What are common causes of leukopenia and anemia in a patient, particularly in the elderly or those with compromised immune systems?

Common Causes of Low White Blood Cell Count and Low Hemoglobin

The most common causes of concurrent leukopenia and anemia (pancytopenia when platelets are also affected) include bone marrow disorders (megaloblastic anemia, aplastic anemia, myelodysplastic syndromes, hematological malignancies), myelosuppressive chemotherapy, autoimmune diseases, infections, and nutritional deficiencies—with the specific etiology requiring systematic evaluation through complete blood count with differential, peripheral smear, and often bone marrow examination. 1

Primary Etiological Categories

Bone Marrow Production Disorders

• Megaloblastic anemia from vitamin B12 or folate deficiency is a leading cause, producing both anemia and leukopenia through ineffective hematopoiesis 1, 2
• Myelodysplastic syndromes affect 10.7% of pancytopenia cases, characterized by ineffective hematopoiesis and dysplastic changes in bone marrow 1
• Aplastic anemia causes pancytopenia through bone marrow failure, requiring immunosuppressive therapy for non-severe cases and hematopoietic stem cell transplantation for severe cases 1
• Hematological malignancies including acute and chronic leukemias directly suppress normal hematopoiesis through bone marrow infiltration 3, 1

Myelosuppressive Chemotherapy

• Chemotherapy agents cause pancytopenia through direct bone marrow suppression, with purine analog-based therapies (fludarabine) and alemtuzumab particularly associated with prolonged myelosuppression 3, 1
• Monitoring for myelosuppression is essential during treatment, with dose reductions or delays often required for grade 3-4 neutropenia and thrombocytopenia 3
• Methotrexate can cause pancytopenia even with low-dose weekly therapy, particularly in patients with impaired renal function or concomitant sulfonamide medications, typically occurring 4-6 weeks after dose increases 1

Autoimmune Diseases

• Systemic lupus erythematosus causes anemia in more than half of patients and leukopenia affecting both granulocytic and lymphocytic lines through autoantibodies 4
• Approximately 10% of SLE patients with positive Coombs' test manifest clinically significant hemolysis 4
• Autoimmune hemolytic anemia can occur with various conditions and should not preclude combination therapy when indicated, though careful observation is required 3

Infectious Causes

• HIV infection commonly causes cytopenias and requires testing in all adult patients with pancytopenia 1
• Hepatitis C virus is associated with cytopenias and warrants screening 1
• Brucellosis commonly presents with mild transaminitis and pancytopenia, with bone marrow culture having the highest diagnostic sensitivity 1
• Ehrlichiosis causes pancytopenia with leukopenia and thrombocytopenia, particularly in immunosuppressed patients who experience more severe symptoms 1
• Hemophagocytic lymphohistiocytosis presents with pancytopenia, fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin 1

Peripheral Destruction and Sequestration

• Hypersplenism with sequestration is a common cause of hematologic abnormalities, often more frequent than bone marrow involvement in sarcoidosis 3
• Compartmentalization of white blood cells to sites of organ involvement causes leukopenia and lymphopenia in the absence of splenomegaly 3

Diagnostic Algorithm

Initial Laboratory Evaluation

• Complete blood count with differential is essential to confirm cytopenias and assess severity, with manual peripheral blood smear examination critical to exclude pseudothrombocytopenia and identify morphological abnormalities 1, 5
• Reticulocyte count helps differentiate between production defects (low reticulocyte count) and peripheral destruction (elevated reticulocyte count) 1
• Check previous blood counts to assess the dynamic development of cytopenias 5

Specific Testing Based on Clinical Context

• Vitamin B12, folate, and iron studies (including ferritin, total iron binding capacity) should be obtained prior to treatment, as megaloblastic anemia is a common reversible cause 3, 1, 2
• HIV and HCV testing is recommended in all adult patients with pancytopenia 1
• Autoimmune workup including ANA and anti-dsDNA should be considered if systemic symptoms suggest autoimmune disease 1

Bone Marrow Examination Indications

• Bone marrow examination is indicated in most cases of pancytopenia, especially in patients over 60 years of age, those with systemic symptoms or abnormal physical findings, and cases where diagnosis remains unclear after initial testing 1
• In immunotherapy-treated patients, maintain a low threshold for bone marrow examination to rule out marrow infiltration, secondary myelodysplastic syndromes, or aplastic anemia 1
• Cytogenetic analysis of bone marrow is essential for diagnosing myelodysplastic syndromes and identifying specific chromosomal abnormalities that guide prognosis and treatment 1

Critical Clinical Pitfalls

Vitamin B12 Deficiency Management

• Vitamin B12 deficiency allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord 2
• Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with vitamin B12 deficiency, but neurologic manifestations will not be prevented and irreversible damage will result if not treated with vitamin B12 2
• Patients with pernicious anemia require monthly injections of vitamin B12 for the remainder of their lives 2

Agranulocytosis Recognition

• Leukopenia with agranulocytosis and fever represents a medical emergency requiring immediate admission and broad-spectrum antibiotics to reduce mortality 5
• White blood cell counts above 100,000 per mm³ represent a medical emergency because of the risk of brain infarction and hemorrhage 6

Sarcoidosis-Related Cytopenias

• In sarcoidosis, hematologic abnormalities (leukopenia, lymphopenia, anemia, thrombocytopenia) raise the possibility of bone marrow involvement, though splenomegaly with sequestration is more common 3
• Baseline complete blood cell count testing is recommended to screen for hematological abnormalities in sarcoidosis patients 3

Drug-Induced Cytopenias

• Medications commonly associated with leukocytosis (corticosteroids, lithium, beta agonists) should be distinguished from causes of leukopenia 6
• Antibiotics, methotrexate, and pyrimethamine can invalidate folic acid and vitamin B12 diagnostic blood assays 2
• Colchicine, para-aminosalicylic acid, and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12 2

Management Priorities

Treat Underlying Cause

• Primary focus is treating the underlying cause with supportive care including transfusions for symptomatic anemia or severe thrombocytopenia 1
• Immunosuppressive therapy is recommended for non-severe aplastic anemia cases 1
• Hypomethylating agents such as azacitidine are recommended for higher-risk myelodysplastic syndromes patients not eligible for stem cell transplantation 1

Supportive Care During Chemotherapy

• Appropriate supportive care is particularly important to ensure full-dose chemotherapy is delivered on schedule in adjuvant and neoadjuvant settings where chemotherapy is used with curative intent 3
• Evaluating the need for erythropoietin support in patients whose hemoglobin levels are less than 11 g/dL may be particularly important, especially in lung cancer patients 3

Infection Management

• Antimicrobial therapy should be directed at the specific pathogen in infection-related pancytopenia, with eradication therapy for H. pylori if positive, and antiviral therapy for HIV/HCV 1