Clinical Practice Pattern of Acquired Thrombotic Thrombocytopenic Purpura in Japan: A Nationwide Inpatient Database Analysis

Introduction: Acquired thrombotic thrombocytopenic purpura (TTP) is a medically emergent disorder that is almost always fatal without proper treatment. While daily plasma exchange is recommended by several guidelines, its optimal frequency is unclear, and until March 2018 plasma exchange up to only three times a week was reimbursed by Japanese health insurance. In addition, rituximab has not been approved for acquired TTP in Japan. While it is known that clinical practice guidelines for TTP treatment in Japan may differ from those in other countries, real-world practice patterns remain unknown. Thus, we evaluated patients' characteristics and clinical practice patterns using a large nationwide inpatient database.

Methods: For this nationwide epidemiologic study, we used the Japanese Diagnosis Procedure Combination inpatient database, which includes discharge abstracts and administrative claims data from more than 1,200 acute-care hospitals and covers approximately 90% of all tertiary-care emergency hospitals in Japan. All hospitalized patients who were diagnosed with TTP (International Classification of Diseases-Tenth Revision, code M311) on admission and who received plasma exchange during hospitalization were included in the study. Patients younger than 18 years were excluded. When patients with the ICD code for TTP were admitted more than once during the study period, we used data only from the first admission. We then evaluated patients' characteristics and clinical practice patterns.

Results: We identified 1,638 patients who were newly diagnosed with acquired TTP from July 2010 to March 2017. The median (interquartile range [IQR]) age was 64 (47-74) years, and 674 (41%) patients were male; 648 (40%) required ICU admission, 447 (34%) required catecholamine, and 497 (30%) required mechanical ventilation. Although relatively contraindicated, 658 (40%) patients received platelet transfusion. In-hospital mortality was 32% (n=529/1,638). Median (IQR) length of hospital stay was 45 (25-78) days, and median total cost was US$40,897 ($24,204-$64,012). Among survivors, 856 (77%) were discharged home and 235 (21%) required subacute rehabilitation or chronic care facility. The median (IQR) interval from admission to plasma exchange was 4 (2-10) days; 385 (24%) patients received plasma exchange on the day of admission. Median (IQR) frequency of plasma exchange within 7 days of initial exchange was 3 (2-5) days; median (IQR) duration of plasma exchange was 10 (4-21) days. Of the 1,519 (93%) patients who received steroids, 1,071 (71%) received steroid pulse therapy. Among the 529 (32%) patients administered immunosuppressants, 221 (13%) received cyclophosphamide, 152 (9.3%) rituximab, 140 (8.6%) cyclosporine, and 86 (5.3%) tacrolimus.

Conclusions: We assessed real-world clinical practice for TTP patients in Japan for the first time using the nationwide inpatient database. Our analysis showed a disparity between guidelines and real-world clinical practice, especially regarding frequency of plasma exchange. Optimal treatment strategy, efficacy, and safety should be evaluated in future studies.