Ch 14a: Hemolytic Anemias: Immune and Complement Pathways

What is immune hemolytic anemia?

A process in which red cells are destroyed prematurely by an immune-mediated process.

What are the two types of hemolysis in immune hemolytic anemia?

Intravascular and extravascular hemolysis.

Where does intravascular hemolysis occur?

Within the vascular system.

Where does extravascular hemolysis occur?

Outside the vascular system, primarily in the liver and spleen.

What confirms hemolysis in immune hemolytic anemia?

A positive direct antiglobulin test (DAT).

What is complement in the context of immune response?

A series of proteins that, when activated, disrupt bacterial or cell membranes.

What are the three pathways to activate complement?

Classical pathway, alternative pathway, and lectin (MBL) pathway.

What initiates the classical pathway of complement activation?

IgG or IgM antibodies.

What is the role of C1 in the classical pathway?

C1 interacts with the Fc region of immunoglobulin and initiates the complement cascade.

What does C3 convertase do?

Cleaves C3 into C3a and C3b, amplifying the complement response.

What is the function of C5 convertase?

Cleaves C5 into C5a (anaphylatoxin) and C5b, initiating cell lysis.

What is the membrane attack complex?

A structure formed by C5b6789 that causes cell lysis.

What triggers the alternative pathway of complement activation?

Microorganisms, polysaccharides, liposaccharides, and aggregates of IgA.

How does the lectin pathway activate complement?

Triggered when mannose-binding lectin attaches to mannose on microbial cell walls.

What is intravascular hemolysis?

Cellular breakdown within the vascular system due to complement activation.

Why is IgM an efficient activator of complement?

Due to its pentameric structure, allowing effective binding and activation.

What laboratory findings indicate intravascular hemolysis?

Hemoglobinemia, hemoglobinuria, elevated indirect bilirubin, and positive DAT.

What is extravascular hemolysis?

Phagocytosis of red cells in the mononuclear phagocyte system, primarily in the liver and spleen.

What are spherocytes indicative of?

Partial phagocytosis in immune-mediated hemolysis.

What role do macrophages play in extravascular hemolysis?

They phagocytize red cells coated with antibodies or complement.

What happens to haptoglobin levels in immune hemolytic anemia?

Haptoglobin is depleted as it binds to lysed red cells.

What is the significance of reticulocytosis in hemolytic anemia?

It indicates the bone marrow's response to increased red blood cell destruction.

What is the primary site of removal for red cells coated with IgG?

The liver, due to its high concentration of macrophages.

What is the role of Fc receptors in immune hemolysis?

They bind immunoglobulin and facilitate phagocytosis by effector cells.

What factors affect the efficiency of IgG in activating complement?

Subclass, proximity of molecules, physical location of the antigen, and avidity.

What are spherocytes?

Spherocytes are abnormally shaped red blood cells often seen in hemolytic anemia.

What laboratory findings may indicate hemolytic anemia?

Elevated indirect bilirubin, LDH, and positive DAT (Direct Antiglobulin Test).

What is alloimmune hemolytic anemia?

A condition where the patient produces antibodies against foreign red cell antigens, often due to transfusion, pregnancy, or transplants.

What is an acute hemolytic transfusion reaction (HTR)?

A reaction caused by IgM antibodies against ABO group antigens, leading to immediate cell lysis.

What are common symptoms of an acute hemolytic transfusion reaction?

Fever, chills, pain at the infusion site, nausea, vomiting, and hypotension.

What is the treatment focus for acute hemolytic transfusion reactions?

Prompt termination of the transfusion and administration of IV fluids to maintain renal function.

What is a delayed hemolytic transfusion reaction (DHTR)?

A reaction that occurs 2-10 days post-transfusion, typically involving IgG antibodies.

What symptoms are associated with delayed hemolytic transfusion reactions?

Mild jaundice, fever, and a fall or lack of rise in hemoglobin levels.

What is hemolytic disease of the newborn (HDN)?

A condition resulting from maternal-fetal blood group incompatibility, leading to destruction of fetal red blood cells.

What triggers maternal immunization in hemolytic disease of the newborn?

Exchange of blood during pregnancy or at delivery.

What are the two major types of hemolytic disease of the newborn?

Those associated with ABO incompatibility and those associated with Rh incompatibility.

What is autoimmune hemolytic anemia?

A condition where the body produces antibodies against its own red blood cells.

What are the two types of autoimmune hemolytic anemia?

Warm type (37°C) and cold type (4-31°C).

What is a positive DAT indicative of in warm autoimmune hemolytic anemia?

Presence of polyspecific IgG and C3d antibodies.

What laboratory findings are associated with autoimmune hemolytic anemia?

Moderate to severe anemia, polychromasia, reticulocytosis, spherocytosis, and increased bilirubin and LDH.

What is the first line of treatment for autoimmune hemolytic anemia?

Corticosteroids like prednisone to reduce antibody synthesis.

What complications can arise from hemolytic anemia?

Renal damage due to hemolysis and potential need for transfusions.

What is the significance of monitoring vital signs during transfusions?

To detect and respond promptly to any transfusion reactions.

What is the role of immunosuppressive drugs in treating autoimmune hemolytic anemia?

They may be used for patients who do not respond to conventional therapy.

What are the common causes of autoimmune hemolytic anemia?

Lymphoproliferative disorders, autoimmune disorders, neoplastic disorders, and viral infections.

What is the risk associated with transfusing incompatible blood?

It can lead to severe transfusion reactions and hemolysis.

What is the significance of anamnestic response in delayed hemolytic transfusion reactions?

It refers to the increase in antibody production upon re-exposure to the antigen.

What are the laboratory findings in delayed hemolytic transfusion reactions?

Typically subclinical, discovered serologically through tests like DAT and IAT.

What is erythroblastosis fetalis?

A term used to describe the increased erythropoiesis in infants due to hemolytic disease of the newborn.

What is the importance of IV fluids in treating acute hemolytic transfusion reactions?

To maintain renal function and prevent damage from hemolyzed red cells.

What is the role of splenectomy in autoimmune hemolytic anemia?

It may be considered if the antibody is IgG and other treatments are ineffective.

What are the common laboratory findings in autoimmune hemolytic anemia?

Moderate to severe anemia, spherocytosis, and increased indirect bilirubin.

What is the significance of a negative DAT in autoimmune hemolytic anemia?

It can occur in patients with clear hemolysis, indicating limitations of the test.

What is splenectomy and when may it be considered?

Splenectomy may be considered in cases of hemolytic anemia.

What types of treatments are available for patients unresponsive to conventional therapy?

Immunosuppressive drugs, IV immunoglobulin, antilymphocytic globulin, anti-CD20 (Rituximab), or plasma exchange.

What are normal cold reacting autoantibodies?

They are present in all normal human sera, including specificities like anti-I, anti-H, and anti-IH.

What distinguishes benign from pathologic cold reacting autoantibodies?

The range of activity; pathological antibodies may react at temperatures above 30°C.

What is cold agglutinin disease (CAD)?

A hemolytic anemia caused by an antibody with a wide range of activity (4° - 30°+ C).

What is the common antibody specificity in cold agglutinin disease?

Almost always anti-I, commonly anti-i, and rarely anti-Pr.

What is acrocyanosis and what causes it in CAD?

A symptom of cold intolerance, causing a bluish tinge in fingertips and toes due to localized agglutination and blood stasis.

What happens to antibodies in cold temperatures in CAD?

They activate, coat cells, and fix complement, leading to hemolysis when returned to warm temperatures.

What does a positive direct antiglobulin test (DAT) indicate in CAD?

It indicates the presence of complement (C3d) on red blood cells.

What are the symptoms of hemolysis in CAD?

Hemoglobinemia, hemoglobinuria, jaundice, and splenomegaly.

What is Cold Agglutinin Syndrome (CAS)?

A transient disorder secondary to infections, often following upper respiratory infections.

What is the treatment for Cold Agglutinin Syndrome?

Generally involves avoiding cold; plasma exchange may help in acute situations.

What is Paroxysmal Cold Hemoglobinuria (PCH)?

A condition almost exclusively in children, associated with viral disorders, causing red cell destruction by cold reacting IgG.

What is the Donath-Landsteiner antibody?

An antibody associated with PCH that binds at low temperatures and activates complement at higher temperatures.

What are the signs of intravascular hemolysis in PCH?

Hemoglobinemia, hemoglobinuria, and bilirubinemia.

How is PCH diagnosed?

By performing a test with blood aliquots held at different temperatures to observe hemolysis.

What is Mixed Autoimmune Hemolytic Anemia (AIHA)?

A condition where patients have antibodies with both warm and cold characteristics.

What is the mechanism of drug-induced immune hemolytic anemia?

It involves antibodies to drugs, metabolites, or red cells coated with drugs.

What is the most common drug implicated in drug-induced immune hemolytic anemia?

Methyldopa, accounting for approximately 70% of cases.

What is the hapten mechanism in drug-induced hemolytic anemia?

The drug nonspecifically adsorbs to red cells and elicits an antibody response.

What is the immune complex mechanism in drug-induced hemolytic anemia?

Formation of an antibody-drug immune complex that activates complement on red cells.

What is membrane modification mechanism in drug-induced hemolytic anemia?

The drug modifies the cell membrane, leading to nonspecific protein adsorption.

What is the significance of a positive DAT in drug-induced hemolytic anemia?

It indicates the presence of antibodies, often IgG, associated with hemolysis.

What are the common signs of hemolytic anemia?

Symptoms include fatigue, pallor, jaundice, and dark urine.

What is the role of complement in hemolysis?

Complement activation leads to cell lysis and removal of red blood cells by macrophages.

What is the recommended sample type for DAT testing?

An EDTA sample to inhibit in vitro complement fixation.

What can be observed in a peripheral blood smear of CAD?

Agglutination and possibly rouleaux formation.