Hemostatic parameters as hypercoagulability indicators in pregnancy

Abstract

The concentrations of plasma proteins involved in the process of coagulation are changed during the normal pregnancy, interfering with balance between procoagulant and anticoagulant systems. These changes include the increased activity of coagulation factors, the increased fibrin production and suppression of fibrinolysis. In this way, the risk of blood loss is reduced by physiological mechanisms, but the risk of thrombosis becomes higher. Thrombosis of placental blood vessels gives rise to placental insufficiency causing the repeated miscarriages, retardation of fetal growth, eclampsia intrauterine death of fetus and pre-term delivery. The causes of these incidents are the changes occurring within protein C coagulation system. The central anticoagulant enzyme is APC, which inactivates the activated factors V and VIII by proteolysis and, in that manner, inhibits the production of thrombin. The resistance to APC is the impairment of blood coagulation characterized by lower sensitivity to anticoagulant activity of APC. This disorder is in 95% of cases, caused by specific factor V gene point mutation and designated as F V Leiden. It is point mutation on locus 1691 where guanin is replaced by adenine what will lead to synthesis of modified F V molecule in which arginine is replaced by glutamine on locus 506. Arginine 506 is the locus of factor Xa binding, and it inhibits the inactivation of factor Va by the action of APC. The testing performed in pregnant women with regular and complicated pregnancy, in different periods, has shown that fibrinogen, fibrin monomer, TAT complex and PAI were good markers of hipercoagulability in pregnancy. The values of protein C activity were within normal limits. Protein S values were below lower limits. Global activity of protein C-anticoagulant pathway and its relation with procoagulant system were presented by quantitative measurement using Pro C Global test, while determination of activated protein C by means of APC sensitivity test was used for identification of persons with APC resistance e.g. with higher risk of thrombosis. Significantly lower PC-NR and APC-NR values were found in pregnant women with repeated miscarriages and in pregnant women with hypertension in relation to pregnant women with regular pregnancy. The results revealed significantly lower APC-anticoagulant activity in pregnancy, particularly in pregnancy associated with complications. Diagnostic accuracy of these parameters as markers of thrombotic changes in pregnancy was tested by ROC analysis. PC-NR and APC-NR showed satisfactory diagnostic accuracy as markers of thrombotic changes in pregnant women, more precisely, they were found to be good indicators of resistance to activated protein C in pregnancy.