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Review
. 2021 Jun 3:17:577-587.
doi: 10.2147/TCRM.S205632. eCollection 2021.

Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions

Virginie Lemiale  1 , Sandrine Valade  1 , Eric Mariotte  1
Affiliations
Review

Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions

Virginie Lemiale et al. Ther Clin Risk Manag. .

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.

Keywords: caplacizumab; refractory; relapsing; rituximab; thrombotic thrombocytopenic purpura.

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Conflict of interest statement

Dr Virginie Lemiale reports they belong to a research group which received fees from gilead, MSD, Alexion, celgene, and baxter, and that biomerieux pay travel for congress, outside the submitted work. Dr Sandrine Valade reports personal fees from Sanofi and Gilead/Kite, and non-financial support from Pfizer, outside the submitted work. Dr Eric Mariotte reports personal fees from Sanofi, outside the submitted work. The authors reported no other potential conflicts of interest for this work.

Figures

Figure 1
Figure 1
Timeline of acute TTP management with favorable (green) and unfavorable (red) outcomes. Non/insufficient response is defined as failure to reach platelet rate >150G/L and/or LDH rate <1.5N and/or occurrence of new/progressive signs of ischemic organ involvement after 5 TPE sessions; Exacerbation is defined as recurrence of any sign of TTP after a phase of clinical response, up to 30 days after the end of therapy; Remission is defined as clinical response maintained over 30 days after cessation of therapy; Relapse is defined as the recurrence of any sign of TTP after remission (ADAMTS13 activity decrease or clinical/biological signs of thrombotic microangiopathy).
Figure 2
Figure 2
Pathophysiology, potential therapeutic targets and available therapy for the management of TTP.
Figure 3
Figure 3
Unresponsive TTP management algorithm.
See this image and copyright information in PMC

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