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

Isabelle A van Zeventer, Aniek O de Graaf, Melanie M van der Klauw, Edo Vellenga, Bert A van der Reijden, Jan Jacob Schuringa, Arjan Diepstra, Luca Malcovati, Joop H Jansen, Gerwin Huls*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 = 167 729), 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 >= 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.

Original languageEnglish
Pages (from-to)3266-3278
Number of pages13
JournalBlood
Volume5
Issue number17
Early online date30-Aug-2021
DOIs
Publication statusPublished - 14-Sep-2021

Keywords

  • UNDETERMINED SIGNIFICANCE ICUS
  • CLONAL HEMATOPOIESIS
  • PLATELET COUNT
  • HEMOGLOBIN CONCENTRATION
  • IDIOPATHIC CYTOPENIAS
  • CLINICAL-SIGNIFICANCE
  • MILD ANEMIA
  • AGE
  • SEX
  • PREVALENCE

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