What is anemia, its types, diagnosis, and treatment options?

Anemia: Comprehensive Study Note

Definition and Pathophysiology

Anemia is a clinical manifestation of decreased circulating red blood cell mass, detected by low blood hemoglobin (Hb) concentration, resulting from three primary mechanisms: decreased RBC production, increased RBC destruction, or blood loss. 1

• Under normal conditions, bone marrow produces approximately 200 billion new cells daily to replace senescent cells removed from circulation 1
• The kidney cortex contains specialized interstitial cells that sense tissue hypoxia and produce erythropoietin in response 1
• Erythropoietin binds to receptors on erythroid colony-forming units (CFU-Es), preventing programmed cell death and allowing RBC expansion 1

Classification Systems

By Severity (ESMO Classification)

• Mild anemia: Hb ≤11.9 g/dL and ≥10.0 g/dL 2
• Moderate anemia: Hb ≤9.9 g/dL and ≥8.0 g/dL 2
• Severe anemia: Hb <8.0 g/dL 2

By WHO Definitions

• Men: Hb <13.0 g/dL 2
• Non-pregnant women: Hb <12.0 g/dL 2
• Pregnant women: Hb <11.0 g/dL 2

By Morphology (MCV-Based)

• Microcytic (<80 fL): Most commonly iron deficiency; also thalassemia, anemia of chronic disease, sideroblastic anemia 1
• Normocytic (80-100 fL): Hemorrhage, hemolysis, bone marrow failure, chronic inflammation, renal insufficiency 1
• Macrocytic (>100 fL): Vitamin B12/folate deficiency (megaloblastic), alcoholism, MDS, certain drugs like hydroxyurea 1

By Mechanism (Kinetic Approach)

• Hyperproliferative disorders: Increased RBC destruction with normal marrow response 1
• Hypoproliferative disorders: Impaired RBC production with inadequate marrow response 1

Diagnostic Evaluation

Initial Assessment

Begin with CBC with indices and peripheral blood smear examination to characterize RBC size, shape, and color. 1

• Reticulocyte count (corrected as reticulocyte index): Normal RI is 1.0-2.0 1
  • Low RI: Decreased RBC production (iron deficiency, B12/folate deficiency, aplastic anemia, marrow dysfunction) 1
  • High RI: Normal/increased production (blood loss or hemolysis) 1

Comprehensive Laboratory Workup

Evaluate for all potential causes before initiating treatment: 3

• Iron studies: Serum iron, TIBC, ferritin, transferrin saturation 1
  • Absolute iron deficiency: Ferritin <30 ng/mL and transferrin saturation <15% 1
• Nutritional markers: Vitamin B12, folate levels 1, 3
• Hemolysis markers: Coombs test, DIC panel, haptoglobin 1
• Renal function: GFR, erythropoietin levels (especially if GFR <60 mL/min/1.73 m²) 1
• Inflammatory markers: To assess chronic disease contribution 3
• Occult blood loss: Stool guaiac, endoscopy if indicated 1
• Bone marrow examination: When diagnosis remains unclear 3

Special Considerations

• Coombs testing recommended for patients with CLL, non-Hodgkin's lymphoma, or autoimmune disease history 3
• Ferritin may be falsely elevated in chronic inflammatory states despite true iron deficiency 1

Etiology by Category

Decreased RBC Production

• Iron deficiency 1
• Vitamin B12/folate deficiency 1
• Chronic kidney disease (erythropoietin deficiency) 1
• Bone marrow infiltration by malignancy 1
• Aplastic anemia 1
• Anemia of chronic disease 1

Increased RBC Destruction

• Hemolytic anemias 1
• Hereditary disorders 1

Blood Loss

• Acute hemorrhage 1
• Chronic blood loss from tumor sites 1
• Gastrointestinal bleeding 1

Multifactorial in Cancer Patients

• Direct marrow suppression by cancer cells 1
• Cytokine-mediated iron sequestration 1
• Chemotherapy/radiation-induced myelosuppression 1
• Nutritional deficiencies 1

Clinical Manifestations

Symptoms

• Fatigue (disproportionate to activity, not relieved by rest in cancer-related anemia) 1
• Exercise dyspnea 1
• Syncope, vertigo, headache 1
• Chest pain 1
• Abnormal menstruation in females 1

Physical Findings

• Pallor 1
• Jaundice (hemolysis) 1
• Splenic enlargement 1
• Petechiae 1
• Heart murmur 1
• Neurologic symptoms (B12 deficiency) 1

Treatment Principles

General Approach

Identify and treat all underlying causes before considering supportive therapies. 3

Specific Treatments by Etiology

Iron Deficiency Anemia

• Oral or IV iron supplementation when ferritin <30 ng/mL and transferrin saturation <15% 1
• Reassess hemoglobin after 4 weeks of treatment 1

Vitamin B12 Deficiency (Pernicious Anemia)

Parenteral vitamin B12 is required for life; oral forms are not dependable. 4

• Initial phase: 100 mcg IM/deep SC daily for 6-7 days 4
• Continuation: Same dose on alternate days for 7 doses, then every 3-4 days for 2-3 weeks 4
• Maintenance: 100 mcg monthly for life 4
• Administer folic acid concomitantly if needed 4

Anemia in Cancer/Chemotherapy Patients

• Treatment threshold: Hb ≤10 g/dL for ESA consideration 3
• Goal: Increase Hb by <2 g/dL or prevent further decline 3
• Avoid targeting Hb 12-14 g/dL in cancer patients not receiving chemotherapy due to increased mortality risk 3
• Use ESAs cautiously in curative-intent treatment 3

Chronic Kidney Disease

• Erythropoietin replacement therapy for patients with low endogenous production 1

Transfusion Considerations

• Restrictive strategy (Hb <6-8 g/dL) associated with better outcomes than liberal strategy 5
• Avoid IV administration of vitamin B12 as it results in urinary loss 4

Clinical Significance

Anemia severity directly impacts quality of life and is a major contributor to cancer-related fatigue, making accurate classification and treatment clinically important. 2

• Men with Hb <12 g/dL and postmenopausal women with Hb <10 g/dL require urgent investigation 2
• Any level of anemia with iron deficiency warrants investigation for gastrointestinal malignancy 2