Morning Report June 17th 2005

Wassim Mchayleh, MD

Thalassemias

Hemoglobin structure• Hb - tetramer of 2 -like and 2 -like

proteins

• Normal Hb– Adult (major): HbA -

(minor): HbA2 -

– Fetal: HbF -

– Embryonic: Hb Gower I -

Demographics: Thalassemia

• Found most frequently in the Mediterranean, Africa, Western and Southeast Asia, India and Burma

• Distribution parallels that of Plasmodium falciparum

α-Thalassemia

• α-Thalassemias are common in Africans and Southeast Asians; up to 30% in black Americans

• Phenotype depends on the number of intact α-globin genes.

SymbolismAlpha Thalassemia

• Greek letter used to designate globin chain:

SymbolismAlpha Thalassemia

/ : Indicates division between genes inherited from both parents:

/

• Each chromosome 16 carries 2 genes. Therefore the total complement of genes in an individual is 4

SymbolismAlpha Thalassemia

- : Indicates a gene deletion:

-/

Classification & TerminologyAlpha Thalassemia

• Normal / • Silent carrier -/ • Minor -/-

--/• Hb H disease --/- (moderate to

severe hypochromic microcytic anemia)• Barts hydrops fetalis --/--

Special Cases: Thalassemia

• Hb H• 4 tetramer• Associated with --/- thalassemia• Moderate to severe hypochromic microcytic

anemia

Special Cases: Thalassemia

• Hb Barts & hydrops fetalis • Barts is a 4 tetramer• Associated with --/--• Lethal

B-Thalassemia

• observed in Mediterranean, sub-Saharan African and Indian descents

SymbolismOther Thalassemia

• Greek letter used to designate globin chain:

SymbolismOther Thalassemia

+: Indicates diminished, but some production of globin chain by gene:

+

SymbolismOther Thalassemia

0 :Indicates no production of globin chain by gene:

0

Classification & Terminology Beta Thalassemia

• Normal /

• Minor /0

/+

• Intermedia 0/+

• Major 0/0

+/+

-Thal Major• Well at birth

• Symptoms start after 6 months with the loss of HbF( ).

• Severe hemolytic anemia with Jaundice, Hepato-Splenomegaly.

• Symptoms from ineffective erythropoiesis bony abnormalities and abnormal skeletal development .

-Thal Minor

• Microcytic hypochromic anemia

• Ht >30 percent ,MCV <75 and normal RDW with high RBC count will differentiate it from Iron deficiency anemia

• Splenomegaly in 10-20%

• Target cells on peripheral smear

-Thal Intermedia

• Symptomatic patients who do not require transfusions

• Increased dietary iron absorption with possible iron overload

• Smptoms of chronic hypoxia( Pulm HTN,CHF)

• Extra-medullary Hematopoiesis

Primary Laboratory InvestigationThalassemia

• Severe cases present with

• Microcytosis

• Hypochromia

• Poikilocytosis

• Tear drops and Target cells

• RBC counts higher than expected for the level of anemia

Laboratory evaluation

• Hemoglobin electrophoresis for diagnosis

• Hb H in severe -thalassemia

• Elevated Hb A2 levels in -thalassemia

• Formal genetic analysis can be necessary to distinguish between them.

Course and TreatmentThalassemia

• Time of presentation

• Related to degree of severity

• Usually in first few years of life

• Untreated severe thalassemia

• --/--: Prenatal or perinatal death

• --/- & --/cs: Normal life span with chronic hemolytic anemia

Course and TreatmentThalassemia

• Untreated thalassemia

• Major: Death in first or second decade of life , chronic transfusion required with iron chelating therapy (Desferrioxamine)

• BMT can be a curable treatment

• Intermedia: Usually normal life span

• Minor/Minima: Normal life span