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ABSTRACT: The assay for ADAMTS13 activity helps clinicians to confirm the clinical diagnosis of idiopathic thrombotic thrombocytopenic purpura. The clinical value of testing for the antigen level of ADAMTS13 protein is, however, less clear.
In this study, both ADAMTS13 antigen and activity levels were measured in 835 sequential samples from 40 consecutive patients who were followed for an average of 29 months throughout the course of acute episode plasma exchange treatment and clinical remission.
During acute episodes, ADAMTS13 activity was severely deficient while ADAMTS13 antigen levels were more variable, ranging from severely deficient to as high as within the reference range. A severe depletion of ADAMTS13 antigen level during acute disease was, however, statistically associated with disease mortality (P=0.0322). For patients who achieved initial clinical responses, ADAMTS13 antigen levels appeared to be restored faster than ADAMTS13 activity to the normal range. Further analysis demonstrated that the ADAMTS13 antigen level at the time of initial clinical recovery was significantly higher in the patients who subsequently achieved a sustained clinical remission than in the group who soon after had an exacerbation (P=0.0187).
Our data suggest that evaluation of ADAMTS13 antigen levels during the course of therapy and follow-up may offer additional useful information for the management of patients with thrombotic thrombocytopenic purpura.
Haematologica 05/2011; 96(10):1521-7. · 6.42 Impact Factor
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ABSTRACT: Approximately 40% of idiopathic thrombotic thrombocytopenic purpura (TTP) patients will suffer an exacerbation (recurrence of TTP within 30 d after their last plasma exchange (PE) procedure), but there are no data to predict who is at greater risk. We studied the clinical utility of demographic and ADAMTS13 biomarker data to predict the risk for exacerbation.
Forty-four acute episodes of idiopathic TTP from 26 patients were studied.
PE was performed plus either prednisone (1 mg/kg/d) or cyclosporin (2-3 mg/kg/d) as adjuncts. PE was continued daily until response (platelet count >150 000/microL and normalized lactate dehydrogenase) and tapered uniformly in all patients. ADAMTS13 biomarkers were studied prior to PE and after achieving a response, but within 7 d of the last PE.
African American race (AA) was associated with an increased risk for exacerbation (P = 0.046). ADAMTS13 at presentation was also significantly lower in patients experiencing an exacerbation (P = 0.0364). After adjusting for the race effect, ADAMTS13 remained marginally significant (P = 0.0569).
AA is significantly associated with an increased risk for exacerbations of TTP. These data also suggest that decreasing pretreatment ADAMTS13 activity was associated with an increased risk for exacerbation, even after accounting for the effect of race.
European Journal Of Haematology 09/2009; 83(6):559-64. · 2.61 Impact Factor
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ABSTRACT: Several reports have been published regarding the use of cyclosporine (CSA) in the treatment of idiopathic thrombotic thrombocytopenic purpura (TTP). We hypothesized that prophylactic CSA therapy may prevent recurrences in patients with a history of multiple relapses of TTP. Nineteen patients with idiopathic TTP were enrolled on prospective studies at Ohio State University between September 2003 and May 2007. Patients achieving remission remained on CSA therapy for 6 months, allowing us to evaluate the efficacy of CSA as prophylactic therapy. CSA was administered orally at a dose of 2-3 mg/kg in twice a day divided dose in all patients and continued for a total of 6 months. Long-term clinical follow-up with serial analysis of ADAMTS13 biomarkers during and after CSA therapy were performed to evaluate the efficacy of CSA as a prophylactic therapy. 17/19(89%) patients completed 6 months of CSA therapy in a continuous remission. Two patients relapsed during therapy with CSA and seven patients relapsed after discontinuing CSA therapy. Ten patients have maintained a continuous remission a median of 21 months (range, 5-46) after discontinuing CSA. The ADAMTS13 data suggest that CSA resulted in a significant increase in the ADAMTS13 activity during therapy with CSA. 8/9(89%) relapsing patients had severely deficient ADAMTS13 activity (<5%) suggesting this is a significant risk factor for relapse of TTP. These data support the hypothesis that prophylactic CSA improves the ADAMTS13 activity and may be effective at preventing relapses in patients at risk for recurrences of TTP.
American Journal of Hematology 09/2008; 83(12):911-5. · 4.67 Impact Factor
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ABSTRACT: 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.
British Journal of Haematology 06/2008; 141(5):651-8. · 4.94 Impact Factor
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ABSTRACT: We hypothesized that cyclosporin (CSA) as adjunct to plasma exchange (PE) improves the efficacy of PE in idiopathic thrombotic thrombocytopenic purpura (TTP) via suppression of the antibody inhibitor of ADAMTS13. Our preliminary findings with CSA and PE as the upfront treatment of TTP suggested that the addition of CSA to PE significantly decreased the exacerbation (disease recurrence within 30 d of the last PE) rates compared to a cohort that received corticosteroids and PE as their upfront therapy of TTP. We present an updated analysis with long-term follow-up of 18 patients with idiopathic TTP treated with concurrent CSA and PE with analysis of serial measurements of ADAMTS13 activity, antigen and inhibitor concentration in the context of clinical outcome data. Overall, 16/18 (89%) patients achieved remission, similar to historical remission rates in idiopathic TTP with PE with only one patient suffering an exacerbation. Clinical responses correlated with improvements in ADAMTS13 activity and suppression of the antibody inhibitor of ADAMTS13. These data suggest that the efficacy of CSA is at least in part related to its suppression of the antibody inhibitor of ADAMTS13 and a subsequent improvement in ADAMTS13 activity and antigen.
British Journal of Haematology 12/2007; 139(3):486-93. · 4.94 Impact Factor
