38 Questions
What occurs when IgG or IgM/C3 is bound to RBC membranes?
Agglutination occurs → positive result
What is the purpose of the indirect antiglobulin test (indirect Coombs' test)?
To detect Ab/Complement coating the red cells
What is added to the indirect Coombs' test to induce agglutination?
Anti-human globulin (AHG)
What is the primary focus of treatment for warm and cold AIHA?
Support and varies based on symptoms
What is the mechanism of drug-induced immune hemolytic anemia?
Drugs induce Ab production against RBCs
What is the site of red cell destruction in drug-induced immune hemolytic anemia?
Spleen, liver, and other sites of the reticuloendothelial system (RES)
What is the purpose of corticosteroid therapy in the treatment of warm and cold AIHA?
To suppress the immune system
How many mechanisms of drug-induced immune hemolytic anemia are described?
Three
What type of mechanism involves the formation of a drug-RBC membrane complex, leading to RBC destruction?
Type 1 - Hapten mediated
Which type of mechanism involves the deposition of complement (C3b) onto RBC surface?
Type 2 - Immune Complex Mediated
What is the role of the drug in Type 3 - True autoimmune HA?
The drug causes antibodies to react with antigens on RBC surface
What is Paroxysmal Nocturnal Hemoglobinuria (PNH) characterized by?
Intravascular hemolysis at night while the patient is asleep
Which of the following drugs is an example of Type 1 - Hapten mediated mechanism?
Penicillin
What is the term for the dark urine produced during intravascular hemolysis?
Hemoglobinuria
Which type of mechanism is characterized by the deposition of complement (C3b) via drug-carrier protein-antibody complex onto RBC surface?
Type 2 - Immune Complex Mediated
What is the term for the episodes of hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Paroxysmal
What is the typical presentation of abdominal pain, ascites, and liver enlargement?
Classical triad
What can ascites affect besides the abdomen?
Lungs and kidneys
What is the characteristic of the peripheral smear in PNH?
Microcytic, hypochromic RBCs
What is the significance of LDH in hemolysis?
LDH indicates tissue breakdown
What is the characteristic of bone marrow examination in PNH?
Hypocellular with erythroid hyperplasia
What is a common laboratory finding in PNH?
Pancytopenia
What is the symptom of deep vein thrombosis (DVT) in the leg?
Pain, swelling, redness, and warmth in one leg
What is the condition called when a clot detaches and travels to the lung?
Pulmonary embolism
What is the term for cold fingers and toes?
Acrocyanosis
What is the test done to detect the interaction between Ab/Complement and RBCs?
Direct Coombs' test
What is bound to antigen on RBC membranes in Warm AIHA?
IgG
What is the term for painful bluish or reddish discoloration of the toes, fingers, ankles, and wrist?
Raynaud phenomenon
What is added to washed patient's RBCs in the direct antiglobulin test?
Antihuman globulin
What type of antibody is bound to antigen on RBC membranes in Cold AIHA?
IgM and complement
What is the primary function of CD55 and CD59 on the RBC membrane?
To protect RBCs from complement-mediated lysis
What is the result of the absence of CD55 and CD59 on the RBC membrane?
Sensitivity to lysis by complement (MAC; C5-C9)
What is the underlying genetic defect in PNH?
Mutation of the PIG-A gene
What is the role of the GPI anchor in PNH?
To anchor GPI-linked proteins to the RBC membrane
What is the consequence of uncontrolled complement activation in PNH?
Chronic intravascular hemolysis
What is the primary function of CD59 in normal conditions?
To regulate the formation of the MAC
What is the result of the PIG-A gene mutation in PNH?
Inactivation of the GPI anchor on the RBC membrane
What is the role of the GPI-linked proteins in PNH?
To protect RBCs from complement-mediated lysis
Study Notes
Lab Analysis of Warm and Cold AIHA
- In warm and cold AIHA, IgG or IgM/C3 is bound to RBC membranes, leading to agglutination and a positive result.
- Indirect antiglobulin test (indirect Coombs' test) detects Ab/Complement coating the red cells following incubation with serum/plasma in the lab.
- Coomb's reagent (Anti-human globulin, AHG) is added, and agglutination occurs, indicating a positive result.
Treatment of Warm and Cold AIHA
- Focus is on support and varies based on symptoms.
- Corticosteroid therapy, specifically prednisone, is used, and may include Rituximab, which targets immune cells responsible for hemolysis.
Drug-Induced Immune Hemolytic Anemia
- Drugs promote antibody production by the body, which then attacks its own red cells.
- The drug induces Ab production, which opsonizes and coats red cells, leading to their destruction in the RES (spleen, liver).
Mechanisms of Drug-Induced Immune Hemolytic Anemia
- Three mechanisms occur:
- Type 1 – Hapten mediated: Antibody IgG against the drug binds to RBC membrane, forming a drug-RBC membrane complex, preparing the RBC for destruction.
- Type 2 – Immune Complex Mediated: Deposition of complement (C3b) via drug-carrier protein-antibody complex onto RBC surface.
- Type 3 – True autoimmune HA: The role of the drug is unclear; the drug appears to cause antibodies that react with antigens on RBC surface, causing hemolysis.
Acquired Intravascular Hemolytic Anemia
Paroxysmal Nocturnal Hemoglobinuria (PNH)
- PNH is an acquired hemolytic anemia affecting hematopoietic stem cells.
- Definition: Paroxysmal (episodes), nocturnal (occurring at night), hemoglobinuria (dark urine during intravascular hemolysis).
Etiology of PNH
- Caused by a deficiency of two GPI anchor proteins, CD55 and CD59, due to a mutation of the PIGA gene in hematopoietic stem cells in the bone marrow.
- The absence of CD55 and CD59 on the RBC membrane leads to uncontrolled complement activation, accounting for hemolysis and other PNH manifestations.
Pathogenesis of PNH
- PIG-A gene mutation causes inactivation of the GPI anchor on the red cell membrane.
- GPI-linked proteins (CD55 and CD59) are absent from the red cell membrane.
- The lack of these proteins renders RBCs sensitive to lysis by complement (MAC; C5-C9), resulting in chronic intravascular hemolysis.
Mechanism of PNH
- In normal conditions, formation of the MAC is under the regulation of CD59.
Lab Findings of PNH
- CBC: Pancytopenia, raised reticulocyte count.
- Hemoglobin and hematocrit: Decreased.
- Peripheral smear: Microcytic, hypochromic RBCs, polychromatic RBCs/reticulocyte (new methylene blue stain/supravital stain).
- Bone marrow examination: Hypocellular with erythroid hyperplasia.
- Biochemistry: LDH is an indicator for tissue breakdown, e.g., hemolysis.
This quiz covers the indirect antiglobulin test, also known as the indirect Coombs' test, which detects antibodies or complement coating red blood cells in the lab. It is used to diagnose warm and cold autoimmune hemolytic anemia (AIHA).
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