Anemia and Polycythemia¶
Chapter 66 | Part 12: Endocrinology
KEY CLINICAL POINTS¶
- Anemia is defined as reduced hemoglobin/hematocrit below population norms, classified by MCV (microcytic, normocytic, macrocytic).
- Erythropoietin (EPO) regulates red cell production, with hypoxia driving its secretion and feedback inhibition maintaining homeostasis.
- Polycythemia is increased hemoglobin/hematocrit, with primary (clonal) or secondary (EPO-driven) causes, requiring distinction between spurious, relative, and absolute increases.
- Diagnostic workup includes CBC, reticulocyte count, MCV, RDW, EPO levels, and bone marrow examination for marrow infiltration or dysfunction.
- Treatment depends on etiology: iron supplementation, EPO therapy, phlebotomy, or addressing underlying conditions like renal disease or tumors.
1. DEFINITION & OVERVIEW¶
Anemia is reduced hemoglobin/hematocrit below population norms. Polycythemia is increased hemoglobin/hematocrit. Anemia is classified by red cell size (MCV) and mechanism (e.g., hemolysis, marrow failure).
Table 66-1: Red Cell Indices¶
| INDEX | FORMULA | NORMAL VALUES | COMMENT |
|---|---|---|---|
| Mean corpuscular volume (MCV) | Hct/RBC count × 10 | 85–95 fL | RBC size |
| Mean corpuscular hemoglobin (MCH) | Hgb/RBC count × 10 | 28.5–32.3 pg | Varies linearly with MCV |
| Mean corpuscular hemoglobin concentration (MCHC) | Hgb/Hct × 100 | 33.8–34.2 g/dL | Changes little in most anemias |
Table 66-2: Hemoglobin/Hematocrit by Age¶
| AGE/SEX | HEMOGLOBIN (g/dL) | HEMATOCRIT (%) |
|---|---|---|
| At birth | 17 | 52 |
| Childhood | 12 | 36 |
| Adolescence | 13 | 40 |
| Adult male | 16 (±2) | 47 (±6) |
| Adult female (menstruating) | 13 (±2) | 40 (±6) |
| Postmenopausal female | 14 (±2) | 42 (±6) |
| AGE/SEX | HEMOGLOBIN (g/dL) | HEMATOCRIT (%) |
|---|---|---|
| During pregnancy | 12 (±2) | 37 (±6) |
1.1 Red Cell Indices¶
MCV (mean corpuscular volume) classifies anemia: microcytic (MCV <80 fL), normocytic (80–100 fL), macrocytic (>100 fL). MCH (mean corpuscular hemoglobin) and MCHC (mean corpuscular hemoglobin concentration) correlate with MCV.
1.2 EPO Regulation¶
EPO is produced by kidney peritubular cells in response to hypoxia. HIF-1 α stabilizes under hypoxia, upregulating EPO. EPO acts on marrow erythroid precursors to stimulate red cell production.
2. EPIDEMIOLOGY¶
Anemia affects 2 billion people globally, with iron deficiency (3.5 billion) and chronic disease (1.5 billion) as leading causes. Polycythemia is less common, with primary (clonal) and secondary (EPO-driven) causes.
2.1 Risk Factors¶
Iron deficiency, chronic inflammation, renal disease, malignancy, and genetic disorders (e.g., thalassemia) increase anemia risk. Polycythemia is linked to hypoxia, tumors, or genetic mutations (e.g., JAK2).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Anemia arises from impaired production (iron deficiency, marrow failure), increased destruction (hemolysis), or blood loss. Polycythemia results from EPO overproduction (primary) or hypoxia (secondary).
3.1 Microcytic Anemia¶
Caused by hemoglobin synthesis defects (thalassemia), iron deficiency, or sideroblastic anemia. Iron deficiency reduces heme synthesis, leading to small, hypochromic cells.
3.2 Macrocytic Anemia¶
Due to DNA synthesis defects (B12/folate deficiency, myelodysplasia) or membrane defects (alcohol, liver disease). Oval macrocytes reflect DNA issues; round macrocytes suggest membrane abnormalities.
3.3 Normocytic Anemia¶
Caused by chronic disease, renal failure, or marrow infiltration (e.g., myeloma). EPO levels are low due to inflammation or renal dysfunction.
4. CLINICAL FEATURES¶
Symptoms include fatigue, dyspnea, pallor, and splenomegaly. Polycythemia presents with erythema, hypertension, and thrombotic events. Physical findings may include splenomegaly or cyanosis.
4.1 Hemolysis Signs¶
Schistocytes, spherocytes, or target cells on blood smear. Jaundice, dark urine, and elevated LDH indicate intravascular hemolysis.
5. DIFFERENTIAL DIAGNOSIS¶
Anemia: iron deficiency, hemolytic anemia, thalassemia, chronic disease. Polycythemia: secondary (hypoxia, tumors) vs. primary (polycythemia vera, JAK2 mutations).
5.1 Anemia Differentials¶
Microcytic: iron deficiency, thalassemia. Macrocytic: B12/folate deficiency, myelodysplasia. Normocytic: chronic disease, renal failure.
6. INVESTIGATIONS & DIAGNOSIS¶
CBC, reticulocyte count, MCV, RDW, EPO levels, and bone marrow biopsy. Polycythemia requires EPO testing, imaging for tumors, and assessment of O2 saturation.
Table 66-3: Red Cell Morphology¶
| PATHOPHYSIOLOGY | DISEASE STATES |
|---|---|
| Macro-ovalocytes | B12/folate deficiency, myelodysplasia |
| Spherocytes | Hereditary spherocytosis, autoimmune hemolysis |
| Target cells | Liver disease, thalassemia |
| Schistocytes | Microangiopathic hemolysis, mechanical heart valves |
| Sickle cells | Sickle cell disease |
6.1 Diagnostic Algorithm¶
- Assess MCV and RDW. 2. Measure EPO and iron studies. 3. Bone marrow exam for infiltration or dysplasia. 4. Imaging for tumors in secondary polycythemia.
7. MANAGEMENT & TREATMENT¶
Iron supplementation for deficiency, EPO therapy for renal failure, phlebotomy for polycythemia, and addressing underlying causes (e.g., tumors, infections).
7.1 Treatment Algorithms¶
- Iron deficiency: oral iron, transfusions if severe. 2. Hemolytic anemia: corticosteroids, immunosuppressants. 3. Polycythemia vera: phlebotomy, hydroxyurea, or interferon.
8. PROGNOSIS & COMPLICATIONS¶
Anemia may lead to organ damage, infections, or mortality. Polycythemia risks thrombosis, hypertension, and cardiovascular events. Early diagnosis improves outcomes.
8.1 Complications¶
Anemia: heart failure, infections. Polycythemia: stroke, myocardial infarction, pulmonary hypertension.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: iron deficiency common; elderly: anemia of chronic disease; renal disease: anemia of inflammation; cancer: marrow infiltration.
9.1 Pregnancy¶
Iron deficiency is prevalent; monitor hemoglobin and consider supplementation. Anemia of pregnancy may mimic chronic disease.
10. KEY POINTS & CLINICAL PEARLS¶
- MCV classification guides anemia diagnosis. 2. EPO levels distinguish hypoxia-driven polycythemia from clonal disorders. 3. Reticulocyte count assesses marrow response. 4. Bone marrow biopsy confirms marrow infiltration or dysplasia.