Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy secondary to a severely decreased A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats 13 (ADAMTS13) activity, resulting in the formation of widespread von Willebrand factor - and platelet-rich microthrombi. ADAMTS13 deficiency is mainly acquired through anti-ADAMTS13 autoantibodies in adults. With modern standards of care, unresponsive TTP has become rarer with a frequency of refractory/relapsing forms dropping from >40% to <10%. As patients with unresponsive TTP are at increased risk of mortality, prompt recognition and early therapeutic intensification are mandatory. Therapeutic options at the disposal of clinicians caring for patients with refractory TTP consist of increased ADAMTS13 supplementation, increased immunosuppression, and inhibition of von Willebrand factor adhesion to platelets. In this work, we focus on possible therapies for the management of patients with unresponsive TTP, and propose an algorithm for the management of these difficult cases.

Bortezomib, a promising alternative for patients with refractory or relapsed thrombotic thrombocytopenic purpura after rituximab treatment

“…With modern standards of treatment including therapeutic plasma exchange, corticosteroids, rituximab and caplacizumab, its refractory/ recurrent frequency has dropped from more than 40% to less than 10%, and mortality rate becomes less than 5%. 1 However, especially after rituximab these unresponsive or recurrent immune-mediated TTP (iTTP) patients are in a life-threatening and challenging condition. It is urgent for clinicians to find other effective immunomodulatory therapies to treat these patients.…”

“…Jie Yin 1,2,3 Hong Tian 1,2,3 Danqing Kong 1,2,3 Yun Li 1,2,3 Chengyuan Gu 1,2,3 Zhaoyue Wang 1,2,3 Depei Wu…”

Therapierefraktäre thrombotisch-thrombozytopenische Purpura

“…Insofern stellt unser Fall eines therapierefraktären Verlaufs eine extreme Ausnahme dieser beschriebenen Beobachtungen dar. In solchen Fällen wird in einzelnen Fallbeispielen eine häufigere Plasmapherese (2-mal täglich) beschrieben, oder der Einsatz von Bortezomib, die Gabe von Vincristin, Ciclosporin A oder eine Splenektomie [ 2 , 8 , 11 ]. Obwohl der Einsatz von Caplacizumab recht preisintensiv ist, sind fortlaufende Plasmapheresen mit einem hohen Verbrauch an Ressourcen (personell, technisch, v. a. aber an gefrorenem Frischplasma) verbunden, weswegen der Einsatz von Caplacizumab in Zukunft stets bei der Behandlung einer TTP mit in Erwägung gezogen werden sollte.…”

Self-limited thrombotic thrombocytopenic purpura

“…The treatment of TTP involves therapeutic plasma exchange (TPE) to replenish ADAMTS-13 and remove ADAMTS-13 inhibitor, administration of high-dose glucocorticoids, rituximab (anti CD-20 antibody), and in certain patients caplacizumab (anti-von Willebrand factor antibody) [4]. A successful response of TTP to these treatments is defined both clinically and serologically and often prompts a several stage response with regards to treatment of refractory disease [5,6]. Initial cure is frequently defined as a platelet measurement above 150 000 for two consecutive days after treatment with plasma exchange.…”