Characterization of Bleeding in Thrombotic Thrombocytopenic Purpura Treated without Caplacizumab

Introduction: The addition of caplacizumab to immune thrombotic thrombocytopenia (iTTP) treatment options has led to a renewed interest in characterizing the epidemiology and risk factors for bleeding in iTTP. Limited data exist on the bleeding risk in iTTP due to systemic underreporting in earlier cohorts.

Methods: To describe the incidence, patterns, and predictors of bleeding in hospitalized iTTP patients, independent of caplacizumab (pre-caplacoizumab era), we retrospectively analyzed the National Inpatient Sample database (2012-2019) and identified all patients aged ≥18 years with a diagnosis of iTTP. Bleeding was identified using ICD-9/10 codes and characterized as major bleeding or non-major bleeding. Factors associated with bleeding were determined by multivariable logistic regression analysis.

Results: We identified 3103 iTTP hospitalizations between 2012-2019. Median age was 49 years (range 18 – 90) and 65.9% were female. Bleeding occurred in 594 (19.1%) episodes and 157 (5.1%) were characterized by major bleeding. Mucocutaneous bleeding (7.6%) was the most frequent type of bleeding and included heavy menstrual bleeding (2.6%), gingival (2.3%), epistaxis (1.4%), and skin/procedure-related bleeding (1.3%). This was followed closely by gastrointestinal bleeding (5.6%). Among patients with major bleeding (table S1), CNS bleeding was the most common at 67 (42.7%), followed by hemothorax/hemopericardium in 55 (35.0%), and hemoperitoneum in 25 (15.9%). Only 37 (1.2%) hospitalizations with bleeding required percutaneous, endoscopic, or surgical intervention for bleeding. More patients in the bleeding group (table 1) received blood transfusions (48.8% vs 33.6%; P<0.001) and platelet transfusions (21.2% vs 12.2%; P<0.001). Major bleeding was independently associated with mortality (OR, 2.62; 95% CI 1.65-4.16).

In multivariable analysis, Asian/Pacific Islander/Native American race (OR, 2.04; 95% CI 1.04-4.01), coronary artery disease (OR, 1.70; 95% CI 1.06-2.74), autoimmune disease (OR, 2.61; 95% CI 1.58-4.30), Charlson comorbidity index ≥ 3 (OR, 2.08; 95% CI 1.25-3.46), and delay ≥ 2 days in plasma exchange initiation (OR, 1.63; 95% CI 1.13-2.34), were significantly associated with major bleeding.

Conclusion: In conclusion, bleeding is a relatively common issue in acute iTTP that has not been adequately addressed in existing literature. Bleeding is mostly mild, with mucocutaneous bleeding being the most common phenotype. However, major bleeding occurs in over 5% and is associated with mortality. Further studies are needed to establish risk factors for bleeding in iTTP, especially given the increasing use of caplacizumab in the treatment of iTTP.