Case Presentation: A 48-year-old female with no known medical history presented after a syncopal episode and one week of malaise and fatigue. She was diagnosed with high output heart failure complicating severe pulmonary hypertension. Hemoglobin was 2.7 g/dL with MCV of 50 fL. She denied menorrhagia, melena, hematuria or hematemesis as well as weight loss or travel history. She reported a balanced diet without restrictions. Work-up was consistent with iron deficiency anemia and positive H. pylori stool antigen. Gastric parietal cell antibody titer was 40.6, but with normal gastrin level and negative intrinsic factor antibody. Pulmonary artery catheterization demonstrated severe pulmonary hypertension with high output heart failure physiology. Colonoscopy was unremarkable. Esophagogastroduodenoscopy was significant for atrophic gastric mucosa and presence of H. pylori on pathology. Remaining extensive workup was non-contributory. She received blood transfusions and intravenous iron with resolution of her symptoms. Her severe PH likely led to right heart failure with congestive hepatopathy in the setting of severe anemia with compensatory high output heart failure physiology. H. pylori treatment was continued at discharge and appropriate follow-up was arranged.
Discussion: Chronic hypoxia is a well-known cause of Pulmonary Hypertension (PH). Chronic anemia can lead to a hypoxic state leading to development of PH. Hypoxia triggers thickening of the medial layer of pulmonary vasculature via stimulation of fibroblast migration and subsequent differentiation into smooth muscle cells. Endothelial cells found in pulmonary vasculature can produce vasoconstrictive mediators and decrease the production of vasodilatory and anti-proliferative mediators such as nitric oxide. Additionally, in vitro studies suggest that hypoxia can induce proliferation of inflammatory mediators such as IL-6 from vascular smooth muscle cells. These combined mechanisms lead to increased pulmonary vascular resistance.Iron deficiency and Iron Deficiency Anemia (IDA) have also been implicated in pulmonary arterial hypertension (PAH), and idiopathic PH. Dysregulation of iron homeostasis causes pulmonary vascular endothelial dysfunction via overexpression of endothelin 1 and suppression of nitric oxide. Hypoxic states induce hypoxia-inducible factors (HIFs) which are thought to play a role in hepcidin suppression. The pro-inflammatory cytokine IL-6 is induced by iron depletion and correlates with lower iron levels in patients with Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH). However, the exact mechanism between these cellular mediators, anemia, and development of PH has not been fully elucidated.
Conclusions: We describe a case of severe anemia, in the setting of H. pylori infection, that led to development of PH. This case emphasizes the importance of routine primary care and age appropriate preventative and cancer screening. The patient did not have any routine care for the majority of her adult life. Her anemia would likely have been detected and treated during routine preventative screening, thereby preventing the above described complications.