Abstract
Background
Diagnosis of platelet function disorders in pediatric patients is complicated by difficulties identifying at risk patients (due to young age, fewer hemostatic challenges) (Gresele, Journal of Thrombosis and Haemostasis, 2015), large quantities of blood required for standard testing, and inability to use large gauge needles to perform phlebotomy increasing the probability of false positive results. Diagnostic testing for pediatric platelet disorders has recently shifted from Light Transmission Aggregometry (LTA) with serotonin release to Whole Blood Impedance Lumi-Aggregometry (WBILA). There is a paucity of literature comparing LTA and WBILA and few studies examining bleeding assessment tools in exclusively pediatric populations. LTA is widely studied and considered the gold standard of platelet testing. However, the newer and less validated WBILA has a lower blood volume requirement making it potentially more suitable for very young patients in need of testing. Therefore, there is a significant need to validate results from WBILA testing to be able to perform platelet testing on young patients.
Aims
The study purpose was to analyze lab testing results and patient characteristics for patients that have had WBILA or LTA with serotonin release and compare results across testing platforms. We also compared performance characteristics for patients with access to both methods. Further, we compared Bleeding Assessment Tool (BAT) scores, age distributions and types of testing results and their occurrences for both types of testing.
Methods
Medical and laboratory records of children evaluated at the Children's Hospital of Philadelphia and at the Hospital of the University of Pennsylvania that were referred for a variety of causes from 1/1/2016 until 6/30/2018 were examined. Males and females referred for concerns for bleeding who are age 2 months to 21 years at time of evaluation were included. In late 2016 the coagulation laboratory at CHOP validated WBILA. Prior to this, patients were tested using LTA. Patient history and demographic information, indication for testing, aggregometry findings and final diagnosis were compared prior to and after this transition. Medical records were used to derive a bleeding score. Approximately 300 records were reviewed.
Results
For LTA with serotonin release, ages were distributed bimodally with peaks at 6 years and 16 years with an average of 10.6 years (SD=5.4 years). The most frequent indications for testing were epistaxis (24%) and easy bruising (20%). For WBILA, ages were distributed bimodally with peaks at 35 months and 15 years with an average of 8.6 years (SD=5.5 years). The most frequent indications for testing were epistaxis (27%) and family history (17%). Average age of patients tested with WBILA was significantly lower than LTA with serotonin release (p=0.0013). No difference in distribution or average BAT scores was seen between patients tested with LTA and WBILA. The percent of abnormal results for cases with LTA testing was 32% versus 27% for WBILA cases, a difference that was not statistically significant. This suggests that the tests have similar diagnostic performance. Additionally, there is a trend towards an association between higher BAT scores and abnormal test results, but not significantly due to few abnormal cases. Finally, comparison of WBILA with LTA results showed that for the 9 patients with both studies, 4 had normal WBILA after borderline abnormal LTA results and 5 had congruent findings.
Conclusions
Our data highlight the differences in results and patient characteristics between LTA and WBILA testing. The most significant difference between the two tests was age distribution, with LTA, which requires more blood, being performed in older patients. In examining test performance, our analysis of BAT scores suggests that in our population a higher BAT score may be associated with higher probability of abnormal result, but differences in scores are small and make it hard to differentiate patients appropriate for testing based on bleeding scores alone. Our rate of abnormal results is similar to that of other populations, and highlights the difficulty of diagnosis in pediatric populations. Based on the consistent frequencies of abnormal findings across test types and the analysis of BAT scores, WBILA may be an acceptable alternative to LTA with serotonin release in young patients needing evaluation for platelet function defects.
Doshi:Bayer: Research Funding. Lambert:Rigel: Consultancy; Summus: Consultancy; Shionogi: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy; Sysmex: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees.
Author notes
Asterisk with author names denotes non-ASH members.