الفهرس 
HEMOGLOBINOPATHIESPATHO-PHYSIOLOGY OFOnly 14 pages are availabe for public view
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Abstract
C
oagulation abnormalities are frequently reported in hemolytic anemias (HA).
Several pathophysiologic mechanisms are common to different HA. SCD and thalassemia represent the most common genetic disorders worldwide. Although they have different pathophysiologies, patients with both diseases share many clinical manifestations, including thrombotic complications.
Several mechanisms can be involved, including abnormal red blood cell (RBC) properties, increased plasma concentrations of microparticles, release of cell-free hemoglobin and RBC arginase resulting in impaired nitric oxide (NO) bioavailability, increased blood concentration of oxidants, and endothelial dysfunction.
The major clinical consequence is an increased tendency to develop venous thrombosis, although the clinical sequelae of hemolysis may include a variety of symptoms caused by NO depletion as a consequence of increased cell- free plasma hemoglobin.
Activation of coagulation results in the formation of thrombin, which in turn is inactivated by complex formation with its major inhibitor AT. This process leads to the appearance and increase of TAT in peripheral blood. In this regard, this study aimed to assess serum TAT in a group of patients with heamoglobinopathies to evaluate its clinical utility in the assessment of hypercoagulability and the risk of thrombotic formation.
In this study serum levels of TAT was assaayed in 60 patients with heamoglobinopathies. These patients were divided into two subgroups, subgroup I (n= 40) who were patients with thalassemia and subgroup II (n= 20) who were patients with SCD. A control group (n=20) who were healthy age-matched children was also included.
All the studied individuals were subjected to full history taking and complete clinical examination. Blood samples were collected for determination of CBC, LDH, ferritin, bilirubin, CBC, PT, PTT, INR, and serum TAT. Assay of serum TAT was carried out using an enzyme linked immunosorbent assay technique.
The results of the present study revealed a statistically highly significant increase in serum levels of TAT in all patients groups when compared to their matched controls. Also, there is a statistically highly significant increase
in serum TAT in thalassemic group when compared with control group alone and a statistically highly significant increase in serum TAT in SCD group when compared with control group alone.
The best diagnostic cut off level for serum TAT level in discriminating thaslassemia group was 115 ug/L, with a diagnostic sensitivity of 92.50%, specificity 80%, negative predictive value 84.2 %, and positive predictive value 90.2 %.
The best diagnostic cut off level for serum TAT level for discrimination SCD from control was 120 ug/L, with a diagnostic sensitivity of 95 %, specificity 95%, negative predictive value 95 %, and positive predictive value 95 %. The area under the curve (AUC) was 0.952.
Coagulation is related to hemolysis, as there is a significant relationship between serum TAT and bilirubin.
In conclusion, it was found that the bulk of evidence demonstrates that there is increased in the coagulation activity in thalassemia and SCD measured by TAT level and this coagulation activity is correlated with the level of hemolysis.
Coagulation activation in patients with heamoglobinopathies appears to be a consequence of many pathophysiologies as the exposure of PS on the outer surface of RBCs membrane, ischemia - reperfusion injury, increased plasma concentrations of microparticles and possibly increased NO scavenging as a result of fragility of RBCs.