What is the approach to examining and managing patients with anemia?

Comprehensive Approach to Examining and Managing Patients with Anemia

The examination and management of anemia requires a systematic approach that includes initial assessment, classification based on morphology and kinetics, targeted investigations, and appropriate treatment based on the underlying cause. 1

Initial Assessment

• Complete blood count (CBC) with indices is essential to characterize anemia and identify if other cytopenias are present 1
• Visual review of peripheral blood smear to confirm the size, shape, and color of red blood cells 1
• Detailed history should include duration and onset of symptoms, comorbidities, family history, medication use (especially NSAIDs, anticoagulants), and exposure to chemotherapy or radiation 1
• Physical examination should look for pallor, jaundice, splenic enlargement, neurologic symptoms, petechiae, heart murmurs, and signs of blood loss 1
• Common symptoms include syncope, exercise dyspnea, headache, vertigo, chest pain, fatigue, and abnormal menstruation in females 1

Classification and Diagnostic Approach

Morphologic Approach (Based on MCV)

• Microcytic (MCV < 80 fL): Most commonly caused by iron deficiency; other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 1
• Normocytic (MCV 80-100 fL): May be caused by hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 1
• Macrocytic (MCV > 100 fL): Usually megaloblastic, indicating vitamin B12 or folate deficiency; non-megaloblastic causes include alcoholism, myelodysplastic syndrome (MDS), and certain medications 1

Kinetic Approach (Based on Reticulocyte Index)

• Reticulocyte index (RI) measures RBC production capacity by bone marrow 1
• Low RI: Indicates decreased RBC production (iron deficiency, vitamin B12/folate deficiency, aplastic anemia, bone marrow dysfunction) 1
• High RI: Indicates normal/increased RBC production (blood loss or hemolysis) 1

Specific Investigations

Iron Deficiency Anemia

• Serum ferritin is the most powerful test for iron deficiency (<12 μg/dl is diagnostic) 1
• Iron panel should include iron level, total iron binding capacity (TIBC), transferrin saturation (<15% suggests iron deficiency) 1
• Ferritin may be falsely elevated in inflammation, malignancy, or liver disease 1
• Transferrin saturation <30% may help diagnosis when ferritin is equivocal 1

Gastrointestinal Evaluation for Iron Deficiency

• GI investigations should be considered in all patients with confirmed iron deficiency anemia unless there is significant non-GI blood loss 1
• Upper GI endoscopy with small bowel biopsies (to rule out celiac disease, present in 2-3% of IDA cases) 1
• Lower GI tract examination (colonoscopy preferred, or CT colonography if colonoscopy not suitable) 1
• Dual pathology (lesions in both upper and lower GI tracts) occurs in 10-15% of patients 1

Cancer-Related Anemia

• Suggested baseline investigations include thorough drug history, peripheral blood smear, iron studies, folate, vitamin B12, reticulocyte count, and assessment for occult blood loss 1
• Consider direct antiglobulin testing (Coombs test) for patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or history of autoimmune disease 1
• Endogenous erythropoietin levels may help predict response in myelodysplasia 1

Genetic Disorders of Iron Metabolism

• Consider genetic disorders when anemia remains unexplained, especially with elevated ferritin and/or transferrin saturation or low transferrin saturation with low-normal ferritin 1
• Family history, anemia refractory to iron supplementation, and features like neurologic disease may indicate genetic disorders 1
• Specific genetic testing may be required for disorders like TMPRSS6 defects, hypotransferrinemia, or sideroblastic anemia 1

Management Strategies

Iron Deficiency Anemia

• Identify and treat the underlying cause (especially GI sources of blood loss) 1
• Iron supplementation (oral or parenteral depending on severity and tolerance) 1

Cancer-Related Anemia

• Address all causes of anemia before considering erythropoiesis-stimulating agents (ESAs) 1
• ESAs may be considered in patients with chemotherapy-induced anemia with Hb ≤10 g/dl 1
• Important caution: ESAs carry risks including increased mortality, myocardial infarction, stroke, and thromboembolism when targeting Hb >11 g/dl 2
• ESAs are not indicated for cancer patients not receiving chemotherapy, when anticipated outcome is cure, or when anemia can be managed by transfusion 2
• Monitor blood pressure carefully during ESA treatment 2

Genetic Disorders

• Treatment depends on specific disorder:
  • For sideroblastic anemia due to ALAS2 defects: Consider pyridoxine (50-200 mg daily initially, then 10-100 mg maintenance) 1
  • For severe congenital sideroblastic anemia: Consider hematopoietic stem cell transplantation 1
  • For iron loading: Phlebotomy or chelation therapy as appropriate 1

Common Pitfalls and Caveats

• Don't accept a dietary cause of iron deficiency without full GI investigation, especially in older patients 1
• Ferritin may be elevated in inflammatory states despite iron deficiency; values <100 μg/dl may still represent iron deficiency in these cases 1
• Dual pathology is common in IDA (10-15%), so finding one potential source of blood loss should not prevent complete evaluation 1
• ESAs carry significant risks including increased mortality and thromboembolism; use with caution and only when clearly indicated 2
• Age, sex, Hb concentration, and MCV are independent predictors of GI cancer risk in IDA and should be considered in risk assessment 1