Thalassemia Syndromes Flashcards
Hb molecule defect found in thalassemia
Deficient synthesis of alpha- or beta-globin chains
Suspected reasoning for (same) geographic distribution pattern that coincides w/ the incidence of malaria and heterzygous state(s) of thalassemia syndromes
Gene defect
3 normal adult hemoglobins
- Hb A
- Hb A2
- Hb F
Globin chain composition and percentage of Hb A
2 alpha
2 beta
> 95%
Globin chain composition and percentage of Hb A2
2 alpha
2 delta
1.5-3.0%
Globin chain composition and percentage of Hb F
2 alpha
2 gamma
=
Globin chain composition of Beta0 thalassemia
Complete absence of beta chain composition
Globin chain composition of Beta+ thalassemia
Reduced production of beta chains
Globin chain composition of alpha0 thalassemia
No alpha chain production
4 genetic possibilities that may occur w/ alpha thalassemia
alpha0 → no alpha chain production
1 functioning alpha chain (Hb H)
2 functioning alpha chains (alpha thal trait)
3 functioning alpha chains (“silent carrier”)
Beta-thalassemia Major
- Clinical features and course of disease
- Severe hemolytic anemia… strong stimulus for erythropoiesis
- “hair on end” appearance in skull Xrays
- Expansion of BM in skull causes jaw bone to jut out…deform head
Beta-thalassemia Major
- Ethnic distribution
Mediterranean and SE Asia
Beta-thalassemia Major
- Clinical features and course of disease
- Severe hemolytic anemia… strong stimulus for erythropoiesis
Beta-thalassemia Major
- CBC results
Too many RBCs for Hb
- Can’t maintain Hb > 7 g/dL
Beta-thalassemia Major
- BM exam
↑ BM iron stores
Beta-thalassemia Major
- Hb ELP pattern
Hb F (↑) > A2 (↑)
Beta-thalassemia Major
- Treatment
- Regular transfusions
- Iron chelation therapy (prevent iron overload)
- Splenectomy
- Diet restrictions (heme)
- Give vit B12 and folate
- BM transplant is definitive
2 mechanisms responsible for early RBC destruction seen in beta-thalassemia major
- Cells in BM (w/ Heinz bodies) leads to ↑↑↑ ineffective erythropoiesis
- Cells in circulation (w/ Heinz bodies) leads to ↑↑↑ intravascular hemolysis
Why do patients w/ beta-thalassemia major have the “hair on end” appearance in skull x-rays and mongoloid appearance to face
Expansion of BM in skull
Beta-thalassemia minor
- Pathology
- Reduced rate of beta chain production
- imbalance results in ppt of excess alpha chains → Heinz bodies
- Milder form of hemolytic and M/H anemia (than thal major)
Beta-thalassemia minor
- Ethnic origin
Mediterranean area, SE Asia, black population of West and North Africa
Beta-thalassemia minor
- Clinical features and course of disease
- Usually presented as mild, asymptomatic hemolytic anemia
- Stressful event may evoke a hemolytic episode
- May present w/ slight splenomegaly
- Patient has normal lifespan
Beta-thalassemia minor
- CBC results
- Too many RBCs for Hb
- Maintain Hb b/w 10-13 g/dL
Beta-thalassemia minor
- RBC morphology
More mild morphology
- slight hypochromasia, slight polychromasia, slight microcytosis
- B.S., Heinz bodies
- occasional nRBCs
Beta-thalassemia minor
- Retic count
Slightly ↑ retic count
Beta-thalassemia minor
- BM exam
↑ BM iron stores??
Beta-thalassemia minor
- Hb ELP pattern
A > A2 (↑) > F (↑)
Beta-thalassemia minor
- Treatment
Not usually required
Hydrops Fetalis Syndrome, aka ____
alpha0-thalassemia
Hydrops Fetalis Syndrome
- Pathology of Hb molecule
Cannot carry O2; cannot carry O2 → infant dies in utero or shortly after delivery
Hydrops Fetalis Syndrome
- Globin chain makeup
Bart’s = 4 gamma
Hydrops Fetalis Syndrome
- Ethnic distribution
SE Asia and Filipino population
Hydrops Fetalis Syndrome
- Compatibility w/ life
Unlikely
Hydrops Fetalis Syndrome
- Hb ELP pattern
Bart’s > Portland
Hb H
- Pathlogy of Hb molecule
Mild to severe, chronic hemolytic anemia
Hb H
- Globin chain makeup
4 beta chains
Hb H
- Unusual characteristic of Heinz bodies
“Pitted golf ball” or “raspberry”
Hb H
- Hb ELP pattern
H > A > A2 > Bart’s
Hb Lepore
- Pathology of Hb molecule
Clinically and morphologically like a beta thal major
Hb Lepore
- Globin chain makeup
Fused delta and beta chain
- No Hb A/A2 produced
Hb Lepore
- Hbs being produed in homozygous state
F (~80%) + Lepore (~20%)
Hereditary Persistence of Hb F (HPHF)
Persistence of fetal Hb in adult life (benign); gamma → beta switch does not occur
HPHF
- Homozygous state
100% Hb F
HPHF
- Heterozygous state
A > Hb F (15-30%)
Kleihaur-Betke stain
- Principle
Assess distribution of Hb F in RBC; mainly performed to determine if an excessive feta-maternal bleed occurred during delivery (and extra Rhogam is required)
Kleihaur-Betke stain
- Normal values
?
Kleihaur-Betke stain
- Staining pattern w/ HPHF
Hb F in each cell is constantly stained (dark pink)
Kleihaur-Betke stain
- Staining pattern w/ hemoglobinopathies (other than HPHF)
Hb F present in varying amounts; staining inconsistent (“speckled”)
Kleihaur-Betke stain
- Appearance of Hb A (adult) cells on smear
Hb A is NOT resistant to acid elution test → “ghost cells”
Kleihaur-Betke stain
- Appearance of Hb F (fetal) cells on smear
Hb F is resistant to acid elution test → cells stain dark pink
Kleihaur-Betke stain, aka ____
Acid elution stain
Beta0 thalassemia
Cooley’s anemia
Beta+ thalassemia
Cooley’s trait
Excessive growth of immature RBCs
Erythroid hyperplasia
