Background & Aim

Thrombotic thrombocytopenic purpura (abbreviated TTP) is a rare complex blood clotting disorder presenting itself by blood clots in small and the smallest blood vessels, leading to multiple organ damage and death in 90% of cases when left untreated.

For the most part we now distinguish between two forms, acquired TTP and congenital (= hereditary or familial) TTP. The congenital form is also called Upshaw-Schulman Syndrome (abbreviated USS), having been named after those who first described it. Upshaw-Schulman Syndrome is caused by genetic defects (mutations) in the ADAMTS13 (= Von Willebrand factor-cleaving protease) gene. This results in functional ADAMTS13 no longer being able to be formed. Hence, ADAMTS13 activity that can be measured in plasma of Upshaw-Schulman Syndrome patients amounts to less than 5% of normal levels.

Various case reports about individual patients have been published since the Von Willebrand factor-cleaving protease (ADAMTS13) and the connection between a serious ADAMTS13 deficiency and TTP have been discovered. Based on this, we estimate that there are currently approximately 150 families with known Upshaw-Schulman in the world. Unfortunately, since too little is known about Upshaw-Schulman Syndrome at this time, the disease is often diagnosed too late or not at all and many patients or their siblings have either died or suffered extremely serious, permanent organ damage from it. This is all the more unfortunate since acute TTP episodes in Upshaw-Schulman Syndrome patients can be successfully treated with simple plasma infusions. Today, there are numerous patients receiving plasma infusions every 2-3 weeks to prevent recurring episodes and living normal lives. The question remains open as to whether all patients should receive this type of preventative treatment, or perhaps certain specific situations warrant the use of some other therapy that may not be as effective in reducing the risk of an episode’s occurring (and what would these specific situations be?).

The aim of the study is to gather information as precisely as possible concerning the course of illness, factors that may trigger episodes (i.e. pregnancy, infections, etc.), plasma therapy and other treatments from as many patients with Upshaw-Schulman Syndrome. During a second step, the information gathered is to be used in development recommendations on therapies. Since it seems possible that the clinical course is influenced by genetic factors (e.g. the ADAMTS13 mutations, Von Willebrand factor level, etc., as the case may be), familial factors, or event transient and environmental factors (taking medications, pregnancy, etc.), these factors will be investigated using a questionnaire, laboratory assessments, and information from family members.

The long-term aim of the study is to build a network, including a knowledge platform, to exchange experiences on therapy, on the occurrence of side-effects during treatment, and on long-term progress, thereby improving treatment and prevention for affected patients. Treating physicians and affected patients will have access to the knowledge platform.

For more detailed information please visit clinicaltrials.gov (NCT01257269).