P1479: COMORBIDITIES AND COMPLICATIONS IN ADULTS WITH PYRUVATE KINASE DEFICIENCY ACCORDING TO HEMOGLOBIN STRATA – A DESCRIPTIVE ANALYSIS FROM THE PEAK REGISTRY

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Pyruvate kinase (PK) deficiency is a rare, congenital hemolytic anemia caused by mutations in the PKLR gene. Hemoglobin (Hb) levels are an important assessment of disease, yet patients (pts) with less pronounced anemia (Hb >10 g/dL) may still experience complications due to the underlying pathophysiology of PK deficiency. Aims: To describe the disease burden of adults with PK deficiency and average Hb >10 g/dL enrolled in the Peak Registry (NCT03481738). Methods: The Peak Registry is an ongoing, retrospective, and prospective observational study of pts with PK deficiency, with 243 pts enrolled as of 13May2022. This analysis included adult pts (≥18 years at enrollment) with Hb data available. Hb data were collected within 3 months prior to enrollment and during follow-up. All Hb data collected ≤61 days post-transfusion were considered ineligible. Pts were grouped into 2 cohorts based on mean Hb value across eligible data: >10 g/dL and ≤10 g/dL. Demographics, clinical characteristics, medical history, hemolysis markers, and select medical complications were summarized descriptively for all pts and for each cohort. Results: Ninety-five pts were included in the analysis (8 pts were excluded as all their Hb measurements were collected ≤61 days post-transfusion), of whom 48 (51%) had mean Hb >10 g/dL. Age and sex were similar between cohorts (Table). In the Hb >10 g/dL cohort, median (range) % reticulocyte count was 5.7% (2.7–40.9), indirect bilirubin was 1.8 mg/dL (0.7–10.8), and ferritin was 304.0 µg/L (34.5–6208.0). In the Hb ≤10 g/dL cohort, the median (range) values for these markers were 25.3% (4.0–43.0), 2.7 mg/dL (0.8–8.1), and 683.5 µg/L (16.6–7050.0), respectively. Thirty-five percent of pts in the Hb >10 g/dL cohort and 83% of pts in the Hb ≤10 g/dL cohort had received ≥1 transfusion in their lifetime; 18% and 40% had received regular transfusions (≥6 transfusions in any 12-month period), respectively. Thirty-three percent of pts with Hb >10 g/dL and 62% of pts with Hb ≤10 g/dL had a history of iron overload. Twenty-seven percent of pts with Hb >10 g/dL and 61% of pts with Hb ≤10 g/dL had received chelation therapy in their lifetime. Thirty-three percent of pts with Hb >10 g/dL had undergone splenectomy, at a median (range) age of 14 years (2–58), compared with 80% of pts with Hb ≤10 g/dL, at a median (range) age of 7 years (2–20). Bone health complications occurred in 21% of pts with Hb >10 g/dL and 40% of pts with Hb ≤10 g/dL. Notably, both cohorts had high proportions of pts with osteopenia/osteoporosis (Hb >10 g/dL: 19%; Hb ≤10 g/dL: 21%). Cholecystitis was also reported at similar levels in both cohorts (Hb >10 g/dL: 21%; Hb ≤10 g/dL: 28%) and substantial numbers of pts experienced jaundice (Hb >10 g/dL: 23%; Hb ≤10 g/dL: 51%). Other complications included biliary events (Hb >10 g/dL: 33%; Hb ≤10 g/dL: 49%), liver complications (Hb >10 g/dL: 5%; Hb ≤10 g/dL: 19%), thromboembolic events (Hb >10 g/dL: 2%; Hb ≤10 g/dL: 9%), cardiac complications (Hb >10 g/dL: 5%; Hb ≤10 g/dL: 9%), and retinal problems (Hb >10 g/dL: 18%; Hb ≤10 g/dL: 0%). Summary/Conclusion: Adults with PK deficiency, including those with less pronounced anemia (Hb >10 g/dL), experienced a wide range of comorbidities and complications. As with pts with lower Hb values, those with Hb >10 g/dL also had hemolysis, transfusion requirements, iron overload, and a need for chelation, as well as serious conditions such as osteoporosis and biliary events. Clinicians should consider that all pts with PK deficiency, regardless of Hb level, require careful monitoring to minimize the risk of long-term complications.Keywords: Pyruvate kinase deficiency, Comorbidities, Hemoglobin, Hemolysis