Vitamin B12 Deficiency Anaemia

Most common cause of anemia worldwide, resulting from inadequate iron for hemoglobin synthesis due to insufficient intake, malabsorption, increased demand, or most importantly in adults; chronic blood loss.

Microcytic, hypochromic anemia. In adult males and postmenopausal women, iron deficiency is presumed to be from GI blood loss until proven otherwise, given malignancy risk.

Etiologies:

• Blood loss: GI (peptic ulcer, malignancy, angiodysplasia, IBD, hookworm/parasitic infection, hemorrhoids, esophageal varices), menstrual (menorrhagia), other (urinary, recurrent epistaxis, blood donation)

• Increased demand: pregnancy, infancy/rapid growth, lactation

• Decreased intake/absorption: dietary insufficiency (vegetarian/vegan without supplementation, poverty/malnutrition), malabsorption (celiac disease, atrophic gastritis, post-gastrectomy/bariatric surgery, H. pylori infection reducing absorption)

• General anemia symptoms: fatigue, weakness, exertional dyspnea, palpitations, pallor (conjunctival, palmar creases, skin)

• Iron deficiency-specific features:

• Koilonychia (spoon-shaped nails)

• Angular stomatitis/cheilitis

• Glossitis (smooth, sore tongue)

• Pica (craving non-food substances; ice/pagophagia is classically associated, also clay, starch)

• Restless legs syndrome

• Hair thinning

• Symptoms/signs of underlying cause: melena/hematochezia (GI bleed), menorrhagia history, dyspepsia/weight loss (malignancy red flags), diarrhea/bloating (celiac/malabsorption)

• Severe/chronic anemia: tachycardia, flow murmur, high-output cardiac failure in extreme cases

• Plummer-Vinson syndrome (rare): triad of iron deficiency anemia, esophageal web, dysphagia; premalignant for esophageal SCC

FBC: microcytic (low MCV), hypochromic (low MCH) anemia; low hemoglobin

Iron studies:

• Serum ferritin: low (most specific test for iron deficiency; but is an acute phase reactant, may be falsely normal/elevated in inflammation/infection/liver disease, so interpret with CRP)

• Serum iron: low

• Total iron-binding capacity (TIBC)/transferrin: elevated (compensatory increase)

• Transferrin saturation: low (<15-20%)

Peripheral blood film: microcytic hypochromic red cells, anisocytosis, poikilocytosis, occasional target cells, pencil cells

Reticulocyte count: low/inappropriately normal for degree of anemia

Mandatory investigation for underlying cause in adults (especially males and postmenopausal females)

GI evaluation:

• Bidirectional endoscopy (upper GI endoscopy + colonoscopy) to exclude malignancy/source of chronic blood loss, even in absence of overt GI symptoms

• Celiac serology (anti-tTG IgA, total IgA): consider in unexplained iron deficiency, especially with additional malabsorption features

• Stool studies for occult blood/parasites (hookworm in endemic areas)

• Menstrual history assessment in women (may explain deficiency without need for GI workup if history clearly supports menorrhagia and age/risk profile is low, per clinical judgment)

Differentials for microcytic anemia: thalassemia trait/disease (normal/high ferritin, disproportionately low MCV relative to hemoglobin level, abnormal hemoglobin electrophoresis, often normal or elevated RBC count), anemia of chronic disease (usually normocytic but can be microcytic, ferritin normal/high, low TIBC: distinguishes from iron deficiency), sideroblastic anemia, lead poisoning.

Oral iron replacement (first-line):

• Ferrous sulfate 200mg od-tds (65mg elemental iron per tablet), or ferrous fumarate, ferrous gluconate; dosing increasingly moving toward once-daily or alternate-day dosing (improves absorption via reduced hepcidin response and improves tolerability vs. traditional multiple-daily dosing)

• Take on empty stomach with vitamin C source (enhances absorption) if tolerated; avoid concurrent tea/coffee/calcium/antacids/PPIs (impair absorption) ; separate by 2 hours

• Side effects: GI upset, constipation, black stools (expected, reassure): dose reduction or alternate-day dosing improves tolerability if significant side effects

• Duration: continue for 3 months after hemoglobin normalizes to replenish iron stores (total treatment course typically 6 months); recheck FBC/ferritin at 2-4 weeks (expect Hb rise ~1g/dL every 2 weeks) to confirm response

IV iron — indicated for: intolerance to oral iron, malabsorption (IBD, celiac, post-bariatric surgery), ongoing significant blood loss exceeding oral replacement capacity, non-adherence, need for rapid correction (e.g., pre-surgery, late pregnancy, heart failure with iron deficiency):

• Formulations: ferric carboxymaltose, iron sucrose, ferric derisomaltose; dosed by weight/Hb deficit calculation

• Risk of hypersensitivity reactions (monitor during/after infusion), hypophosphatemia (particularly ferric carboxymaltose)

Blood transfusion: reserved for severe symptomatic anemia (hemodynamic instability, severe symptoms, active significant bleeding) not for iron deficiency correction alone in stable patients.

Treat underlying cause: essential: endoscopic management of bleeding source, H. pylori eradication if present, gluten-free diet if celiac, deworming if parasitic, gynecological management of menorrhagia (hormonal treatment, tranexamic acid, or surgical options).

Dietary counseling: iron-rich foods (red meat, poultry, fish; heme iron better absorbed than plant/non-heme iron from legumes, leafy greens, fortified cereals), vitamin C to enhance non-heme iron absorption.

Follow-up: FBC and ferritin at 2-4 weeks then monthly until normalized, then 3 months after completing course to confirm sustained correction and stores replenished; investigate for recurrence if anemia recurs.