Towards a rapid diagnostic test for thrombotic thrombocytopenic purpura

Thrombotic Thrombocytopenic Purpura (TTP) is an orphan disease that yearly affects 10 out of 1 000 000 people worldwide. Although no Belgian patient registry exists, it can be estimated that (based on French data) in the last 15 years, 150 new TTP patients arose. Upon an acute TTP episode, patients arrive in the hospital with various complaints (purpura, fever, haemolytic anaemia, neurological manifestations, renal dysfunction…), which impedes a fast and correct diagnosis and therefore leads to an initial misdiagnosis for 20% of TTP patients. A fast and correct diagnosis is crucial in the patients’ treatment as immediate plasma exchange therapy can lower the mortality from 90% to 10 - 20%. Patients with thrombotic microangiopathies (TMAs) that are not linked with TTP also benefit from a fast diagnostic TTP test, as this can avoid the sometimes unnecessary plasma exchange in their specific condition. Acute phase TTP is characterized by an ADAMTS13 activity lower than 10%, which makes it a unique marker for TTP. Nowadays this ADAMTS13 activity is tested in specialized centres, which causes the results to be only known 3 to 5 days after shipment. This project wants to establish a fast diagnostic assay that can diagnose TTP in only 20 minutes. This has advantages for both acute phase diagnosis and follow-up of TTP patients that are in remission. The diagnostic assay will use the Fiber Optic Surface Plasmon Resonance (FO-SPR, FOx Biosystems) technique to measure ADAMTS13 activity, auto-ADAMTS13 antibody levels and ADAMTS13 antigen levels in patient’s plasma/serum. Next, precoating of the biosensor will reduce the assay time to about 20 minutes (as future goal). Afterwards the assay will be adjusted for whole blood analysis and additionally the possibility of TTP diagnosis starting from dried blood spots will be assessed and developed.