Plasminogen activator inhibitor-2 and impaired fibrinolysis in pregnancy and sickle cell anemia

Abstract

PurposeThis is the first study that aimed to determine antigen levels in plasma and genotypes of PAI-2 in pregnant and non-pregnant homozygous sickle cell anemia (SCA) patients.MethodsThe study subjects were all Bahraini females in the reproductive age group. The study population included 31 pregnant homozygous SS (SCA) patients. Three control groups were also studied to evaluate the effect of pregnancy and SCA on PAI-2 levels and fibrinolysis: (1) 31 healthy non-pregnant volunteers; (2) 31 cases of normal pregnancy; and (3) 20 non-pregnant SCA patients. Pregnancies were screened in the second (TM2) and third (TM3) trimesters. Global coagulation, fibrinolysis rate (euglobulin clot lysis time, ECLT), PAI-2 antigen (ELISA), and PAI-2 Ser(413)/Cys polymorphism (restriction fragment length polymorphism analysis) were determined.ResultsFeto-maternal complications were documented in both pregnancy groups. PAI-2 antigen levels were undetectable in the non-pregnant groups, but was quantifiable in both pregnant groups. Impaired fibrinolysis rate and rising PAI-2 levels with progression of pregnancy were observed in both healthy and SCA subjects. These changes were more prominent in SCA, although the rise in ECLT was less steep and PAI-2 antigen levels were not significantly different compared to normal pregnancy in the third trimester. No correlation was observed between PAI-2 genotypes and plasma antigen levels. Also, no significant difference in feto-maternal complications was found in normal (n = 25) versus SCA pregnant patients (n = 30).ConclusionsThese observations suggest that with progression of pregnancy, increasing PAI-2 levels contribute to the hypercoagulable state, particularly in SCA patients.