HEMONC: Protein C levels in beta-thalassemia major patients in the east Nile delta of Egypt

Protein C levels in beta-thalassemia major patients in the east Nile delta of
Egypt
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<p><span style="font-size: small; font-family: verdana,geneva;">Tamer H. Hassan, Rabab M. Elbehedy, Doaa M. Youssef, Ghada E. Amr</span></p> on 14/06/2010 07:18:00
 
Protein C is a vitamin K-dependent serine protease and naturally occurring
anticoagulant that plays a role in the regulation of hemostasis by inactivating
factors Va and VIIIa in the coagulation cascade. Human protein C circulates as a
2-chain zymogen, but functions at the endothelial and platelet surface following
conversion to activated protein C by limited proteolysis with thrombin in
complex with the cell surface membrane protein, thrombomodulin.1
Thalassemias are inherited hemoglobinopathies characterized by a structural
hemoglobin defect. These hereditary diseases have significant morbidity and
mortality and affect individuals of African-American heritage, as well as those
of Mediterranean, Middle Eastern, and Southeast Asian descent.2
Despite the difficulties associated with treatment, standards of care for
thalassemic patients have improved in recent years, resulting in almost a
doubling of the average life expectancy. As a consequence, additional previously
undescribed complications are now being recognized. In particular, profound
hemostatic changes have been observed in patients with beta-thalassemia major,
especially splenectomized cases. The presence of a higher than normal incidence
of thromboembolic events and the existence of prothrombotic hemostatic anomalies
in the majority of the patients, even from a very young age, have led to the
recognition of the existence of a chronic hypercoagulable state in thalassemic
patients.3
Several etiologic factors may play a role in the pathogenesis of the
hypercoagulable state in thalassemia such as platelet activation and increased
circulating aggregates,4,5 shortened platelet survival,6 increased urinary
excretion of thromboxane A2 and prostacyclin metabolites,7 decreased levels of
naturally occurring anticoagulants such as protein C and protein S, and an
elevated plasma level of thrombin-antithrombin complex have also been
reported.8,9 A mechanism involving the loss of membrane phospholipid asymmetry
in thalassemic red or erythroid cells, with the exposure of procoagulant
phosphatidylserine in the outer leaflet of the red cell membrane has also been
proposed.10
The lower protein C levels in thalassemia are either due to decreased production
or increased consumption. Therefore, a coagulation imbalance exists in patients
with thalassemia, which in turn may be responsible for the adverse clinical
effects observed in those patients.2 We investigated the status of the protein C
anticoagulant pathway in thalassemic patients and its relationship to the
hypercoagulable state in thalassemia major.