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Test Code GNADM Hereditary Thrombotic Thrombocytopenic Purpura, ADAMTS13 Gene, Next-Generation Sequencing, Varies


Ordering Guidance


This test is designed to detect disease-causing variants in the ADAMTS13 gene and to be utilized for genetic confirmation of a clinical diagnosis of hereditary thrombotic thrombocytopenic purpura (TTP). Genetic testing for hereditary TTP should only be considered if a patient’s clinical presentation and initial ADAMTS-13 activity and functional inhibitor screens indicate a diagnosis.

 

This test does not measure ADAMTS-13 activity or the presence/absence of inhibitors. For assessment of ADAMTS-13 activity and inhibitor status, order ADM13 / ADAMTS13 Activity and Inhibitor Profile, Plasma.

 

Testing for the ADAMTS13 gene as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies

 

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the ADAMTS13 gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


Rare Coagulation Disorder Patient Information is required. Testing may proceed without the patient information. However, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send it with the specimen.



Specimen Required


Specimen Type: Whole blood

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

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


Forms

1. Rare Coagulation Disorder Patient Information (T824) is required.

2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

Useful For

Evaluating hereditary thrombotic thrombocytopenic purpura (TTP) in patients with a personal or family history suggestive of thrombotic microangiopathy

 

Confirming a hereditary TTP diagnosis with the identification of known or suspected disease-causing alteration(s) in the ADAMTS13 gene

 

Determining the disease-causing alterations within the ADAMTS13 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of hereditary TTP

 

Identifying the causative alterations for genetic counseling purposes

 

Prognosis and risk assessment based on the genotype-phenotype correlations

 

Carrier testing for close family members of an individual with a diagnosis of hereditary TTP

 

This test is not intended for prenatal diagnosis.

Genetics Test Information

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the ADAMTS13 gene associated with hereditary thrombotic thrombocytopenic purpura (TTP). See Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for hereditary TTP.

Testing Algorithm

The clinical workup for hereditary thrombotic thrombocytopenic purpura (TTP)  should begin with a plasma ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats) activity assay performed on a specimen collected before initiation of plasma therapy.

 

Clinical scoring systems, such as the PLASMIC score, may assist in providing guidance for the necessity of ADAMTS-13 activity testing.(1)

 

Genetic testing for hereditary TTP is indicated if:

-ADAMTS-13 activity is less than 10% and a functional inhibitor screen as measured by the Bethesda assay is negative (defined as less than 0.4 Bethesda units)

-Non-TTP medical conditions that may be associated with severe ADAMTS-13 deficiency (≤10%) have been excluded, eg, hemolytic uremic syndrome, hematopoietic stem cell and solid-organ transplantation, liver disease, disseminated intravascular coagulation, malignancy, viral infection (eg, HIV), sepsis, pregnancy (preeclampsia/eclampsia or HELLP [hemolysis, elevated liver enzymes and low platelets] syndrome), and medications, such as antiplatelet agents, calcineurin inhibitors, and certain chemotherapeutics

 

International expert groups have provided recommendations on best practices for ADAMTS-13 assays in clinical laboratories and established testing algorithms for the identification of TTP.(2,3)

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

ADAMTS13 Gene, Full Gene NGS

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome or congenital TTP (cTTP), is a rare blood condition associated with germline variants in the ADAMTS13 gene. It is inherited in an autosomal recesssive manner with variable expressivity.(4)

 

Hereditary TTP is characterized by a severe deficiency of the ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 13) protease resulting in the abnormal accumulation of ultra-large von Willebrand factor multimers, which are thought to aggregate with platelets to form occlusive microvascular platelet-rich thrombi.(3-5)

 

Systemic platelet thrombi lead to the classic pentad of TTP findings: thrombocytopenia, microangiopathic hemolytic anemia (intravascular hemolysis and presence of peripheral blood schistocytes), fever, neurologic symptoms (ischemic attack and stroke), and kidney dysfunction. While some individuals with hereditary TTP may have symptoms that present at birth, others can remain asymptomatic for decades. Although patients are at significant risk for complications of microvascular thrombosis throughout their lives, two periods appear to be associated with particularly severe risk: the first days of life and pregnancy.(5,6)

 

Acquired, immune-mediated TTP (caused by the presence of autoantibodies to ADAMTS-13) is more common than hereditary TTP and can be distinguished through ADAMTS-13 antibody or inhibitor assays.(3)

 

Several other non-TTP causes of thrombotic microangiopathy and severe ADAMTS-13 deficiency should be excluded prior to genetic testing, including hemolytic uremic syndrome, hematopoietic stem cell and solid-organ transplantation, liver disease, disseminated intravascular coagulation, malignancy, viral infection (eg, HIV), sepsis, pregnancy (preeclampsia/eclampsia or HELLP [hemolysis, elevated liver enzymes and low platelets] syndrome), and medications, such as antiplatelet agents, calcineurin inhibitors, and certain chemotherapeutics.(3,7,8)

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(10) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Day(s) Performed

Varies

Report Available

28 to 42 days

Specimen Retention Time

Whole blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81479

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GNADM ADAMTS13 Gene, Full Gene NGS 99960-7

 

Result ID Test Result Name Result LOINC Value
619230 Test Description 62364-5
619231 Specimen 31208-2
619232 Source 31208-2
619233 Result Summary 50397-9
619234 Result 82939-0
619235 Interpretation 69047-9
619236 Additional Results 82939-0
619237 Resources 99622-3
619238 Additional Information 48767-8
619239 Method 85069-3
619240 Genes Analyzed 82939-0
619241 Disclaimer 62364-5
619242 Released By 18771-6