Early vs late plasmapheresis in TTP: A u.s. national study on in-hospital mortality

Abstract Introduction Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy that requires prompt recognition and treatment. Plasmapheresis (PP) remains the cornerstone of therapy. The presence of unexplained microangiopathic hemolytic anemia and thrombocytopenia warrants initiation of PP. However, the largest prior study investigating the timing of PP on mortality included only 163 patients. This study aimed to evaluate the impact of timing on in-hospital mortality using a national database. Methods The National Inpatient Sample (2016–2021) and ICD-10 codes were used to identify adults (age ≥18 years) with TTP who underwent PP in the United States. As this database is encounter-based, each entry was considered an individual TTP episode and classified into early (within 48 hours of admission) and late PP groups. Demographic and clinical variables, including thrombocytopenia, acute heart failure, metabolic encephalopathy, and hepatic dysfunction, were identified using ICD-10 codes. Multivariate regression models were constructed to assess the mortality risk associated with treatment delay and to compare early versus late intervention. A p-value <0.05 was considered statistically significant. Results Of the recorded 23,060 TTP episodes, 26.54% were treated with PP. The majority received the procedure within 48 hours of admission (early 74.35% vs. late 25.65%). Patients in the early PP group were more likely to be younger (age <60: 75.6% vs. 71.9%), female (68.35% vs. 64.33%), African American (47.8% vs. 43.75%), and treated at large-sized hospitals (65.05% vs. 60.51%) compared to those treated later. However, private insurance was slightly more common in the late treatment group (43.13% vs. 40.75%). Patients in the early treatment group had lower rates of acute heart failure (3.74% vs. 6.05%), metabolic encephalopathy (6.59% vs. 11.46%), and hepatic dysfunction (1.43% vs. 5.1%). The mortality rate was lower in the early PP group (5.82% vs. 15.61%, p<0.001). Early PP within 48 hours remained independently associated with reduced mortality compared to the late group (OR 0.54, 95% Cl 0.3-0.96, p<0.05). Among those treated early, patients with age over 65 years, those who received blood transfusions, and those admitted over the weekends (all p<0.05) had higher mortality. Initiating PP on Day 2 compared to Day 0 was associated with a 99% higher odds of mortality (OR 1.99, 95% CI 1.15–3.43, p<0.05). Conclusion In this large U.S. national cohort, early initiation of plasmapheresis was associated with reduced in-hospital mortality among patients with TTP. Delays in treatment were associated with a stepwise increase in mortality, underscoring the critical importance of timely intervention. Future studies should explore the impact of earlier immunosuppression and the development of a scoring system to risk-stratify TTP episodes and guide individualized management.