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ADAMTS13 Activity with Reflex to ADAMTS13 Inhibitor

Test code(s) 14532

Question 1. What method is used for the activity assay?

A chromogenic, enzyme-linked immunosorbent assay (ELISA) method is used.

Question 2. What interfering substances affect the results of this assay?

Bilirubin >20 mg/dL or hemolysis >1500 mg/dL will interfere with this assay.

Question 3. What prompts reflex to ADAMTS13 inhibitor testing?

Inhibitor testing is performed (at additional charge) if the ADAMTS13 activity is ≤30%.

Question 4. What method is used for the inhibitor assay?

ADAMTS13 inhibitors are measured using the same ELISA method. The patient’s sample is heat-inactivated and mixed with an equal volume of pooled normal plasma (PNP) before testing. After testing, the residual activity is calculated, and the inhibitor concentration is expressed in Bethesda equivalent units (BEUs).

ADAMTS13 inhibitors are generally IgG antibodies to the ADAMTS13 molecule and are pathologic because they inactivate ADAMTS13 activity. Quantitative assays for ADAMTS13 antibodies exist, but they do not address the inhibitory activity of the antibody. Antibody tests are also not highly specific for the presence of ADAMTS13 inhibitors: up to 4% of healthy individuals and 13% of patients with systemic lupus erythematosus have detectable levels of ADAMTS13 antibodies.1,2

Question 5. How does plasma exchange affect the assay?

Plasma exchange may raise the observed ADAMTS13 activity and lower the inhibitor level.

Question 6. What if my patient is in remission but has low levels of ADAMTS13 activity?

Several studies have associated decreased ADAMTS13 levels and/or a persistent inhibitor during remission with risk of recurrence.3

Question 7. What is Upshaw-Schulman syndrome?

Upshaw-Schulman syndrome is a rare, congenital deficiency of ADAMTS13. Patients with this condition may present with episodes of thrombotic thrombocytopenic purpura (TTP) during childhood or pregnancy. The syndrome may also be the cause of unexplained thrombocytopenia or hemolysis in adults. In patients with Upshaw-Schulman syndrome, severe deficiency of ADAMTS13 activity may persist during remission.

Question 8. Which drugs are associated with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)?

The following have been associated with drug-induced TTP/HUS4,5:

  • Chemotherapeutic agents (eg, mitomycin-C, deoxycoformycin, α-interferon, gemcitabine, cisplatin)
  • Quinine
  • Calcineurin inhibitors (eg, cyclosporine, tacrolimus)
  • Thienopyridines (eg, ticlopidin, clopidogrel)

Question 9. How can I predict my patient’s ADAMTS13 activity if the results of an ADAMPTS13 activity test are not yet available, in order to decide whether to initiate plasma exchange?

The PLASMIC score may be helpful. This tool, developed and validated by researchers at Harvard and the University of Alabama, Birmingham, helps predict the risk of thrombotic microangiopathy with an ADAMTS13 activity level ≤10% (a level consistent with TTP).6 The PLASMIC scoring system, which incorporates a combination of laboratory and clinical findings, is summarized in Table 1.

For each finding, the patient is assigned a score of 1. All points are added up to generate a final PLASMIC score. Researchers have identified 3 risk categories for severe ADAMTS13 deficiency (activity ≤10%) based on the PLASMIC score (Table 2).6

The PLASMIC score is only a predictor of ADAMTS13 activity and should not be used to replace ADAMTS13 activity measurement. Instead, it should be used as a management tool to decide when to initiate plasma exchange. Note: this score has not been validated for children.7

References

  1. Masias C, Cataland SR. The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis. Blood. 2018;132(9):903-910. doi:10.1182/blood-2018-02-791533
  2. 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
  3. Bettoni G, Palla R, Valsecchi C, et al. ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2012;10(8):1556-1565. doi:10.1111/j.1538-7836.2012.04808.x
  4. Zakarija A, Bennet C. Drug-induced thrombotic microangiopathy. Semin Thromb Hemost. 2005;31(6):681-690. doi:10.1055/s-2005-925474
  5. Dlott JS, Danielson CFM, Blue-Hnidy DE, et al. Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review. Ther Apher Dial. 2004;8(2):102-111. doi:10.1111/j.1526-0968.2003.00127.x
  6. Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157-e164. doi:10.1016/S2352-3026(17)30026-1
  7. Williams LA, Marques MB. Pathology consultation on the diagnosis and treatment of thrombotic microangiopathies (TMAs). Am J Clin Pathol. 2016;145(2):158-165. doi:10.1093/ajcp/aqv086
This FAQ is provided for informational purposes only and is not intended as medical advice. A clinician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document FAQS.112 Version: 2
Version 2 effective 10/15/2020 to present
Version 1 effective 03/31/2016 to 10/15/2020
Version 0 effective 12/20/2013 to 03/30/2016