Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse

Abstract

Summary Idiopathic thrombotic thrombocytopenic purpura (TTP) is characterized by frequent recurrences. Effective screening for relapses will enable intervention prior to overt episodes of TTP. The present study used a modified assay to detect ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13) activity as low as 0·5%. This analytical improvement permits adequate measurement of ADAMTS13 activity levels in 97% of remission samples used for statistical modelling. ADAMTS13 activity and ADAMTS13 antibody (IgG) were measured in 157 serial samples prospectively collected from 24 TTP patients during periods of clinical remission. These patients were followed‐up quarterly for an average of 23 months, during which time nine episodes of TTP relapse occurred among six patients. Finally, logistic regression modelling was used to define the relationship between ADAMTS13 activity levels (0·5–100%) and the probability of TTP relapses. Our data demonstrated that lower ADAMTS13 activity and younger age were significantly associated with higher risk of relapse in the 3 months after specimens were taken. In contrast, ADAMTS13 antibody IgG levels were not predictive of TTP relapses. Identification of low ADAMTS13 activity during clinical remission as a key risk factor for TTP relapses provides a new screening strategy to identify patients who may benefit from prophylactic therapy prior to disease relapses.

High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study

“…On this basis, there is general agreement that all patients in the acute phase have to receive the most effective treatment [21], and we suggest that, at least presently, the best option is represented by concomitant PE and high dose corticosteroids. At the opposite, three clinical studies clearly showed that patients with severe ADAMTS13 deficiency during remission have a much higher likelihood of relapse [22][23][24]. Since reports of single patients or small case series suggested that chimeric anti-CD20 monoclonal antibodies or cyclosporine help to restore normal ADAMTS13 activity and prevent recurrences, it may be that administration of these drugs to patients with a persistent defect of ADAMTS13 improves their long-term prognosis.…”

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

“…Inhibitory auto-antibodies identified during the acute episode may be associated with a worse prognosis. Once patients are in remission, severe protease deficiency or the presence of inhibitors is associated with an increased risk of relapse [94] . Congenital TTP occurs due to mutations in ADAMTS13 [95] .…”

Principles of Separation

“…The "idiopathic" acquired form of thrombotic thrombocytopenic purpura (TTP) is considered to be an autoimmune condition caused by formation of inhibitory autoantibodies (usually IgG) against the ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs-13) protease (25)(26)(27)(28)(29)(30). ADAMTS13 is the vWf-cleaving metalloprotease that is deficient in activity either by a congenital genetic mutation or an acquired autoimmune condition in TTP (25,28,29).…”