Hematology Sickle Cell Disease Overview

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Questions and Answers

What is a common clinical manifestation of aplastic anemia?

Frequent generalized infections (correct)

Marked lymphadenopathy

Enlargement of the liver and spleen

Pancytosis

What type of anemia results from the deposition of fibrin strands in small vessels?

Microangiopathic hemolytic anemia (correct)

Iron deficiency anemia

Aplastic anemia

Hemolytic anemia

Which of the following is NOT a known cause of secondary aplastic anemia?

Chloramphenicol

Fanconi’s anemia (correct)

Viral hepatitis

Ionizing radiation

What is the typical reticulocyte count in a patient with aplastic anemia?

Decreased reticulocyte count Signup and view all the answers

Which of the following best describes the pathogenesis of aplastic anemia?

Substantial reduction in the number of stem cells Signup and view all the answers

What is the typical hemoglobin level observed in patients with sickle cell disease?

6–9 g/dL Signup and view all the answers

Which complications are associated with sickle cell disease during pregnancy?

More common painful episodes in the last trimester Signup and view all the answers

What laboratory finding is characteristic of sickle cell disease?

Presence of Howell-Jolly bodies Signup and view all the answers

What is the most common symptom of sickle cell trait?

Haematuria Signup and view all the answers

Which of the following interventions is not typically part of the routine management for sickle cell disease?

Chemotherapy Signup and view all the answers

How does sickle cell disease affect the spleen over time?

The spleen eventually infarcts and shrinks Signup and view all the answers

What role does hydroxyurea play in the management of sickle cell disease?

It helps to increase fetal hemoglobin (HbF) Signup and view all the answers

Which type of infections are particularly associated with sickle cell disease due to loss of splenic function?

Bacterial infections, specifically Gram-negative sepsis Signup and view all the answers

Which characteristic laboratory finding is specifically associated with cold autoimmune hemolytic anemia?

Positive direct Coomb's test with C3d Signup and view all the answers

What is the primary antibody type involved in cold autoimmune hemolytic anemia?

IgM Signup and view all the answers

Which of the following conditions can lead to secondary cold autoimmune hemolytic anemia?

Lymphoproliferative disorders Signup and view all the answers

What is a common clinical feature observed in patients with cold autoimmune hemolytic anemia?

Acrocyanosis Signup and view all the answers

In which scenario would alloimmune hemolytic anemia most likely occur?

Following blood transfusion of incompatible blood types Signup and view all the answers

Which type of anemia is caused by mechanical damage to red blood cells?

Non-immune hemolytic anemia Signup and view all the answers

What is a typical response seen in the blood film of a patient with warm autoimmune hemolytic anemia?

Spherocytes and reticulocytes Signup and view all the answers

Which of the following statements about cold autoimmune hemolytic anemia is incorrect?

Spherocytosis is more pronounced than in warm AIHA. Signup and view all the answers

Which statement about the effect of chronic hemolysis in anaemia is true?

Jaundice results from chronic heme turnover and increased bilirubin production. Signup and view all the answers

What characterizes vaso-occlusive crises in sickle cell anemia?

They can be triggered by factors such as dehydration. Signup and view all the answers

What is a potential consequence of aplastic crisis in sickle cell patients?

Shortened RBC lifespan can lead to life-threatening anemia. Signup and view all the answers

Which complication is most commonly associated with acute sickle chest syndrome?

It is the most common cause of death in sickle cell disease. Signup and view all the answers

What distinguishes a hemolytic crisis in sickle cell patients?

It can lead to a catastrophic drop in hematocrit. Signup and view all the answers

Which statement accurately reflects the variability of clinical expression in Hb SS?

Some patients may have an almost normal life with few crises. Signup and view all the answers

What is a common symptom of chronic hemolysis associated with biliary function?

Gall stones due to cholelithiasis. Signup and view all the answers

What percentage of sickle cell patients are at risk of stroke?

7% Signup and view all the answers

What is the primary cause of the sickle β-globin abnormality in sickle cell disease?

Substitution of valine for glutamic acid in the β chain Signup and view all the answers

Which of the following factors does NOT influence the polymerization of HbS in circulating red cells?

Presence of decarboxylated hemoglobin Signup and view all the answers

What type of hemolysis characterizes sickle cell disease?

Both intravascular and extravascular hemolysis Signup and view all the answers

Which of the following clinical features is NOT associated with sickle cell disease?

Fibrosis of lung tissue Signup and view all the answers

Which morphological change occurs in red blood cells due to deoxygenation in sickle cell disease?

Formation of sickle-shaped cells Signup and view all the answers

What does the presence of oxidant substances in sickle cell disease lead to?

Enhanced blood viscosity Signup and view all the answers

Which state is characterized by the loss of deformability in SS erythrocytes?

Deoxygenated state Signup and view all the answers

The interaction of HbS with which condition can also lead to sickling?

Thalassemia Signup and view all the answers

What characterizes acquired hemolytic anemia?

Presence of autoantibodies against self red cell antigens Signup and view all the answers

Which of the following statements about autoimmune hemolytic anemia is correct?

It can be caused by the body producing antibodies against its own red cells. Signup and view all the answers

Which classification of hemolytic anemia involves antibody-mediated mechanisms?

Acquired hemolytic anemia Signup and view all the answers

With respect to the direct Coombs test, which interpretation is accurate?

A positive result indicates acquired hemolytic anemia. Signup and view all the answers

What is the main mechanism of deterioration in warm autoimmune hemolytic anemia?

Enhanced phagocytosis of red cells by macrophages Signup and view all the answers

What defines the difference between warm and cold autoimmune hemolytic anemia?

The temperature at which the antibody interacts with red cells Signup and view all the answers

Which precursor condition is associated with increased Hb S levels?

Sickle cell disease Signup and view all the answers

What is a significant concern when managing a patient with hereditary hemolytic anemia?

Potential complications associated with anesthesia Signup and view all the answers

Study Notes

Hematology Lecture Notes

Sickle cell disease (SCD) is a group of hemoglobin disorders.
It results from inheriting the sickle β-globin gene, with a specific abnormality.
The abnormality is caused by substituting valine for glutamic acid in position 6 of the β chain.
The homozygous state (HbSS or sickle cell anemia) is the most prevalent form of sickle cell disease.
Interactions between HbS and thalassemia or certain variant hemoglobins can also lead to sickling.
The term sickle cell disease (SCD) encompasses all conditions associated with hemoglobin sickling in red blood cells.

Pathophysiology

Deoxygenation of HbS triggers the formation of large polymers.
This change in shape causes the red blood cell to become rigid and distorted, characteristically forming a sickle shape.
Sickling leads to membrane fragmentation and complement-mediated lysis, causing intravascular red blood cell destruction.
Red blood cell membrane damage also triggers extravascular hemolysis due to trapped abnormal cells or phagocytosis by macrophages.
Intracellular polymers cause red blood cell membrane changes, oxidant substance generation, and abnormal adherence to vascular endothelium.
Deformed blood and increased blood viscosity contribute to vascular occlusion.

Factors Affecting Hb Polymerization

The oxygenation status of the circulating red blood cells influences Hb polymerization.
The intracellular hemoglobin S concentration plays a role.
The presence of non-sickle hemoglobins (HbF) can also affect polymerization.

Clinical Features

Hemolytic anemia: A hallmark of the condition.
Crises: Severe episodes including vaso-occlusive, aplastic, or hemolytic crisis.
Mulitple Organ Damage: Microinfarcts in the heart, skeleton, spleen, and central nervous system.
Symptoms of Anemia: Symptoms may be mild relative to the severity of anemia. Hb S releases oxygen to tissues more readily than Hb A.
Clinical Expression: Clinical expression is quite variable among patients. Some have almost normal lifespans, while others experience severe crises even as infants, with potentially fatal outcomes in early childhood or young adulthood.
Effects of Chronic Hemolysis: Anemia in severe cases results in a higher probability of stroke and renal dysfunction. Conversely, higher hemoglobin levels correlate with higher incidences of painful episodes, avascular necrosis, and acute chest syndrome. Jaundice arises from rapid heme turnover and bilirubin generation. Cholelithiasis (gallstones) results from red blood cell destruction and excess bilirubin in the hepatobiliary system.
Painful Crises: Common, sporadic, and influenced by infection, acidosis, dehydration, or deoxygenation.
Visceral Crises: Acute sickle chest syndrome (most common cause of death), splenic or hepatic sequestration. Priapism (prolonged painful erection), and liver/kidney damage are also potential complications.
Hand-foot syndrome: Painful dactylitis, a frequent initial manifestation, causing swelling and pain in the hands and feet.
Aplastic Crisis: Usually due to parvovirus B19 infection, causing a sudden and potentially life-threatening decrease in red blood cell production.
Hemolytic Crisis: A catastrophic decrease in hematocrit, with increased jaundice and reticulocyte count, from unknown reasons.

Other Organ Damage

Brain/spinal cord: Stroke may occur in 7% of patients, sometimes silently.
Leg ulcers: Deep, non-healing skin ulcers, often on the medial malleolus.
Autosplenectomy: Gradual destruction of the spleen due to repeated infarcts in childhood.
Pulmonary hypertension: A potential complication.

Infections

Early loss of splenic function, coupled with the inability of the body to produce specific IgG antibodies to polysaccharide antigens, increases the risk of severe sepsis (gram-negative septicaemia).
Pneumonia, urinary tract infections, and osteomyelitis are relatively common. Infections are often serious.

Pregnancy

Hemoglobin levels tend to decrease in pregnancy.
Painful crises may be more frequent in the last trimester.
Increased risk of preeclampsia.
Risk to the fetus.

Growth and Development

Children with SCD may have normal birth weights but experience delayed developmental milestones.

Lab Findings

Hemoglobin levels are typically low (6-9 g/dL).
Sickle cells and target cells are often present in the blood.
Splenic atrophy may cause Howell-Jolly bodies in blood.
Blood screening tests for sickling are positive when deoxygenated.
Hemoglobin electrophoresis shows absence of Hb A in Hb SS. Hb F amounts vary, often lower in severe cases.

Therapy

Routine health care (avoid precipitation factors, folic acid, hydration and nutrition).
Transfusion therapy.
Hydroxyurea to increase HbF.
Pain management.
Bone marrow transplantation.
Gene therapy.

Sickle Cell Trait

Benign condition with no anemia and normal blood cell appearance.
Hematuria (blood in the urine) is a common symptom, thought to be related to minor renal papillary infarcts.
Hb S levels are between 25-45% of total hemoglobin.
Require careful monitoring during anesthesia, pregnancy, and high altitude.

Hemolytic Anemias

Classified as hereditary and acquired.
Hereditary: Membrane defects (e.g. HS, PNH), metabolic defects (e.g. G6PD), defective hemoglobin synthesis (e.g. HbS, thalassemias).
Acquired: Immune or non-immune causes.

Acquired Hemolytic Anemias

Immune-mediated: Antibodies against red blood cells, classified as warm or cold.
- Warm: IgG antibodies, more commonly seen. Usually associated with spherocytosis, elevated bilirubin, elevated LDH, and positive direct Coomb's test. Common clinical presentations include fatigue, jaundice, and splenomegaly.
- Cold: IgM antibodies, typically associated with agglutination/rouleaux formation and cold temperature-dependence.
Non-Immune-mediated: Red cell fragmentation syndromes (e.g. mechanical trauma from artificial heart valves or DIC)

Direct Coombs Test (DAT)

Used to detect antibodies or complement proteins attached to red blood cells which helps classify hemolytic anemia as acquired or hereditary.
Negative result suggests hereditary hemolytic anemia while a positive result suggests acquired hemolytic anemia.

Autoimmune Hemolytic Anemias (AIHAs)

Antibodies produced by the body targeting its own red blood cells.
Classified into warm (IgG mediated) and cold (IgM mediated).
Positive DAT indicative of disease.
Clinical features will vary depending on causes.

Alloimmune Haemolytic Anaemias

Antibodies from one individual react against red blood cells of another.
ABO incompatibility in transfusions and Rh disease of the newborn are notable examples.

Non-Immune Haemolytic Anemias

Physical damage to red blood cells leads to fragmentation syndromes.
This can happen due to various factors like artificial heart valves, mechanical heart valves, or arteriovenous malformations.
DIC implicated as a cause for microangiopathic hemolytic anemia associated with abnormal small vessels.

Aplastic Anemia

Characterized by pancytopenia (low red blood cells, white blood cells, and platelets).
Caused by bone marrow aplasia.
Etiology includes primary (congenital) or secondary factors (e.g. radiation, chemicals, and certain drugs, and viral hepatitis).
Clinical features include anemia, infections, bleeding manifestations. Key lab findings are reduced reticulocytes, selective neutropenia, and thrombocytopenia. Bone marrow shows hypoplasia with significant fat replacement.

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Description

This quiz explores the fundamentals of sickle cell disease, including its genetic and molecular basis. Learn about the pathophysiology that leads to the characteristic sickling of red blood cells and the implications for affected individuals. Test your knowledge on the different forms of sickle cell disease and related hemoglobin disorders.