Hematology
Anemia
Reduced hemoglobin or red cell mass — classified by size, cause, and oxygen delivery
Anemia is a deficit in the blood's capacity to carry oxygen, defined by hemoglobin below 13 g/dL in men or 12 g/dL in women. The classical workup partitions cases by red cell size: microcytic (MCV < 80 fL — iron deficiency, thalassemia, chronic disease), normocytic (MCV 80-100 — acute blood loss, hemolysis, marrow failure), and macrocytic (MCV > 100 — B12, folate, alcohol, hypothyroidism). Reticulocyte count separates poor production from increased destruction. Symptoms — fatigue, dyspnea, pallor, palpitations — reflect compensation: increased cardiac output and 2,3-BPG shifting the oxygen-hemoglobin curve.
- Hemoglobin threshold (men)< 13 g/dL
- Hemoglobin threshold (women)< 12 g/dL
- Microcytic / normocytic / macrocytic cutoffsMCV < 80 / 80-100 / > 100 fL
- Most common cause globallyIron deficiency (estimated 1.2 billion people)
- Reticulocyte count normal0.5-2.5%
- Transfusion threshold (most patients)Hb < 7 g/dL
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Why anemia matters
- Primary care. Anemia is the most common abnormal CBC finding and an early indicator of malignancy, malabsorption, or chronic kidney disease.
- Surgery. Preoperative anemia independently predicts postoperative mortality and is now actively corrected before elective procedures.
- Cardiology. Anemia worsens angina, heart failure, and ischemic outcomes; correcting iron deficiency in HF reduces hospitalization.
- Oncology. Cancer-related anemia from marrow infiltration, chemotherapy, and inflammation drives fatigue and treatment intolerance.
- Pregnancy. Iron deficiency in pregnancy raises preterm delivery and low birth weight risk; routine supplementation is standard.
- Pediatrics. Iron deficiency in infancy impairs neurodevelopment irreversibly even after correction.
- Critical care. ICU anemia is multifactorial — phlebotomy, blunted EPO, inflammation — and restrictive transfusion strategies are now standard.
Common misconceptions
- "Low hemoglobin means iron deficiency." The differential is wide; treating empirically with iron can mask cancer or B12 deficiency.
- "Normal ferritin rules out iron deficiency." Inflammation raises ferritin; a value under 100 with chronic disease can still mean depletion.
- "Transfuse to fix the number." Restrictive thresholds (Hb 7) outperform liberal ones in most patients.
- "Folate replaces B12." Folate corrects the anemia but the neurological damage of B12 deficiency progresses silently.
- "Macrocytic always means B12 or folate." Alcohol, liver disease, hypothyroidism, hydroxyurea, and MDS all enlarge red cells.
- "Iron deficiency in older men is dietary." It is GI blood loss until colonoscopy and endoscopy say otherwise.
Frequently asked questions
How is anemia first classified?
By mean corpuscular volume (MCV). Microcytic anemia (MCV < 80) suggests iron deficiency, thalassemia, anemia of chronic disease, or sideroblastic anemia. Normocytic anemia (MCV 80-100) is divided by reticulocyte response — high indicates hemolysis or blood loss; low indicates marrow failure or early iron deficiency. Macrocytic anemia (MCV > 100) splits into megaloblastic (B12, folate, hydroxyurea) and non-megaloblastic (alcohol, liver disease, hypothyroidism, MDS).
How does iron deficiency develop?
Body iron is recycled efficiently — only 1-2 mg/day enters and leaves. Deficiency means chronic loss exceeding absorption. In premenopausal women, menstruation is the leading cause. In men and postmenopausal women, GI bleeding is assumed until proven otherwise — colon cancer must be ruled out. Pregnancy doubles iron requirement. Bariatric surgery, celiac disease, and PPIs all impair absorption. Ferritin under 30 ng/mL is diagnostic.
Why does B12 deficiency take years to appear?
The liver stores 2-5 years of B12. Causes include pernicious anemia (autoimmune destruction of gastric parietal cells, loss of intrinsic factor), terminal ileal disease (Crohn's, surgery), and strict vegan diets. Beyond macrocytic anemia, B12 deficiency causes subacute combined degeneration of the spinal cord — peripheral neuropathy, ataxia, and cognitive change that may not fully reverse if treatment is delayed. Folate corrects the anemia but masks neurological progression.
What signs distinguish hemolysis?
Increased reticulocytes, elevated indirect bilirubin and LDH, low haptoglobin, and hemoglobinuria in intravascular hemolysis. The peripheral smear is diagnostic — schistocytes signal microangiopathic hemolysis (TTP, HUS, DIC, mechanical valves), spherocytes suggest hereditary spherocytosis or autoimmune hemolytic anemia, sickle forms diagnose sickle cell, and bite cells appear in G6PD deficiency. Direct antiglobulin (Coombs) test separates immune from non-immune causes.
How does anemia of chronic disease work?
Inflammation drives hepatic hepcidin, which degrades ferroportin in macrophages and enterocytes. Iron is locked away from erythropoiesis even when stores are adequate. Ferritin is normal or high (acute-phase reactant), transferrin saturation low, and the anemia is mild and normocytic to slightly microcytic. Treatment targets the underlying disease; iron supplementation is usually unhelpful and can worsen infection. Hepcidin antagonists are an emerging therapeutic target.
When do we transfuse?
Restrictive thresholds save lives in most settings. Hemoglobin under 7 g/dL is the standard trigger in stable hospitalized patients; under 8 g/dL in patients with cardiac disease or undergoing orthopedic surgery. Active bleeding, symptomatic anemia, and acute coronary syndrome may justify earlier transfusion. Each unit of packed red cells raises Hb by approximately 1 g/dL. Liberal transfusion increases mortality, cost, and TRALI risk.
What's the role of erythropoietin?
The kidney senses hypoxia via HIF, stimulating EPO production that drives marrow erythropoiesis. In chronic kidney disease, EPO production fails — recombinant EPO (epoetin, darbepoetin) corrects the resulting anemia but raises stroke and thrombosis risk if hemoglobin is targeted above 11.5 g/dL. EPO doping in cycling exploits the same biology illicitly. HIF stabilizers (roxadustat, daprodustat) are oral alternatives now in clinical use.