Abstract

A severely reduced ADAMTS13 activity due to inhibitory autoantibodies is a key feature of acquired thrombotic thrombocytopenic purpura (TTP), leading to the persistence of ultralarge VWF multimers, platelet aggregation and disturbance of microcirculation.

We followed 39 patients (8 male, 31 female, mean age 38 years) with clinical signs of TTP over a period between 5 days to 16 years and observed a total of 53 episodes of TTP. ADAMTS13 was measured with a collagen-binding assay and the FRETS-VWF73 based Technozym ADAMTS-13 assay (activity and antigen, respectively). ADAMTS13 inhibitor was measured with a modified Bethesda method with both the above mentioned assays, and with the Technozym ADAMTS-13 INH ELISA.

Thirty-one patients had autoimmune TTP, and 47 episodes of TTP were analyzed in these patients. In all acute episodes, ADAMTS13 activity was below the detection limit (<0.05 U/ml), but ADAMTS13:Ag levels were below 0.1 U/ml only in 55% of the episodes. Anti-ADAMTS13 antibodies were detected in all episodes. Treatment consisted of plasma exchange (89% of the episodes), immunoadsorption (6%), steroids (70%), rituximab (15%), splenectomy (11%), aspirin (74%). Median time to platelet count normalization was 20 days (range 4–91 days), not related to the ADAMTS13-inhibitor titer. Platelet counts, LDH levels, and reticulocyte counts were better predictors of treatment response. Plasma exchange did not directly influence ADAMTS13 levels or clear the inhibitors. Three patients died during the first episode (myocardial infarction), one in 2nd relapse. ADAMTS13 activity increased >0.2 U/ml in 66% of the episodes (after median 160 days). In the remaining cases anti-ADAMTS13 antibodies persisted during remissions for up to 2 years. In 3 cases the antibody reoccurred after initial normalization of ADAMTS13 activity, and clinical relapses followed. In total, 21 relapses were observed after a median of 46 months (range 1– 87), all associated with low ADAMTS13 levels. Rituximab was given in 7 cases of relapsing TTP and resulted in complete, durable clearance of the antibodies in 100%.

Determination of ADAMTS13-related parameters is useful to distinguish between autoimmune, hereditary, and secondary forms of TTP and to choose an appropriate therapy. It is also useful to predict the risk of relapse in patients with TTP in remission.

Disclosures: No relevant conflicts of interest to declare.

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