Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal disorder with a mortality rate of 90-95% if left untreated. With plasma exchange and appropriate immunosuppression, the mortality rate is reported to be roughly 10%. Recent reports of patients with fully optimized therapy, including caplacizumab, estimate mortality rate of acute TTP at ~5% or less. We conducted this retrospective cohort registry study to examine differences in mortality through different treatment eras at a large volume single center.

Methods: Adults (≥18 years of age) with confirmed iTTP in the Ohio State University (OSU) TTP registry from 06/2003 to 06/2025 were included. All patients in the registry are followed longitudinally every 3-6 months until death or loss of follow up. All acute episodes at OSU are principally managed by or under the guidance of one of the investigators in a uniform fashion since the registry's inception. All participant deaths were systematically recorded and adjudicated as TTP related if death was during an acute TTP episode, whether index or relapse event. From 2003-2010, all episodes were treated with PEX and corticosteroids. From 2010, all patients received rituximab with acute episodes. From 2019, all patients received caplacizumab +/- PEX, corticosteroids, and rituximab. Thus, patients who experienced death were categorized into treatment periods A (2003-2009), B (2010-2018), or C (2019-2025) given uniformity of therapy. Differences between groups were tested using the Fischer exact test for categorical variables and Wilcoxon Rank Sum test for continuous variables. All statistical analyses were performed in STATA v17.

Results: Since registry inception in 2003, a total of 29 participants have died with a median follow up time of 11.4 years since diagnosis (IQR 4.6 – 18.4). Twelve (41%) deaths were TTP-related (during an acute episode) and 17 (59%) were non-TTP related (from other causes during clinical remission). Among decedents, 72% identified as White and 69% were female. There were no significant differences in age, sex , or ethnicity between TTP-related and non-TTP related deaths. Understandably, duration of follow up was significantly shorter for TTP-related deaths vs non-TTP-related deaths (4.4 years [IQR 0.02-13.6] vs 12.8 [IQR 7.2-19.8] p = 0.02)

A total of 7 patients died in treatment period A (2003-2009), 13 in treatment period B (2010-2018) and 9 in treatment period C (2019-2025). The proportion of acute TTP-related deaths was 57% (4/7, 95% CI, 22–86%) in treatment period A, 46% (6/13, 95% CI, 22–73%) in period B, and 22% (2/9, 95% CI, 5–60%) in period C; however this trend did not reach statistical significance (p = 0.388) likely due to low sample size and event rate. Notably, the 2 TTP-related deaths in era C were treated at outside facilities without the use of caplacizumab. Conclusion: Over more than 2 decades, the proportion of deaths attributed to acute TTP episodes in a large tertiary referral center has consistently declined across treatment eras, coinciding with sequential adoption of modern therapeutics. Notably, no patients treated with caplacizumab in their acute course has died in the modern treatment era. Importantly, our data also shows that over 50% of TTP-related deaths occurred after a median follow up 4.4 years with 25% occurring after 13 years. Moreover, non-TTP related deaths encompassed 59% of the overall mortality in our cohort over time, emphasizing the importance of longitudinal follow up in all patients for relapse prevention and management of long-term complications which contribute to these outcomes.

This content is only available as a PDF.
2025
Sign in via your Institution