Peripheral blood cytopenias in the aging general population and risk of incident hematological disease and mortality

Abstract

Peripheral blood cytopenias may precede the development of hematological malignancies and frequently pose clinical challenges in the older population. The natural course of (mild) cytopenias during aging and their association with hematological disorders in community-dwelling individuals are not well studied. Within the population-based Lifelines cohort (n = 167729), we studied changes in peripheral blood counts, occurrence of cytopenias, and associated hematological outcomes in the context of aging. Development of hematological malignancies and (cause-specific) mortality were evaluated by linkage to nationwide registries. Anemia and thrombocytopenia emerged with older age, in line with a general age-related decline in these blood counts. For neutropenia, no increase in prevalence with older age was observed. Using standard reference limits to define cytopenias, anemia (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.59-2.12), thrombocytopenia (HR, 1.58; 95% CI, 1.32-1.89), and, especially the concomitant presence of anemia and thrombocytopenia (HR, 4.75; 95% CI, 2.98-7.55) were associated with inferior overall survival. Only a minor proportion of deaths was explained by diagnosed hematological malignancies, with the majority attributable to other causes. Neutropenia, either isolated (HR, 0.88; 95% CI, 0.73-1.06) or combined with another cytopenia, did not affect overall survival. For individuals aged ≥60 years, 5-year cumulative incidence of hematological malignancies was 0.60% (95% CI, 0.50-0.70), with higher incidences among those with anemia (P < .001) or thrombocytopenia (P < .001) but not neutropenia (P = .201). Highest cumulative incidences of diagnoses and mortality from hematological malignancies were observed in individuals with >1 cytopenia. We conclude that anemia and thrombocytopenia, but not neutropenia, are associated with inferior overall survival of community-dwelling individuals. Hematological malignancies develop in a small fraction of these cases.

Clonal Hematopoiesis: Role in Hematologic Non-Hematologic

“…Thus, the analysis of the incidence of cytopenias in the aging, making use of the prospective and population-based Lifelines cohort comprising 167,729 community-dwelling individuals living in the northern part of The Netherlands, showed anemia in 4,2% of cases, thrombocytopenia in 1.6% and neutropenia in 4.8%. 236 Anemia and thrombocytopenia increased with older age, while neutropenia showed no increase in prevalence with older age; anemia and thrombocytopenia and particularly the concomitant presence of anemia and thrombocytopenia were associated with reduced overall survival; for individuals aged ≥60 years the incidence of hematological malignancies was higher among individuals with anemia or thrombocytopenia but not neutropenia. 236 The highest incidence and mortality of hematological malignancies were observed in individuals with >1 cytopenia.…”

“…236 Anemia and thrombocytopenia increased with older age, while neutropenia showed no increase in prevalence with older age; anemia and thrombocytopenia and particularly the concomitant presence of anemia and thrombocytopenia were associated with reduced overall survival; for individuals aged ≥60 years the incidence of hematological malignancies was higher among individuals with anemia or thrombocytopenia but not neutropenia. 236 The highest incidence and mortality of hematological malignancies were observed in individuals with >1 cytopenia. 236 It is important to point out that the diagnosis of ICUS does not imply evidence of a clonal disorder.…”

“… 236 The highest incidence and mortality of hematological malignancies were observed in individuals with >1 cytopenia. 236 …”

“…236 The highest incidence and mortality of hematological malignancies were observed in individuals with >1 cytopenia. 236 It is important to point out that the diagnosis of ICUS does not imply evidence of a clonal disorder. However, the exploration of ICUS subjects in various studies showed that a part of these patients displayed somatic mutations.…”

Dynamin-2 deficiency causes age- and sex-dependent neutropenia and myelodysplasia in mice

“…This comes in parallel with recent reports in a human population cohort in the Netherlands, where aging women show a tendency towards lowering their neutrophil numbers, whereas aging men showed decreasing hemoglobin levels. 34 The mechanism for the male/female difference is unclear. It might implicate differences in inflammation profiles.…”