Incidence of Acquired Thrombotic Thrombocytopenic Purpura Episodes in adults in Germany: Results of a Hospital Level Study and Projection to National Estimates

Scientific Research Question: Acquired thrombotic thrombocytopenic Purpura (aTTP) is an ultra-orphan disease with a reported annual incidence of 1.5 to 6.0 acute episodes per million in Europe. The goal of this study was to assess the incidence of aTTP in Germany.

Methodology: National German hospital statistics provide annual estimates of hospitalizations related to “Thrombotic Microangiopathy” (TMA) [ICD-10 M31.1] and “Hemolytic uremic syndrome” (HUS) [ICD-10 D59.3], but it remains unclear which of these patients were suffering from aTTP episodes. To obtain the proportion of aTTP episodes within the national TMA/HUS population a retrospective hospital-level study was performed. Patients were considered to have a confirmed diagnosis of aTTP if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned the diagnosis of aTTP. The differentiation between initial and recurrent aTTP episodes was performed on the basis of medical records. The aggregated hospital data were then projected to the national level using logistic regression techniques to reflect the 95% confidence intervals (95%CI) around the mean estimates. Additionally we performed a systematic literature search for German aTTP incidence estimates following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Findings: The systematic literature search did not provide incidence estimates of TTP episodes in Germany. For the hospital-based study, the 30 German hospitals with the highest annual number of TMA cases were invited to participate. Eight centers (≈27%) delivered relevant retrospective data according to a pre-defined data collection form. In total 600 hospitalization episodes related to the primary or secondary diagnosis of TMA/HUS were determined and extracted by the participating centers for the years 2014 to 2017. This reflects ≈10% of the national German episodes within a four year period. Using the latest available national data (year 2016) as estimation basis, a total number of 170 aTTP episodes per year is projected (95%CI: 130–209). The majority were newly diagnosed acute aTTP episodes (n = 119; 95%CI 104–126), and 51 were recurrent aTTP episodes (95%CI: 26–83). Hence, the annual incidence of aTTP episodes was 2,5 / million adults in Germany (95%CI: 1,9–3,0). The annual incidence of newly diagnosed episodes (1,7 / million adults; 95%CI: 1,5–1,8) compares well with estimates from the French aTTP registry (1,5 / million).

Conclusions: The determined annual incidence of newly diagnosed aTTP episodes (1.7 / million adults) and the overall annual incidence of aTTP episodes (2,5 / million adults) in Germany is confirming the ultra-orphan character of aTTP. A comparison with the French aTTP registry provides excellent external validation results.