Bleeding Severity and Health Care Utilization in Patients with Platelet Function Disorders

Abstract Introduction: Disorders affecting any platelet pathway mediating adhesion, activation, aggregation and procoagulant surface exposure can result in a bleeding diathesis. Platelet function disorders (PFDs) are classified based on abnormalities in cytoskeleton, membrane phospholipids adhesive protein receptors, soluble agonist receptors, platelet granules or signal transduction pathways. Due to variability in platelet dysfunction, the clinical presentation and hence the treatment of bleeding manifestations in these patients vary. Use of a bleeding assessment tool can help in the assessment of bleeding severity, predict recurrent bleeding events in patients and help in predicting rates of hospitalization in these patients. Severe PFDs likely have higher BAT scores, and higher rates of hospitalization; but has not been reported widely. Resource utilization in PFDs is largely undescribed or quantified, yet a very important factor in the delivery of health care. Our study aims to assess bleeding severity at diagnosis and assess health care utilization (number of ER visits, hospitalizations, procedures and medications used) in patients with platelet dysfunction, to understand the burden of illness in these patients. Methods: This is an IRB-approved, two-institution retrospective analysis of 26 patients with PFDs younger than 21 years of age, from 2012 - 2018. Patients included were diagnosed with a PFD during the study period at Rainbow Babies and Children's Hospital and Children's Healthcare of Atlanta. The International Society on Thrombosis and Hemostasis - Bleeding Assessment Tool (ISTH - BAT) was used to assess bleeding severity at diagnosis. Demographic characteristics, diagnostic labs, details of hospitalizations, ER visits, outpatient procedures, details on medications, transfusions, and length of stay at these visits were collected via medical record abstraction. Descriptive statistics were used to summarize results. Results: 26 patients were included, of which 10 were male and 16 were female. The age of presentation with symptoms ranged from 2 months to 13 years of age. The mean age of platelet function diagnosis was 5 years, except for the most severe PFDs, who presented prior to 1 years of age. The 2 most common symptoms at presentation were easy bruising (n =11, 42%) and epistaxis (n = 8, 30%). Of the 26 patients, we had 2 patients (7.7%) with Bernard Soulier syndrome, 5 patients (19.2%) with Glanzmann Thrombasthenia, 7 patients (27%) with dense granule storage pool defect and 12 patients (46.1%) with one or more agonist aggregation defects. Light transmission aggregometry was used for diagnosis in 26 (100%), release assay in 5 (19.2%), and platelet electron microscopy in 7 (26.9%) patients. ISTH BAT scores were highest for patients with more severe platelet dysfunction, such as Bernard Soulier syndrome and Glanzmann Thrombasthesia (mean score = 9) and lower for milder PFDs (mean score = 2). The BAT scores among patients with 1, 2 or 3 agonist defects were similarly low at an average score of 2. Rates of ER visits, outpatient procedures and hospitalizations were higher in patients with higher BAT scores, i.e. more severe platelet dysfunction as seen in Table 1. Of the 5 patients with Glanzmann's Thrombasthenia, 3 were started on Novo7 prophylaxis, indicating severity of symptoms in these patients. Platelet transfusions were only used in severe disorders, while amicar was the preferred modality in milder platelet dysfunction, minor procedures and minor bleeds. Conclusions: Based on our retrospective analysis, we conclude that patients with milder platelet dysfunction have lower BAT scores at presentation, lower bleeding manifestations and therefore less health care utilization. In our study, higher BAT scores in patients signified severe platelet dysfunction and recurrent bleeding episodes, requiring frequent ER visits and hospitalizations. We plan to continue this study on a larger patient database to estimate resource utilization from a national perspective, and to identify independent predictors of increased resource use for these patients and understand the economic impact of platelet function defects. Disclosures Sidonio: Kedrion: Research Funding; Novo Nordisk: Other: Advisory Board; Shire: Other: Advisory Board, Research Funding; CSL Behring: Other: Advisory Board; Genentech: Other: Advisory Board, Research Funding; Grifols: Other: Advisory Board, Research Funding; Biomarin: Other: Advisory Board; Octapharma: Other: Advisory Board; Bioverativ: Other: Advisory Board, Research Funding; Uniqure: Other: Advisory Board. Ahuja: Bayer: Honoraria; Shire: Honoraria, Speakers Bureau; Bioverativ: Honoraria, Speakers Bureau.