Age‐related prevalence and clinical significance of neutropenia ‐ isolated or combined with other cytopenias: Real world data from 373 820 primary care individuals

Palmblad, Jan; Siersma, Volkert; Lind, Bent; Bjerrum, Ole Weis; Hasselbalch, Hans Carl; Andersen, Christen Lykkegaard

doi:10.1002/ajh.25756

Cited by 11 publications

(17 citation statements)

References 26 publications

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“…The prevalence of moderate neutropenia (ie, neutrophils ,1.5 3 10 9 /L) was comparable to a general practice registry cohort of comparable ethnicity. 30,31 However, the prevalence of mild neutropenia (neutrophils ,1.8 3 10 9 /L) in our population-based cohort was relatively high compared with this general practice-based cohort and might also reflect differences in sample population. 30,31 Severe neutropenia, in accordance with previous studies, [30][31][32] was very uncommon.…”

Section: Discussionmentioning

confidence: 61%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 61%

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

et al. 2021

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“…5,26 It is extremely unlikely for chronic isolated neutropenia to progress to sinister diagnoses like hematological malignancies. 27 The finding of this study should provide an insight into the practicing haematologists about the prevalence and magnitude of the benign ethnic neutropenia in our population. Ideally, a long-term follow-up is needed to confirm the good prognosis of the condition in our population.…”

Section: Discussionmentioning

confidence: 78%

<p>The Prevalence of Isolated Neutropenia at High Altitude in Southern Saudi Arabia: Does Altitude Affect Leucocyte Count?</p>

Alkhaldy¹,

Awan²,

Abouzaid³

et al. 2020

IJGM

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Introduction: Isolated neutropenia is a common problem in hematology practice. Benign ethnic neutropenia (BEN) is the common form of neutropenia worldwide and it affects mainly African and Middle Eastern ethnicities. Most cases of isolated mild and moderate neutropenia are benign and associated with no clinical significance. The aim of this study was to estimate the prevalence of isolated neutropenia at high-altitude southern Saudi Arabia. Methods: A large dataset of complete blood counts (CBCs) was analyzed for walk-in patients of both genders, of age ranges from 12 to 60 years doing blood tests at a commercial lab for high altitude − 2,270 meters above sea level-(HA) group, and from sea level SL group. Abnormal biochemical or CBC results were excluded before analysis. Results: For HA group, 3123 CBCs were analyzed and for SL group 18,427 CBCs were analyzed. The prevalence of mild neutropenia, defined as absolute neutrophil count (ANC) in the range of 1.0−.5× 10 9 /L, was 12.4% (n=399) versus 5.6% (n=1025), while moderate neutropenia, defined as ANC of 0.5-1 × 10 9 /L, was present 6% (n=191) versus 1.45% (n=269) in the high altitude and sea level groups, respectively. Severe neutropenia, defined as neutrophil count less than 0.5-1 × 10 9 /L, was rare in both groups. Conclusion: Isolated neutropenia is common in Saudis living at high altitude. While benign ethnic neutropenia (BEN) is thought to be the major contributing factor to this high prevalence, other factors including environmental factors and altitude are possible contributing factors along with underlying ethnic neutropenia.

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“…When clinicians encounter neutropenia, they first should exclude the most common causes of low ANCs (ie viral infections and haematological malignancies) 1 . Graves’ hyperthyroidism as a cause of neutropenia should be primarily considered due to the occurrence of clinical manifestations of thyrotoxicosis, then biochemically confirmed.…”

Section: Discussionmentioning

confidence: 99%

“…In the included papers, hyperthyroidism was documented by confirmatory thyroid function tests, thyroid scintigraphy and/or thyrotropin receptor antibodies (TRAb). To code and extract the number of neutropenic patients and define the degree of neutropenia and its resolution, we adopted the following definitions 1,15 : subnormal neutropenia when ANC ranged from 1.5 to <1.8 × 10 9 /L; mild neutropenia when ANC ranged from 1.0 to <1.5 × 10 9 /L; moderate neutropenia when ANC ranged from 0.5 to <1 × 10 9 /L; and severe neutropenia (agranulocytosis) when ANC was <0.5 × 10 9 /L. We defined normal neutrophil count an ANC between the threshold of neutropenia (<1.8 × 10 9 /L) or the presence of neutrophilia (ANC > 7.4 × 10 9 /L) 1 …”

Section: Methodsmentioning

confidence: 99%

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Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis

Scappaticcio

Maiorino

Maio

et al. 2020

Clinical Endocrinology

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Background and Objective Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new‐onset hyperthyroidism. The aim of this systematic review and meta‐analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting. Methods A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non‐English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta‐analysis was performed with DerSimonian and Laird method (random‐effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I2 statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two‐sided P‐value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included. Results The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta‐analysis. Results of the meta‐analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves’ hyperthyroidism was 10% (CI 5%‐19%, I2 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 109/L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable. Conclusions Graves’ disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.

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Age‐related prevalence and clinical significance of neutropenia ‐ isolated or combined with other cytopenias: Real world data from 373 820 primary care individuals

Cited by 11 publications

References 26 publications

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

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

<p>The Prevalence of Isolated Neutropenia at High Altitude in Southern Saudi Arabia: Does Altitude Affect Leucocyte Count?</p>

Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis

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