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)

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    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).