FAST4TMA - Rapid Hospital-Based and out-Patient ADAMTS13 Testing

Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy caused by the severe deficiency of ADAMTS13 ( a disintegrin and metalloproteinase with a thrombo spondin type 1 motif, member 13). The rapid recognition of a patient with iTTP is critical to starting effective treatment ¹, with ADAMTS13 testing results in <72 hours considered “ideal” for diagnosing TTP ² and is cost-effective when performed at a laboratory that can turn-around testing in <24 hours ³. In a patient in remission from iTTP, recommendations for surveillance ADAMTS13 testing are unclear, with ISTH guidelines offering no explicit time frame ¹ but the USTMA (United States Thrombotic Microangiopathy Alliance) recommending testing every 3 months once in remission ⁴. However, many hospitals are unable to provide ADAMTS13 testing in-house and patients may not have access to regular out-patient ADAMTS13 monitoring. As part of the USMTA's grassroots efforts to serve patients with TMA, a first-ever program was launched to provide a free and rapid ADAMTS13 testing, i.e., <24-hours upon sample receipt. Both hospitalized and out-patients are eligible, including an option for mobile phlebotomy for patients unable to have testing performed through a laboratory. This abstract represents the preliminary results of this ground-breaking program.

Methods: The USTMA was founded in 2019 and is currently the only organization serving patients with TMA, composed of 20 academic research sites. Following a survey of member patients asking if free ADAMTS13 testing would be beneficial that was overwhelmingly positive, a collaborative partnership with Machaon Diagnostics was established. ADAMTS13 activity with reflex inhibitor and antibody testing occurs the same day upon sample receipt, with results made immediately available to the ordering physician. Out-patient testing is performed either through the request of an iTTP patient (and ordered through their treating physician) or made by an ordering physician. In the out-patient setting, either a kit is mailed to the patient to be drawn at their local laboratory, or in cases of iTTP patients who are unable to travel to a laboratory, a mobile phlebotomy unit can be dispatched to their residence.

Results: An initial survey asking, “If you could get ADAMTS13 drawn at home, for free, would you?” elicited a response of “Yes” from 90% of respondents (n=104/130) within 72 hours. Following the creation of the “FAST4TMA” (Fast, Accurate, Simple Testing for TMA) program, it was announced on the USTMA website and through social media. Currently n=22 patients have requested out-patient ADAMTS13 testing, n=20/22 already diagnosed with iTTP, consisting of 5/22 males, 14/22 females, 3/22 declining to answer, with n=9/22 requests occurring on the first day of the FAST4TMA program (06/25/23). The majority of patients, n-17/22, requested ADAMTS13 testing via a mobile phlebotomy unit.

Discussion: In this initial analysis of the FAST4TMA program, we show that a patient-centered out-patient program that is free and able to provide testing at home is eagerly desired by patients. This will have the potential to detect early immunologic relapses, preventing clinical relapses. While in-patient testing has not yet been performed at the time of writing, it is anticipated that this will also provide benefits to TMA patients, particularly in removing barriers to rapid ADAMTS13 testing.

References:

• J Thromb Haemost. 2020;18:2496-2502.

• Blood (2020) 136 (Supplement 1): 5-6

• Vox Sang. 2020 Jul;115(5):433-442.

• USTMA. Out-patient management of TTP. https://www.ustma.org/outpatient-management-ofttp.