Summary of "CCH Session 5 - Hemolytic Anemia, 18th June'23 IAP Delhi, Certificate Course Hematology"

Summary of “CCH Session 5 - Hemolytic Anemia, 18th June‘23 IAP Delhi, Certificate Course Hematology”

This session, led by Dr. Sunil Gomer, provides a comprehensive overview of hemolytic anemia, focusing on its pathophysiology, classification, clinical features, diagnosis, and management. Detailed discussions cover hereditary spherocytosis, G6PD deficiency, sickle cell anemia, and thalassemia. The lecture also addresses complications, diagnostic challenges, and treatment options including transfusions, chelation therapy, and stem cell transplantation.

Main Ideas and Concepts

1. Definition and Pathophysiology of Hemolytic Anemia

Hemolytic anemia occurs when red blood cell (RBC) destruction exceeds bone marrow production.
Normal RBC lifespan is approximately 120 days; premature destruction can be intravascular or extravascular.
Intravascular hemolysis: releases hemoglobin into blood and urine (hemoglobinuria).
Extravascular hemolysis: occurs mainly in spleen and liver, increasing indirect (unconjugated) bilirubin.

2. Classification of Hemolytic Anemia

Intracorpuscular (intrinsic) defects:
- Membrane defects: hereditary spherocytosis, elliptocytosis, stomatocytosis.
- Enzymatic defects: G6PD deficiency, pyruvate kinase deficiency.
- Hemoglobinopathies: qualitative defects (sickle cell disease), quantitative defects (thalassemia).
Extracorpuscular (extrinsic) defects:
- Immune causes:
  - Isoimmune (e.g., hemolytic disease of newborn, incompatible transfusions).
  - Autoimmune hemolytic anemia (warm/cold antibodies).
- Secondary immune causes: infections (CMV, EBV, mycoplasma), drugs (e.g., penicillin, primaquine).
- Non-immune causes: drugs (benzene, vitamin K), infections (malaria, infectious mononucleosis).

3. Differentiating Intravascular vs. Extravascular Hemolysis

Both types show increased indirect bilirubin, elevated LDH, and decreased haptoglobin.
Hemoglobinuria and hemosiderinuria are features of intravascular hemolysis.
Clinical signs such as cola-colored urine suggest intravascular hemolysis.

4. Clinical Features of Hemolytic Anemia

Acute hemolysis: sudden jaundice, pallor, cola-colored urine, back/limb pain, shock in severe cases.
Chronic hemolysis: anemia (mild to moderate), jaundice, splenomegaly, gallstones, failure to thrive.
Specific signs include leg ulcers (especially in thalassemia intermedia), intermittent jaundice, and family history of anemia.

5. Key Diagnostic Features and Tests

Anemia accompanied by jaundice, splenomegaly, and gallstones.
Peripheral smear findings:
- Spherocytes (hereditary spherocytosis).
- Sickled cells (sickle cell anemia).
- Polychromasia (reticulocytosis).
Osmotic fragility test: increased in hereditary spherocytosis.
EMA test (flow cytometry): detects RBC membrane protein deficiency in hereditary spherocytosis.
Direct Coombs test (DCT): positive in autoimmune hemolytic anemia.
G6PD enzyme assay: best performed 3 months post-hemolytic episode to avoid false normal results.
Sickling test: sodium metabisulfite induced sickling for sickle cell diagnosis.
Hemoglobin electrophoresis/HPLC: for thalassemia and sickle cell disease.

6. Detailed Disease Discussions

Hereditary Spherocytosis (HS)

Presents with anemia, jaundice, splenomegaly; may cause neonatal jaundice.
Diagnosis: peripheral smear (spherocytes), increased MCHC and RDW, osmotic fragility, EMA test.
Clinical crises include hemolytic, aplastic, and sequestration crises.

G6PD Deficiency

Most common enzymatic cause of hemolytic anemia.
Hemolysis triggered by infections, certain drugs (antimalarials, analgesics, nitrofurantoin), and fava beans.
Presents with acute hemolysis, jaundice, cola-colored urine, back pain.
Timing of testing is critical; avoid testing during acute hemolysis.

Sickle Cell Anemia

Qualitative hemoglobin defect (glutamic acid replaced by valine).
Presents with vaso-occlusive crises: dactylitis, bone pain, abdominal pain, CNS infarcts, acute chest syndrome.
Complications: autosplenectomy after 5-6 years, leg ulcers, retinopathy, growth retardation.
Diagnosis: peripheral smear, sickling test, hemoglobin electrophoresis.
Management includes penicillin prophylaxis, hydroxyurea (to increase HbF), transfusions, and stem cell transplant.

Thalassemia

Quantitative hemoglobin defect: alpha or beta chain deficiency.
Presents in infancy with anemia, failure to thrive, hepatosplenomegaly, bone deformities (“chipmunk facies”).
Complications: iron overload causing endocrinopathies (diabetes, hypothyroidism, hypogonadism), cardiomyopathy.
Diagnosis: HPLC, family history, genetic testing.
Management:
- Regular transfusions (goal Hb ~9-9.5 g/dL).
- Iron chelation (deferoxamine, deferiprone, deferasirox).
- Hydroxyurea.
- Bone marrow transplantation.
Non-transfusion dependent thalassemia (thalassemia intermedia) managed with supportive care and sometimes hydroxyurea or thalidomide (research phase).

7. Management Principles

Blood transfusions guided by hemoglobin levels, symptoms, growth, and bone changes.
Iron chelation to prevent organ damage from iron overload.
Hydroxyurea in sickle cell disease and some thalassemia intermedia cases.
Stem cell transplantation (matched sibling or haploidentical donor) as curative option.
Avoidance of triggers in G6PD deficiency and close monitoring.
Immunosuppressive therapy (steroids, immunoglobulins, rituximab) in autoimmune hemolytic anemia.
Penicillin prophylaxis and vaccination in sickle cell disease to prevent infections.

8. Additional Points

Importance of detailed family history and clinical examination.
Role of prenatal diagnosis and “savior sibling” concept in thalassemia for stem cell transplantation.
Challenges in diagnosis and treatment in resource-limited settings.
Emerging therapies and ongoing research (e.g., monoclonal antibodies, thalidomide).

Methodology / Key Diagnostic and Management Steps

Diagnosis of Hemolytic Anemia

Clinical suspicion based on anemia, jaundice, splenomegaly, and family history.
Laboratory evaluation includes:
- CBC with reticulocyte count (reticulocytosis indicates hemolysis).
- Peripheral smear for RBC morphology (spherocytes, sickled cells, polychromasia).
- Direct Coombs test for autoimmune hemolysis.
- Osmotic fragility test and EMA test for hereditary spherocytosis.
- G6PD enzyme assay (delay testing until 3 months post-hemolysis).
- Hemoglobin electrophoresis/HPLC for hemoglobinopathies.
- Serum bilirubin (indirect), LDH (elevated), haptoglobin (decreased).
- Urine analysis for hemoglobinuria in intravascular hemolysis.
- Imaging (ultrasound) for gallstones and organomegaly.

Management of Specific Conditions

Hereditary Spherocytosis:
- Folic acid supplementation.
- Splenectomy in severe cases.
- Monitor for hemolytic and aplastic crises.
G6PD Deficiency:
- Avoidance of oxidative drugs and triggers.
- Supportive care during hemolytic episodes.
Sickle Cell Disease:
- Penicillin prophylaxis and immunizations.
- Hydroxyurea to increase fetal hemoglobin.
- Pain management during crises.
- Transfusions for severe anemia or complications.
- Stem cell transplantation for cure.
Thalassemia:
- Regular transfusions to maintain Hb ~9-9.5 g/dL.
- Iron chelation therapy (deferoxamine, deferiprone, deferasirox).
- Monitor and treat endocrine complications.
- Consider hydroxyurea or thalidomide in thalassemia intermedia.
- Stem cell transplantation as curative therapy.

Transfusion Guidelines

Indicated if Hb <7 g/dL on two occasions or with clinical symptoms.
Use best-matched blood to avoid alloimmunization.
Monitor iron overload and start chelation when ferritin >1000 ng/mL.

Stem Cell Transplantation

Sibling HLA matching preferred; haploidentical transplant emerging.
Prenatal diagnosis and “savior sibling” concept for planned stem cell donors.

Speakers / Sources Featured

Dr. Sunil Gomer – Main speaker, expert in hematology and meta oncology, in charge of meta oncology division at Babasaheb Ambedkar Medical College.
Other faculty members and delegates from IAP Delhi Certificate Course Hematology.
Mention of other clinicians/researchers:
- Dr. Anupam Suchday (Gangaram Hospital)
- Dr. Gaurav Kharya
- Dr. Payal Malhotra
- Dr. Gauri Kapoor
- Dr. Dinesh Burani
- Dr. Jignesh Chandra (research on thalidomide)
Session includes Q&A with participants and discussions on clinical practice and research.

This session serves as a detailed primer on hemolytic anemias, emphasizing clinical recognition, differential diagnosis, laboratory evaluation, and current management strategies, especially in the Indian context.