Hemoglobinopathies

What is the difference between Thalassemia and hemoglobinopathies?

Thalassemia is a quantitative defect whereas hemoglobinopathies are a qualitative defect

Alpha genes are inherited on what chromosome?

Chromosome 16

Beta and gamma defects are inherited on what chromosome?

Chromosome 11

Where is the defect in beta chain coding? What chain is increased in beta thalassemia?

1. mRNA

2. Alpha chain

Babies with beta thalassemia are normal until when?

Until beta/gamma switch occurs around 1 year old

What is the hemoglobin level for beta thal major?

2.5-6.0 g/dL

What is the hemoglobin level for beta-thal intermedia?

6.0-9.5 g/dL

What is the hemoglobin level for beta-thal minor?

9.5-13.5 g/dL

What are clinical syndromes accompanying beta-thal major?

1. Hairy bone

2. Extramedullary hematopoiesis → hepatomegaly and splenomegaly

3. Bone deformities due to marrow expansion

4. Iron overload

5. Cardiac failure

What are four treatments for beta-thalassemia major? What is the primary method?

1. Hypertransfusion (beta-thalassemia major)

2. Iron chelating agents

3. BM transplant

4. Hydroxyurea

What does hydroxyurea do?

Switches on gamma gene)

What is the normal beta/alpha chain ratio?

< 0.25

What color is urine if it has increased bilirubin?

Dark brown

What is hydrops fetalis?

1. Alpha thalassemia major

2. Four deletions

3. Not compatible with life

What chains are produced in excess in alpha thalassemia? What types of hemoglobin do they form?

1. Beta and gamma

2. Hemoglobin H (4 beta chains) and Bart’s (four gamma chains)

What is the hemoglobin percentage breakdown in alpha thalassemia major?

1. 80-90% Bart’s

2. 10-20% Portland

3. Hb H may not be present

What do heinz bodies indicate?

Unstable hemoglobin

What is the treatment for Hb H disease in alpha-thalassemia?

1. Splenectomy

2. Transfusion independent but may have hemolytic crisis

What genes are increased in HPFH?

Gamma chains and alpha genes that combine to form HbF

What is the Kleihauer-Betke acid elution stain used for?

To assess distribution of Hb F in the RBCs and categorize into pancellular or heterocellular variants of HPFH

Thalassemia has what kind of anemia?

Microcytic, hypochromic

What populations are susceptible to beta-thal?

1. Mediteraneans

2. SE asians

3. Middle east

4. India

5. Pakistan

What populations are susceptible to alpha thal?

1. SE asians

2. Chinese

What populations are susceptible to Hgb S/B Thal?

1. Africans

2. Mediterranean’s

What stains are used to detect Heinz bodies?

1. Cresyl blue

2. Supravital

What are three ways to quantitate Hb F?

1. Chromatography

2. RID

3. Alkali denaturation

What hemoglobinopathies/thalassemias do not have target cells?

1. Hb S/Thalassemia

2. HPFH

What three hemoglobinopathies/thalassemias have a hemolytic component?

1. Beta-thalassemia

2. Hb S Thalassemia

3. Hemoglobin C

Which hemoglobinopathy/thalassemia has neutrophilia with left shift and thrombocytosis?

Sickle cell

Which hemoglobinopathy/thalassemia has leukopenia and thrombocytopenia?

Beta thalassemia

What two disorders have hairy bone?

1. Beta Thalassemia

2. Sickle cell

What disorder has teardrop cells?

Beta thalassemia

Beta thalassemia and Hemoglobin S both have what features in common?

1. NRBC’s

2. Anisocytosis

3. Basophilic Stippling

4. Retics

5. Increased bilirubin

What disorder has Hb H inclusions, and what do these look like?

1. Alpha thalassemia

2. Golf ball or raspberry that stains green-blue

What are three components of Hemoglobin C disease?

1. Hb C crystals

2. Retics

3. Target cells

What are two characteristics of Hb SC disease?

1. Hint of sickle cells (folded boat shape)

2. SC crystals that are intraerythrocytic and blunt-ended

What is the MCV result for beta thalassemia?

< 65 fL

How does HPFH impact RBC count and H & H?

RBC count and H & H are both increased to compensate for the increased oxygen affinity

What is the hemoglobin and retic result for Alpha/thal Hb H?

1. Hb: 7-10 g/dL

2. Retics: 5-10%

What shapes can be seen on the Hb S blood smear?

1. Sickles

2. Spherocytes

3. Siderocytes

4. Howell-Jolly bodies

5. Megaloblastic cells

What are the results for Uric acid, LD, Ferritin, Inflammation, and Haptoglobin in Hb S?

1. Increased uric acid

2. Increased LD

3. Increased Ferritin

4. Increased Inflammation markers

5. Decreased haptoglobin

What is the HCT and HGB result for hemoglobin SC disease?

1. HCT > 25%

2. HGB: 10-14 g/dL

What are three forms of treatment for Hb S?

1. General medical care

2. Acute vaso-occlusive crisis

3. Long-term transfusion therapy

What is included in general medical care?

1. Hydration

2. Analgesics

3. Avoiding strenuous exercise

4. Avoiding high altitudes

5. Prevention of infections

What is included in vaso-occlusive crisis treatment?

1. Pain relief

2. Blood exchange for transfusion

What is IEF used for in HGB S?

Separates Hgb S from Hgb D and G

List the order of HEP starting with origin?

1. Origin

2. C

3. S

4. F

5. A

6. Barts H

7. Cellulose acetate

What test should you perform if you get a positive result with the alkaline HEP?

Acid HEP

What reagent is used in the solubility test and what does it do?

1. Sodium dithionite

2. Reduces Fe2+ to Fe3+, deoxygenated

What errors can cause false negatives in the solubility test?

1. Severe anemia

2. High Hb F and low Hb S

What errors can cause false positives on the dithionite solubility test?

1. Hb variants

2. Elevated plasma proteins and lipids

What is the BM like in sickle cell?

Hyperplastic

Why might sickle cell patients have megaloblastic maturation?

Folate deficiency

How long does a vaso-occlusive crisis usually last?

4-5 days

What triggers a vaso-occlusive crisis?

1. Infection

2. Decreased atmospheric oxygen pressure

3. Acidosis

4. Dehydration

5. Slow blood flow

What can recurrent episodes of vaso-occlusive crises lead to?

1. Infarctions of genitourinary tract

2. Splenomegaly in early childhood

3. Dactylitis

4. “Hand-foot” syndrome

What are outcomes of slow blood flow?

1. Thrombosis

2. Stroke

3. Blindness

4. Chronic leg ulcers

What is acute splenic sequestration?

Splenic pooling → mass decrease in RBC’s and resulting in hypovolemia, shock, and thrombocytopenia

What are three other complications of sickle cell?

1. Aplastic crisis

2. Iron overload

3. Acute chest syndrome

What is an aplastic crisis, and what triggers it?

1. A temporary shutdown of red cell prouction

2. Follows viral, bacterial, or mycoplasmal infections

How do you monitor iron overload?

Serum ferritin

What is acute chest syndrome?

Resembles pneumonia

What kind of hemolysis is involved in Hb S?

Exravascular

What are four characteristics of a sickle cell?

1. Intracellular dehydration

2. Leaky and rigid membrane

3. Heinz body formation

4. Redistribution of phospholipids on membrane

Who is most susceptible to hemoglobin E?

SE Asians

Who is most susceptible to Hb C?

West african

What gene mutation is involved in Hb S?

1. B6 (A3) Glu → Val

What mutation is involved in Hb C?

B6 (A3) Glu → Lys