Low white blood count
Pro Research Analysisby 
Searched over 200M research papers
Low White Blood Cell Count: Causes, Implications, and Clinical Insights
Genetic Factors Influencing Low White Blood Cell Count
Genetic Loci and Ethnic Variations
Research has identified significant genetic factors contributing to variations in white blood cell (WBC) counts among different ethnic groups. A notable study using admixture mapping found a strong association between a locus on chromosome 1q and WBC counts in African Americans. This locus affects the expression of the Duffy blood group antigen, with individuals carrying the common West African allele exhibiting lower WBC counts compared to those with European alleles 1. Another study confirmed that a regulatory variant in the Duffy Antigen Receptor for Chemokines gene is responsible for the reduced neutrophil count observed in people of African descent 8.
Polygenic Predisposition
A polygenic predisposition to lower WBC counts has been shown to have clinical consequences. Individuals with a genetic predisposition to lower WBC counts are at a decreased risk of identifying pathology on bone marrow biopsies but are more susceptible to leukopenia when treated with chemotherapeutics or immunosuppressants. This predisposition also increases the likelihood of discontinuing treatments like azathioprine due to adverse effects 4.
Clinical Implications of Low White Blood Cell Count
Chronic Kidney Disease (CKD) Progression
In elderly patients, a low WBC count is independently associated with the progression of chronic kidney disease (CKD). A study involving elderly patients with pre-dialysis CKD stages G2-G5 found that those with lower WBC counts had a significantly higher risk of CKD progression compared to those with moderate WBC counts 2.
Impact on Athletes
Elite athletes, particularly those involved in endurance sports like cycling and triathlon, often exhibit lower WBC counts. This reduction is likely an adaptive response to the high metabolic stress associated with these sports rather than an indication of underlying pathology 3.
Schizophrenia and Antipsychotic Treatment
In patients with schizophrenia, total WBC count (TWBCc) serves as an index of chronic inflammation and is associated with clinical symptoms and metabolic alterations. Lower baseline TWBCc has been found to predict better responses to antipsychotic treatments, with significant decreases in TWBCc observed following short-term treatment with certain antipsychotics 9.
Treatment Considerations for Low White Blood Cell Count
Infection Management in Cancer Patients
Patients with cancer, particularly those undergoing chemotherapy or bone marrow transplants, often experience low WBC counts, making them highly susceptible to infections. Fever is a common early sign of infection in these patients, and prompt treatment with broad-spectrum antibiotics is crucial. Studies comparing different antibiotic combinations have found similar efficacy and safety profiles, emphasizing the importance of early and aggressive treatment to manage infections in these immunocompromised patients 6.
Dialysis and White Blood Cell Count
Patients undergoing regular hemodialysis for chronic renal failure often exhibit lower total WBC and neutrophil counts. This reduction is attributed to the adherence of neutrophils and mononuclear cells to the dialysis membrane, highlighting the need for careful monitoring and management of WBC counts in these patients 10.
Conclusion
Low white blood cell count can result from various genetic, clinical, and lifestyle factors. Understanding the underlying causes and implications is crucial for effective management and treatment. Genetic predispositions, particularly among different ethnic groups, play a significant role in WBC count variations. Clinically, low WBC counts are associated with disease progression in conditions like CKD and impact treatment responses in diseases such as schizophrenia and cancer. Tailored treatment strategies and vigilant monitoring are essential to mitigate the risks associated with low WBC counts.
Sources and full results
Most relevant research papers on this topic
Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies.
A genetic locus on chromosome 1q is strongly associated with lower white blood cell count in African Americans, explaining approximately 20% of population variation in white blood cell count.
Observational Study
Highly CitedLow white blood cell count is independently associated with chronic kidney disease progression in the elderly: the CKD-ROUTE study
Low white blood cell count is independently associated with chronic kidney disease progression in elderly patients.
Observational Study
Rigorous JournalLower white blood cell counts in elite athletes training for highly aerobic sports
Elite athletes in aerobic sports like cycling and triathlon have significantly lower white blood cell counts, likely due to an adaptive response rather than underlying pathology.
Observational StudyClinical consequences of a polygenic predisposition to benign lower white blood cell counts
A genetic predisposition to benign lower white blood cell counts can increase the risk of leukopenia, leukoencephalopathy, and discontinuing azathioprine treatment in clinical care.
Observational Study
PreprintMeta‐analysis of total and differential white blood cell counts in schizophrenia
Schizophrenia is associated with increased total white blood cell count, indicating low-grade inflammation in the brain.
Meta-Analysis
Very Rigorous JournalHighly CitedTreatment of Fever in Hospitalized Patients with Low White Blood Cell Counts
Piperacillin plus ciprofloxacin and piperacillin plus tobramycin both have similar efficacy and safety for treating fever in hospitalized cancer patients with low white blood cell counts.
RCT
Large Human TrialLarge-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases.
16 common genetic variants are associated with white blood cell traits and autoimmune diseases, suggesting a shared genetic architecture with inflammatory and autoimmune diseases.
Meta-AnalysisRigorous JournalReduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene
The Duffy Null polymorphism, rs2814778, is associated with reduced neutrophil count in African Americans, indicating a novel genetic phenotype for this gene.
Observational StudyHighly CitedThe Role of Total White Blood Cell Count in Antipsychotic Treatment for Patients with Schizophrenia
Lower total white blood cell count in schizophrenia patients predicts better drug response and mediates the effects of certain metabolic measures on improving negative symptoms.
RCTWhite blood count in patients on regular haemodialysis
Regular haemodialysis in chronic renal failure patients leads to the lowest total white cell and neutrophil counts, with the highest lymphocyte counts.
Observational Study