Cold Agglutinin Disease Quiz

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Questions and Answers

What is the function of the 'I' and 'i' antigens?

They determine blood type in the ABO system.

Their function is unknown. (correct)

They are involved in immune system signaling.

They help regulate blood clotting.

Which cells are primarily responsible for phagocytosing C3b-coated red blood cells in cold agglutinin disease (CAD)?

Eosinophils

Neutrophils

Lymphocytes

Kupffer cells (correct)

What is the typical optimum temperature for antigen binding to cold agglutinins?

15 to 20°C

28 to 30°C

3 to 4°C (correct)

37°C

What is the primary mechanism of hemolysis in cold agglutinin disease (CAD)?

Complement-mediated extravascular hemolysis. (A) Signup and view all the answers

What type of antibody is most commonly associated with cold agglutinins?

IgM (D) Signup and view all the answers

What is the significance of a cold agglutinin titer ≥64?

It indicates a high concentration of antibodies. (D) Signup and view all the answers

What is the typical thermal amplitude of pathogenic cold agglutinins?

28 to 30°C or more (C) Signup and view all the answers

Which of the following is NOT a typical clinical manifestation associated with cold agglutinin disease?

Kidney failure (B) Signup and view all the answers

What percentage of individuals with warm AIHA typically exhibit anemia-related symptoms?

75% (B) Signup and view all the answers

Which underlying condition is NOT commonly associated with warm AIHA?

Chronic lung disease (C) Signup and view all the answers

In what circumstance is splenomegaly particularly considered in patients with warm AIHA?

As a result of an underlying lymphoproliferative disorder (B) Signup and view all the answers

What is the typical hemoglobin level at presentation for a patient with warm AIHA?

7 to 10 g/dL (D) Signup and view all the answers

Which of the following tests is most likely to show a positive result for a patient suspected of having warm AIHA?

Direct Antiglobulin Test (DAT) (B) Signup and view all the answers

Thromboembolic events in AIHA may include which of the following?

Deep vein thrombosis (B) Signup and view all the answers

Which condition is associated with a positive DAT for C3d only?

Cold agglutinin disease (CAD) (A) Signup and view all the answers

Which of the following conditions could indicate intravascular hemolysis in warm AIHA?

Haemoglobinuria (B) Signup and view all the answers

What is the primary reason for delaying splenectomy until an individual is older than six years?

To minimize the risk of sepsis due to absent splenic function (A) Signup and view all the answers

Which genes are associated with hereditary elliptocytosis?

SPTA1 and EPB41 (B) Signup and view all the answers

In patients with hereditary pyropoikilocytosis, what characteristic morphology is observed in red blood cells?

Anisopoikilocytosis with elliptocytes and fragmented RBCs (B) Signup and view all the answers

What role does folic acid supplementation play in patients with haemolytic conditions?

Supports red blood cell production during pregnancy and moderate to severe haemolysis (A) Signup and view all the answers

What is the primary cause of chronic haemolysis in pyruvate kinase deficiency?

Reduced pyruvate kinase enzyme activity (B) Signup and view all the answers

Which of the following statements about family testing in relation to hereditary conditions is accurate?

It may provide useful information for individuals of childbearing age. (D) Signup and view all the answers

Which statement best describes the genetic inheritance pattern of G6PD deficiency?

X-linked recessive (C) Signup and view all the answers

What consequence results from the oxidation of sulfhydryl groups on hemoglobin in G6PD deficiency?

Formation of Heinz bodies (D) Signup and view all the answers

What is the typical inheritance pattern of hereditary elliptocytosis?

Autosomal dominant (B) Signup and view all the answers

What additional surgical procedure may be performed simultaneously with splenectomy if indicated?

Cholecystectomy (B) Signup and view all the answers

How does G6PD deficiency affect the structure of red blood cells when exposed to oxidants?

Formation of methemoglobin and cross-bonding of hemoglobin occurs (B) Signup and view all the answers

What type of haemolysis is most commonly associated with pyruvate kinase deficiency?

Extravascular (A) Signup and view all the answers

Which type of anaemia can result from hereditary pyropoikilocytosis?

Severe symptomatic haemolytic anaemia (B) Signup and view all the answers

Why are most heterozygous females for G6PD deficiency usually clinically unaffected?

Skewed X inactivation leads to normal G6PD function (A) Signup and view all the answers

What is the estimated global prevalence of G6PD deficiency?

400 to 500 million people (A) Signup and view all the answers

What is the major consequence of red blood cells becoming rigid and non-deformable in G6PD deficiency?

Destruction by reticuloendothelial macrophages (D) Signup and view all the answers

Which populations are most commonly affected by HE/HPP?

Individuals of African, Mediterranean, or Southeast Asian descent (A) Signup and view all the answers

What is the primary purpose of osmotic gradient ektacytometry (OGE) in diagnosing HE/HPP?

To confirm the diagnosis when RBC morphology is unclear (D) Signup and view all the answers

In what situation should splenectomy be considered for individuals with HE?

In cases of severe chronic hemolysis (C) Signup and view all the answers

What is a common feature of South East Asian Ovalocytosis RBCs?

Stomatocytic elliptocytosis morphology (A) Signup and view all the answers

What management is typically needed for most individuals with HE?

No specific therapy or follow-up care (A) Signup and view all the answers

What genetic factor increases the risk for having a severely affected child in cases of HE?

Consanguinity between parents (C) Signup and view all the answers

Why might EMA binding results be considered less helpful in diagnosing HE/HPP?

Results of EMA binding are variable (C) Signup and view all the answers

What diagnostic challenge can arise with HE/HPP in terms of clinical presentation?

Variable clinical presentation from asymptomatic to severe hemolytic anemia (A) Signup and view all the answers

What is the time frame within which plasma exchange (PEX) should be initiated for TTP after referral?

Within 4 to 8 hours (B) Signup and view all the answers

Which treatment should be avoided in patients with TTP?

Platelet transfusion (C) Signup and view all the answers

In the case of the 5-year-old girl with pallor and jaundice showing abnormal small, round red cells, what is the suggested diagnosis?

Hereditary Spherocytosis (D) Signup and view all the answers

Which of the following would NOT be a treatment option for Secondary Warm Autoimmune Hemolytic Anemia?

Plasma exchange (C) Signup and view all the answers

What is the primary purpose of initiating monoclonal anti-CD20 therapy in patients with acute iTTP?

Turn off antibody production by B lymphocytes (C) Signup and view all the answers

Study Notes

Haemolytic Anaemia

Haemolytic anaemia is a condition where red blood cells (RBCs) are destroyed prematurely, leading to a deficiency of these cells in the blood.
This premature destruction can be caused by intrinsic RBC defects (e.g., haemoglobin, enzyme, or membrane defects) or extrinsic factors (e.g., autoimmune diseases, vascular defects, toxins, or heat).
Intravascular haemolysis occurs when RBCs are directly destroyed within the blood vessels.
Extravascular haemolysis happens when intact but abnormal RBCs are phagocytosed by macrophages in the spleen and liver.

Learning Objectives

Red blood cell enzyme pathways and possible deficiencies.
Basic structure of the red blood cell membrane.
Defects in the red blood cell membrane (both congenital and acquired).

Classification of Haemolytic Anaemia

Categorization based on whether the defect lies outside or inside the red blood cell (RBC).
Immune haemolytic anaemia (DAT positive): Further categorized based on the type of antibody (warm, cold, mixed).
Non-immune haemolytic anaemia (DAT negative): The defect lies inside the RBC.

Pathophysiology

The breakdown of red blood cells—the process by which bilirubin and other byproducts are produced.
The various pathways for the processing and excretion of these byproducts.
The roles of the liver, spleen, and bone marrow in the process.

Blood Film Clues

Bite cells, blister cells, or irregularly shaped red blood cells (poikilocytosis) suggest oxidative haemolysis.
Spherocytes or microspherocytes suggest immune haemolysis.
Schistocytes suggest thrombotic microangiopathy.

Autoimmune Haemolytic Anaemia (AIHA)

Autoimmune-mediated destruction of red blood cells (RBCs) by autoantibodies.
Properties and target specificities of the autoantibodies vary.
Classification as primary (no obvious cause) or secondary (caused by an underlying condition, like lymphoma, infection, or medication).
Co-existence with autoimmune thrombocytopenia (Evan's syndrome).
Haemolysis initiated when autoantibodies bind to the RBC membrane, which triggers complement activation or other mechanisms.
RBC destruction through extravascular or intravascular pathways.

Warm Antibody Haemolytic Anaemia

Warm AIHA is due to IgG antibodies active at normal body temperature.
Antibodies react with RBC antigens at warmer temperatures.
Primary or secondary to an underlying condition (e.g., lymphoma).
Antibodies frequently bind to all RBCs in a reaction called panagglutination.

Cold Antibody Haemolytic Anaemia (CAHA)

Pathophysiology of CAHA is characterized by IgM antibodies reacting with RBCs at low temperatures, resulting in their extravascular lysis.
The antibodies typically target the I or i blood group antigens.
Titer (the concentration of the antibody) generally above 32 is clinically significant.

Paroxysmal Cold Haemoglobinuria (PCH)

Uncommon autoimmune haemolytic anaemia where antibodies bind to red blood cells at cold temperatures, fixing complement, and leading to intravascular haemolysis.
Characterised by Donath-Landsteiner antibodies, which react to RBCs at cold temperatures, leading to complement-mediated damage.

Drug-Induced Haemolytic Anaemia

Immune mechanisms: Antibiotics, diclofenac, and certain chemotherapeutic agents.
Oxidative mechanisms: Primaquine, dapsone, and some other drugs.
Specific drug examples (table provided).
Methæmoglobinemia: Some antibiotics and other drugs.
Thrombotic microangiopathy: Certain drugs.

Inherited Haemolytic Anaemias

Red blood cell membrane defects: Hereditary spherocytosis, hereditary elliptocytosis, pyropoikilocytosis (including cases of hereditary spherocytic elliptocytosis).
Hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP): Genetic disorders characterized by abnormal red blood cell shapes (elliptocytes, spherocytes).

Microangiopathic Haemolytic Anaemia (MAHA)

A non-immune hemolytic disorder where red blood cells are fragmented due to abnormal blood vessel structure or function.
Caused by various conditions (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome).
Key feature is schistocytes and fragmented red blood cells on examination (blood film).

Thrombotic Thrombocytopenic Purpura (TTP)

Caused by deficient ADAMTS13 activity resulting in clotting factors, VWF build-up, microthrombi formation, and eventually red blood cell damage.
Diagnosis relies on clinical symptoms and laboratory findings which include abnormal blood test results.

Case Studies

Provided case details including symptoms, investigations, and likely diagnoses.

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Description

Test your knowledge on cold agglutinin disease (CAD) and its mechanisms. This quiz covers antigen functions, immune responses, and clinical manifestations associated with CAD. Perfect for students in hematology or those interested in autoimmune disorders.