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HelpTest ID ADAMP ADAMTS13 Activity with Reflex Inhibitor Profile, Plasma
Ordering Guidance
Order the profile when considering a diagnosis of immune thrombotic thrombocytopenic purpura (iTTP), also known as acquired thrombotic thrombocytopenic purpura (aTTP). This diagnosis should be considered in a patient presenting with hemolytic anemia and thrombocytopenia. In patients with known iTTP/aTTP, the profile (rather than the single order ADAMTS13 activity) should be ordered if wanting to monitor presence of ADAMTS13 inhibitor.
Shipping Instructions
Send both vials in the same shipping container.
Specimen Required
Patient Preparation: Fasting preferred
Collection Container/Tube: Light-blue top (3.2% sodium citrate)
Submission Container/Tube: Plastic vials
Specimen Volume: 2 mL in 2 plastic vials each containing 1 mL
Collection Instructions:
1. Specimen must be collected prior to replacement therapy.
2. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing
3. Centrifuge, transfer all plasma into a plastic vial, and centrifuge plasma again.
4. Aliquot plasma (1 mL per aliquot) into 2 separate plastic vials, leaving 0.25 mL in the bottom of centrifuged vial.
5. Freeze plasma immediately (no longer than 4 hours after collection) at -20° C or, ideally, below -40° C.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. Each coagulation assay requested should have its own vial.
Specimen Stability Information: Frozen 2 years
Forms
1. If not ordering electronically, complete, print, and send one of the following with the specimen:
-Renal Diagnostics Test Request (T830)
-Coagulation Test Request (T753)
2. Coagulation Patient Information (T675)
Useful For
Assisting with the diagnosis of immune or acquired thrombotic thrombocytopenic purpura
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| ADAMS | ADAMTS13 Activity Assay, P | Yes | Yes |
| ADMI | ADAMTS13 Interpretation | No | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| ADMB | ADAMTS13 Inhibitor Titer, P | No | No |
| AADAM | ADAMTS13 Profile Interpretation | No | No |
Testing Algorithm
Testing begins with the ADAMTS13 activity assay to evaluate the percent activity. If the ADAMTS13 activity is less than 30%, the inhibitor titer and ADAMTS13 profile interpretation will be performed.
Method Name
ADAMS, ADMB: Fluorescence Resonance Energy Transfer (FRET)
ADMI, AADAM: Technical Interpretation
Reporting Name
ADAMTS13 Act w/Inhibitor Prof, PSpecimen Type
Plasma Na CitSpecimen Minimum Volume
2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma Na Cit | Frozen | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Thrombotic thrombocytopenic purpura (TTP), a rare (estimated incidence of 3.7 cases per million) and potentially fatal thrombotic microangiopathy syndrome, is characterized by a pentad of symptoms: thrombocytopenia, microangiopathic hemolytic anemia (intravascular hemolysis and presence of peripheral blood schistocytes), neurological symptoms, fever, and kidney dysfunction. A large majority of patients initially present with thrombocytopenia and peripheral blood evidence of microangiopathy and, in the absence of any other potential explanation for such findings, satisfy criteria for early initiation of plasma exchange, which is critical for patient survival. TTP may rarely be congenital (Upshaw-Shulman syndrome) but, far more commonly, is acquired. Acquired TTP may be considered primary or idiopathic (the most frequent type) or associated with distinctive clinical conditions (secondary TTP) such as medications, hematopoietic stem cell or solid organ transplantation, sepsis, and malignancy.
The isolation and characterization of an IgG autoantibody frequently found in patients with idiopathic TTP clarified the basis of this entity and led to the isolation and characterization of a metalloprotease called ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats), which is the target for the IgG autoantibody, leading to a functional deficiency of ADAMTS13. ADAMTS13 cleaves the ultra-high-molecular-weight multimers of von Willebrand factor (VWF) at the peptide bond Tyr1605-Met1606 to disrupt VWF-induced platelet aggregation. The IgG antibody prevents this cleavage and leads to TTP. Although the diagnosis of TTP may be confirmed with ADAMTS13 activity and inhibition studies, the decision to initiate plasma exchange should not be delayed pending results of this assay.
Reference Values
ADAMTS13 Activity Assay
≥70%
Although not verified, the pediatric (<1 years old) reference range could be similar to or lower than that of adults.
ADAMTS13 Inhibitor Titer
<0.5 BU
Interpretation
Less than 10% ADAMTS13 activity is highly indicative of thrombotic thrombocytopenic purpura (TTP) in an appropriate clinical setting. The presence of ADAMTS13 measurable Bethesda titer is most consistent with an acquired (autoimmune) TTP.
Cautions
This ADAMTS13 activity assay is an in vitro assay using a synthetic substrate peptide in a static liquid environment. The measured ADAMTS13 activity may not reflect the true in vivo biological ADAMTS13 activity.
Not all patients with a clinical diagnosis of idiopathic thrombotic thrombocytopenic purpura (TTP) have a severe ADAMTS13 deficiency. Conversely, patients with other non-TTP conditions may have a severe ADAMTS13 deficiency (≤10%). These conditions include hemolytic uremic syndrome, hematopoietic stem cell and solid organ transplantation, liver disease, disseminated intravascular coagulation, sepsis, pregnancy, and certain medication. Therefore, TTP remains a clinical diagnosis.
Interferences of the ADAMTS13 activity assay include high levels of endogenous von Willebrand factor, hyperlipidemia, hyperbilirubinemia (bilirubin concentration >30mg/dL), and cleavage by other proteases.
Samples collected in EDTA instead of 3.2% sodium citrate will result in artificially reduced ADAMTS13 activity.
Recent plasma exchange or plasma transfusion may falsely normalize ADAMTS13 levels, thus potentially masking the diagnosis of TTP.
The impact of ADAMTS13 levels and presence of inhibitors on overall survival, ultimate clinical outcome, responsiveness to plasma exchange, and relapse are still controversial. Therefore, clinical correlation is recommended.
Clinical Reference
1. Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood. 2008;112(1):11-18. doi:10.1182/blood-2008-02-078170
2. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood. 2010;116(20):4060-4069. doi:10.1182/blood-2010-07-271445
3. Upshaw JD Jr. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med. 1978;298(24):1350-1352. doi:10.1056/NEJM197806152982407
4. Chiasakul T, Cuker A. Clinical and laboratory diagnosis of TTP: an integrated approach. Hematology Am Soc Hematol Educ Program. 2018;2018(1):530-538. doi:10.1182/asheducation-2018.1.530
5. Mackie I, Mancini I, Muia J, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13. Int J Lab Hematol. 2020;42(6):685-696. doi.10.1111/ijlh.13295
Method Description
The ADAMTS13 activity is measured by a fluorescence resonance energy transfer-based assay using a synthetic fragment of von Willebrand factor as substrate. Cleavage of this small fragment by the ADAMTS13 protease generates fluorescence that is directly proportionate to the quantification of ADAMTS13 activity. (Package insert: ATS-13 ADAMTS13 Activity Assay 2.0. Immucor; 08/2023)
Day(s) Performed
Monday through Friday, Sunday
Report Available
1 to 3 daysTest 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
85397
85335 (if appropriate)