Hemolytic Anemia Classification and Causes

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Questions and Answers

What type of autoantibodies does methyldopa induce against RBC?

IgA autoantibodies

IgE autoantibodies

IgG autoantibodies

IgM autoantibodies (correct)

Primary cold agglutinin is caused by IgG antibodies.

False

What is a common symptom associated with paroxysmal cold hemoglobinuria?

Mild jaundice

Which of the following infections can precipitate acute hemolytic crises in G6PD deficiency?

Meningococcal septicaemia Signup and view all the answers

PIGA is required for ___ synthesis.

PIP Signup and view all the answers

Which drug is known to cause immune hemolytic anemia by binding to RBC membranes?

Quinidine Signup and view all the answers

What is the treatment option for paroxysmal nocturnal hemoglobinuria?

Eculizumab Signup and view all the answers

Match the following symptoms with their associated conditions:

Mild jaundice = Paroxysmal cold hemoglobinuria Acrocyanosis = Cold autoimmune hemolytic anemia Chronic intravascular hemolysis = Paroxysmal nocturnal hemoglobinuria Spherocytosis = Burns Signup and view all the answers

What are the classifications of hemolytic anemia?

Hereditary and acquired; intravascular and extravascular. Signup and view all the answers

What are the clinical manifestations of hemolytic anemia?

Intravascular hemolysis causes hemoglobinemia and hemoglobinuria; extravascular hemolysis leads to jaundice, splenomegaly, and hyperbilirubinemia. Signup and view all the answers

What laboratory findings indicate hemolytic anemia?

Increased serum bilirubin, reticulocytosis, and decreased haptoglobin. Signup and view all the answers

What disorders can cause hemolytic anemia?

G6PD deficiency, autoimmune hemolytic anemia (AIHA), hereditary spherocytosis. Signup and view all the answers

The primary defect in hereditary spherocytosis involves the _____ skeleton of red blood cells.

membrane Signup and view all the answers

Describe intravascular hemolysis.

RBCs burst due to mechanical forces or damaging agents in circulation. Signup and view all the answers

What is an osmotic fragility test used for?

To assess the stability of red blood cell membranes. Signup and view all the answers

Which of the following is a cause of acquired hemolytic anemia?

Autoimmune mechanisms Signup and view all the answers

Sickle cell disease is considered a type of acquired hemolytic anemia.

False Signup and view all the answers

Match the type of hemolytic anemia with its cause.

G6PD Deficiency = Oxidative stress Autoimmune Hemolytic Anemia = Antibody-mediated destruction Hereditary Spherocytosis = Membrane defects Sickle Cell Anemia = Abnormal hemoglobin Signup and view all the answers

Study Notes

Classification of Hemolytic Anemia

Hemolytic anemia is classified into hereditary and acquired forms.
Hereditary causes:
- Membrane defects, such as hereditary spherocytosis and hereditary elliptocytosis.
- RBC metabolism defects, including G6PD deficiency and thalassemia.
Acquired causes:
- Immune hemolytic anemia (Autoimmune, Alloimmune, drug-associated).
- Secondary causes include infections and red cell fragmentation syndromes.
- Intravascular (RBC lysed in circulation) vs. Extravascular (RBC destruction by macrophages in the spleen).

Causes and Clinical Manifestations

Intravascular Hemolysis:
- Mechanisms: Mechanical forces, biochemical agents, physical agents damage RBCs.
- Clinical features: Hemoglobinemia, hemoglobinuria, hemosiderinuria, loss of iron, low haptoglobin.
Extravascular Hemolysis:
- Macrophage-mediated destruction of abnormal RBCs.
- Clinical features: Hyperbilirubinemia, jaundice, splenomegaly, bilirubin-rich gallstones, low haptoglobin.

Laboratory Findings

Increased RBC Breakdown:
- Elevated serum bilirubin, urine urobilinogen, faecal stercobilinogen.
- Absent haptoglobin, indicative of free hemoglobin.
Increased RBC Production:
- Reticulocytosis, erythroid hyperplasia evident in the bone marrow.
Damaged RBCs:
- Abnormal morphology, osmotic fragility tests, and specific enzyme, protein, and DNA tests.

Pathogenesis and Specific Disorders

G6PD Deficiency:
- An inherited enzyme defect affecting RBC metabolism.
- Symptoms include neonatal jaundice, acute hemolytic anemia during oxidative stress (e.g., infections, certain foods).
- Bite cells and Heinz bodies observed on blood smear.
Autoimmune Hemolytic Anemia (AIHA):
- Caused by antibodies binding to RBCs, leading to their destruction.
- Warm AIHA characterized by IgG antibodies, while cold AIHA involves IgM antibodies.
- Diagnosis via direct antiglobulin test (DAT) that shows antibody coating on RBCs.
Hereditary Spherocytosis:
- Genetic condition causing spherical RBCs due to defects in membrane proteins (spectrin, ankyrin).
- Clinical features: Jaundice, splenomegaly, and cholelithiasis are common.
- Investigations reveal dark spherocytes and increased osmotic fragility.
Hereditary Elliptocytosis:
- Mutations in spectrin cause elliptical RBCs and can lead to milder hemolytic anemia.
- Presents with microspherocytes and poikilocyte features on smear.
South-East Asian Ovalocytosis:
- Genetic mutation providing resistance to malaria but can cause hemolytic anemia.

Treatment Options

General Treatment:
- Blood transfusions for symptomatic anemia.
- Folate supplementation in hereditary forms.
- Splenectomy may be indicated for cases with excessive spleen-mediated RBC destruction.
For Autoimmune Hemolytic Anemia:
- Treatment often includes corticosteroids and immunosuppressive therapy.
- Rituximab is used for refractory cases.
For G6PD Deficiency:
- Avoidance of oxidant stress triggers, supportive care such as transfusions during crises.### Aggressive Lymphoma and Immune Hemolytic Anemia
May transform into aggressive lymphoma but is usually self-limiting.
Complement factors detectable on RBCs in lab tests as IgM is eluted off in the cold agglutinin.

Treatment Approaches

Keep the patient warm to promote circulation.
Treatment includes alkylating agents, rituximab, splenectomy, and corticosteroids.

Drug-Induced Immune Hemolytic Anemia

Penicillin: Antibodies directed against drug-RBC membrane complex.
Quinidine: Causes complement deposition through drug-protein (antigen)-antibody complex.
Methyldopa: Autoimmune antibodies bind to RBCs, inducing hemolysis.

Red Cell Fragmentation Syndromes

G6PD deficiency can precipitate acute hemolytic crises due to infections.
Meningococcal septicaemia, malaria, and Clostridium perfringes lead to intra and extravascular hemolysis.
Oxidative intravascular hemolysis associated with drugs like sulfasalazine and dapsone.

Chemical and Physical Agents

High copper levels in Wilson's disease lead to acute hemolytic anemia.
Chemical poisoning from lead, chlorate, or arsine results in severe hemolysis.
Burns can cause spherocytosis and acanthocytosis.

Secondary Hemolytic Anemia

Liver diseases associated with hemolysis include:
- Zieve’s syndrome: Alcohol-induced.
- Wilson’s disease: Copper oxidation of RBC membrane.
- Chronic immune hepatitis can lead to autoimmune hemolytic anemia (AIHA).
- End-stage liver disease impacts RBC membranes due to lipid changes.
In kidney diseases, hemolysis may occur due to Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP).

Paroxysmal Nocturnal Hemoglobinuria (PNH)

X-linked disorder caused by a mutation in the PIGA gene, essential for phosphatidylinositol glycan (PIP) synthesis.
Chronic intravascular hemolysis leads to hemosiderinuria and free hemoglobin.
RBCs become sensitive to complement lysis, resulting in venous thrombosis complications.
Flow cytometry shows the loss of CD55 and CD59 expression.
Treatments include Eculizumab, iron therapy, and stem cell transplant as a definitive approach.

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Description

This quiz covers the classification of hemolytic anemia into hereditary and acquired forms, along with their causes and clinical manifestations. It delves into specific conditions and the mechanisms of both intravascular and extravascular hemolysis, highlighting significant clinical features. Test your knowledge on this vital aspect of hematology.