What is the next step in managing a patient with elevated white blood cell (WBC) count and absolute neutrophil count (ANC), chronic gastrointestinal (GI) blood loss without anemia, negative celiac disease test, normal erythrocyte sedimentation rate (ESR), and elevated C-reactive protein (CRP) level of 11.9?

Management of Elevated WBC/ANC with Chronic GI Blood Loss, Normal ESR, and Elevated CRP

Proceed urgently with bidirectional endoscopy (gastroscopy and colonoscopy) to identify the source of chronic GI blood loss, as this presentation suggests occult gastrointestinal pathology that requires investigation regardless of the absence of anemia. 1, 2

Immediate Diagnostic Priorities

Why Investigation is Warranted Despite No Anemia

• Chronic GI blood loss without anemia still requires full gastrointestinal evaluation, as there is no evidence that the absence of anemia is less indicative of important disease than its presence 1
• The elevated CRP (11.9) combined with chronic blood loss and leukocytosis suggests an inflammatory or neoplastic process that demands investigation 3
• Your patient's normal ESR with elevated CRP is an important discordance—CRP rises more rapidly and specifically with acute inflammation, while ESR may remain normal early in disease or with certain pathologies 4

Bidirectional Endoscopy as First-Line Investigation

Upper endoscopy (EGD) and colonoscopy should be performed as the cornerstone evaluation, with the following specific objectives: 1, 2

• During gastroscopy: Obtain small bowel (duodenal) biopsies even though celiac serology is negative, as 3-5% of iron deficiency cases are from celiac disease and serology can be falsely negative 1
• Examine carefully for: Cameron's erosions in hiatal hernias, gastric antral vascular ectasia (GAVE), angiodysplasias, peptic ulcers, and upper GI malignancies 5
• During colonoscopy: Evaluate for colonic neoplasia, angiodysplasia, inflammatory bowel disease, and other sources of occult bleeding 1
• Do not stop at finding minor lesions—complete both upper and lower GI evaluation as dual pathology occurs in 10-15% of patients 2

Interpreting the Inflammatory Markers

The Elevated WBC/ANC and CRP Pattern

• Elevated CRP with normal ESR and leukocytosis suggests active inflammation rather than chronic disease alone 3, 4
• In inflammatory bowel disease specifically, higher CRP levels and WBC counts independently predict complications including pseudopolyp formation and fistula development 3
• This pattern warrants investigation for inflammatory bowel disease (Crohn's disease or ulcerative colitis), particularly given the chronic GI blood loss 1, 3

Distinguishing from Anemia of Chronic Disease

• While your patient lacks anemia currently, the elevated CRP suggests potential for anemia of chronic disease (ACD) if inflammation persists 6, 7
• The key distinction: True iron deficiency from GI blood loss requires endoscopic source identification and treatment, whereas ACD requires treating the underlying inflammatory condition 6
• Inflammation-driven hepcidin elevation can cause iron retention in macrophages, potentially masking iron deficiency even with ongoing blood loss 6, 7

Additional Investigations to Consider

Laboratory Studies

• Measure serum ferritin to assess iron stores—ferritin <12 μg/dL is diagnostic of iron deficiency, though it may be falsely elevated above this threshold due to your patient's elevated CRP 1, 5
• Check transferrin saturation if ferritin is equivocal (12-100 μg/dL)—saturation <30% supports iron deficiency despite inflammation 1, 8
• Obtain complete blood count with red cell distribution width (RDW)—elevated RDW may indicate combined deficiency states 1
• Urinalysis to exclude renal tract blood loss as a contributor 1

If Bidirectional Endoscopy is Negative

Proceed with small bowel investigation only if red flags are present: 9

• Involuntary weight loss
• Persistent or worsening abdominal pain
• Progressive elevation of CRP
• Development of anemia despite negative upper and lower endoscopy

Small bowel capsule endoscopy is the preferred modality, as angiectasias account for up to 80% of obscure bleeding causes 5

Critical Pitfalls to Avoid

• Never assume the chronic blood loss is explained by hemorrhoids, NSAIDs, or other medications without proper endoscopic confirmation 2
• Do not defer investigation based on the absence of anemia—the chronic blood loss itself mandates evaluation 1
• Do not attribute findings solely to inflammation without excluding structural lesions, as inflammatory markers can coexist with neoplasia 1, 3
• Remember that negative celiac serology does not exclude celiac disease—duodenal biopsies should still be obtained during gastroscopy 1

Treatment Considerations Pending Investigation

• Hold off on empiric iron supplementation until the source of bleeding is identified, as this may mask ongoing blood loss 1
• Review and document all medications, particularly NSAIDs, aspirin, and anticoagulants, but do not let their presence deter full investigation 2
• Monitor hemoglobin closely while awaiting endoscopy, as the chronic blood loss may eventually lead to anemia requiring intervention 1