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C0447: Prevention of Pregnancy Complications in Women with Multiple Pregnancy and Thrombophilia
POSTERS / Thrombosis Research 133S3 (2014) S35–S123
obstetric complications. Women with personal or family history of thromboembolism or with history of obstetric complications should be screened for thrombophilia. C0443 UNCLEAR CASE OF RECURRENT THROMBOSIS IN PREGNANCY: ROLE OF ACQUIRED ADAMTS-13 DEFICIENCY 1
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V.O. Bizadze , A. Makatsariya , S.V. Akinshina . Department of obstetrics and gynecology, I.M. Sechenov First Moscow State Medical University, Russia; 2 I.M.Sechenov First Moscow State Medical University. Moscow, Russia Background: We present an unclear clinical case of thrombothic storm associated with pregnancy. Methods: Patient Z, 24 years old, at presentation in 2007 pregnancy 15 weeks. In 2005 after the emergency cesarean section for obstetric indications developed PE, treated by LMWH. After the artificial abortion in 2006 recurrent PE was diagnosed. After acute treatment with LMWH patient was switched to warfarin. Results: FV Leiden, prothrombin G20210A, protein S, C, antithrombin III deficiency – negative, normal homocystein level, homozygous polymorphism of PAI-1 4G/5G, heterozygous polymorphisms of t-PA I/D, Gp-III 1565 Gplba, GpIba 434 C/T, proinflammatory cytokines IL-1b −31T/C, CD46 5032 C/G, IL-6 −174 G/C, TNF-a −308G/A. Repeat testing for antiphospholipid antibodies, anticardiolipins, LA, anti-beta2-glycoprotein was negative. Pregnancy was followed to term under therapeutic doses of LMWH guided by D-dimer and elective c.s. was performed. We continued LMWH 6 weeks postpartum and then replaced by warfarin (INR 2.0–3.0). In 2009 patient suffered ischemic stroke in next pregnancy, which was terminated at 10 weeks and switched to LMWH. After 2 weeks patient discontinued LMWH and suffered recurrent TIA. In 2012 we determined ADAMTS-13 inhibitor in titer of 55 IU/ml. Conclusions: Despite history of “thrombothic storm” patient has no strong thrombogenic thrombophilia. Determining of ADAMTS-13 activity and inhibitor may be a useful tool in case of otherwise unexplained pregnancy-related thrombosis. C0445 PREVALENCE OF APA IN THE STRUCTURE OF IVF-FAILURE REASONS J.Kh. Khizroeva1 , V.O. Bitsadze1 , A. Makatsariya2 . 1 Department of obstetrics and gynecology, I.M. Sechenov First Moscow State Medical University, Russia; 2 I.M.Sechenov First Moscow State Medical University. Moscow, Russia Background: It has been suggested an association between APA circulation and IVF failure. The proposed mechanism of such failure includes abnormal implantation, placentation, and early embryonic vascular compromise. Methods: ELIZA-method was used to measure IgM/IgA APA screen (includes anticardiolipin, antiphosphatidylethanolamine, antiphosphatidylinositol, antiphospatidic acid, antiphosphatidylglycerol, antiphosphatidylcholine, and antiphosphatidylserine), anti-b2-glycoprotein I (GPI), antiannexin V, antiprothrombin in 267 women underwent IVF procedures and 80 healthy pregnant women. Among these 267 women 178 had IVF failures (I group) and 89 with pregnancy after IVF (II group). Results: I group – positive APAs were detected in 75 (42%), anticardiolipin in 16 (8.9%), antiannexin V in 44 (24.7%), antib2-GPI in 56 (31%), antiprothrombin in 24 (13.5%) women with IVF failure. II group – APAs in 17 (19%), anticardiolipin in 4 (4.5%), antiannexin V in 9 (10%), anti-b2-GPI in 13 (15%), antiprothrombin in 7 (8%) women with succeed pregnancy after IVF compared with 3 (3.4%) of APAs, 1 (1.3%) anticardiolipin, 3 (3.8%) anti-b2-GPI and no antiannexin V and antiprothrombin in controls (p < 0.001).
S111
Conclusions: APA should be considered an important risk factor of IVF failures. Patients who are involved with an IVF programme should be tested for the presence of APA prior to initiation of an IVF cycle. A complete APA panel is necessary for diagnosing implantation failure associated with APS. C0447 PREVENTION OF PREGNANCY COMPLICATIONS IN WOMEN WITH MULTIPLE PREGNANCY AND THROMBOPHILIA A. Makatsariya1 , V.O. Bitsadze2 , J.Kh. Khizroeva2 . 1 Department of obstetrics and gynecology, I.M. Sechenov First Moscow State Medical University, Russia; 2 I.M.Sechenov First Moscow State Medical University. Moscow, Russia Background: To evaluate the efficiency of anticoagulant, antioxidants and vitamins (folic acid, group B) in the course of preparation for IVF, in the IVF protocols, during multiple pregnancy and in the postnatal period. Methods: The comparative analysis of 50 women with the physiological course of multiple pregnancy (I group) and at 50 women with pathological course of pregnancy after IVF. Genetic thrombophilia (mutations in genes of factor V, prothrombin, fibrinogen), deficiency of protein C, antithrombin III, hyperhomocysteinemia and APA circulation were evaluated. Results: In healthy women of I group thrombophilia was revealed in 7 women. In the II group different forms of thrombophilia were found in 48 (96%) women: factor V Leiden mutation in 8 (16%), prothrombin gene G20210A in 6 (12%), hyperhomocysteinemia in 17 (34%), APS in 22 (11%). The combined forms of thrombophilia (APA in combination with genetic defects and hyperhomocysteinemia) in 15%. Moderate preeclampsia developed in 34 (17%), placental abruption with antenatal death of both fetuses in 5 women, placental abruption with antenatal death of 1 fetus in 10 women, chorionic abruption at the early terms of pregnancy in 10 women with multiple pregnancy after IVF. Premature birth at term 29–32 weeks took place in 15 women. Thromboses (ileofemoral, jugular veins) in 2 women at the I trimester of pregnancy and in 2 women postnatally. 70 alive babies were born. Fetal losses were associated with antenatal death in 12 women (14 babies). Results showed the pathogenetic role of an initial thrombophilia in the development of complications of multiple pregnancy after IVF. The additional factor is hormonal therapy carried out in the IVF protocols. Conclusions: The conducted research allows to assume the necessity of application of anticoagulant, antioxidant therapy and vitamins from the fertile cycle and during all pregnancy. C0514 INCREASED CIRCULATING PROCOAGULANT MICROPARTICLES ARE ASSOCIATED WITH RECURRENT IMPLANTATION FAILURE AFTER IN VITRO FERTILIZATION AND EMBRYO TRANSFER J.C. Reverter1 , E. Garcia1 , M.A. Martinez-Zamora2 , L. Martin1 , G. Casals2 , J. Monteagudo1 , S. Civico2 , F. Carmona2 , J. Balasch1 , D. Tassies1 . 1 Hospital Clinic, Hemotherapy and Hemostasis Department, Barcelona, Spain; 2 Hospital Clinic, Obstetrics and Neonatology Department, Barcelona, Spain Background: Recurrent implantation failure (RIF) following embryo transfer (ET) is a major problem in in vitro fertilization (IVF) treatments. Women with haemostatic defects may be at increased risk of miscarriage and preclinical pregnancy loss. Microparticles (MP) are small plasma membrane fragments released from activated or apoptoic cells. Increased levels of MP are found in several diseases such as atherosclerosis and inflammatory and autoimmune disorders. MP have procoagulant activity and are able to potentiate coagulation. The aim of this study was to investigate procoagulant MP levels in patients with unexplained RIF.
obstetric complications. Women with personal or family history of thromboembolism or with history of obstetric complications should be screened for thrombophilia. C0443 UNCLEAR CASE OF RECURRENT THROMBOSIS IN PREGNANCY: ROLE OF ACQUIRED ADAMTS-13 DEFICIENCY 1
1
1
1
V.O. Bizadze , A. Makatsariya , S.V. Akinshina . Department of obstetrics and gynecology, I.M. Sechenov First Moscow State Medical University, Russia; 2 I.M.Sechenov First Moscow State Medical University. Moscow, Russia Background: We present an unclear clinical case of thrombothic storm associated with pregnancy. Methods: Patient Z, 24 years old, at presentation in 2007 pregnancy 15 weeks. In 2005 after the emergency cesarean section for obstetric indications developed PE, treated by LMWH. After the artificial abortion in 2006 recurrent PE was diagnosed. After acute treatment with LMWH patient was switched to warfarin. Results: FV Leiden, prothrombin G20210A, protein S, C, antithrombin III deficiency – negative, normal homocystein level, homozygous polymorphism of PAI-1 4G/5G, heterozygous polymorphisms of t-PA I/D, Gp-III 1565 Gplba, GpIba 434 C/T, proinflammatory cytokines IL-1b −31T/C, CD46 5032 C/G, IL-6 −174 G/C, TNF-a −308G/A. Repeat testing for antiphospholipid antibodies, anticardiolipins, LA, anti-beta2-glycoprotein was negative. Pregnancy was followed to term under therapeutic doses of LMWH guided by D-dimer and elective c.s. was performed. We continued LMWH 6 weeks postpartum and then replaced by warfarin (INR 2.0–3.0). In 2009 patient suffered ischemic stroke in next pregnancy, which was terminated at 10 weeks and switched to LMWH. After 2 weeks patient discontinued LMWH and suffered recurrent TIA. In 2012 we determined ADAMTS-13 inhibitor in titer of 55 IU/ml. Conclusions: Despite history of “thrombothic storm” patient has no strong thrombogenic thrombophilia. Determining of ADAMTS-13 activity and inhibitor may be a useful tool in case of otherwise unexplained pregnancy-related thrombosis. C0445 PREVALENCE OF APA IN THE STRUCTURE OF IVF-FAILURE REASONS J.Kh. Khizroeva1 , V.O. Bitsadze1 , A. Makatsariya2 . 1 Department of obstetrics and gynecology, I.M. Sechenov First Moscow State Medical University, Russia; 2 I.M.Sechenov First Moscow State Medical University. Moscow, Russia Background: It has been suggested an association between APA circulation and IVF failure. The proposed mechanism of such failure includes abnormal implantation, placentation, and early embryonic vascular compromise. Methods: ELIZA-method was used to measure IgM/IgA APA screen (includes anticardiolipin, antiphosphatidylethanolamine, antiphosphatidylinositol, antiphospatidic acid, antiphosphatidylglycerol, antiphosphatidylcholine, and antiphosphatidylserine), anti-b2-glycoprotein I (GPI), antiannexin V, antiprothrombin in 267 women underwent IVF procedures and 80 healthy pregnant women. Among these 267 women 178 had IVF failures (I group) and 89 with pregnancy after IVF (II group). Results: I group – positive APAs were detected in 75 (42%), anticardiolipin in 16 (8.9%), antiannexin V in 44 (24.7%), antib2-GPI in 56 (31%), antiprothrombin in 24 (13.5%) women with IVF failure. II group – APAs in 17 (19%), anticardiolipin in 4 (4.5%), antiannexin V in 9 (10%), anti-b2-GPI in 13 (15%), antiprothrombin in 7 (8%) women with succeed pregnancy after IVF compared with 3 (3.4%) of APAs, 1 (1.3%) anticardiolipin, 3 (3.8%) anti-b2-GPI and no antiannexin V and antiprothrombin in controls (p < 0.001).
S111
Conclusions: APA should be considered an important risk factor of IVF failures. Patients who are involved with an IVF programme should be tested for the presence of APA prior to initiation of an IVF cycle. A complete APA panel is necessary for diagnosing implantation failure associated with APS. C0447 PREVENTION OF PREGNANCY COMPLICATIONS IN WOMEN WITH MULTIPLE PREGNANCY AND THROMBOPHILIA A. Makatsariya1 , V.O. Bitsadze2 , J.Kh. Khizroeva2 . 1 Department of obstetrics and gynecology, I.M. Sechenov First Moscow State Medical University, Russia; 2 I.M.Sechenov First Moscow State Medical University. Moscow, Russia Background: To evaluate the efficiency of anticoagulant, antioxidants and vitamins (folic acid, group B) in the course of preparation for IVF, in the IVF protocols, during multiple pregnancy and in the postnatal period. Methods: The comparative analysis of 50 women with the physiological course of multiple pregnancy (I group) and at 50 women with pathological course of pregnancy after IVF. Genetic thrombophilia (mutations in genes of factor V, prothrombin, fibrinogen), deficiency of protein C, antithrombin III, hyperhomocysteinemia and APA circulation were evaluated. Results: In healthy women of I group thrombophilia was revealed in 7 women. In the II group different forms of thrombophilia were found in 48 (96%) women: factor V Leiden mutation in 8 (16%), prothrombin gene G20210A in 6 (12%), hyperhomocysteinemia in 17 (34%), APS in 22 (11%). The combined forms of thrombophilia (APA in combination with genetic defects and hyperhomocysteinemia) in 15%. Moderate preeclampsia developed in 34 (17%), placental abruption with antenatal death of both fetuses in 5 women, placental abruption with antenatal death of 1 fetus in 10 women, chorionic abruption at the early terms of pregnancy in 10 women with multiple pregnancy after IVF. Premature birth at term 29–32 weeks took place in 15 women. Thromboses (ileofemoral, jugular veins) in 2 women at the I trimester of pregnancy and in 2 women postnatally. 70 alive babies were born. Fetal losses were associated with antenatal death in 12 women (14 babies). Results showed the pathogenetic role of an initial thrombophilia in the development of complications of multiple pregnancy after IVF. The additional factor is hormonal therapy carried out in the IVF protocols. Conclusions: The conducted research allows to assume the necessity of application of anticoagulant, antioxidant therapy and vitamins from the fertile cycle and during all pregnancy. C0514 INCREASED CIRCULATING PROCOAGULANT MICROPARTICLES ARE ASSOCIATED WITH RECURRENT IMPLANTATION FAILURE AFTER IN VITRO FERTILIZATION AND EMBRYO TRANSFER J.C. Reverter1 , E. Garcia1 , M.A. Martinez-Zamora2 , L. Martin1 , G. Casals2 , J. Monteagudo1 , S. Civico2 , F. Carmona2 , J. Balasch1 , D. Tassies1 . 1 Hospital Clinic, Hemotherapy and Hemostasis Department, Barcelona, Spain; 2 Hospital Clinic, Obstetrics and Neonatology Department, Barcelona, Spain Background: Recurrent implantation failure (RIF) following embryo transfer (ET) is a major problem in in vitro fertilization (IVF) treatments. Women with haemostatic defects may be at increased risk of miscarriage and preclinical pregnancy loss. Microparticles (MP) are small plasma membrane fragments released from activated or apoptoic cells. Increased levels of MP are found in several diseases such as atherosclerosis and inflammatory and autoimmune disorders. MP have procoagulant activity and are able to potentiate coagulation. The aim of this study was to investigate procoagulant MP levels in patients with unexplained RIF.