Comorbidities and complications in adults with pyruvate kinase deficiency

• Authors: Audra N Boscoe, Agios Pharmaceuticals, Inc.,; Yan Yan, Agios Pharmaceuticals, Inc.,; Elizabeth Hedgeman, IBM Watson Health, Ann Arbor; Eduard J van Beers, University of Utrecht; Hanny Al-Samkari, Harvard Medical School; Wilma Barcellini, Ospedale Maggiore Policlinico; Stefan W Eber, Technical University, Munich; Bertil Glader, Stanford University; Hassan M Yaish, University of Utah; Satheesh Chonat, Emory University; Mukta Sharma, University of Missouri Kansas City; Kevin HM Kuo, University of Toronto; Ellis J Neufeld, St Jude Children's Research Hospital; Heng Wang, DDC Clin Special Needs Children; Madeleine Verhovsek, McMaster University; Sujit Sheth, Weill Cornell Medical College; Rachael F Grace, Harvard Medical School
• Journal Title: EUROPEAN JOURNAL OF HAEMATOLOGY
• Volume: Volume 106, Number 4
• Publisher: WILEY | 2021-01-24, Pages 484-492
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1111/ejh.13572
• Subjects: Health Sciences, Oncology; Chemistry, Pharmaceutical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; blood transfusion; comorbidity; pyruvate kinase deficiency; DISEASE; PATHOGENESIS; THALASSEMIA; POPULATION; PREVALENCE; RISK

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.