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

Neutropenia (NP), that is, an absolute blood neutrophil count (ANC) <1.5 g/L, accompanies various diseases. However, the clinical significance of NP, detected in routine complete blood cell counts (CBC) in primary care, is poorly characterized. Here, from a primary care resource with ANCs from >370 000 individuals, we identified and followed neutropenic subjects for the next 4 years for novel ICD-10 based diagnoses of viral infections and hematological malignancies (ie, previously identified major outcomes in NP individuals) in Danish nationwide health registers. Risk estimates were assessed for children/adolescents (1-18 years) and adults (19-90 years) in relation to NP severity, and for isolated NP, bi- or pancytopenias. We found that NP was observed in 4.9% of children and in 1.9% of adults. The lower the ANC, the likelier was a diagnosis of viral infections or hematological malignancies established during the ensuing 4 years. Among neutropenic children, unspecified viral infections predominated, followed by mononucleosis (with other cytopenias in only 7% and 25% of the cases, respectively). All NP children with acute leukemia presented with bi- or pancytopenia from start of follow-up. In NP adults, hepatitis, followed by HIV, were the most common infections, and acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDSs) the predominating hematological malignancies. Adult NP patients, subsequently diagnosed with hepatitis, HIV or AML, MDS, were bi- or pancytopenic in 42%, 47%, 90% and 91% of cases, respectively. Thus, presence of NP in even one CBC may be the first sign of a latent viral or hematological disorder requiring careful follow-up.