Can a positive Helicobacter pylori (H. pylori) test result contribute to the development of anemia?

Can H. pylori Cause Anemia?

Yes, a positive H. pylori test can cause anemia, specifically iron deficiency anemia, which is recognized as an established extragastric manifestation of H. pylori infection with Grade A evidence supporting testing and eradication. 1, 2

Mechanism and Clinical Significance

H. pylori infection leads to anemia through multiple pathways:

• Chronic occult blood loss from gastritis or peptic ulcers caused by the infection 2
• Impaired iron absorption due to atrophic gastritis and hypochlorhydria (reduced stomach acid) that develops with chronic H. pylori infection 1
• Iron sequestration by the bacteria itself, as H. pylori can capture and utilize iron from human lactoferrin through outer membrane receptors 3

The Maastricht IV/Florence Consensus Report formally recognizes iron-deficiency anemia as a confirmed extragastric manifestation with Evidence level 1a and Grade A recommendation. 2

Evidence for Treatment Benefit

The AGA guidelines recommend noninvasive testing for H. pylori in patients with iron deficiency anemia, followed by treatment if positive. 1

The evidence supporting treatment is compelling:

• Pooled analysis of 3 randomized controlled trials showed patients who received H. pylori eradication therapy plus iron supplementation had a mean hemoglobin improvement of 2.2 g/dL greater than those receiving iron supplementation alone (95% CI, 1.3–3 g/dL) 1
• Ferritin levels improved by an additional 23.2 ng/mL (95% CI, 12.2–34.3 ng/mL) in the H. pylori treatment group 1
• Long-term recovery rates in one case series showed 75% of patients recovered from anemia at 6 months and 91.7% at 12 months after H. pylori eradication, with ferritin increasing from 5.7 to 24.5 μg/L 4

Diagnostic Approach

For patients with iron deficiency anemia and negative bidirectional endoscopy:

• Use noninvasive testing (urea breath test or stool antigen test) rather than routine gastric biopsies, as this provides substantial cost savings with adequate sensitivity and specificity 1
• Avoid serology tests for active infection diagnosis, as antibodies only indicate exposure and cannot differentiate between current and previously eradicated infection 1
• Ensure proper test timing: withhold antibiotics and bismuth for at least 4 weeks, PPIs for at least 7 days before testing 1

Important Caveats

One contradictory study from 2019 found no difference in anemia resolution between H. pylori-treated and untreated patients (24.3% vs 26.5% continued anemia, p=0.71), with both groups showing similar hemoglobin improvements. 5 However, this conflicts with the pooled RCT data that informed the AGA guidelines and should be weighed against the higher-quality evidence supporting treatment. 1

Additional benefits beyond anemia resolution include decreasing the risk of gastric cancer, as H. pylori is a class I carcinogen. 1 This provides further justification for testing and treatment even when the direct anemia benefit might be questioned.

Clinical Algorithm

1. Identify iron deficiency anemia with appropriate laboratory testing
2. Perform bidirectional endoscopy if indicated based on age (>45 years) or alarm symptoms (weight loss, dysphagia, etc.) 1
3. If endoscopy is negative, proceed with noninvasive H. pylori testing (urea breath test or stool antigen) 1
4. If H. pylori positive, treat with standard eradication therapy (triple or quadruple therapy for 10-14 days) plus iron supplementation 6
5. Expect improvement in hemoglobin and ferritin over 6-12 months following successful eradication 4

The quality of evidence was rated as low due to lack of blinding in RCTs and inclusion of primarily pediatric populations, but the recommendation remains conditional in favor of testing and treatment given the potential benefits and minimal harms. 1