Clinical Medicine Lecture: _____ Topic: ____________________________________________________________ Date: ______________

Alpha Thalassemias Beta Thalassemias

Hereditary anemias (autosomal recessive inheritance) characterized by Hereditary anemias (autosomal recessive inheritance) characterized by
reduced or absent production of 1 or more of the alpha globulin chains: reduced or absent production of 1 or more of the beta globulin chains:
1. Alpha Thalassemia Silent Carrier (Alpha Thalassemia Minima) Normal: beta/beta (homozygous beta, normal normal), neither + nor
o No clinical abnormalities may be hematologically normal or have 0
slight reductions in MCV and MCH 1. Beta Thalassemia Minor
o 3 functional alpha globin genes o Heterozygous beta/beta0
2. Alpha Thalassemia Minor (Alpha Thalassemia Trait) Production = 50% of normal
o Clinically normal, but frequently have minimal microcytic, o Heterozygous beta/beta+
Etiology hypochromic anemia and reduced MCV and MCH (RBC count is Production = close but not normal
(Pathophysiology): usually increased >5.5x1012/L) 2. Beta Thalassemia Intermedia
o 2 functional alpha globin genes o Homozygous beta+/beta+
3. Hemoglobin H Disease (Alpha Thalassemia Intermedia) High rate of beta globin synthesis (but not as good as beta/beta+)
o Moderate to severe alpha thalassemia 3. Beta Thalassemia Major (Cooley Anemia)
o 1 functional alpha globin genes o Homozygous beta+/beta+
4. Hydrops Fetalis Very low rate of beta globin synthesis
o Most severe (almost all fetuses die in utero) all 4 alpha globin o Homozygous beta0/beta0
genes are missing Absent beta globin synthesis
o 0 functional alpha globin genes Beta+ results in an increase in the proportions of Hemoglobin A2 and F
Alpha thalassemias with 2 missing genes on a given allele are more Most commonly reported in Mediterranean, African, and Southeast
Risk Factors common in Asian ancestry Asian populations
(Demographics): Ancestry from regions where malaria is endemic (Asian, Mediterranean,
or Middle Eastern descent)
Clinical Typical S/S of anemia for Silent Carrier and Trait Beta Thalassemia Intermedia and Cooley Anemia (Beta Thalassemia
Manifestations In Hemoglobin H Disease, symptoms are consistent with a chronic Major) are normal at birth, but 6 mo. = Lifelong Hemolytic State
(Signs and hemolytic anemia o Cooley Anemia is a severe anemia requiring transfusion, whereas
Symptoms): o Episodes of severe pallor and anemia Beta Thalassemia Intermedia usually only requires transfusions
o Exacerbations of hemolysis may occur when patients are exposed to during stress or during aplastic crises
stressors (pregnancy, infections, fever, ingestion of oxidative o Both are associated with hepatosplenomegaly and bony deformities
compounds, or drug use) o In Cooley Anemia, also have stunted growth, jaundice, and
o History of transfusions to treat the above thrombophilia
Beta Thalassemia Minor is clinically insignificant
Complications can include the following: o Lifelong hemolytic, mild, microcytic anemias
o Hepatosplenomegaly
o Leg ulcers
o Gallstones
o Prominent frontal bossing
o Marked overgrowth of the maxillae
o Ribs and long bones becoming boxlike and convex
o Premature closure of epiphyses resulting in shortened limbs
o Osteopenia and fractures
 o Intellectual disability syndromes
Diagnostic Studies: 1. CBC 1. CBC
o Silent Carrier o Beta Thalassemia Minor
Hgb normal Hgb 10-12 g/dL
MCH normal (27-33 pg/cell) to slightly decreased (~26 pg/cell) Hct 20-40%
MCV normal (80-96 fL/cell) to slightly decreased (75-85 MCV 55-75 fL
fL/cell) RBC count normal or increased
o Trait o Beta Thalassemia Intermedia
Hgb normal Hgb 6-11 g/dL
MCH more decreased than silent carrier (22 pg) Hct 17-33%
MCV more decreased than silent carrier (65-75 fL) MCV 55-75 fL
o Hemoglobin H Disease RBC count normal or increased
Hgb moderate to severe decrease (7-10 g/dL) o Beta Thalassemia Major (Cooley Anemia)
MCH more decreased than trait (55-65 fL) Hgb may be <3 g/dL
MCV more decreased than trait (20 pg) Hct may be <10%
o Hydrops Fetalis MCV <55 fL
Hgb severe decrease (~44 g/dL) 2. Peripheral Smear and Reticulocytes
MCV increased (110-120 fL) o RBC Appearance microcytic, hypochromic (or normochromic)
2. Peripheral Smear and Reticulocytes Beta Thalassemia Minor mildly abnormal: above + target cells
o RBC Appearance microcytic, hypochromic Beta Thalassemia Intermedia abnormal: above + basophilic
In hemoglobin H Disease get small misshapen red cells, stippling
hypochromia, microcytosis, and targeting. With brialliant Beta Thalassemia Major (Cooley Anemia) bizarre: above +
cresyl blue stain with see Hb H inclusion bodies. severe microcytosis (very pale), severe poikilocytosis, and
o Reticulocytes Too many: good marrow response to RBC loss or nucleated RBCs
destruction BY MARROW THAT HAS BUILDING BLOCKS (iron, o Reticulocytes Too many: good marrow response to RBC loss or
etc.) destruction BY MARROW THAT HAS BUILDING BLOCKS AND
Silent Carrier normal (not decreased) RESPONDING TO HEMOLYSIS
Trait normal (not decreased) Beta Thalassemia Minor normal or slightly elevated
Hemoglobin H Disease 5-10% elevated (the higher the count, Beta Thalassemia Intermedia elevated
the more severe the hemolysis) Beta Thalassemia Major (Cooley Anemia) elevated
3. Iron Studies should be NORMAL 3. Iron Studies should be NORMAL
o Microcytic, hypochromic + NL iron studies = order 4. Hemoglobin electrophoresis Abnormal (DIAGNOSTIC)
electrophoresis! Might be thalassemia!! 5. Prenatal Diagnosis
4. Hemoglobin electrophoresis Abnormal (quantitates and identifies o DNA analysis for the presence of thalassemia mutation of chorionic
different hemoglobin types) villi at 8-10 weeks gestation or amniocentesis at 14-20 weeks.
o Hydrops fetalis
Hemoglobin Barts 80%
Hemoglobin Portland 10-20%
Hemoglobin H 0-10%
o Hemoglobin H Disease
Hemoglobin Barts/H at birth, 25-40% of hemoglobin is
Hemoglobin Barts (decreases later and is replaced by excess
Hemoglobin H)
Remainder is Hemoglobin A, A2, and F
 o Trait
Hemoglobin A 85-95%
Hemoglobin Barts 5-15% at birth
No significant Hemoglobin A2, F, or H
o Silent carriers
Hemoglobin A 96-98%
Hemoglobin Barts 0-2% at birth
Hemoglobin A2 low or normal amounts
No significant Hemoglobin F or H
5. Alpha Thalassemia Mutations Panel
o Definitive/Gold Standard
6. Other
o Indirect hyperbilirubinemia, elevated lactate dehydrogenase levels,
reduced haptoglobin
o Imaging studies ultrasonography of the liver, gallbladder, and
spleen (hepatosplenomegaly and gallstones are common in
Hemoglobin H Disease)
If mild, (trait and silent carriers) may not need treatment Beta Thalassemia Minor and Intermedia often do not require any specific
If severe anemia (<7 g/dL), may require lifelong transfusion therapy treatment (may require transfusion support)
o Hemoglobin H Beta Thalassemia Major (Cooley Anemia) will require chronic
PRBC transfusion therapy transfusion therapy (goal is to maintain hemoglobin at 9-10 g/dL) with
Allogeneic hematopoietic stem cell transplantation curative iron chelation to prevent transfusional iron overload (hemosiderosis),
Treatment (First & o Hydrops fetalis which results in a clinical picture similar to hemochromatosis
Second Line): Requires uterotransfusions for survival and then continued o Splenectomy
lifelong transfusions o Cholecystectomy
Allogeneic hematopoietic stem cell transplantation (curative) if o Allogenic bone marrow or hematopoietic transplantation may be
survive after birth curative in some patients
If symptoms of hypersplenism, splenectomy (Hemoglobin H) o Supportive measures diet and activity
o Other emerging therapies
Hematology for all, esp. Hemoglobin H Disease and Hydrops fetalis Hematology for all, esp. for Beta Thalassemia Major (Cooley Anemia)
Referral:
Genetic counseling for all