الفهرس 
Pathophysiology of thalassemiaOnly 14 pages are availabe for public view
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Abstract
Thalassemia refers to a syndrome of diseases characterized by decreased or
absent production of one or more globin chains. Beta thalassemia is due to deficient
production of beta globin chains, which causes a relative excess of alpha globin chains.
These excess alpha globin chains are insoluble and precipitate within the red cell,
leading to a variety of clinical manifestations. The severity of subsequent clinical
manifestations depends on the degree of alpha globin chain excess. The symptoms are
severe in patients homozygous for impaired beta globin synthesis and much less severe
in heterozygotes, who generally have mild anemia and no symptoms. Alpha thalassemia
is due to decreased production of alpha globin chains, resulting in a relative excess of
beta globin chains.
Presently, red blood cell transfusion requirements have been used to classify the
patients with thalassemia into 2 major groups that include 1) transfusion-dependent
thalassemia (TDT), and 2) non-transfusion-dependent thalassemia (NTDT).
Transfusion-dependent thalassemia refers to the patients who require a regular blood
transfusion for survival that includes patients with severe forms of thalassemia. Nontransfusion-
dependent thalassemia refers to those patients who require an occasional red
blood transfusion in certain circumstances e.g., surgery, pregnancy or infection. The
patients with NTDT includes patients with a moderate severity of thalassemia.
The diversity of disease-related complications among patients with thalassemia is
complicated by the wide spectrum of genotypes and clinical risk factors. Endocrine
disorders and left ventricular disorders are more prevalent in patients with TDT.
Thrombosis, pulmonary hypertension, right ventricular disorders, and silent cerebral
infarction are more common in patients with NTDT. Moreover, a specific clinical risk
factor, splenectomy, is a strong risk factor for pulmonary hypertension and thrombosis
in patients with thalassemia.
Growth/differentiation factor-15 (GDF-15) is a divergent member of the
transforming growth factor β superfamily. GDF-15 is often induced under stress
conditions, seemingly to maintain cell and tissue homeostasis; however, a moderate
increase in GDF-15 blood levels is observed with age. Highly elevated GDF-15 levels
are mostly linked to pathological conditions including inflammation, myocardial
ischemia, and notably cancer. Marrow expansion, tissue hypoxia, and erythroblast
apoptosis caused by globin chain imbalances may all be needed to induce the extremely
high concentrations of GDF15 detected in the serum of β-thalassemia patients.
GDF‐15 has been recognized as a consistent biomarker of CVE in patients with
ACS or stable CAD. GDF‐15 levels are independently related to age, high‐sensitivity Creactive
protein (hs‐CRP), natriuretic peptides, and renal dysfunction in patients with
established CAD. GDF‐15 concentrations are enhanced in patients with multivessel
disease and with a history of myocardial infarction (MI) or heart failure. GDF‐15 is in
fact associated with subclinical atherosclerosis. GDF‐15 functions as a
proinflammatory factor in the process of atherosclerosis via TGFβRII signaling,
especially in the early stage and acute inflammatory stage.
The aim of our study was to to evaluate CIMT (as a surrogate marker for
subclinical atherosclerosis) and GDF-15serum level in adults with transfusion
dependent β-thalassemia; unravel their possible correlation with clinical, histologic and
laboratory variables (including cardiovascular risk factors); and lastly to detect the
association between GDF-15 and atherosclerosis.
Summary,