Contributions
Abstract: EP710
Type: E-Poster Presentation
Session title: Enzymopathies, membranopathies and other anemias
Background
Pyruvate kinase (PK) deficiency is a rare, hereditary disease caused by autosomal recessive mutations in the PKLR gene, where a glycolytic defect causes reduced adenosine triphosphate levels, leading to hemolytic anemia. Serious complications such as osteoporosis, pulmonary hypertension, sepsis, iron overload, and liver cirrhosis are associated with the disease and its therapy. Treatment is supportive only, and comprises splenectomy, blood transfusions, iron chelation, and management of disease-related morbidity. Identifying PK deficiency in real-world data is challenging due to a lack of diagnosis codes and treatments that are specific to the disease. Hence, population-based studies of PK deficiency using claims or electronic health record databases are limited. In addition, data on mortality in this patient (pt) population are lacking and limited to a few individual case reports.
Aims
This study aimed to identify pts with a PK deficiency diagnosis as documented by physicians and to compare their mortality to an age- and gender-matched cohort of individuals without the disease.
Methods
Pts with ≥1 diagnosis code related to PK deficiency (ie, anemia due to disorders of glycolytic enzymes, other hemolytic anemias due to enzyme deficiency, or unspecified hereditary hemolytic anemia) from January 1995–July 2019 were selected from the US Veterans Health Administration (VHA) database. Inclusion criteria required physicians’ notes to contain the words “pyruvate”, “kinase”, and “deficiency.” A manual review of these notes was performed to identify pts with a physician-documented diagnosis of PK deficiency (PK deficiency cohort). The index date for this cohort was defined as the date of the first medical record with a diagnosis code related to PK deficiency. Each pt in this cohort was matched 1:5 by age at index, sex, and index year (yr) (±1 yr) to pts 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 yr. Survival time from the index date was compared between the PK deficiency cohort and their non-PK deficiency cohort matches using a univariate Cox proportional hazards model with robust standard error estimation.
Results
A total of 18 pts met inclusion criteria for the PK deficiency cohort and were matched to 90 individuals in the non-PK deficiency cohort. For both cohorts, mean age at index was 57 yrs, 94% were male, 83–85% were white, and mean Charlson Comorbidity Index score was 0.4–0.5 (no significant differences between cohorts). The median follow-up was 6 yrs for the PK deficiency cohort and 8 yrs for the non-PK deficiency cohort. During this period, 9 (50%) and 28 (31%) deaths were observed in the PK deficiency and non-PK deficiency cohorts, respectively. The median time to death was 10.9 yrs for the PK deficiency cohort and 17.1 yrs for the non-PK deficiency cohort (hazard ratio: 2.3; p=0.0306); the Kaplan–Meier curves for both cohorts are shown in the Figure. Ten yrs post-index, 42% and 28% of pts had died in the PK deficiency and non-PK deficiency cohorts, respectively.
Conclusion
Results of this study suggest that pts with PK deficiency may be at an increased risk of mortality. Further research to understand cause of death in this population is warranted, as is the replication of this study using larger sample sizes and other real-world data sources that better represent females and the pediatric and adolescent PK deficiency age groups.
Keyword(s): Hemolytic anemia, Mortality, Pyruvate kinase deficiency, Survival
Abstract: EP710
Type: E-Poster Presentation
Session title: Enzymopathies, membranopathies and other anemias
Background
Pyruvate kinase (PK) deficiency is a rare, hereditary disease caused by autosomal recessive mutations in the PKLR gene, where a glycolytic defect causes reduced adenosine triphosphate levels, leading to hemolytic anemia. Serious complications such as osteoporosis, pulmonary hypertension, sepsis, iron overload, and liver cirrhosis are associated with the disease and its therapy. Treatment is supportive only, and comprises splenectomy, blood transfusions, iron chelation, and management of disease-related morbidity. Identifying PK deficiency in real-world data is challenging due to a lack of diagnosis codes and treatments that are specific to the disease. Hence, population-based studies of PK deficiency using claims or electronic health record databases are limited. In addition, data on mortality in this patient (pt) population are lacking and limited to a few individual case reports.
Aims
This study aimed to identify pts with a PK deficiency diagnosis as documented by physicians and to compare their mortality to an age- and gender-matched cohort of individuals without the disease.
Methods
Pts with ≥1 diagnosis code related to PK deficiency (ie, anemia due to disorders of glycolytic enzymes, other hemolytic anemias due to enzyme deficiency, or unspecified hereditary hemolytic anemia) from January 1995–July 2019 were selected from the US Veterans Health Administration (VHA) database. Inclusion criteria required physicians’ notes to contain the words “pyruvate”, “kinase”, and “deficiency.” A manual review of these notes was performed to identify pts with a physician-documented diagnosis of PK deficiency (PK deficiency cohort). The index date for this cohort was defined as the date of the first medical record with a diagnosis code related to PK deficiency. Each pt in this cohort was matched 1:5 by age at index, sex, and index year (yr) (±1 yr) to pts 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 yr. Survival time from the index date was compared between the PK deficiency cohort and their non-PK deficiency cohort matches using a univariate Cox proportional hazards model with robust standard error estimation.
Results
A total of 18 pts met inclusion criteria for the PK deficiency cohort and were matched to 90 individuals in the non-PK deficiency cohort. For both cohorts, mean age at index was 57 yrs, 94% were male, 83–85% were white, and mean Charlson Comorbidity Index score was 0.4–0.5 (no significant differences between cohorts). The median follow-up was 6 yrs for the PK deficiency cohort and 8 yrs for the non-PK deficiency cohort. During this period, 9 (50%) and 28 (31%) deaths were observed in the PK deficiency and non-PK deficiency cohorts, respectively. The median time to death was 10.9 yrs for the PK deficiency cohort and 17.1 yrs for the non-PK deficiency cohort (hazard ratio: 2.3; p=0.0306); the Kaplan–Meier curves for both cohorts are shown in the Figure. Ten yrs post-index, 42% and 28% of pts had died in the PK deficiency and non-PK deficiency cohorts, respectively.
Conclusion
Results of this study suggest that pts with PK deficiency may be at an increased risk of mortality. Further research to understand cause of death in this population is warranted, as is the replication of this study using larger sample sizes and other real-world data sources that better represent females and the pediatric and adolescent PK deficiency age groups.
Keyword(s): Hemolytic anemia, Mortality, Pyruvate kinase deficiency, Survival