Mortality Among Veterans with a Diagnosis of Pyruvate Kinase (PK) Deficiency: A Real-World Study Using US Veterans Health Administration Data

Background: Pyruvate kinase (PK) deficiency is a rare, inherited disorder caused by autosomal recessive mutations in the PKLR gene, whereby a glycolytic defect causes reduced adenosine triphosphate levels and leads to hemolytic anemia. Patients with PK deficiency can experience serious complications associated with the disease and its treatment, including osteoporosis, pulmonary hypertension, sepsis, iron overload, and liver cirrhosis. The current standard of care for PK deficiency is supportive, including blood transfusions, splenectomy, iron chelation therapy and/or interventions for other disease-related morbidity. There is no approved therapy for this condition. Identifying PK deficiency in real-world data is challenging due to a lack of diagnosis codes and treatments that are specific to PK deficiency. As a result, population-based studies of PK deficiency using claims or electronic health record databases are limited. In addition, data on mortality in this patient population are lacking and limited to a few individual case reports. This study aimed to identify patients with a PK deficiency diagnosis as documented by physicians and to compare their mortality to an age- and gender-matched cohort of individuals without PK deficiency. Methods: Patients with ≥ 1 diagnosis code related to PK deficiency (i.e., anemia due to disorders of glycolytic enzymes [International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) D55.2], other hemolytic anemias due to enzyme deficiency [ICD-9-CM 282.3], or unspecified hereditary hemolytic anemia [ICD-9-CM 282.9, ICD-10-CM D58.9]) between January 1995 and July 2019 were selected from the US Veterans Health Administration (VHA) database. To be considered for inclusion, physicians’ notes were required to contain the words “pyruvate”, “kinase”, and “deficiency.” A manual review of these physicians’ notes was performed to identify patients with a physician-documented diagnosis of PK deficiency (PK deficiency cohort). The index date for the PK deficiency cohort was defined as the date of the first medical record with a diagnosis code related to PK deficiency. Each patient in the PK deficiency cohort was matched 1:5 by age at index, sex, and index year (± 1 year) to patients from the general VHA population with no diagnosis codes related to PK deficiency (non-PK deficiency cohort). The index date for the non-PK deficiency cohort was defined as a random visit date during their match’s index year. S