Can Constipation or Drug Use Cause Leukocytosis?
Yes, both constipation (particularly when complicated by stercoral colitis) and certain medications can cause leukocytosis, though through different mechanisms and with varying degrees of severity.
Constipation as a Cause of Leukocytosis
Constipation itself does not typically cause leukocytosis, but severe constipation complicated by stercoral colitis can produce marked leukocytosis 1.
A documented case demonstrated a 9-year-old with chronic constipation who developed stercoral colitis and presented with a white blood cell count of 66,000/mm³—a dramatic elevation that resolved after manual disimpaction and supportive care 1.
The mechanism involves inflammatory response to colonic wall ischemia and necrosis caused by pressure from impacted stool, triggering a systemic inflammatory reaction with neutrophil mobilization 1.
Stercoral colitis represents a serious complication of severe constipation that can mimic infectious or malignant processes, and the leukocytosis serves as a marker of the inflammatory severity 1.
Clinical Context for Constipation-Related Leukocytosis
Clostridium difficile infection should be strongly considered in hospitalized patients with constipation or diarrhea who develop leukocytosis, particularly if they have recent antibiotic exposure 2.
C. difficile-positive patients demonstrate mean WBC counts of 15,800/mm³ compared to 7,700/mm³ in C. difficile-negative patients 2.
Leukocytosis can appear in three patterns with C. difficile: sudden increase with symptom onset, unexplained elevation preceding diarrhea (serving as a harbinger), or worsening of pre-existing leukocytosis 2.
Marked leukocytosis (>15 × 10⁹/L) is a sign of severe C. difficile colitis and should prompt aggressive management 3.
Drug-Induced Leukocytosis
Multiple medications are well-established causes of leukocytosis through direct bone marrow stimulation or demargination of white blood cells 4, 5.
Medications Most Commonly Associated with Leukocytosis
Corticosteroids are the most common pharmacologic cause, producing neutrophilia through demargination of neutrophils from vessel walls and reduced migration from blood to tissues 4, 5.
Lithium stimulates granulocyte colony-stimulating factor production, leading to sustained neutrophilia 4, 5.
Beta-agonists cause acute leukocytosis through demargination mechanisms 4, 5.
Anticholinergic medications (such as clidinium in Librax) can indirectly contribute to leukocytosis by causing severe constipation that may progress to stercoral colitis 6, 1.
Important Considerations for Drug-Induced Leukocytosis
Drug-induced leukocytosis is typically mild to moderate (rarely exceeding 25,000-30,000/mm³) and characterized by mature neutrophils without left shift 4, 5.
The peripheral white blood cell count can double within hours after certain stimuli (including medications) due to large bone marrow storage pools and intravascularly marginated neutrophils 5.
Physical and emotional stress can also elevate WBC counts through similar demargination mechanisms, which should be considered in the differential 4, 5.
Critical Red Flags Requiring Further Investigation
Extremely elevated WBC counts (>100,000/mm³) represent a medical emergency due to risk of leukostasis, brain infarction, and hemorrhage, and suggest primary bone marrow disorders rather than reactive causes 4, 7.
Suspect primary bone marrow disorders when leukocytosis is accompanied by: concurrent red blood cell or platelet abnormalities, weight loss, bleeding or bruising, hepatosplenomegaly, lymphadenopathy, or immunosuppression 4, 5.
Aggressive hydration (2.5-3 liters/m²/day) should be implemented immediately in cases of severe leukocytosis, with consideration of hydroxyurea (50-60 mg/kg/day) to rapidly reduce counts 7, 8.
Baseline metabolic panel, uric acid, LDH, and phosphate should be checked to assess tumor lysis syndrome risk in patients with marked leukocytosis 8.
Practical Clinical Approach
When evaluating leukocytosis in the context of constipation or medication use:
First, assess severity: WBC >100,000/mm³ requires emergency evaluation for hyperleukocytosis; WBC 15,000-30,000/mm³ suggests reactive process 4, 7.
Review medication list for corticosteroids, lithium, beta-agonists, and anticholinergics 4, 5.
Evaluate for complications of constipation: abdominal tenderness, fever, or signs of peritonitis suggest stercoral colitis requiring imaging 1.
Test for C. difficile in any patient with recent antibiotic exposure, particularly if leukocytosis is marked (>15,000/mm³) 3, 2.
Obtain peripheral blood smear to assess white blood cell maturity and morphology—mature cells suggest reactive process, while immature forms or blasts suggest malignancy 4, 5.