Hemolytic Anemia: Clinical Case and Viva Q&A

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Clinical Case of Hemolytic Anemia in Children

A 4-year-old boy is brought to the pediatric emergency department by his parents with complaints of progressive pallor, fatigue, and yellowing of the eyes for the past week. The parents also noticed that his urine has become darker over the last few days.

History:

  • No significant past medical history
  • No recent infections or medication use
  • No family history of anemia or jaundice

Physical Examination:

  • Pale conjunctiva and mucous membranes
  • Icteric sclera
  • Mild hepatosplenomegaly
  • Tachycardia (heart rate 120 bpm)
  • No lymphadenopathy or rash

Laboratory Results:

  • Hemoglobin: 7.2 g/dL (normal range: 11.5-13.5 g/dL)
  • Reticulocyte count: 8% (normal range: 0.5-2.5%)
  • Mean Corpuscular Volume (MCV): 85 fL (normal range: 75-87 fL)
  • Total bilirubin: 3.8 mg/dL (normal range: 0.3-1.2 mg/dL)
  • Direct bilirubin: 0.5 mg/dL (normal range: 0-0.3 mg/dL)
  • Lactate dehydrogenase (LDH): 580 U/L (normal range: 110-295 U/L)
  • Haptoglobin: < 10 mg/dL (normal range: 30-200 mg/dL)

Further Investigations:

  • Peripheral blood smear: Spherocytes present
  • Direct Coombs test: Negative
  • Osmotic fragility test: Increased

Diagnosis:

Based on the clinical presentation and laboratory findings, the child is diagnosed with hereditary spherocytosis, a type of hemolytic anemia.

Management:

The child is admitted for further evaluation and management, including:

  • Blood transfusion to correct severe anemia
  • Folic acid supplementation
  • Genetic counseling for the family
  • Discussion of potential splenectomy in the future
Clinical Presentations of Hemolytic Anemia in Children
  1. Acute Onset with Severe Symptoms:
    • Sudden pallor, fatigue, and shortness of breath
    • Jaundice and dark urine
    • Tachycardia and potential heart failure symptoms
    • Abdominal pain due to hepatosplenomegaly
  2. Chronic, Mild Anemia with Intermittent Exacerbations:
    • Persistent mild pallor and fatigue
    • Intermittent jaundice
    • Growth retardation or delayed puberty
    • Recurrent gallstones
  3. Neonatal Hemolytic Anemia:
    • Severe jaundice within 24-48 hours of birth
    • Hepatosplenomegaly
    • Risk of kernicterus if untreated
    • Hydrops fetalis in severe cases
  4. Hemolytic Anemia Secondary to Infection:
    • Fever and other signs of infection
    • Acute onset of anemia symptoms
    • Possible hepatosplenomegaly
    • May be associated with specific infections (e.g., malaria, babesiosis)
  5. Drug-Induced Hemolytic Anemia:
    • Onset of symptoms after starting new medication
    • Can be acute or gradual
    • May be accompanied by other drug reaction symptoms (e.g., rash)
  6. Exercise-Induced Hemolytic Anemia:
    • Symptoms primarily after intense physical activity
    • Dark urine post-exercise
    • Fatigue and reduced exercise tolerance
  7. Hemolytic Anemia with Thrombosis:
    • Signs of hemolysis along with thrombotic events
    • Can include stroke, pulmonary embolism, or deep vein thrombosis
    • Seen in conditions like paroxysmal nocturnal hemoglobinuria
  8. Hemolytic Uremic Syndrome Presentation:
    • Triad of hemolytic anemia, thrombocytopenia, and acute kidney injury
    • Often preceded by bloody diarrhea
    • Pallor, petechiae, and oliguria/anuria
Viva Questions and Answers on Hemolytic Anemia in Children
  1. Q: What is hemolytic anemia?
    A: Hemolytic anemia is a condition characterized by premature destruction of red blood cells, leading to a decrease in the total red blood cell mass. This results in a reduced capacity to deliver oxygen to tissues.
  2. Q: How do you classify hemolytic anemias?
    A: Hemolytic anemias can be classified as:
    • Intrinsic (hereditary): Due to defects within the red blood cell (e.g., membrane defects, enzyme deficiencies, hemoglobinopathies)
    • Extrinsic (acquired): Due to factors outside the red blood cell (e.g., immune-mediated, mechanical, infectious, drug-induced)
  3. Q: What are the common hereditary causes of hemolytic anemia in children?
    A: Common hereditary causes include:
    • Membrane defects: Hereditary spherocytosis, hereditary elliptocytosis
    • Enzyme deficiencies: G6PD deficiency, pyruvate kinase deficiency
    • Hemoglobinopathies: Sickle cell disease, thalassemias
  4. Q: What are the key laboratory findings in hemolytic anemia?
    A: Key laboratory findings include:
    • Decreased hemoglobin and hematocrit
    • Elevated reticulocyte count
    • Increased indirect (unconjugated) bilirubin
    • Elevated lactate dehydrogenase (LDH)
    • Decreased haptoglobin
    • Presence of schistocytes or other abnormal RBC morphologies on peripheral blood smear
  5. Q: How does hereditary spherocytosis present in children?
    A: Hereditary spherocytosis typically presents with:
    • Anemia (which can be mild to severe)
    • Jaundice
    • Splenomegaly
    • Gallstones (in older children and adults)
    • Intermittent exacerbations, often triggered by infections
  6. Q: What is the pathophysiology of G6PD deficiency?
    A: Glucose-6-phosphate dehydrogenase (G6PD) deficiency results in:
    • Reduced ability to protect RBCs against oxidative stress
    • Increased susceptibility to hemolysis when exposed to oxidative agents (certain foods, drugs, or infections)
    • X-linked inheritance pattern, more common in males
  7. Q: How do you diagnose autoimmune hemolytic anemia (AIHA)?
    A: Diagnosis of AIHA involves:
    • Clinical presentation of hemolysis
    • Positive direct Coombs test (direct antiglobulin test)
    • Presence of warm or cold autoantibodies
    • Exclusion of other causes of hemolysis
  8. Q: What is the difference between warm and cold AIHA?
    A:
    • Warm AIHA: Antibodies react optimally at 37°C, usually IgG type, often idiopathic or associated with lymphoproliferative disorders or autoimmune diseases
    • Cold AIHA: Antibodies react best at 4°C, usually IgM type, can be idiopathic or associated with infections (e.g., Mycoplasma pneumoniae, Epstein-Barr virus)
  9. Q: How do you manage acute hemolytic crisis in a child with sickle cell disease?
    A: Management includes:
    • Prompt pain control
    • Hydration (IV fluids)
    • Oxygen therapy if hypoxic
    • Blood transfusion if severe anemia or organ dysfunction
    • Treat underlying triggers (e.g., infections)
    • Consider exchange transfusion for severe complications
  10. Q: What is the role of splenectomy in hereditary spherocytosis?
    A: Splenectomy in hereditary spherocytosis:
    • Reduces hemolysis and improves anemia
    • Usually considered in severe cases or those with significant splenomegaly
    • Often delayed until after 6 years of age due to infection risk
    • Requires careful consideration of risks vs. benefits
    • Necessitates lifelong antibiotic prophylaxis and vaccinations
  11. Q: How do you diagnose and manage hemolytic disease of the newborn?
    A: Diagnosis and management include:
    • Maternal and infant blood type and antibody screening
    • Direct Coombs test on infant's blood
    • Monitor bilirubin levels closely
    • Phototherapy for hyperbilirubinemia
    • Exchange transfusion if severe
    • IVIG in selected cases
    • Long-term follow-up for anemia
  12. Q: What are the potential complications of chronic hemolytic anemia in children?
    A: Potential complications include:
    • Growth retardation and delayed puberty
    • Skeletal changes (e.g., frontal bossing, maxillary hyperplasia)
    • Cholelithiasis
    • Iron overload (especially if frequently transfused)
    • Extramedullary hematopoiesis
    • Pulmonary hypertension in some cases
  13. Q: How does alpha-thalassemia differ from beta-thalassemia in terms of clinical presentation?
    A:
    • Alpha-thalassemia: Can range from asymptomatic (silent carrier) to severe (Hb Bart's hydrops fetalis). Milder forms may present with microcytic anemia.
    • Beta-thalassemia: Ranges from mild (thalassemia minor) to severe (thalassemia major). Thalassemia major presents in infancy with severe anemia, hepatosplenomegaly, and growth retardation.
  14. Q: What is pyruvate kinase deficiency and how is it diagnosed?
    A: Pyruvate kinase deficiency is:
    • An autosomal recessive disorder of glycolysis in RBCs
    • Leads to ATP depletion and premature RBC destruction
    • Diagnosed by measuring pyruvate kinase enzyme activity in RBCs
    • Genetic testing can confirm the diagnosis
  15. Q: How do you manage a child with G6PD deficiency?
    A: Management includes:
    • Education about avoiding triggers (certain foods, drugs, chemicals)
    • Prompt treatment of infections
    • Management of acute hemolytic episodes (supportive care, possible transfusion)
    • No specific treatment needed between episodes
    • Genetic counseling for the family
  16. Q: What is paroxysmal nocturnal hemoglobinuria (PNH) and how does it present in children?
    A: PNH is:
    • An acquired disorder due to a somatic mutation in the PIGA gene
    • Results in complement-mediated hemolysis
    • Presents with hemolytic anemia, thrombosis, and cytopenias
    • Rare in children but can occur
    • Diagnosed by flow cytometry showing absence of GPI-anchored proteins
  17. Q: How do you differentiate between immune and non-immune hemolytic anemias?
    A: Differentiation includes:
    • Immune: Positive direct Coombs test, often acute onset, may have history of recent infection or medication
    • Non-immune: Negative direct Coombs test, may have family history, specific RBC morphologies on blood smear (e.g., spherocytes, sickle cells)
  18. Q: What is the approach to a child presenting with acute hemolysis and fever?
    A: Approach includes:
    • Rapid assessment of hemodynamic status and degree of anemia
    • Blood cultures and appropriate infectious workup
    • Evaluation for both immune and non-immune causes of hemolysis
    • Consider specific infections (e.g., malaria, babesiosis)
    • Supportive care and possible transfusion if severe
    • Treat underlying infection if identified
  19. Q: What is the role of folic acid supplementation in chronic hemolytic anemias?
    A: Folic acid supplementation:
    • Compensates for increased folate utilization due to accelerated erythropoiesis
    • Prevents megaloblastic changes secondary to folate deficiency
    • Typically recommended in chronic hemolytic anemias (e.g., sickle cell disease, thalassemia)
    • Usual dose is 1 mg daily in children
  20. Q: How does hemolytic anemia affect iron metabolism?
    A: Effects on iron metabolism include:
    • Increased iron absorption due to increased erythropoiesis
    • Risk of iron overload, especially in transfusion-dependent anemias
    • Potential need for iron chelation therapy in chronically transfused patients
    • Importance of monitoring ferritin levels in chronic cases
  21. Q: What is the significance of reticulocyte count in hemolytic anemia?
    A: Reticulocyte count significance:
    • Elevated in hemolytic anemia, indicating increased bone marrow response
    • Helps differentiate hemolytic anemia from other causes of anemia
    • Can be used to monitor disease activity and response to treatment
    • May be inappropriately low if there's concurrent bone marrow suppression or nutritional deficiency
  22. Q: How do you manage a child with hereditary spherocytosis who develops cholelithiasis?
    A: Management approach:
    • Evaluate the severity of spherocytosis and frequency of hemolytic episodes
    • Consider combined splenectomy and cholecystectomy if symptomatic
    • Ensure appropriate vaccinations before splenectomy (encapsulated organisms)
    • Discuss risks and benefits of splenectomy with family
    • Consider partial splenectomy in younger children to preserve some splenic function
  23. Q: What is the pathophysiology of hemolytic uremic syndrome (HUS)?
    A: Pathophysiology of HUS:
    • Often triggered by Shiga toxin-producing E. coli infection
    • Toxin causes endothelial damage in small blood vessels
    • Results in microangiopathic hemolytic anemia
    • Leads to thrombocytopenia due to platelet consumption
    • Causes acute kidney injury due to renal microvascular thrombosis
  24. Q: How do you diagnose and manage drug-induced immune hemolytic anemia?
    A: Diagnosis and management:
    • Suspect based on timing of drug administration and onset of hemolysis
    • Positive direct Coombs test (usually IgG or IgG + complement)
    • Discontinue the offending drug immediately
    • Supportive care, including transfusions if necessary
    • Consider steroids in severe cases
    • Avoid re-exposure to the drug in the future
  25. Q: What is the role of genetic testing in hereditary hemolytic anemias?
    A: Role of genetic testing:
    • Confirms diagnosis in cases where biochemical tests are inconclusive
    • Identifies specific mutations, which may have prognostic value
    • Allows for family screening and genetic counseling
    • Useful in prenatal diagnosis for severe forms of hemolytic anemia
    • May guide treatment decisions in some cases
  26. Q: How does hypersplenism contribute to the pathophysiology of hemolytic anemia?
    A: Hypersplenism contribution:
    • Increased splenic sequestration of abnormal RBCs
    • Accelerates the destruction of both normal and abnormal RBCs
    • Can lead to pancytopenia in severe cases
    • May exacerbate anemia in conditions like thalassemia and spherocytosis
    • Can improve after splenectomy in appropriate cases
  27. Q: What are the indications for red blood cell transfusion in hemolytic anemia?
    A: Indications for transfusion:
    • Severe symptomatic anemia (e.g., hemodynamic instability, tissue hypoxia)
    • Rapid fall in hemoglobin
    • Aplastic crisis in chronic hemolytic anemias
    • Preoperative optimization in some cases
    • Chronic transfusion programs in certain conditions (e.g., severe thalassemia)
  28. Q: How do you approach a child with suspected enzyme deficiency hemolytic anemia?
    A: Approach to suspected enzyme deficiency:
    • Detailed history including family history and ethnic background
    • Look for triggers of hemolysis (drugs, infections, oxidative stress)
    • Evaluate CBC, reticulocyte count, and peripheral blood smear
    • Specific enzyme assays (e.g., G6PD, pyruvate kinase)
    • Consider genetic testing for confirmation and family studies
    • Provide appropriate counseling and management based on the specific deficiency
  29. Q: What is the importance of the osmotic fragility test in diagnosing hereditary spherocytosis?
    A: Importance of osmotic fragility test:
    • Demonstrates increased RBC fragility in hypotonic solutions
    • Characteristic finding in hereditary spherocytosis
    • Can be normal in mild cases or after recent transfusion
    • Helps differentiate spherocytosis from other causes of hemolytic anemia
    • May be replaced by more specific tests like eosin-5'-maleimide (EMA) binding test in some centers
  30. Q: How does hemolytic anemia affect growth and development in children?
    A: Effects on growth and development:
    • Chronic anemia can lead to growth retardation and delayed puberty
    • Increased metabolic demands due to chronic hemolysis
    • Potential nutritional deficiencies (e.g., folate, zinc)
    • Skeletal changes in severe cases (e.g., frontal bossing in thalassemia)
    • Psychosocial impacts of chronic illness
    • Importance of regular monitoring and early intervention
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