Thrombotic Thrombocytopenic Purpura (TTP): Treatment

Thrombotic Thrombocytopenic Purpura (TTP): overview

This algorithm addresses treatment of acquired immune thrombotic thrombocytopenic purpura (TTP), defined by ADAMTS13 activity below 10%.

The acute episode is a medical emergency managed with daily plasma exchange (PLEX) until recovery, corticosteroids given together with PLEX for immunosuppression, and the anti-von Willebrand factor nanobody caplacizumab. Caplacizumab is supported by HERCULES, which showed reduced TTP recurrence and thromboembolic events and a shorter time to platelet response when added to plasma exchange and immunosuppression, making it the first targeted therapy approved for this condition. Rituximab, an anti-CD20 antibody, is used up front as a frontline adjunct for immunomodulation and also contributes to relapse prevention. For patients in remission, preemptive rituximab is given when ADAMTS13 activity falls, to prevent clinical relapse. The chart thus combines removal of the inhibitory antibody and replacement of ADAMTS13 through PLEX with targeted blockade of platelet adhesion and B-cell-directed immunosuppression.

Trials behind this algorithm

Plasma Exchange for TTP Rock GA et al, NEJM, 1991; PMID: 2062330
HERCULES Scully M et al, NEJM, 2019; PMID: 30625070

Background reading: Thrombotic microangiopathies (TTP, HUS) and PNH board review notes.

Thrombotic Thrombocytopenic Purpura (TTP): the algorithm in words

Starting point: Acquired TTP ADAMTS13 < 10% (immune). Full background: Thrombotic microangiopathies (TTP, HUS) and PNH notes.

Acute episode (first-line): Emergent: Plasma exchange (PLEX) (daily until recovery); Immunosuppress: Corticosteroids (+ PLEX); Anti-VWF: Caplacizumab (HERCULES).
Immunomodulation (first-line): Anti-CD20: Rituximab (frontline adjunct / relapse prevention).
Relapse prevention (second-line): Preemptive: Rituximab for falling ADAMTS13 (in remission).