Sickle Cell Disease Overview

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Questions and Answers

What is a primary characteristic of hemolytic anemia caused by increased destruction of red blood cells?

Normal red blood cell lifespan

Decreased production of hemoglobin

Elevated LDH levels (correct)

Low levels of reticulocytes

Which statement best describes the effect of sickle cell hemoglobin on red blood cells?

Increases RBC flexibility

Enhances oxygen carrying capacity

Reduces hemoglobin stability

Causes permanent deformation of RBC shape (correct)

What term describes the genetic basis for hemoglobinopathies?

Acquired mutations in somatic cells

Inherited mutations in globin genes (correct)

Viral infections disrupting RBC production

Environmental factors altering hemoglobin structure

In the context of hemoglobinopathies, what does the term 'structural hemoglobinopathies' refer to?

Alterations in amino acid sequences of hemoglobin Signup and view all the answers

What is a common clinical consequence of the increased stiffness of red blood cells in sickle cell disease?

Diminished capillary transit of RBCs Signup and view all the answers

What is the average lifespan of red blood cells in a patient with Sickle Cell Anemia?

17 days Signup and view all the answers

Which of the following complications is NOT associated with Sickle Cell Anemia?

Hypertension Signup and view all the answers

What is the most common bacterial pathogen associated with morbidity and mortality in Sickle Cell Anemia?

H. influenzae Signup and view all the answers

Which treatment option is considered a medical emergency for Sickle Cell Anemia patients experiencing acute episodes?

Oxygen Signup and view all the answers

Sickle Cell Trait (Hgb AS) is characterized by which of the following genetic variations?

One copy of the normal β globin gene and one copy of the abnormal βs globin gene Signup and view all the answers

Which laboratory finding is typically elevated in both extravascular and intravascular hemolysis?

Bilirubin, Unconjugated Signup and view all the answers

What does polychromatophilia indicate in the context of hemolytic anemia?

Increased marrow production of young RBCs Signup and view all the answers

Which type of antibody is associated with warm antibody autoimmune hemolysis?

IgG Signup and view all the answers

In the case of intravascular hemolysis, which of the following would you expect to find in the urine?

Hemoglobin Signup and view all the answers

Which treatment option is NOT typically utilized for autoimmune hemolytic anemia?

Antibiotics Signup and view all the answers

What is the main consequence of haptoglobin levels in hemolytic anemia?

It is absent in intravascular hemolysis. Signup and view all the answers

What is a characteristic feature seen in warm antibody autoimmune hemolysis?

Gradual onset of symptoms Signup and view all the answers

Which of the following describes the Coombs test?

It detects circulating antibodies in serum. Signup and view all the answers

Study Notes

Hemolytic Anemia: Clinical Features

Hereditary: Longstanding mild to moderate hyperbilirubinemia, possible jaundice.
Autoimmune: Gradual onset of fatigue.
Pallor: A pale appearance.
Splenomegaly: Enlarged spleen.
Dark Urine: Hemoglobin in the urine, observed in intravascular hemolysis.

Autoimmune Hemolysis

Warm Antibody (usually IgG):
- Idiopathic (associated with SLE, lymphoma, CLL, etc.)
- Drug-induced (e.g., PCN, Quinidine).
Cold Antibody (usually IgM):
- Cold Agglutinin Disease (rare).
- Secondary to conditions like Mycoplasma infection, viral infections, CLL, or lymphoma.

Coombs Test

Direct: Detects antibodies or complement bound to red blood cell (RBC) surface components.
Indirect: Detects circulating antibodies in serum that react with RBC surface components.

Lab Analysis of Hemolytic Anemia

Bilirubin: Accumulates in unconjugated form when large amounts of heme are released from destroyed RBCs.
Haptoglobin: Rapidly clears free hemoglobin by the liver.
Polychromatophilia: Purple-hued young RBCs on blood smear, indicates increased red blood cell production.
Reticulocyte Count: Number of young RBCs (reticulocytes).
Hemosiderin: Storage iron (Fe) in the urine from overloaded renal tubules.

Laboratory Evaluation of Hemolysis

Extravascular vs Intravascular Hemolysis: Categorization based on location of destruction.
Hematological Findings (plasma/serum, urine): Detailed analysis indicating elevation or absence of certain components.

Treatment of Hemolytic Anemia

Suppress Immune System: High-dose steroids (with slow tapering).
Splenectomy: Removal of the spleen.
Monoclonal Anti-Lymphocyte Antibodies: Antibodies targeting specific immune cells. (e.g., Anti-CD20)
Chemotherapy: Chemical treatment targeting rapidly dividing cells.

Case 3: Patient Presentation

70-year-old male, presenting with severe anemia.
Symptoms: malaise, frequent upset stomach, occasional headaches, shortness of breath, vague abdominal pain, memory issues, easy bruising, and weight loss (18 lbs in 9 months).
No fever, night sweats, or other significant medical history.

Case 3 (cont.): Physical Exam

Awake, slow speech.
Normal vital signs.
Shiny, smooth tongue.
Clear lungs, soft 2/6 holosystolic murmur.
Diffuse abdominal tenderness; no palpable masses.
Moderate arthritic changes, decreased vibratory sensation, wide-based gait, can't maintain balance with feet together and eyes closed.
CBC abnormalities: WBC, RBC, hemoglobin, MCV, MCH, MCHC, platelets.

Megaloblastic Anemias: Overview

Mature RBCs and their precursors are larger than normal.
Cytoplasmic protein synthesis is normal, but nuclear division is slowed.
Larger cells with immature or hypersegmented nuclei.
Bone marrow cellularity is increased, but most cell production is ineffective, resulting in ineffective erythropoiesis.
WBCs show hypersegmentation.

Causes of Megaloblastic Anemias

Inadequate Intake/Absorption: Folate and Vitamin B12 deficiencies.
Drugs that impair DNA Metabolism (chemotherapy): Purine and pyrimidine antagonists (e.g., 6-mercaptopurine, azathioprine, 5-fluorouracil, cytosine arabinoside). Others such as procarbazine, hydroxyurea, and acyclovir.
Metabolic Disorders (rare): Hereditary orotic aciduria, Lesch-Nyhan syndrome.
Unknown Etiology (rare): Refractory megaloblastic anemia, Di Guglielmo’s syndrome, congenital dyserythropoietic anemia.

Pathophysiology of B12 and Folate Deficiency

Both B12 and Folate are needed for DNA synthesis.
Deficiency impairs blood cell maturation.
Cell division slows; cytoplasmic growth is typical.
Immature or hypersegmented nuclei.

Causes of Folate Deficiency

Inadequate intake (unbalanced diet, common in alcoholics, teenagers, some infants).
Increased requirements (pregnancy, infancy).
Malignancy, increased hematopoiesis (chronic hemolytic anemias), chronic exfoliative skin disorders, hemodialysis
Malabsorption (tropical or non-tropical sprue, drugs, impaired metabolism (inhibitors of dihydrofolate reductase, alcohol, or rare enzyme deficiencies)).

Causes of B12 Deficiency

Inadequate intake (vegetarians).
Malabsorption: Defective release, gastric achlorhydria, partial gastrectomy, drugs blocking acid secretion, inadequate production of intrinsic factor (IF), pernicious anemia, total gastrectomy, congenital absence or functional abnormality of IF.
Malabsorption (cont.): Terminal ileum disorders (sprue, regional enteritis, resection), neoplasms/granulomatous disorders, competition for cobalamin (fish tapeworm, bacteria "blind loop" syndrome), drugs (p-aminosalicylic acid, colchicine, neomycin).
Others: Nitrous oxide, transcobalamin II deficiency, congenital enzyme defects.

Diagnosis of Megaloblastic Anemia

Anemia: Presence of anemia,
Elevated MCV: and oval macrocytes.
Elevated RDW: red cell distribution width.
Low Reticulocyte Count: presence of young red blood cells.
Ineffective erythropoiesis: hypercellular bone marrow.
Elevated unconjugated bilirubin, elevated LDH (isoenzyme 1): Liver dysfunction
Low serum folate and/or B12: Deficiencies.
Elevated serum homocysteine, methylmalonic acid: Further indication of B12 deficiency.
Pernicious Anemia: Presence of anti-IF antibodies (anti-intrinsic factor) and/or anti-parietal cell antibodies.

Vitamin B12 Treatment

Preparations: Cyanocobalamin injection (IM or SC), oral cyanocobalamin, nasal spray (expensive).

Folic Acid Treatment & Clinical Uses

Preparations: Oral folic acid (generic), parenteral folic acid (rarely used).
Clinical Uses: Deficiency prevention/treatment, neural tube defects prevention in infants (recommended for childbearing women). May reduce risk of occlusive vascular disease.

Treatment of B12/Folate Deficiency

B12: Intramuscularly weekly x 4, then monthly dosing.
Folate: Orally 1 mg/day.
Treat B12 deficiency first to avoid worsening neurological symptoms.

Case 4: Patient Presentation (20-year-old African-American Male)

Presenting with acute pain in hands/feet.
Symptom history: recent fever, runny nose, cough, pain episodes.
Physical exam: pain, high temp, tachycardia, mild scleral icterus, exquisite hand and foot tenderness, 2/6 holosystolic murmur, 80% neutrophil count.
Lab results: low Hgb, elevated MCV, elevated platelets, elevated reticulocyte count, elevated bilirubin, normal renal/liver/glucose/electrolytes.
Diagnosis: Acute crisis related to possible hemolytic anemia (DDx).

DDx: Differential Diagnosis

Increased Production: Reticulocytosis.
Increased Destruction: Elevated LDH.
Sickle Cells/Hemoglobinopathies

Hemoglobinopathies

Inherited mutations in globin genes.
- Altered Structure: Structural hemoglobinopathies (e.g., sickle cell disease)
Altered Production: Reduced or absent globin chain synthesis (e.g., thalassemias).

Common Hemoglobin Forms and Variants

Detailed listing of common forms of hemoglobin with percentages and comments.

Pathophysiology of Hgb SS (Sickle Cell)

Decreased solubility leads to polymerization of hemoglobin at low oxygen and pH.
Polymerized hemoglobin forms stiff, sticky fibers.
Causes RBC damage and destruction.

Sickle Cell Anemia (Hgb SS): Presentation and Diagnosis

Lifelong hemolytic anemia: Decreased RBC lifespan.
Variable symptom-free periods: alternating with painful vaso-occlusive crises.
Multisystem effects: Including splenic dysfunction and CNS effects (stroke, retinal bleeding). Various other GI, GU presentations.
Diagnosis: Family history, peripheral blood smear review, hemoglobin electrophoresis.

Sickle Cell Trait (Hgb AS): Presentation and Diagnosis

Heterozygote; one normal beta globin gene and one abnormal beta globin gene (sickle).
Usually asymptomatic.
25-40% abnormal hemoglobin.
Painless hematuria or normal blood tests.

###Treatment of Sickle Cell Anemia

Acute Crisis: Pain medication, hydration, oxygen, transfusions (sometimes exchange transfusions).
Chronic: Hydroxyurea, bone marrow transplantation.

Anemia Classification

Summary classifications of different types of anemia based on MCV.

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Description

Test your knowledge on the characteristics and complications of Sickle Cell Disease and related hemoglobinopathies. This quiz covers various aspects such as genetic factors, treatment options, and clinical outcomes associated with the disease.