Dataset Information

Comorbidities and complications in adults with pyruvate kinase deficiency.

ABSTRACT:

Objectives

Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.

Methods

Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Frequencies of select conditions were compared with an age- and sex-matched cohort from a general insured US population without PK deficiency.

Results

Compared with the matched population (n = 1220), patients with PK deficiency (n = 122) had significantly higher lifetime rates of osteoporosis, liver cirrhosis, and pulmonary hypertension; splenectomy and cholecystectomy rates were also significantly higher in the 8 years before the index date. Sixty-five (53.3%) patients with PK deficiency were classified as regularly transfused, 30 (24.6%) as occasionally transfused, and 27 (22.1%) as never transfused. Regularly transfused patients were significantly more likely than never transfused patients to have had splenectomy, cholecystectomy, and/or thrombosis. Liver iron overload was reported in 62% of patients and occurred regardless of transfusion cohort.

Conclusions

Even never transfused patients with PK deficiency had higher rates of select comorbidities and complications than individuals without PK deficiency.

SUBMITTER: Boscoe AN

PROVIDER: S-EPMC7985869 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Comorbidities and complications in adults with pyruvate kinase deficiency.

Boscoe Audra N AN Yan Yan Y Hedgeman Elizabeth E van Beers Eduard J EJ Al-Samkari Hanny H Barcellini Wilma W Eber Stefan W SW Glader Bertil B Yaish Hassan M HM Chonat Satheesh S Sharma Mukta M Kuo Kevin H M KHM Neufeld Ellis J EJ Wang Heng H Verhovsek Madeleine M Sheth Sujit S Grace Rachael F RF

European journal of haematology 20210124 4

<h4>Objectives</h4>Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.<h4>Methods</h4>Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Frequencies of select conditions were compared with an age- ...[more]

PMID: 33370479

Similar Datasets

Project description:BackgroundPyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220).MethodsAll validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline. Completion rates and baseline response distributions were characterized using descriptive statistics. Item response modelling was used to inform a weighted scoring system. Reliability was assessed by internal consistency and test-retest reliability; and validity by convergent and known-groups analyses.ResultsOf the 80 adults enrolled, baseline data were available for 77 (96.3%) and 78 (97.5%) patients for the PKDD and PKDIA, respectively. Item responses skewed right, indicating that mean values exceeded median values, especially for items utilizing a 0-10 numeric scale, which were subsequently recoded to a 0-4 scale; 4 items were removed from the PKDIA due to redundancy or low relevance to the trial population. Both the PKDD and PKDIA demonstrated high internal consistency (McDonald's coefficient ω = 0.86 and 0.90, respectively), test-retest reliability (intra-class coefficients of 0.94 and 0.87, respectively), and convergent validity with other PROs (linear correlation coefficients [|r|] between 0.30-0.73 and 0.50-0.82, respectively).ConclusionsThe findings provide evidence of validity and reliability for the PKDD and PKDIA, the first disease-specific PRO measures for PK deficiency, and can therefore increase understanding of, and more accurately capture, the wider impact of PK deficiency on health-related quality of life. Trial registration ClinicalTrials.gov, NCT03548220. Registered June 07, 2018; https://www.Clinicaltrialsgov/ct2/show/NCT03548220 .

Dataset Information

Comorbidities and complications in adults with pyruvate kinase deficiency.

Objectives

Methods

Results

Conclusions

Publications

Comorbidities and complications in adults with pyruvate kinase deficiency.

Similar Datasets

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