Causes of Decreased WBC and RBC Count

Primary Causes

Simultaneous decreases in both white blood cell (WBC) and red blood cell (RBC) counts are most commonly caused by bone marrow suppression, nutritional deficiencies, or systemic diseases that affect hematopoiesis, according to the National Comprehensive Cancer Network 1, 2
Bone marrow infiltration by cancer cells directly suppresses hematopoiesis, affecting both red and white cell production, as reported by the American Journal of Hematology and the National Comprehensive Cancer Network 3, 1
Myelodysplastic syndromes cause ineffective production of multiple cell lines, according to the National Comprehensive Cancer Network 2
Leukemia, particularly in advanced stages, can suppress normal bone marrow function, as stated by the National Comprehensive Cancer Network 1

Iron deficiency can affect both RBC production and WBC production in severe cases, as noted by Praxis Medical Insights 4
Vitamin B12 and folate deficiencies impair DNA synthesis, affecting rapidly dividing cells including both RBC and WBC precursors, according to the National Comprehensive Cancer Network and the Journal of Crohn's and Colitis 2, 5

Chemotherapy agents cause myelosuppression affecting multiple cell lines, as reported by the American Journal of Hematology and the National Comprehensive Cancer Network 3, 6
Radiation therapy to bone marrow-containing areas leads to radiation-induced myelosuppression, according to the National Comprehensive Cancer Network 2
Certain antibiotics, anticonvulsants, and immunosuppressants can cause bone marrow suppression, as stated by the National Comprehensive Cancer Network 1

COVID-19 has been associated with both decreased RBC and WBC counts through multiple mechanisms, as reported by Cell Death and Disease 7
Systemic lupus erythematosus (SLE) can cause autoimmune hemolytic anemia and leukopenia, according to Cell Death and Disease and the Journal of Crohn's and Colitis 7, 5
Chronic kidney disease affects erythropoietin production and can lead to both anemia and leukopenia, as noted by the American Journal of Hematology and Cell Death and Disease 3, 7
Hypersplenism causes sequestration and destruction of both RBCs and WBCs, according to the American Journal of Hematology 3
Chronic liver disease affects multiple hematologic parameters, as reported by the National Comprehensive Cancer Network 2
Inflammatory bowel disease can cause both anemia and leukopenia through multiple mechanisms, according to the Journal of Crohn's and Colitis 5

Evaluate for bone marrow failure vs. peripheral destruction/sequestration, as recommended by the National Comprehensive Cancer Network 1, 2
Check reticulocyte count - low counts suggest production problem, high counts suggest destruction or loss, as noted by Praxis Medical Insights 8
Assess for nutritional deficiencies (iron studies, B12, folate), as recommended by Praxis Medical Insights 4
Consider medication review for potential bone marrow suppressants, as reported by the American Journal of Hematology 3
Autoimmune markers if autoimmune condition is suspected, according to the Journal of Crohn's and Colitis 5
Imaging to assess for splenomegaly if hypersplenism is suspected, as noted by the American Journal of Hematology 3

In cancer patients, the pathogenesis is often multifactorial, including direct marrow infiltration, treatment effects, and nutritional factors, as reported by the American Journal of Hematology and the National Comprehensive Cancer Network 3, 6
Always consider medication effects as potentially reversible causes before pursuing extensive workup, as stated by the National Comprehensive Cancer Network 1