percy MJ, Lee FS. Familial erythrocytosis: molecular links to red blood cell control. Haematologica. 2008;93(7):963-967

4. Huang LJ, Shen YM, Bulut GB. Advances in understanding the pathogenesis of primary familial and congenital polycythaemia. Br J Haematol. 2010;148(6):844-852

5. Maran J, Prchal J. Polycythemia and oxygen sensing. Pathol Biol. 2004;52(5):280-284

6. Lee F. Genetic causes of erythrocytosis and the oxygen-sensing pathway. Blood Rev. 2008;22(6):321-332

7. Merchant SH, Oliveira JL, Hoyer JD, Viswanatha DS. Erythrocytosis. In: His ED, ed. Hematopathology. 2nd ed. Elsevier Saunders; 2012: 722-723

8. Zhuang Z, Yang C, Lorenzo F, et al. Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia. N Engl J Med. 2012;367(10):922-930

9. Oliveira JL, Coon LM, Frederick LA, et al. Genotype-phenotype correlation of hereditary erythrocytosis mutations, a single center experience. Am J Hematol. 2018. doi:10.1002/ajh.25150

10. Gangat N, Oliveira JL, Hoyer JD, Patnaik MM, Pardanani A, Tefferi A. High-oxygen-affinity hemoglobinopathy-associated erythrocytosis: Clinical outcomes and impact of therapy in 41 cases. Am J Hematol. 2021;96(12):1647-1654. doi:10.1002/ajh.26375

11. Gangat N, Oliveira JL, Porter TR, et al. Erythrocytosis associated with EPAS1(HIF2A), EGLN1(PHD2), VHL, EPOR or BPGM mutations: the Mayo Clinic experience. Haematologica. 2022;107(5):1201-1204. doi:10.3324/haematol.2021.280516

Method Description
Describes how the test is performed and provides a method-specific reference

A hematopathologist expert in these disorders evaluates the case, appropriate tests are performed, and an interpretive report is issued.

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 25 days if structural or molecular studies are required.

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

Not Applicable

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83020-26

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
REVEI Erythrocytosis Interpretation 59466-3
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
608426 Erythrocytosis Interpretation 59466-3
608440 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | PHP Pdf | CMS Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports