What causes a decrease in both White Blood Cell (WBC) and Red Blood Cell (RBC) counts?

Causes of Decreased WBC and RBC Count

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. 1

Primary Causes

Bone Marrow Disorders

• Bone marrow infiltration by cancer cells directly suppresses hematopoiesis, affecting both red and white cell production 1
• Myelodysplastic syndromes cause ineffective production of multiple cell lines 1
• Aplastic anemia results in pancytopenia (decreased RBCs, WBCs, and platelets) due to stem cell dysfunction 2
• Leukemia, particularly in advanced stages, can suppress normal bone marrow function 1

Nutritional Deficiencies

• Iron deficiency can affect both RBC production (causing microcytic hypochromic anemia) and WBC production in severe cases 3
• Vitamin B12 and folate deficiencies impair DNA synthesis, affecting rapidly dividing cells including both RBC and WBC precursors 1

Medications and Treatments

• Chemotherapy agents cause myelosuppression affecting multiple cell lines 1
• Radiation therapy to bone marrow-containing areas leads to radiation-induced myelosuppression 1
• Certain antibiotics, anticonvulsants, and immunosuppressants can cause bone marrow suppression 1

Systemic Causes

Infections

• Viral infections (particularly HIV, hepatitis, CMV, EBV) can suppress bone marrow function 4
• Severe bacterial infections may cause bone marrow suppression or increased peripheral destruction of cells 4
• COVID-19 has been associated with both decreased RBC and WBC counts through multiple mechanisms 1

Autoimmune Conditions

• Systemic lupus erythematosus (SLE) can cause autoimmune hemolytic anemia and leukopenia 1
• Rheumatoid arthritis and other autoimmune disorders may affect multiple cell lines 2

Other Systemic Disorders

• Chronic kidney disease affects erythropoietin production and can lead to both anemia and leukopenia 1
• Hypersplenism causes sequestration and destruction of both RBCs and WBCs 1
• Chronic liver disease affects multiple hematologic parameters 1
• Inflammatory bowel disease can cause both anemia and leukopenia through multiple mechanisms 1

Diagnostic Approach

Initial Assessment

• Evaluate for bone marrow failure vs. peripheral destruction/sequestration 1
• Check reticulocyte count - low counts suggest production problem, high counts suggest destruction or loss 5
• Assess for nutritional deficiencies (iron studies, B12, folate) 3
• Consider medication review for potential bone marrow suppressants 1

Advanced Workup

• Peripheral blood smear to evaluate cell morphology 6
• Bone marrow biopsy if primary bone marrow disorder is suspected 2
• Autoimmune markers if autoimmune condition is suspected 1
• Imaging to assess for splenomegaly if hypersplenism is suspected 1

Special Considerations

• Ethnic variations exist in normal WBC ranges - African Americans typically have lower baseline WBC and neutrophil counts 7
• Nucleated RBCs in peripheral blood can falsely elevate WBC counts on automated analyzers 8
• Decreased RBC deformability can be an early indicator of infection, preceding changes in WBC count 4

Clinical Pearls

• The combination of decreased WBC and RBC often indicates a more serious systemic disorder than either finding alone 6
• When both cell lines are affected, bone marrow examination is frequently warranted to determine the underlying cause 2
• In cancer patients, the pathogenesis is often multifactorial, including direct marrow infiltration, treatment effects, and nutritional factors 1
• Always consider medication effects as potentially reversible causes before pursuing extensive workup 1