Mild platelet function defects (MPFD) are a variable group of common inherited disorders characterized by mucocutaneous bleeding and excessive bleeding with trauma, surgery and procedures. The diagnosis is often based on subjective interpretations of expensive platelet function tests that require a substantial volume of blood. Furthermore, the diagnosis of MPFD can significantly limit participation in contact sports and physically demanding careers. To explore these issues, a retrospective chart review of patients from the Comprehensive Center for Bleeding Disorders of the BloodCenter of Wisconsin with a diagnosis of MPFD, and who had at least one follow-up evaluation was undertaken. The majority of patients had been evaluated by a two-step process; initially screened with CBC, PT, PTT, TT and a von Willebrand factor (VWF) panel. If these tests were normal, platelet function was assessed with light transmission aggregometry and chemiluminesence detection of ATP release in platelet rich plasma by the agonists TRAP, arachidonic acid (0.5 nM), ADP (10 uM), collagen (2.5 ug/mL) and high and low dose ristocetin.One hundred forty-eight patients diagnosed with a primary MPFD between 1982-2014 and with at least one recorded follow-up were identified. Bleeding scores were assigned by a system incorporating principles developed for the ISTH bleeding assessment tool. Patients ranged in age from 2 months to 57 years. For assessment of age on platelet function, patients were grouped as follows: Group A <2 years (N=23), Group B 2-4 years (N=33), Group C 5-8 years (N=36), Group D 9-16 years (N=30), and group E >16 years (N=26).At diagnosis, median bleeding score was 3 (range 0-12). Bleeding scores increased with age (p<.0001); the median (range) score was 2 (0-8) for A, 2 (0-5) for B, 3 (0-9) for C, 3 (0-7) for D and 4 (0-12) for E. There was no difference in gender by age group except group E with 23 females and 1 male; twenty of the 23 females reported menorrhagia. One hundred twenty eight (86%) of the patients had abnormal ATP release (122) or platelet aggregation (6) in the presence of ADP, the most common defect identified. Of those with abnormal release of ATP, 50% had another platelet function abnormality; there was no difference in bleeding scores between those with either single or multiple abnormalities. Of those who did not have abnormal aggregation or release with ADP, 8 had an abnormal response(s) with collagen alone and 1 had abnormal ATP release with arachidonic acid alone. At the most recent follow-up visit, (median 97 months, range 1-368 ) after the initial evaluation, the interim median bleeding scores were lower; for each age group the bleeding score (range) was 2 (0-8) for A, 1 (0-6) for B, 3 (0-7) for C, 2 (0-8) for D and 3.5 (0-10) for E. When compared to the oldest group (E), groups B and D showed a statistically significant difference (p <0.05).Twenty-nine of the patients had follow-up platelet function studies; of these, 13 (all were children) had a significant decrease in bleeding score and normalization of platelet function studies. There were no differences in age, gender, or family history of bleeding between those with persistent MPFD and those with normal follow-up platelet function tests. The persistent group had higher initial (p<0.03) and follow-up (p<0.02) bleeding scores. Those with normalization had a significant decrease in bleeding scores from diagnosis to follow-up (p<0.01) while the persistent MPFD group had no difference.These results suggest that a more targeted approach utilizing the analysis of ATP release by ADP, with TRAP release to confirm the presence of granules, will identify the majority of patients with mild platelet function defects. For those with suspected MPFD and normal ATP release with ADP, a full panel of agonists followed by additional step-wise evaluation as recommended by the ISTH should be undertaken. Limiting initial platelet function testing will reduce the volume of blood required and the cost. The reassessment of platelet function studies in patients with MPFD whose bleeding symptoms subside will identify a subset of these patients with normalization of platelet function. This group will no longer require treatment for procedures and restrictions of career choices or athletic pursuits. Thus, by utilizing a standard approach, patients with MPFD can be diagnosed and managed more efficiently and effectively with less cost to both the patient and healthcare system. DisclosuresFriedman:Alexion: Speakers Bureau; Novo Nordisk: Consultancy; CSL-Behring: Consultancy; Instrumentation Laboratories: Consultancy. Flood:Baxter: Consultancy; CSL Behring: Consultancy. Jobe:Bayer: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees; CSL-Behring: Membership on an entity's Board of Directors or advisory committees. Gill:Bayer: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees; CSL-Behring: Membership on an entity's Board of Directors or advisory committees.