ALPHA THALASSEMIA
Barts Hydrops Fetalis Hb H Disease
Infos Deletion of all four globin
chains
Observed in Southeast
Asians
Clinical findings Underweight, edematous,
demonstrate ascites
(accumulation of serous fluid
in the abdominal cavity), and
disintended abdomens
Marked
hepatosplenomegaly
Laboratory findings Hypochromia
Variable reticulocytosis
Nucleated red cell
precursor
Tests Hb electrophoresis (alkaline
pH) shows fast-moving band
80% HbBarts& 20% Hb
Portland and little or no Hb H
(Both migrates faster than
HbBarts)
Treatment
TOLEDO, ML
Hb H-Constant Spring Disease
Deletion of three globin
genes
Widespread in Southeast
asia, Middle east and
Mediterranean island
Results from decreased
synthesis of chains and the
resultant formation of
unstable Hb H ()
Splenomegaly and anemia
st
tend to develop at 1 yr of life
as well as mental
retardation
Microcytic, hypochromic
Detected microscopically
Resemble golf ball (pitted
inclusions) & Hb H
inclusions occur in multiples
Brilliant cresyl blue causes
the precipitation of Hb H in
vitro
Hb electrophoresis (alkaline
pH) shows 20-40% HbBarts
then gradually replaced by
Hb H ()
Require no therapy; oxidant
drug should be avoided
Thalassemia Minor
Consists of 2 normal
chains, 1 normal chain
and one abnormal chain
that has 172 amino acids
Occurs in Orientals
Hb CS migrates behind Hb A
Hemolysis should be
applied to the electro support
medium when Hb SC is
suspected
The Silent Carrier
Decrease in chain thalassemia
synthesis; maybe hetero or
homo but neither condition Associated with one gene
produces clinical disease deletion
Benign
Common in Southereast
asia, Chinese and Filipinos Common in Asians, Chinese
and Filipinos
Microcytosis in the
presence of normal Hb A
and Hb F (very suggestive of
thalassemia minor)
Microcytic and slightly Blood count is normal with
hypochromic with slightly decreased MCV and
decreased MCV and MCH MCH
Target cells and other 1% to 2% Hb Barts but
poikilocytes are common normal in adults
Rare Hb H inclusions may
be found due to slight globin
imbalance
Modified BCB inclusion body
test enhances the
precipitation of Hb H for it to
become more visible
 BETA THALASSEMIA
Thalassemia Major Thalassemia Intermedia Thalassemia Minor Thalassemia Minima
Infos 4 genotypes Genes are less severely affected Asymptomatic No clinical or laboratory
0 : no globin chain production Impairment of -chain synthesis is less than the T. Little or no associated anemia abnormality detected
: decreased globin chain production major Peripheral blood erythrocyte: morphologically Usually discovered
1. 0/ 0 a. Homozygous + Thalassemia (+/ +) abnormal accidentally or during family
2. (/ (Mediterranean form) o Mild Black Form a. Heterozygous (/) or +( +/ ) studies
3. 0 / o American and African Blacks Thalassemia Genotype (SC/ ) indicated
4. ()Lepore/() Lepore (Hb Lepore) - 2 normal b. Homozygous Thalassemia (()/ ()) o Thalassemia trait or High-Hb A2 silent form (sc denotes silent
chains & 2 abnormal non- chains o American blacks, Arabs, Greeks, and Italians Thalassemia carrier) of an abnormal -
o Caused by the deletion of and structural o Caused by the combination of a normal globin gene
genes on the chromosome 11 pairs gene and either a or a + gene
c. Doubly Heterozygous Thalassemia Varieties b. Heterozygous Thalassemia ([] /)
o May be found in conjuction with , +, and Hb o Normal produced normal chains
Lepore o Deletion of the and genes on paired
chromosome 11
c. Heterozygous Hb Lepore ([] Lepore/ )
o One globin gene is normal
o Hb Lepore is produced from a second
fusion gene
Clinical findings Usually present with severe anemia w/in 1st year of life Growth and development of children: NORMAL Heterozygous Thalassemia: Hematocrit may be as
Excessive ineffective erythropoiesis bone marrow Adult: problems with iron overload low as 0.25 L/L during pregnancy
expansion marked skeletal deformities; distortion of ribs &
vertebrae; pathologic fractures of long bones
Protrusion of upper teeth & overbite dental & orthodontic
problems
Peripheral blood Hb: 2.5 6.5 g/dl Hemoglobin value: 7-10 g/dL (can be sustained so Increased erythrocyte count Electrophoresis, RBC
Numerous nucleated RBCs no need for routine transfusion) Marked decreased in MCV and MCH morphology and count, MCV
Microcytic& hypochromic Microcytic and hypochromic Normal or slightly decreased MCHC and MCH: NORMAL
Target cells & basophilic stippling Marked anisocytosis and poikilocytosis Microcytic and hypochromic, anisopoikilocytosis,
RPI: <3.0 Target cells are common target cells and basophilic stippling Slight decrease in -globin
Leucocytes: increased Peripheral blood film: basophilic stippling and Nucleated RBCs are ABSENT production that results in a
Platelet: normal nucleated RBCs Hb men: 12.9 g/dL; Women: 10.9 g/dL decrease / chain ratio
Reticuocyte counts is slightly elevated
Heterozygous Thalassemia: Hct women and
children: <0.31 L/L; Men: 0.37 L/L
Bone marrow Hypercellular Significant erythroid hyperplasia Slight erythroid hyperplasia
Marked erythroid hyperplasia

Special Hemoglobin Electrophoresis on Cellulose Acetate Hemoglobin electrophoresis at alkaline pH initial Special stains for erythrocyte inclusions are NEGATIVE
Hematologic Tests Acid elution technique for qualitative analysis of Hb F - screening procedure
helpful in differentiating thalassemia major disorders from
HPFH
Osmotic fragility test: markedly decreased
Chemistry Unconjugated bilirubin: mild elevation To differentiate microcytosis in Thalassemia minor
Urine urobilinogen & fecal urobilin: may be increased from IDA
Serum ferritin & iron: elevated
Transferrin often fully saturated (bec of iron overload
problem)

Treatment Blood transfusion Supportive; most patients have normal life span No treatment; Normal life span
Activation of globin gene expression
Allogeneic bone marrow transplantation
Gene therapy
TOLEDO, ML