757: Low levels and activity of circulating alpha-1 antitrypsin are a possible cause for severe preeclampsia Academic Article uri icon

abstract

  • antitrypsin are a possible cause for severe preeclampsia Guy Twina, Eli C Lewis, Galit Shahaf, Shimrit Yaniv Salem, Tamar Madar, Joel Baron, Arnon Wiznitzer, Moshe Mazor, Gershon Holcberg, Eyal Sheiner Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Faculty of Health Sciences, BeerSheva, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Clinical Biochemistry, Faculty of Health Sciences, Beer-Sheva, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Meitar, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, IL, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, Israel OBJECTIVE: Alpha-1 antitrypsin (AAT) inhibits a wide variety of proteases and possesses anti-inflammatory and tissue-protective properties. During normal pregnancy, circulating AAT rises towards the third trimester. AAT was previously linked to placental and pregnancy complications. Preeclampsia is a multisystem pregnancy disorder of unknown cause. An immunological insight into the origin of preeclampsia was previously suggested. The purpose of the present prospective study was to examine whether low plasma concentration and activity of AAT might correlate with severe preeclampsia. STUDY DESIGN: A prospective case control study was conducted comparing patients with severe preeclampsia (n 23) and patients without preeclampsia (n 18). AAT activity and concentration were determined in maternal serum samples by standard ELISA and enzymatic assays. Samples were performed in duplicates and repeated twice for each sample in separate sessions. RESULTS: Patients with severe preeclampsia depicted AAT levels that were 1.91 / 0.08 fold lower than control (3.854 / 0.2662 vs. 7.397 / 0.3404 mg/ml; p 0.001). The reduced levels of AAT in patients with severe preeclampsia correlated with reduced protease inhibitory capacity (46.56 / 2.082% vs. 67.08 / 1.748%, p 0.001). CONCLUSION: Alpha-1 antitrypsin concentrations and activity are lower in parturients with severe preeclampsia. Accordingly, AAT may play an important role in the pathogenesis of preeclampsia. Further prospective studies are required to elucidate such association. 758 Severe preeclampsia is associated with altered thrombin generation and clot structure Erin Morris, Heather Major, Robert A. Campbell, Andrew S. Weyrich University of Utah, OB/GYN, Salt Lake City, UT, University of Utah, Internal Medicine, Salt Lake City, UT OBJECTIVE: Markers of increased coagulation, including platelet activation and fibrin deposition in renal and placental vasculature, have been described in preeclampsia. We hypothesized that women with preeclampsia have altered measures of procoagulant activity. STUDY DESIGN: Women with preeclampsia (PE) meeting ACOG criteria were matched by gestational age to women with normal pregnancies. Nonpregnant reproductive-age women comprised an additional control group. Venous blood was centrifuged to collect platelet poor plasma (PPP). Thrombin generation was measured using a fluorogenic assay. Clot formation was measured by spectrophotometry. To remove microparticles, PPP was ultracentrifuged at 100,000 x g for 60 minutes. Thrombin generation and clot formation were measured in parallel with uncentrifuged PPP. Fluorescently labeled fibrinogen was added to PPP and clot structure was analyzed using confocal microscopy. RESULTS: 25 participants were recruited to each comparison group. Comparisons of thrombin generation and clot formation parameters are summarized below. Pregnant controls and women with PE had significant differences in thrombin generation and clot formation compared to nonpregnant controls, as expected (p 0.05). Women with PE had a significantly greater area under the curve (AUC) in thrombin generation as compared to pregnant controls (p 0.049). Women with severe PE 34 weeks gestation (n 14) were noted to have a trend toward increased peak thrombin (p 0.07), and greater AUC (p 0.005) with more dense clot structure (p 0.006) when compared to matched pregnant controls. These differences were abrogated by removal of microparticles. CONCLUSION: Significant prothrombotic changes are induced by pregnancy. These changes are magnified in women with PE, who have greater total thrombin generation (AUC) compared to pregnant controls. The more severe phenotype of this disorder, women with severe PE 34 wks, have further alterations in procoagulant activity, including increased peak thrombin, total thrombin, and more dense clot structure that appear to be microparticle mediated. www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease Poster Session V

publication date

  • January 1, 2012