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63 The pathogenetic role of thrombophilia in women with polycystic ovary syndrome and metabolic syndrome
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2nd Int. Symp. on Women’s Health Issues in Thrombosis and Haemostasis / Thrombosis Research 119 Suppl. 1 (2007) S97–S118
Conclusions: There is genetic hypofibrinolysis in patients with MS. It may play an important part in impaired invasion cytotrophoblast and impaired placental development. The patients with MS are at higher risk of developing not only various obstetric complications but thrombosis, thromboembolism. Timely antithrombotic prophylaxis may not only prevent thrombotic events but it may be a key of successful outcome of pregnancy. 62 The relationship between levels of circulating microparticles, complications of pregnancy and resistance of blood flow in the feto-maternal circulation O. Salomon, B.-Z. Katz, R. Dardik, D.M. Steinberg, R. Achiron, U. Seligsohn. The Amalia Biron Research Institute of Thrombosis and Hemostasis and Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer; Institute of Hematology, Tel Aviv Medical Center and Department of Statistics and Operations Research, Tel Aviv University, Israel Uteroplacental thrombosis has been implicated in the pathogenesis of fetal loss, intrauterine growth restriction (IUGR) and preeclampsia. The role of inherited and acquired thrombophilias in such pregnancy complications is controversial. Recently, increased levels of circulating procoagulant microparticles (MPs) were related to fetal loss and preeclampsia (Laude et al. Thromb Haemost 2001; 85: 18, Gonzalez-Quintero et al. Am J Obstet Gynecol 2004; 191: 1418). In this study, we measured at the 24th week of gestation the level of MPs derived from endothelial cells,platelets, and monocytes by flow cytometry using monoclonal antibodies against CD31, CD41 and CD14, respectively in 262 healthy unrelated primipara with a spontaneous singleton pregnancy. Expression of tissue factor and phosphatidylserine on MPs were measured by a monoclonal antibody and annexin 5, respectively. All women were followed thereafter until delivery. IUGR and small for gestational age (SGA) at birth were recorded in 58 out of 262 (22%) women, and pregnancy induced hypertension (PIH) and preeclampsia (PE) developed in 35 (15%) women. The levels of CD31 and CD41- positive MPs in women with and without IUGR, SGA, PIH or PE did not differ significantly. However, the level of CD31 at 24 weeks of gestation was negatively correlated with blood flow resistance in the left uterine artery at 24 weeks of gestation measured by multigate ultrasound Doppler (r = 0.18, p = 0.005) but was not significantly correlated with resistance in the placental, umbilical or right uterine artery. Levels of MPs- positive for tissue factor, annexin 5 or CD14 were neglible and thus comparisons between women with and without complications were not calculated. Also, there was no significant difference in levels of these MPs between women with and without the common inherited or acquired thrombophilias (factor V Leiden, prothrombin mutation and lupus anticoagulant). These data indicate that measurement of the level of MP at the 24th week of gestation has no predictive value for development of PIH, PE, IUGR or SGA. 63 The pathogenetic role of thrombophilia in women with polycystic ovary syndrome and metabolic syndrome T.B. Pshenichnikova, E.B. Perederyeva, A.D. Makatsariya. Sechenov Moscow Medical Academy, Moscow, Russia Object: to determine the diagnostic value of testing for inherited and acquired forms of thrombophilia in patients with metabolic syndrome (MS), polycystic ovary syndrome (PCOS) to optimize the treatment of these patients. Methods: 50 patients aged 18 to 35 years with PCOS and MS who had the fetal loss syndrome and infertility in past history. Estimation of the count and functional activity of platelets, the markers of thrombinemia and fibrinogenesis (TAT, D-dimer); testing for acquired, hereditary forms of thrombophilia. Results: In women with MS and PCOS the multigenic defects were verified in 100% of cases; the feature of multiple mutations is that the 4G/5G polymorphism of PAI-1 was found in 92% of cases,
the 4G/4G phenotype of the gene PAI-1 was verified in 67.4% of cases. Acquired antiphospholipid antibodies were verified in 40% of cases. All women of the study group underwent laparoscopic surgery including electrocautery. Considering the presence of thrombophilia in patients we used antithrombotic prophylaxis involved low molecular-weight heparin (LMWH), vitamins B, folic acid, antioxidants. LMWH was discontinued 12 hours before laparoscopic surgery and restarted 24 hours after laparoscopic surgery. There were not any thrombotic events and hemorrhagic complications neither laparoscopic surgery nor postoperative period. Conclusions: Patients with PCOS, MS and the uncovered thrombophilia are at higher risk of developing thrombosis, thromboembolism including preoperative and postoperative periods. Timely differential antithrombotic prophylaxis may prevent thrombotic events in these patients. We suggest that differential antithrombotic prophylaxis may optimize the treatment of infertility in these patients. It requires more research. 64 Protein Z in pregnancies complicated by intrauterine growth retardation K.C. Quack Loetscher1 , R. Stiller1 , M. Roos2 , R. Zimmermann2 . 1 Clinic of Obstetrics, Zurich University Hospital, Zurich, Switzerland, 2 Department of Biostatistics, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland Introduction: Changes in the coagulation and fibrinolytic systems during pregnancy lead to a higher risk of thromboembolism. These changes include the increase of many clotting factors, as well as a significant fall in activity of fibrinolytic proteins, such as protein C. Protein Z is a vitamin-K-dependent plasma glycoprotein and inhibits the activation of factor X by serving as a cofactor to a plasma proteinase inhibitor. Protein Z deficiencies have been reported in women with unexplained early fetal loss, and antibodies to protein Z can contribute to adverse pregnancy outcomes. Aim: The aim of this study was to determine the range of protein Z in normal pregnancy at different gestational weeks and to compare these normal levels with protein Z concentrations in mothers with intrauterine growth retardation (IUGR) affected fetuses. Results: In the longitudinal study we found a 20% increase (p = 0.0006) of protein Z from first trimester to delivery and a 30% decrease (p < 0.0001) 6 to 12 weeks after delivery. In the subgroup of mothers with IUGR we found low protein Z values in the range of 14th 36th percentile compared to normal pregnancy values (p = 0.02). Conclusion: Our data show a progressive increase in protein Z levels with gestational age in normal pregnancies that return to normal 6 12 weeks postpartum. Protein Z levels are significantly lower in mothers of fetuses affected by IUGR. The normal increase of protein Z during pregnancy may exert a protective effect, and reduce thrombotic events in the placenta, which could contribute to IUGR. unter Tulip Vena Cava Filter in prevention 65 Retrievable G¨ of pulmonary embolism in patients indicated to obstetric operation M. Proch´ azka3 , M. K¨ ocher1 , E. Buri´ ankov´ a1 , J. Proch´ azkov´ a2 , 2 1 3 1 ˇ a , M. Lubuˇsk´ y . Dept of Radiology, Faculty V. Krˇ cov´ a , M. Cern´ Hospital, Olomouc, Czech Republic, 2 Dept. of Hematooncology, Faculty Hospital, Olomouc, Czech Republic, 3 Dept. of Obstetrics and Gynaecology, Faculty Hospital Olomouc, Czech Republic Aim: To evaluate on a limited group of patients the place of retrievable G¨ unter Tulip Vena Cava Filter in the prevention of pulmonary embolism in patients with acute deep vein trombosis before obstetric operations and to discuss the technical demands associated with its implantation and retrieval.
2nd Int. Symp. on Women’s Health Issues in Thrombosis and Haemostasis / Thrombosis Research 119 Suppl. 1 (2007) S97–S118
Conclusions: There is genetic hypofibrinolysis in patients with MS. It may play an important part in impaired invasion cytotrophoblast and impaired placental development. The patients with MS are at higher risk of developing not only various obstetric complications but thrombosis, thromboembolism. Timely antithrombotic prophylaxis may not only prevent thrombotic events but it may be a key of successful outcome of pregnancy. 62 The relationship between levels of circulating microparticles, complications of pregnancy and resistance of blood flow in the feto-maternal circulation O. Salomon, B.-Z. Katz, R. Dardik, D.M. Steinberg, R. Achiron, U. Seligsohn. The Amalia Biron Research Institute of Thrombosis and Hemostasis and Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer; Institute of Hematology, Tel Aviv Medical Center and Department of Statistics and Operations Research, Tel Aviv University, Israel Uteroplacental thrombosis has been implicated in the pathogenesis of fetal loss, intrauterine growth restriction (IUGR) and preeclampsia. The role of inherited and acquired thrombophilias in such pregnancy complications is controversial. Recently, increased levels of circulating procoagulant microparticles (MPs) were related to fetal loss and preeclampsia (Laude et al. Thromb Haemost 2001; 85: 18, Gonzalez-Quintero et al. Am J Obstet Gynecol 2004; 191: 1418). In this study, we measured at the 24th week of gestation the level of MPs derived from endothelial cells,platelets, and monocytes by flow cytometry using monoclonal antibodies against CD31, CD41 and CD14, respectively in 262 healthy unrelated primipara with a spontaneous singleton pregnancy. Expression of tissue factor and phosphatidylserine on MPs were measured by a monoclonal antibody and annexin 5, respectively. All women were followed thereafter until delivery. IUGR and small for gestational age (SGA) at birth were recorded in 58 out of 262 (22%) women, and pregnancy induced hypertension (PIH) and preeclampsia (PE) developed in 35 (15%) women. The levels of CD31 and CD41- positive MPs in women with and without IUGR, SGA, PIH or PE did not differ significantly. However, the level of CD31 at 24 weeks of gestation was negatively correlated with blood flow resistance in the left uterine artery at 24 weeks of gestation measured by multigate ultrasound Doppler (r = 0.18, p = 0.005) but was not significantly correlated with resistance in the placental, umbilical or right uterine artery. Levels of MPs- positive for tissue factor, annexin 5 or CD14 were neglible and thus comparisons between women with and without complications were not calculated. Also, there was no significant difference in levels of these MPs between women with and without the common inherited or acquired thrombophilias (factor V Leiden, prothrombin mutation and lupus anticoagulant). These data indicate that measurement of the level of MP at the 24th week of gestation has no predictive value for development of PIH, PE, IUGR or SGA. 63 The pathogenetic role of thrombophilia in women with polycystic ovary syndrome and metabolic syndrome T.B. Pshenichnikova, E.B. Perederyeva, A.D. Makatsariya. Sechenov Moscow Medical Academy, Moscow, Russia Object: to determine the diagnostic value of testing for inherited and acquired forms of thrombophilia in patients with metabolic syndrome (MS), polycystic ovary syndrome (PCOS) to optimize the treatment of these patients. Methods: 50 patients aged 18 to 35 years with PCOS and MS who had the fetal loss syndrome and infertility in past history. Estimation of the count and functional activity of platelets, the markers of thrombinemia and fibrinogenesis (TAT, D-dimer); testing for acquired, hereditary forms of thrombophilia. Results: In women with MS and PCOS the multigenic defects were verified in 100% of cases; the feature of multiple mutations is that the 4G/5G polymorphism of PAI-1 was found in 92% of cases,
the 4G/4G phenotype of the gene PAI-1 was verified in 67.4% of cases. Acquired antiphospholipid antibodies were verified in 40% of cases. All women of the study group underwent laparoscopic surgery including electrocautery. Considering the presence of thrombophilia in patients we used antithrombotic prophylaxis involved low molecular-weight heparin (LMWH), vitamins B, folic acid, antioxidants. LMWH was discontinued 12 hours before laparoscopic surgery and restarted 24 hours after laparoscopic surgery. There were not any thrombotic events and hemorrhagic complications neither laparoscopic surgery nor postoperative period. Conclusions: Patients with PCOS, MS and the uncovered thrombophilia are at higher risk of developing thrombosis, thromboembolism including preoperative and postoperative periods. Timely differential antithrombotic prophylaxis may prevent thrombotic events in these patients. We suggest that differential antithrombotic prophylaxis may optimize the treatment of infertility in these patients. It requires more research. 64 Protein Z in pregnancies complicated by intrauterine growth retardation K.C. Quack Loetscher1 , R. Stiller1 , M. Roos2 , R. Zimmermann2 . 1 Clinic of Obstetrics, Zurich University Hospital, Zurich, Switzerland, 2 Department of Biostatistics, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland Introduction: Changes in the coagulation and fibrinolytic systems during pregnancy lead to a higher risk of thromboembolism. These changes include the increase of many clotting factors, as well as a significant fall in activity of fibrinolytic proteins, such as protein C. Protein Z is a vitamin-K-dependent plasma glycoprotein and inhibits the activation of factor X by serving as a cofactor to a plasma proteinase inhibitor. Protein Z deficiencies have been reported in women with unexplained early fetal loss, and antibodies to protein Z can contribute to adverse pregnancy outcomes. Aim: The aim of this study was to determine the range of protein Z in normal pregnancy at different gestational weeks and to compare these normal levels with protein Z concentrations in mothers with intrauterine growth retardation (IUGR) affected fetuses. Results: In the longitudinal study we found a 20% increase (p = 0.0006) of protein Z from first trimester to delivery and a 30% decrease (p < 0.0001) 6 to 12 weeks after delivery. In the subgroup of mothers with IUGR we found low protein Z values in the range of 14th 36th percentile compared to normal pregnancy values (p = 0.02). Conclusion: Our data show a progressive increase in protein Z levels with gestational age in normal pregnancies that return to normal 6 12 weeks postpartum. Protein Z levels are significantly lower in mothers of fetuses affected by IUGR. The normal increase of protein Z during pregnancy may exert a protective effect, and reduce thrombotic events in the placenta, which could contribute to IUGR. unter Tulip Vena Cava Filter in prevention 65 Retrievable G¨ of pulmonary embolism in patients indicated to obstetric operation M. Proch´ azka3 , M. K¨ ocher1 , E. Buri´ ankov´ a1 , J. Proch´ azkov´ a2 , 2 1 3 1 ˇ a , M. Lubuˇsk´ y . Dept of Radiology, Faculty V. Krˇ cov´ a , M. Cern´ Hospital, Olomouc, Czech Republic, 2 Dept. of Hematooncology, Faculty Hospital, Olomouc, Czech Republic, 3 Dept. of Obstetrics and Gynaecology, Faculty Hospital Olomouc, Czech Republic Aim: To evaluate on a limited group of patients the place of retrievable G¨ unter Tulip Vena Cava Filter in the prevention of pulmonary embolism in patients with acute deep vein trombosis before obstetric operations and to discuss the technical demands associated with its implantation and retrieval.