Iron Deficiency Anemia: Causes

Pathogenesis (development of disease)

Iron deficiency anemia (microcytic hypochromic anemia) is a form of anemia caused by a blood formation disorder. In this case, the formation of hemoglobin (blood pigment) is disturbed due to the lack of iron. This leads to a decrease in erythrocyte volume (mean cell size of red blood cells; MCV ↓) and also to a decrease in the content of hemoglobin in the erythrocyte (MCH ↓). In gastrointestinal (GI) disorders, iron deficiency and iron deficiency anemia are due to iron loss from bleeding, iron malabsorption from mucosal (mucosal) damage, and postoperative conditions (see below).

Etiology (causes)

Biographic causes

  • Women of childbearing age (- 20%).
  • Pregnant women – due to their increased iron requirements
  • Hormonal factors
    • Growth
    • Puberty

Behavioral causes

  • Nutrition
    • Unbalanced diet
    • Vegetarian, vegan
    • Micronutrient deficiency (vital substances) – iron; see Prevention with micronutrients.
  • Physical activity
    • Athletes (“sports anemia” due to blood volume expansion, which particularly affects the plasma volume (= blood volume without the corpuscular components (blood cells) → reduction of Hb concentration and the hematocrit (proportion of red blood cells in the volume of blood); however, athletes can also develop “true” anemia, which is most often caused by an iron deficiency) – competitive athletes and ambitious recreational athletes in the endurance field
  • Blood donors

Causes related to disease

  • Obesity (overweight) – due toobesity-associated inflammation.
  • Angiodysplasia (vascular malformations from medium-sized arteries and veins) of the stomach and duodenum (duodenum) with hemorrhage (prevalence (disease frequency) of iron deficiency anemia: 5-10%)
  • Anorexia nervosa (anorexia).
  • Blood clotting disorders
  • Bleeding (esp. in chronic gynecological or gastrointestinal bleeding)/bleeding anemia.
  • Chronic inflammation, unspecified
  • Chronic heart failure (cardiac insufficiency)
  • Chronic infections, unspecified
  • Chronic renal failure → restriction of renal erythropoietin synthesis (synonyms: erythropoietin, EPO), which stimulates erythropoiesis; furthermore, there is impaired iron incorporation and shortened erythrocyte (red blood cell) lifespan
  • Chronic inflammatory bowel diseases such as ulcerative colitis or Crohn’s disease / inflammatory anemia.
  • Diverticular disease – among the most common causes of bleeding in the lower gastrointestinal tract (prevalence of iron deficiency anemia: 25%)
  • GAVE syndrome (engl. gastric antral vascular ectasia, watermelon stomach) – stands for radial vascular dilatation of the gastric mucosa, moving from the pylorus (stomach gate) to the gastric corpus (stomach body) (prevalence of iron deficiency anemia: 2-3 %)
  • Gastritis (gastric mucosal inflammation; prevalence of iron deficiency anemia: n/a).
  • Hemorrhoids
  • Helicobacter pylori infection and associated gastritis; after eradication therapy, anemia disappeared
  • Hiatal hernia (hiatal hernia).
  • Intestinal parasitic infections (prevalence of iron deficiency anemia: 33-61%).
    • Helminthiasis (Ancylostomatidae (hookworms); Trichuris trichiura (whipworm))
  • Short bowel syndrome – due tomalabsorption and gastrointestinal bleeding (prevalence of iron deficiency anemia: 30-37%).
  • Carcinomas – especially the gastric and colon carcinoma/tumor anemia.
  • Malassimilation syndrome – complex of symptoms of different genesis of different clinical pictures as a result of malabsorption, maldigestion or a combination of both.
  • Malignant (malignant) systemic diseases.
  • Malnutrition (especially in young children and vegetarians; seniors).
  • Malnutrition (especially seniors)10-40%)
  • Non-variceal upper gastrointestinal tract bleeding (prevalence of iron deficiency anemia: 80%).
  • Esophagitis (inflammation of the esophagus) and hiatal hernia (hiatal hernia) (prevalence of iron deficiency anemia: 8-42%)
  • Esophageal variceal hemorrhage – bleeding from veins in the wall of the esophagus.
  • Gastrointestinal tract tumors/gastrointestinal tract tumors (prevalence of iron deficiency anemia: 50-60%)
    • Small intestinal tumors
    • Colorectal tumors (tumors of the colon and rectum).
    • Esophageal tumors (tumors of the esophagus).
    • Polyps
  • Ulcus ventriculi et duodeni (stomach and duodenal ulcers).
  • Celiac disease (gluten-induced enteropathy) (prevalence of iron deficiency anemia: 32-69% %).

Medications

  • Analgesics – NSAID (non-steroidal anti-inflammatory drug): e.g., acetylsalicylic acid (ASA) or non-ASA NSAID (2 to 4-fold increase in fecal blood loss) (prevalence of iron-deficiency anemia: 10-40% %).
  • Antiprotozoal agents
    • Analogue of the azo dye trypan blue (suramin).
    • Pentamidine
  • Chelating agents (D-penicillamine, trieethylenetetramine dihydrochloride (Trien), tetrathiomolybdenum).
  • Direct factor Xa inhibitor (rivaroxaban).
  • Immunosuppressants (thalidomide).
  • Janus kinase inhibitors (ruxolitinib).
  • Monoclonal antibodies – pertuzumab
  • MTOR inhibitors (everolimus, temsirolimus).
  • Neomycin
  • P-aminosalicylic acid (mesalazine)
  • Proton pump inhibitors (PPI; acid blockers) – patients on continuous PPI therapy are more often affected by iron deficiency: this depends on therapy duration and dosage
  • Thrombin inhibitor (dabigatran).
  • Tuberculostatics (isoniazid, INH; rifampicin, RMF).
  • Antivirals

Operations

  • Operations with increased blood loss
  • Condition after
    • Gastric resection (partial stomach removal; impaired absorption).
    • Bariatric surgery (biliopancreatic diversion (BPD), Roux-Y gastric bypass (RYGP), tubular gastric surgery, SG) (prevalence of iron deficiency anemia: 20-50%).
    • Ileoanal pouch (surgical procedure in which a direct anastomosis (connecting duct) is created between the last section of the ileum (scrotum) and the anus with creation of a reservoir) – due to development of symptomatic or asymptomatic pouchitis; cause of iron deficiency anemia is mucosal bleeding (mucosal hemorrhage) and impaired iron absorption (prevalence of iron deficiency anemia: 6-21%)

Other possible causes

  • Bloodletting as therapy for other blood disorders
  • Hemodialysis (kidney replacement procedure)

Legend: Prevalences see above