ADAMTS-13 may not predict disease or outcome in patients with Thrombotic Thrombocytopenic Purpura

Background The pathophysiology of Thrombotic Thrombocytopenia Purpura (TTP) has been questioned since described in 1924. In 1998, Tsai [1] and Furlan [2] demonstrated a relationship of low levels of ADAMTS-13 with an IgG inhibitor in acquired idiopathic TTP. This study reports on a series of TTP patients treated with solvent/detergent plasma (SDP) or cryosupernatant plasma (CSP) and focuses on the correlation of their presentation, clinical response and outcome with the levels of ADAMTS-13, the inhibitor and VWF multimers. Methods Plasma exchange was carried out in patients with the clinical diagnosis of acquired idiopathic TTP. ADAMTS-13 enzyme activity and inhibitor levels, VWF multimers and platelet count were analyzed in correlation with patient outcome. This RCT was intended to compare outcome in 280 patients treated either with cryosupernatant or solvent-detergent heated plasmas. The primary end point was survival at six months. Results Data on 61 TTP patients were obtained from 16 centres across Canada. The study was then closed prematurely due to removal of one of the interventional products from the market. ADAMTS-13 enzyme activity and inhibitor levels varied considerably among study participants. At baseline, only 12/49 (24.5%) had ≤ 10% enzyme activity and 20/49 (41%) had levels ≥ 80%; whereas 16/49 had ≥ 80% inhibitors; 19/49 had ≤ 10% inhibitors 18/49 (37%) had no inhibitors. No unusually large VWF multimers were identified in any of the patients at presentation. The 6-month, all-cause mortality rates for patients randomized to receive CSP vs. SDP were 3/34 (9%; 95% CI: 3%, 23%) and 1/27 (4%; 95% CI: 1%, 18%), respectively, with a difference of 5% (95% CI: -11%, 20%). Conclusion Although this study was underpowered to compare solvent/detergent vs. cryosupernatant plasma, our data suggest that ADAMTS-13 activity and inhibitor level at baseline cannot differentiate TTP response to plasma exchange therapy.