What causes anemia in men without trauma or gastrointestinal bleeding?

Causes of Anemia in Men Without Injury or Gastrointestinal Bleeding

In men presenting with anemia without obvious bleeding, the primary non-bleeding causes are celiac disease (causing malabsorption), chronic NSAID use (often unreported), nutritional deficiencies, chronic kidney disease, and chronic inflammatory conditions. 1, 2

Malabsorption Disorders

Celiac disease is found in 3-5% of all iron deficiency anemia cases and must be screened for in every patient with unexplained anemia. 1, 2 This is accomplished through:

• Tissue transglutaminase antibody (IgA type) testing with concurrent total IgA level 3
• Upper endoscopy with duodenal biopsies if serology is positive or clinical suspicion remains high 1, 2

Other malabsorption causes include:

• Previous gastrectomy or bariatric surgery, which impairs iron absorption 2, 3
• Chronic proton pump inhibitor (PPI) therapy, which reduces gastric acid needed for iron absorption 2
• Gastric atrophy and bacterial overgrowth 2
• Small bowel disease, resection, or bypass procedures 2

Medication-Induced Blood Loss

• NSAIDs (including over-the-counter ibuprofen, naproxen, and aspirin) are common and frequently unreported causes of occult gastrointestinal blood loss, even without overt bleeding symptoms. 4
• Anticoagulants and antiplatelet agents can unmask underlying vascular lesions like angiodysplasia 1
• Explicitly asking about all NSAID use is essential, as patients often don't consider over-the-counter medications worth mentioning 4

Nutritional Deficiencies

• Poor dietary iron intake, particularly in men of lower socioeconomic status with limited access to iron-rich foods 5
• Vitamin B12 deficiency from pernicious anemia (intrinsic factor deficiency), strict vegetarian diets, or gastric atrophy 6, 7
• Folate deficiency, though less common in men than nutritional iron deficiency 7, 8

Chronic Disease States

Approximately one-third of anemia cases in older men are due to chronic inflammation or chronic kidney disease. 8

• Chronic kidney disease causes anemia through reduced erythropoietin production 1, 8
• Chronic inflammatory conditions (rheumatoid arthritis, inflammatory bowel disease, chronic infections) cause anemia of chronic disease through hepcidin-mediated iron sequestration 7, 8
• Androgen deprivation therapy in prostate cancer survivors causes normochromic normocytic anemia through suppression of erythropoiesis 1

Non-Gastrointestinal Blood Loss

• Urinary tract bleeding from bladder lesions, kidney stones, or malignancy—urinalysis should be performed in all cases 5, 2
• Chronic epistaxis or other mucosal bleeding 2
• Frequent blood donation 1, 2

Unexplained Anemia

In approximately one-third of elderly men, no specific cause can be identified despite thorough investigation—this "unexplained anemia" may result from age-related bone marrow resistance to erythropoietin and chronic subclinical inflammation. 7, 8

Critical Diagnostic Approach

When gastrointestinal bleeding has been excluded through negative bidirectional endoscopy:

• Screen for celiac disease with tissue transglutaminase antibody (mandatory) 1, 3
• Check urinalysis to exclude urinary tract bleeding 5
• Obtain comprehensive medication history focusing on NSAIDs and anticoagulants 4
• Assess renal function (creatinine, eGFR) to evaluate for chronic kidney disease 8
• Check inflammatory markers (CRP, ESR) if chronic disease suspected 9, 8
• Consider vitamin B12 and folate levels, particularly in older men or those with dietary restrictions 6, 8

Small bowel investigation with capsule endoscopy is not routinely recommended after negative bidirectional endoscopy unless red flags are present (involuntary weight loss, abdominal pain, elevated CRP). 3

Common Pitfalls

• Assuming all anemia in men must be from gastrointestinal bleeding—this misses treatable malabsorption and nutritional causes 2, 3
• Failing to ask specifically about over-the-counter NSAID use 4
• Not screening for celiac disease, which is present in 3-5% of cases 1, 2
• Accepting "unexplained anemia" diagnosis before excluding urinary tract bleeding, celiac disease, and medication causes 3, 8
• Using falsely elevated ferritin in inflammatory states to exclude iron deficiency—always check CRP alongside ferritin 9