ADAMTS13 Activity with Reflex to ADAMTS13 Inhibitor

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

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

Inhibitor testing is performed (at additional charge) if the ADAMTS13 activity is ≤0.30 IU/mL.

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

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

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

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.

The following have been associated with drug-induced TTP/HUS^4,5:

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

The PLASMIC⁶ (Table) 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 ≤0.10 IU/mL (a level consistent with TTP).⁶ The PLASMIC scoring system incorporates a combination of laboratory and clinical findings, with each condition listed below adding 1 point to the score:

• Platelet count < 30 x 10⁹/L
• Hemolysis (reticulocyte count >2.5%, undetectable haptoglobin, or indirect bilirubin >2 mg/dL)
• No active cancer
• No history of solid-organ or stem-cell transplant
• Mean corpuscular volume < 90 fL
• International normalized ratio < 1.5
• Creatinine < 2.0 mg/dL

The risk of severe ADAMTS13 deficiency associated with each risk score, or risk score range, is shown below⁶:

• 0-4: low risk
• 5: intermediate risk
• 6 or 7: high risk
  

^{a Ranges are based on derivation from 2 separate validation cohorts; originally reported as the proportion of the individuals with ADAMTS13 activity <10%.}

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