P1479: COMORBIDITIES AND COMPLICATIONS IN ADULTS WITH PYRUVATE KINASE DEFICIENCY ACCORDING TO HEMOGLOBIN STRATA – A DESCRIPTIVE ANALYSIS FROM THE PEAK REGISTRY
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".