Ordering Guidance

Polycythemia vera should be excluded prior to testing as it is much more common than hereditary erythrocytosis and can be present even in young patients. A JAK2 V617F or JAK2 exon 12 variant should not be present. More sensitive variant-specific test for JAK2 V617F is highly recommended prior to ordering this test. Additionally, alpha and beta chain high-oxygen affinity hemoglobin variants should be excluded prior to ordering this test panel.

See Erythrocytosis Genotyping Comparison Chart for a comparison of erythrocytosis testing options.

Recommended Testing for JAK2 negative lifelong or familial elevated hemoglobin levels:

Tier 1: REVE2 / Erythrocytosis Evaluation, Blood

Tier 2: NHEP / Hereditary Erythrocytosis Gene Panel, Next-Generation Sequencing, Varies

The comprehensive panel (NHEP) is recommended for most patients with idiopathic erythrocytosis because HE can be associated with novel variants with low incidence.

This focused panel (NHEM) utilizes next generation sequencing to assay the most common genes associated with hereditary erythrocytosis (HE) when the comprehensive panel is not indicated. This panel's genes are similar to those assessed by the Sanger sequencing-based HEMP / Hereditary Erythrocytosis Mutations, Whole Blood reflex from REVE2 and, aside from deletion/duplication analysis, has limited value in the setting of a negative or non-diagnostic REVE2 or HEMP result.

For an evaluation including hemoglobin electrophoresis testing and a Sanger sequencing panel of hereditary erythrocytosis variant analysis of the most common gene regions associated with hereditary erythrocytosis in an algorithmic fashion, order REVE2.

The hemoglobin genes, HBA1/HBA2 and HBB, are not interrogated in this assay.

Multiple gene panels are available. For more information see Hereditary Erythrocytosis Gene Panel and Subpanel Comparison.

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Shipping Instructions

Necessary Information

1. Erythrocytosis Patient Information is strongly recommended but not required. Testing may proceed without the patient information; however, it aids in providing a more thorough interpretation. Ordering healthcare professionals are strongly encouraged to complete the form and send it with the specimen

2. If form is not provided, include the following information with the test request: clinical diagnosis, pertinent clinical history (ie, complete blood cell count results and relevant clinical notes), and differentials based on any previous bone marrow studies, clinical or morphologic presentation.

Specimen Required

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with whole blood testing. For information about testing patients who have received a bone marrow transplant, call 800-533-1710.

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days

Additional Information: To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred) < 24 hours/Ambient < 24 hours

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred) < 24 hours/Refrigerated <24 hours

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.