Structural Hemoglobinopathies Flashcards
What is the genetic defect that causes HbC disease?
This genetic defect of hemoglobin is due to substitution of glutamic acid (charged negative) to lysine (charged positive) in the B globin chain at the same point as the substitution in HbS (sixth position of the B chain)
What is the clinical presentation of a HbCC patient?
- Mild hemolytic anemia (Hemolysis by spleen due to HbC crystals)
- Splenomegaly (abdominal pain) (due to extravascular hemolysis)
- Crystallized HbC —> Rigid RBC membrane
What are the laboratory findings for an HbCC patient?
- Hb: 8-12 g/dl (mild anemia)
- Reticulocytes: 4-8% (increased due to compensation)
- MCV and MCH normal
- MCHC increased (due to cellular dehydration)
P.B.
- Normocytic normochromic RBCs
- 90% target cells
- 5% spherocytes
- HbC crystals (especially after splenectomy)
- Lysine is a charged amino acid that does not precipitate, but for a very strange reason,
results in targeting— any RBC that contains HbC in any amount undergoes targeting.*
What is the Hb electrophoresis pattern for an HbCC patient?
• No HbA
• HbC >90%
• HbF 1-7% (slightly increased in some instances)
What is the treatment for HbCC disease?
Patients generally are asymptomatic and treatment is not required.
How does HbC migrate along the electrophoresis in both alkaline and acidic pH?
In alkaline pH, HbC migrates with HbA2
In acidic pH, HbC migrates alone
What is the clinical presentation and laboratory diagnosis of HbC trait (HbAC heterozygous)
The heterozygout is absolutely symptomless but very unlike HbS, 30-40% of the RBC(s) are target cells. The rest are normal. With HbS trait, there is no abnormality at all.
On electrophoresis:
60-70% HbA
30-40% HbC
N.B: An abnormal Hb results in reduced amounts.
What is the clinical presentation and laboratory diagnosis of HbC trait (HbAC heterozygous)
The heterozygout is absolutely symptomless but very unlike HbS, 30-40% of the RBC(s) are target cells. The rest are normal. With HbS trait, there is no abnormality at all.
On electrophoresis:
60-70% HbA
30-40% HbC
N.B: An abnormal Hb results in reduced amounts.
What is the genetic defect that causes HbD disease?
There are several hemoglobin D variants that migrate in the same position as HbS but do not
cause sickling. Many variants are named for the place where they were discovered, such as HbD-
Los Angeles (also known as Hb-D Punjab), in which glutamic acid is substituted by glutamine in
the 121st position of the B chain.
What is the clinical presentation of Homozygous HbD disease?
• Mild hemolytic anemia
• Splenomegaly (due to extravascular hemolysis)
just like HbCC
What is the laboratory diagnosis of HbD disease? Including electrophoresis.
- RBC parameters (Hb, Hct) are low
- RBC indices (MCV, MCH, MCHC) are normal
P.B.
- Normocytic Normochromic RBCs
- Numerous Target cells
Hb electrophoresis
95% HbD
Others: HbA, HbA2, HbF
How does HbD migrate on gel electrophoresis in different pHs?
In alkaline pH, HbD migrates along with HbS —> which is why elimination of possibility of sickle cell anemia is crucial in the diagnosis of HbD disease
In acidic pH, HbD migrates along with HbA far away from HbS
What is the laboratory diagnosis of HbD heterozygous trait?
*Normal peripheral blood smear
*Electrophoresis shows 30-40% HbD, the remainder being HbA, A2 and F.
The next step is to do the sickling test. In this case, if it is negative —> HbD disease.
What is the most common beta chain variant?
HbE
What is the genetic defect of HbE disease?
The genetic defect of HbE disease is the substitution of glutamic acid by lysine on the 26th amino acid.
It is both a qualitative (due to substitution of amino acid) and quantitative (due to decreased B chain synthesis) hemoglobinopathy
