Publication Date:
2018-11-29
Description:
Introduction Autoimmune TTP (aTTP) is a rare life-threatening microangiopathy characterized by hemolytic anemia, thrombocytopenia, and severe ADAMTS-13 deficiency. Daily therapeutic plasma exchange (TPE) and preemptive use of rituximab have considerably improved patient outcome. However, a high proportion of patients still experience relapse and several studies are evaluating the role of ADAMTS-13 activity and its inhibitors to predict disease recurrence. In this study, in a large prospective cohort of aTTP patients, we aimed to characterize the therapeutic approach, the clinical outcome and the predictive variables of relapse. Methods From 2002 to 2018, 163 TTP cases were referred to our Centers. Blood samples were obtained from all patients at diagnosis. In 84 patients (58F/26M) samples were collected also during follow-up: 74 had autoimmune, 4 congenital, 3 drug-induced, and 3 BMT-related TTP. ADAMTS-13 activity and inhibitors by mixing studies (chromogenic assay), and anti-ADAMTS-13 Ab (ELISA) were measured in plasma. A complete ADAMTS-13 activity deficiency (15U/ml was considered positive. Hemoglobin (Hb), platelets (Plt), and hemolysis parameters (i.e. aptoglobin (apt), bilirubin, LDH, reticulocytes) were monitored during follow up. Treatment response was defined as: complete response (CR) = Plt〉150x109/L for at least 2 days and LDH normalization, lasting for 30 days; exacerbation = recurrent disease within 30 days after reaching CR; refractoriness = no treatment response by day 30. Data are expressed as median and range. Results All 74 patients with aTTP had complete ADAMTS-13 activity deficiency (0%, range 0-9) and high anti-ADAMTS-13 Ab (70 U/ml, 22-373). In acute phase, blood parameters were: Plt 2x109/L (12-49), Hb 8.8 g/dL (4.1-12.8), apt 5.5 mg/dL (0.1-44), and LDH 1688 U/L (312-7007). All patients were treated in first-line with TPE and high-dose corticosteroids (median n. TPE 9, 5-24). Vincristine, high-dose immunoglobulin and N-acetylcysteine were used in 9, 4, and 1 cases, respectively. Fifty-eight patients were evaluable for treatment response. Two early deaths were due to myocardial infarction and diffuse rectal ischemia after 7 and 10 days from diagnosis, respectively (unresponsive to 7 and 8 cycles of TPE). Twenty-five patients (43%) obtained a CR after a median time to response (mTTR) of 10 days (4-18) and a median number (n.) of TPE of 7 (5-14); 19 obtained a suboptimal response: 12 exacerbation (mTTR 31days (16-62), median TPE n. 14 (7-24)), and 7 refractory (mTTR 42.5 (27-86), median TPE n. 11 (8-19)). ADAMTS-13 activity, Ab, Pts, Hb and hemolysis parameters at diagnosis were not predictive for suboptimal response. Sixteen patients with a suboptimal response were treated with Rituximab, obtaining a CR in all cases. At remission, 55% of patients showed normal levels (〉50%) of ADAMTS-13, while 20% moderate (21-50%), 8.6% severe (10-20%), and 12% complete (
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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