Acute Idiopathic Thrombotic Thrombocytopenic Purpura: Predicting Relapse and Response to Treatment.
Authors: Scully Marie , Starke Richard , Mackie Ian , Machin Samuel J. 
Published: October 2019

Abstract
Thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening disorder. Idiopathic, antibody mediated disease accounts for 70% of cases of acute TTP, primarily IgG. We reviewed all cases of acute idiopathic TTP with serial samples available from diagnosis, relapse and in clinical remission to determine if there were factors predicting relapse and the benefit of Rituximab in preventing further episodes. All 25 cases presented with ADAMTS 13 activity <5%(NR 66–126%), during an acute TTP episode. Group A received Rituximab: 3 males and 10 females, the median age of presentation was 36.5 years (17–57 years), 2 were Afro Caribbean and 11 Caucasian. The median number of relapses prior to Rituximab were 4; 2 patients had>10 episodes each. A number of immunosuppressive/immunomodulatory therapies had been used in the past. Patients had clinical organ ischaemic episodes, including significant neurological events in all. In 8/13 patients, ADAMTS 13 activity was <5% through out clinical remission. Relapse was associated with increased IgG antibody levels. Since receiving Rituximab there has been an increase ADAMTS 13 activity within the normal range for 6 patients and > 25% for the remaining 2. In 3/13, ADAMTS 13 activity was maintained in the normal range by cyclosporine (CSA), stopping therapy associated with an acute relapse within 4–6 weeks. We substituted CSA for weekly Rituximab therapy (375mg/m2) over 4 weeks. In 2 patients, ADAMTS 13 activity was recordable in the normal range in clinical remission. A decrease activity and increase IgG antibody was associated with relapse. All patients had IgG antibodies to ADAMTS 13, which are negative post Rituximab therapy. Median follow-up post Rituximab is 18 months (8–33). In 3 patients, a second course of Rituximab was given between 18–24 months. Preceding a further course of Rituximab, ADAMTS 13 activity fell from the normal range to < 10% in all 3 and in 1 patient there was an associated significant rise in IgG anti-ADAMTS antibody level. In group B-no Rituximab therapy: 4 male and 8 females, median age at presentation-41.5 years (27–63); 3 Afro Caribbean, 1 Asian and 8 Caucasian. All presented with clinically significant organ ischaemia, including neurological features in 11/12. Seven cases had only 1 acute episode, 2 cases had 2 acute episodes and 3 had a chronic relapsing course. In 4 cases, ADAMTS 13 activity <5% during clinical remission; relapse associated with increased anti-ADAMTS IgG antibodies. In 5 patients, ADAMTS 13 activity increased to 25–50% in clinical remission. Three cases have a chronic relapsing course; 2 maintain ADAMTS 13 activity>50% on CSA. The 3rd has normal activity and negative IgG titres in remission. In conclusion: There were no specific phenotypic characteristics predictive of relapse. Of the patients in clinical remission with ADAMTS 13 activity <5%, the risk of relapse is doubled and is associated with increased IgG antibody titre. In patients who received Rituximab, normalisation of ADAMTS 13 activity can be attained. However, this is not always sustained and relapse in 2 patients post Rituximab was associated with a decrease in activity before an increase in antibody titre. Therefore, monitoring of ADAMTS 13 activity/IgG antibody to ADAMTS 13 following an episode of acute TTP can predict patients most likely to relapse. Elective therapy with Rituximab can prevent acute clinical features. Substitution of CSA in patients with chronic relapsing disease with Rituximab prevents the need for ongoing therapy.