Fibrinolytic changes in pregnant women on highly active antiretroviral therapy

Abstract

Objectives:To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART).Methods:Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV).Results:The mean ± standard error of mean (SEM) of PFC was 4.02±0.13g/l and ELT from the test subjects was 378±15 mins was significantly higher (p<0.05) compared with the control subjects (PFC 3.46±0.12g/l and ELT 267±9.0mins). The PCV or hematocrit values in the test subject was 29.1±0.38%, which was significantly lower (p<0.05) compared with the control subject (31.3±0.43%). The PV in the test subject was 1.76±0.02 mPa/s, while the control subjects was higher (1.73±0.02 mPa/s). This increase was not statistically significant (p>0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern.Conclusion:Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia.

Therapeutics targeting the fibrinolytic system

“…Thus, C-suPAR, which lacks the D1 domain, cannot be captured by ATF-HSA. Using this approach, we found that the plasma levels of active suPAR in 20 pregnant women were significantly higher than those in healthy donors, which was consistent with the effects of the overactivation of the fibrinolytic system required for uterine remodeling 136,137 .…”

“…Thus, peptides derived from the uPAR-binding regions of uPA have been studied as uPAR antagonists to interrupt uPA-uPAR interactions. Å6, an 8-mer peptide derived from uPA (residues [136][137][138][139][140][141][142][143], demonstrated excellent anticancer and anti-metastatic effects in experimental models and preclinical studies [92][93][94] . Å6 also entered phase I and II clinical trials for cancer treatment [95][96][97] .…”

Highly active antiretroviral therapy increases fibrinolytic and protein activity in pregnant women

“…(19) The catalytic activity of protein C is enhanced by the vitamin-K-dependent cofactor, deficiency of which distorts the delicate balance between procoagulant and anticoagulant proteins, thus introducing a prothrombotic state. (20) Also in this study, protein S was significantly increased in HIV-positive women on HAART, when compared to those not on HAART and HIV seronegative women. This may be attributed to the direct effect of antiretroviral therapy.…”

Effect of highly active antiretroviral therapy (HAART) on some specific clotting profile in Human Immunodeficiency Virus -(HIV) positive pregnant women

“…[ 11 12 ] Opportunistic infections, related malignancies, acquired hypercoagulable state, and endothelial dysfunction have been attributed to a lot of these changes in pregnancy and HIV infections. [ 13 14 ] Furthermore, antiretroviral drugs containing protease inhibitors are proposed to cause endothelial dysfunction by their effects on the metabolism of lipid and glucose. [ 15 ] Factors II and V were significantly reduced in HIV-positive pregnant women when compared to HIV-negative pregnant women.…”