Hamostaseologie 2019; 39(S 01): S1-S92
DOI: 10.1055/s-0039-1680106
SY06 TTP and PNH
Georg Thieme Verlag KG Stuttgart · New York

Eleven Relapses in a Cohort of 78 Patients with Immune Thrombotic Thrombocytopenic Purpura (iTTP): Data from the German TTP-Registry

C. von Auer
1   Department of Hematology, Oncology and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
2   Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
I. Schmidtmann
3   Institut für Medizinische Biometrie, Epidemiologie und Informatik, Mainz, Germany
,
L. Bach
2   Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
M. Jureta
2   Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
T. Falter
4   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
H. Rossmann
4   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
K. Jurk
2   Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
I. Scharrer
5   Department of Hematology, Oncology and Pneumology, Formerly University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
B. Lämmle
6   Center for Thrombosis and Hemostasis (CTH), Formerly University Medical Center of the Johannes Gutenberg University, Mainz, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
13 February 2019 (online)

Also available at
 
 

    Background: Autoimmune TTP (iTTP) is a rare, life-threatening thrombotic microangiopathy (TMA) caused by severe ADAMTS13 deficiency (< 10%). Despite therapy the mortality remains 10–20% and survivors are at risk of relapse (30–50%). The occurrence of severe ADAMTS13 deficiency during remission may predict risk of relapse.

    Aims: Supported by the German Federal Ministry of Education and Research we set up the first prospective iTTP- registry in Germany in 2016. In this analysis we aimed to investigate the characteristics of severe ADAMTS13 deficiency and its prognostic features.

    Methods: Since 07/2016 patients (pts) in our center were consecutively enrolled with acute episodes or in remission with follow-up visits planned every 3 months. We collected standardized longitudinal clinical and laboratory parameters from each visit. ADAMTS13 activity was analyzed with the FRETS-VWF73 assay.

    Results: From 07/2016 to 07/2018 we enrolled 85 pts, 7 with other TMAs and 78 with iTTP (57 female, 21 male, aged 22–88 years, median 50 years), 7 with acute bout and 71 in remission (1–23 prior bouts, median 2). 61/78 Pts had at least 2 follow-up visits (range 2–21, median 6), time period between visits was 1–494 days (median 91 days). In remission, 35/78 pts had a persisting normal ADAMTS13 activity (≥50%) during the observation period, none of them relapsed. 43/78 Pts dropped at least once < 50%, 8/43 pts had continuous activity levels < 10% without relapse. 9/78 Pts (2 male, 7 female, age 25–67 years, median 46 years) had 11 relapses during the observation period. One relapse occurred during pregnancy. All pts survived and achieved complete remission with standard therapy. Before relapse, 7/9 pts showed a decline in ADAMTS13 activity < 2% and relapsed 0–260 days (median 46.5 days) later. 4/9 Pts showed a steep decline corresponding to a reduction by at least a factor 2 within 3 months (values ≥50% to < 50%). This steep decline showed a strong association with occurrence of relapse (p < 0.0001). 1/9 Pts (pregnant) showed a decline from >50% to < 10% after 43 days and relapsed the same day. 1/9 Pts was enrolled with ADAMTS13 already < 2%. Three other pts also showed an ADAMTS13 activity decline during follow-up to < 10%, but not to < 2%, none of them relapsed. We also included baseline ADAMTS13 activity level, age and sex into a Cox regression model, however none of them were found to be significantly associated with relapse.

    Conclusions: Our results highlight the substantial number of iTTP patients in remission with deficient ADAMTS13 activity. A rapid decline of ADAMTS13 activity during quarterly follow up intervals seems to be associated with a high risk of relapse. The pre-emptive therapy with anti-CD20 monoclonal antibody rituximab (off label) or corticosteroids to prevent an acute episode in these cases seems reasonable but needs further examination.


    #

    No conflict of interest has been declared by the author(s).