Throbmoembolic phenomena (both venous and arterial) are common in thalassemia, particularly following splenectomy [Citation[1], Citation[2]], with abnormalities in the levels of coagulation factors and their inhibitors reported to be one potential mechanism Citation[3]. We compared the levels of protein C, protein S, and antithrombin III (AT III) in splenectomized with those in nonsplenectomized patients with β-thalassemia major in Iran for the first time.
Fifty-nine consecutive β-thalassemic major patients (28 males; aged 4–26 years with a mean of 12.3 years; 12/59 splenectomized) without evidence of chronic active hepatitis, diabetes, and renal problems were investigated ≥25 days after their latest transfusion. Patients received regular blood transfusions to maintain pretransfusional hemoglobin levels between 9 and 10 g/dL, as well as desferrioxamine subcutaneously, according to the severity of iron overload. Patients did not have a history of thrombotic event and were not on anticoagulant therapy.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and prothrombin time (PT) were measured to evaluate the severity of liver damage and serum ferritin was measured to determine the degree of iron overload. Proteins C and S were determined by an amidolytic method using the Staclot kit (Diagnostica Stago, Parsippany, NJ, USA) and AT III was assayed by the chromogenic method using the Stachrome kit (Diagnostica Stago).
Demographic and clinical data of patients are shown in . Patients in the two groups were not statistically different in sex, but splenectomized patients were older (p =. 019), due to a higher incidence of hypersplenism necessitating splenectomy at older ages, and had lower protein C levels (p =. 033). Levels of protein S, AT III, ALT, AST, serum ferritin, and PT were not significantly different between the two groups.
TABLE 1 Demographic and Clinical data of Patients
The effects of splenectomy on natural anticoagulants have not been studied sufficiently. AT III levels remained normal in a study on 34 post-splenectomy subjects Citation[4]. On the other hand, only a few studies, with inconsistent results, have compared the level of natural anticoagulants between splenectomized and nonsplenectomized thalassemic patients. A previous study on 24 splenectomized and 8 nonsplenectomized thalassemic patients revealed decreased AT III levels in the splenectomized group Citation[2]. Another study on an even smaller number of patients showed decreased levels of proteins C and S (particularly protein C) in splenectomized patients Citation[5]. On the other hand, three previous studies noted that there was no difference between splenectomized and nonsplenectomized patients with regard to protein C, protein S, and AT III [Citation[6], Citation[7], Citation[8]]. Protein C and protein S levels in thalassemia have not been related to levels of serum transaminases or albumin, eliminating liver dysfunction as a cause of these abnormalities Citation[9].
We demonstrated a significant decrease in protein C, but not in protein S or AT III levels in splenectomized compared to nonsplenectomized thalassemic patients. Moreover, the lower level of protein C in splenectomized patients was not due to more severe liver damage or iron overload. However, the reason for the finding of selective protein C deficiency in postsplenectomy thalassemic patients is not clear for the authors at the moment. Although this study was the largest one on the subject so far, the power is still low and negative results (especially for protein S, which showed a nonsignificant decrease in the splenectomized group) should be treated cautiously.
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