(P-TA-4) Immature platelet count responses in pediatric thrombotic thrombocytopenic purpura patients suggests need for prolonged therapy and platelet instability

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and reduced or absent ADAMTS13 activity, with varying degrees of organ ischemia. Previous studies using absolute immature platelet count (A-IPC) dynamics to characterize presentation and management of iTTP have been described however data in pediatric patients is limited

Study

Design/Methods: We conducted a retrospective study to analyze the immature platelet count responses of pediatric patients suspected of iTTP treated with TPE at our institution. Information gathered included platelet count, hematocrit/hemoglobin, lactate dehydrogenase, creatinine, blood urea nitrogen, body mass index (BMI), blood type, immunosuppression given, number of TPE needed among other variables. A-IPC were derived by obtaining an immature platelet fraction (IPF) with a complete blood count prior to start of TPE (baseline) and prior to each daily procedure. A-IPC=IPF x platelet count

Results/Findings: Five patients were identified: three teenagers, one adolescent and one toddler. Mean age of patient cohort was 12.8 (1-19 range). The majority of patients were female (4) and 4 were obese (mean BMI 40.3). The 1 year old patient had a normal weight for her age (9.0 Kg). Patients had significant thrombocytopenia (mean 14.4 x 10⁹/L). Patients were anemic with mean hemoglobin of 7.6 and a mean hematocrit of 23.3. In all cases A-IPC results suggested iTTP diagnosis prior to ADAMTS13 results were available since this was below the reference range (mean 0.6 x 10⁹/L). All patients had ADAMTS13 activity < 10% and 4/5 patients had a significant inhibitor to ADAMTS13 (mean activity 5.2, mean inhibitor 4.7). Patients uniformly had normal renal function tests. Patients also experienced volatility in both A-IPC and platelet counts, which concomitantly declined on therapy, followed by the former improving two days prior to corresponding platelet count change. Notably, all five patients required an extended TPE and immunosuppression treatment period until platelet counts remain sustained and stabilized ( > 150 x 10⁹/L). Mean number of TPE needed to result in a sustained recovery was 30.4 and all five needed rituximab to be given at 375 mg/m². Patients saw recovery of platelet counts with A-IPC which remained higher compared to contemporary historical adult patients with high ADAMTS13 inhibitor but whose A-IPC returned to baseline upon recovery

Conclusions: Pediatric iTTP patients had prolonged therapy regimens to recover from the disease. Responses were protracted, unstable and remained so for duration of hospitalization. A-IPC confirmed ADAMTS13 deficiency in all cases. A-IPC remained high even after recovering from disease. Additional studies are needed to determine mechanisms driving A-IPC to remain higher than adult patients