Abstract
Introduction: Acquired Thrombotic thrombocytopenic purpura (aTTP) is a life-threatening condition in which prompt treatment can significantly reduce morbidity and mortality. Current guidelines recommend initiating caplacizumab (CPZ) only after confirming the diagnosis of aTTP through ADAMTS-13 activity testing. However, this assay is not universally available, leading to delays in the initiation of this life-saving treatment. Locally, the ADAMTS-13 test is sent to an accredited external overseas laboratory, with an expected turnaround time of 5 to 14 days. In this study, we aimed to evaluate the efficacy and safety of pre-emptive CPZ initiation, that is, administration in patients with a high clinical suspicion of aTTP prior to confirmation by ADAMTS-13 testing. Methods: The medical records of all patients treated with CPZ for aTTP at the National Center for Cancer Care and Research in Qatar between March 2021 and January 2025 were retrospectively reviewed. Data collection was standardized and included demographics, clinical symptoms and laboratory findings at baseline and follow-up post CPZ, duration and intent of treatment (definitive or pre-emptive), turnaround time to ADAMTS-13 result, efficacy outcomes, adverse events, and survival status at last follow-up. Descriptive statistics were used to analyze the findings. Results A total of 12 patients received CPZ during the study period, with a median follow-up duration of 330 days (range 43–1,460). Of these, 8 patients received CPZ pre-emptively, while 4 received it as definitive treatment following diagnostic confirmation. The majority were female (n = 7; 58.3%), none of whom were pregnant. The median age at the time of CPZ initiation was 38.5 years (range 23–77). Two patients had baseline comorbidities, but only 1 of them had autoimmune disease (systemic lupus erythematosus). Most patients presented with central nervous system symptoms (n=9; 75%) and purpura (n=8; 66.7%), but none had a proven organ infarction. One patient had significant menorrhagia at presentation. High bilirubin and renal dysfunction were reported in 92% and 50% of patients, respectively. The median Hemoglobin value and median PLT count at diagnosis was 8.35 g/dL (range 4 - 12) and 12.5 x 103/mL (range 3 - 40) respectively. The median PLASMIC score was 6.5 (range 5 to 7) being above 4 for all patients. TTP diagnosis remained unconfirmed with ADAMTS-13 in one patient (PLASMIC score of 6) due to sample rejection at external lab. One patient was misdiagnosed (ADAMTS-13 returned as 48% after 3 days of pre-emptive therapy). He was excluded from efficacy analysis, and CPZ was discontinued after 3 doses of CPZ. This patient died 90 days later due to sepsis and multi-organ failure, unrelated to CPZ treatment. Diagnosis was confirmed in all remaining ten patients with a median ADAMTS-13 activity of 5% (range 3 - 6). The median turnaround time from testing to result availability was 10 days (range 7 to 26). All patients received plasma exchange (median 11 sessions (range 6-15), corticosteroids (median 40 days; range 25 - 45), rituximab (median of 4 doses; range 3 to 8) and CPZ (median of 28 doses (range 10 to 34)). The median time from CPZ initiation to ADAMTS-13 result availability, among the pre-emptive patients, was 8 days (range 3 - 46). The median duration of hospital and ICU stay was 21 (range 10 - 143) and 18 (range 3 - 42) days, respectively. All patients with confirmed aTTP (n=11) were alive at the last follow-up. Ten remained in sustained remission, while 1 experienced an episode of disease recurrence. All patients demonstrated a clinical response to treatment. Hemolysis markers, liver function, and PLT counts normalized in all cases, with a median PLT peak count of 253 × 10³/μL (range 168–533), achieved within a median of 7 days from CPZ initiation (range 4–18). No long-term disease sequelae, morbidity, or mortality were observed during the follow-up period. There were two grade 3 bleeding events (1 gastrointestinal and 1 vaginal) noted among patients. No serious adverse events related to CPZ were observed. Conclusion: Pre-emptive initiation of CPZ, guided by clinical judgment and validated international risk scores, appears to be a safe and effective strategy to avoid treatment delays and reduce morbidity and mortality when ADAMTS-13 testing is not readily available. Larger, prospective studies are warranted to strengthen the evidence base and support broader implementation of this approach.
