(ATS13, ATS13 INHIB, ATS13 AB)
ADAMTS13, a serum protease that cleaves multimers of von Willebrand Factor into smaller oligomeric fragments. ADAMTS13 activity is severely reduced in acquired and congenital forms of thrombotic thrombocytopenic purpura (TTP), leading to very large circulating multimers of von Willebrand Factor, and may be moderately reduced in other conditions such as disseminated intravascular coagulation, sepsis, hepatic dysfunction, and pregnancy. Assessment of ADAMTS13 activity is an important component of the initial assessment of a patient with evidence for a thrombotic microangiopathy such as atypical hemolytic uremic syndrome (aHUS) and TTP, suggesting atypical hemolytic uremic syndrome if ADAMTS13 activity is normal or moderately reduced, and TTP if ADAMTS13 activity is severely reduced. ADAMTS13 testing will be offered in a reflex testing algorithm.
Each of the three tests in the panel requires 0.5mL of plasma (total of 1.5mL plasma or 3mL blood), and must be sent in a citrated (blue top) tube. The tests are listed in as ADAMTS13 Activity, ADAMTS13 Inhibition Test, and ADAMTS13 Inhibitor Antibody. Turnaround time for this assay is 24 hours during weekdays, to enhance the ability to make the diagnosis of TTP quickly and allow more rapid and appropriate intervention with definitive therapy, specifically plasmapheresis.
ADAMTS13 is a serum protease that cleaves ultralarge multimers of von Willebrand Factor (vWF) into smaller oligomeric subunits, thus regulating the interaction of platelets with vWF in the microvasculature. Absent or severely deficient (<10%) ADAMTS13 activity allows formation of platelet microthrombi, which in turn obstructs arterioles and capillaries, generating the clinical sequelae of TTP. ADAMTS13 activity is measured by Fluorescence Resonance Energy Transfer (FRET) using the substrate FRETS-VWF73 (Kokame et al, Br J Haematol. 2005 Apr;129(1):93-100).
In patients with thrombotic thrombocytopenic purpura (TTP). ADAMTS13 Activity may be severely decreased (<10%) in the presence of an inhibitor, typically an IgG autoantibody, but may also be severely decreased due to mutations in the ADAMTS13 gene leading to a quantitative or qualitative defect of the ADAMTS13 protein. To separate these entities, the presence of an inhibitor is determined by measuring the ability of heat-treated patient plasma to inhibit ADAMTS13 Activity as measured by FRET in normal plasma; inhibitor activity is expressed as percent inhibition of the ADAMTS13 Activity of pooled normal plasma. In this assay, 50% inhibition is roughly equivalent to 1.0 Bethesda unit/mL. Strong antibody-mediated inhibition of ADAMTS13 activity (>90%) is seen in approximately half of the patients with acquired or idiopathic TTP. The significance of milder ADAMTS13 inhibition is unclear, particularly when the overall ADAMTS13 level is not severely decreased. The assay used does not distinguish between antibody-mediated and non-specific ADAMTS13 inhibition.
1ml PPP frozen
Autoantibodies (typically IgG) that neutralize or enhance clearance of ADAMTS13 may severely inhibit ADAMTS13 activity and therefore allow the accumulation of ultralarge multimers of vWF in plasma, and ultimately adhesion to platelets in the microvasculature leading to the clinical sequelae of thrombotic thrombocytopenic purpura (TTP). These autoantibodies are believed to be the major cause for idiopathic TTP. This test detects and quantifies autoantibodies against ADAMTS13 by ELISA. Patients with idiopathic TTP usually require therapeutic plasma exchange to achieve clinical remission. Persistence of ADAMTS13 deficiency or an inhibitor/antibody during clinical remission suggests an increased risk for recurrence of symptomatic TTP.
Specimen requirements 1ml Serum frozen
ADAMTS13 activity, ADAMTS13 inhibition test, ADAMTS13 antibody level
This panel testing ADAMTS13 Activity utilizes a reflexive testing algorithm. ADAMTS13 Activity is always performed by Fluorescence Resonance Energy Transfer (FRET). If the ADAMTS13 Activity is less than or equal to 30%, the ADAMTS13 Inhibition Test is performed. If the amount of ADAMTS13 Inhibition is found to be greater than 30% , the ADAMTS13 Inhibiting Autoantibody is performed. Thrombotic thrombocytopenic purpura (TTP) is generally characterized by an ADAMTS13 Activity <10%.
1ml Serum frozen and 1ml PPP frozen