Thalassemia
Definition: Autosomal recessive disorders in which there is qualitative hemoglobinopathy due to defective globin
chain production
Diagnostic approach
What are the criteria for anemia?
1. Hemoglobin:
1. Male = Hb <13.5 g/dL.
2. Female = Hb 11.5 g/dL.
What are the types of normal Hemoglobin?
Type of hemoglobin Hb name Structure of hemoglobin
At Early embryonic stages
Gower I 2ζ+2ɛ
Embryonic hemoglobin Gower II 2α+2ɛ
Portland 2ζ+2γ
At birth
Fetal Hb Hb F α2 / γ2
Adult Hb Hb A α2 / β2
At adult age
Hb A1 α2 / β2
Adult Hb
Hb A2 α2 / δ2
Fetal Hb Hb F α2 / γ2
Anemia type HB MCV MCHC Ferritin Iron binding serum iron
MCH RDW
capacity
Iron deficiency low low <76 fl low low/normal decreased increased decreased increased
Megaloblastic low high >100 increased low 32 to raised/normal increased
fl/cell 36 g/dL
>32 pg
Chronic illness low low/normal low low normal/ increased normal / decreased decreased normal
Alpha low or low low low normal normal normal or increased
Thalassemia normal /increased
increased
Beta low low low low increased/normal normal increased/normal increased
Thalassemia
Complications:
Anaemia due to the deficiency of haemoglobin.
Hepatosplenomegaly : abnormal enlargement of the abdomen.
Iron overload as a result of repeated blood transfusion. Consequently, a patient may
develop further complications such as:
1. Endocrine complications such as diabetes, glucose intolerance, decreased production of
growth hormone and hypogonadism
2. Cardiac disorders , for example, congestive heart failure or arrhythmias
3. Hepatic disorders such as cirrhosis and liability to have HCV
Medical management:
Regular transfusions until HGB > 9 gm/dl
Folic acid supplements
Iron Chelation therapy to prevent iron overload if ferritin >1000.
Genetic therapy ( when its available )
Psychological therapy
β-thalassemia minor β-thalassemia β-thalassemia major
intermedia
clinical manifestations usually mild, and patients generally Symptoms can include Clinical manifestations appear
have good quality of life. anemia, hyperbilirubinemia, in infancy and include severe
occasionally splenomegaly, mild bone and hepatosplenomegaly. anemia characterized by
changes, leg ulcers, or cholelithiasis. These patients generally extreme pallor, jaundice,
present with better growth, Hepatosplenomegaly and
development, and sexual signs of abnormal thalassemic
maturation than TM patients, facies are usually present.
and they typically live longer
before dying of complications
of chronic anemia with
pulmonary hypertension, iron-
induced cardiac disease, or
liver failure.
Massive splenomegaly is often
associated with
hypersplenism, which
contributes to progressive
anemia neutropenia and
thrombocytopenia, and it
warrants a trial of regular
transfusions to improve splenic
size and function, although
splenectomy may be required.
elevated HbA2 levels. High levels of Thalassemia Intermedia characterized by severe
Lab HbF are also seen, depending on the patients whose ferritin > 500 anemia (range, 1-7 g/dL of
underlying genetic mutation. μg/dL, monitoring of iron Hb), hemolysis, and massive
A carrier's RBC is microcytic (mean excess using only serum IE.
corpuscular volume < 79 fL) and ferritin is insufficient, we
hypochromic. recommend annual
assessments of liver iron
concentration (LIC) by T2*
(MRI).
does not require specific treatment The majority of the patients
TTTT In pregnant women, significant will require transfusions at
anemia (Hb < 7 g/dL) may develop some point in their lives or
(usually by the third trimester), when hemolytic or aplastic
requiring 1-5 mg/day of folic acid and crises associated with acute
supportive transfusion therapy. infections, folate deficiency,
hypersplenism, or pregnancy
occur.
They have a moderate
hemolytic anemia, maintaining
Hb levels > 7 g/dL without
transfusion support. When
their transfusion requirements
reach > 8 units per year, they
are reclassified as β-
Thalassemia major.
Thalassemia Intermedia
patients who develop
progressive anemia, fatigue,
and cardiopulmonary
complications also require
regular transfusions to
maintain Hb levels > 9-10
g/dL.
Iron chelation therapy when
LIC >5-7 mg/g dry weight and
to prevent serious endocrine
and cardiac complications
similar to those seen in
Thalassemia major patients.
treatment strategies:
Transfusion therapy
Confounding factors that might aggravate the degree of anemia, including folic acid deficiency and acute febrile illness, blood loss, or
coinheritance of glucose-6-phosphate dehydrogenase deficiency, need to be addressed simultaneously with transfusion therapy.
Transfusions of washed, leukocyte-depleted RBCs are recommended for all the patients to reduce the incidence of febrile and
urticarial reactions as well as infectious cytomegalovirus contamination.
Once a pretransfusion Hb level > 9-10 g/dL is achieved, transfusions are administered at 2- to 4-week intervals.
Splenectomy
The therapeutic rationale for splenectomy, is to decreasing the transfusion requirement, and consequently reducing iron overload
Therefore, we recommend splenectomy when the calculated annual transfusion requirement is > 200 to 220 mL RBCs/kg per year
( 2 units packed RBCs monthly ).
Iron chelation therapy
Exjade or Jadenu
deferoxamine [DFO] Deferasirox
(Desferal) (Exjade or Jadenu)
Indications in regularly transfused thalassemia patients. with a
serum ferritin level > 1000 μg/dL and an LIC > 3 mg
Fe/g dry weight
Dose The initial recommended dose is 30-40 mg/kg per day Daily use of a single oral dose of 20-30 mg/kg
for daily use 5-7 days each week per day.
Some patients may benefit by escalating the
Dosage modifications may also be guided by annual dose up to 40 mg/kg per day.
monitoring of LIC with dose adjustments to maintain
LIC of 3-7 mg Fe/g dry weight.
Administration Continuous slow SC infusions with a lightweight oral
portable battery-operated pump
Cautions Close monthly monitoring of serum ferritin
and creatinine levels and liver function is
indicated. discontinuation of DFX is
required in cases of unexplained
progressive increase in transaminase,
progressive increase in serum creatinine,
or progressive GI symptomatology
Managing complications
Cardiac complications
Cardiac failure and serious arrhythmias are the major causes of life-threatening morbidity and mortality in iron-overload
patients. Therefore, cardiac function is monitored annually beginning at 7 or 8 years of age by electrocardiogram,
echocardiogram, 24-hour Holter monitor, and recently by cardiac T2* MRI, which can detect preclinical cardiac iron
accumulation.
Managing endocrinopathies
prediabetic or diabetic states caused by pancreatic destruction, which might benefit from metformin administration or
indicate the need for insulin therapy.
Hypercoagulable state
These include the existence of a hypercoagulable state, particularly in splenectomized patients. The addition of
prophylactic antithrombotic therapy for high-risk patients with TI who have associated risk factors, such as surgery,
immobilization, and pregnancy, should be considered, as should the use of antiplatelet aggregating agents for patients
with significant thrombocytosis.
Referancies:
1- Clevland Clinic. Thalassemias: Diagnosis and Tests
2- National Heart, Lung, and Blood Institute
3- Oxford hematology
4- Blood journal (American society of hematology)
