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P-059 LMWH in prophylaxis of repeated complications of multiple pregnancy in women with thrombophilia
Abstracts / Thrombosis Research 131, Suppl. 1 (2013) S71–S103
P-055 The circulating endothelial cells level and coronary heart disease in women O. Sirotkina 1,2 , V. Feoktistova 1 , A. Laskovets 1 , I. Leonova 1 , L. Gaykovaya 1 , S. Boldueva 1 , T. Vavilova 1 1 I.I. Mechnikov North-West State Medical University; 2 B.P. Konstantinov Petersburg Nuclear Physics Institute, St-Petersburg, Russia Objectives: The vascular endothelium plays a pivotal role in blood flow regulation, vascular permeability and thrombogenesis. While endothelial dysfunction is a risk factor for cardiovascular diseases. The aim of our study was to investigate the quantity of circulating endothelial cells (CEC) in women with coronary heart disease (CHD) and in healthy controls. Materials and methods: We examined 41 women with CHD (mean age 51±1) and 50 healthy women (mean age 48±2). Level of CEC was determined in venous blood by flow cytometry using a fluorescently-labeled antibodies specific to CD45 and CD146 as a number of nucleate cells with specified size and positive binding to anti-CD146, but negative binding to anti-CD45. Results: Mean level of CEC in controls was 3.84±0.39 cells/ml (0–12 cells/ml) and in group with CHD – 6.71±1.88 cells/ml (1–78 cells/ml). There were no differences in CEC number between studied groups. However, when we selected the menopausal women with CHD the significant differences were found: the level of CEC was 9.45±3.71 cells/ml and 4.10±0.81 cells/ml in menopausal women and menstrual women groups, respectively (p=0.04). There were no significant differences in CEC number between menopausal women and menstrual women in control group. Conclusion: CEC level in women with CHD varied widely, but was significantly higher among menopausal women compared with menstrual.
P-056 Molecular mechanisms and different clinical manifestations of APS D.K. Khizroeva, V.O. Bitsadze, A.D. Makatsariya I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: Recent studies give evidence of a distinct correlation between APS and such complications during pregnancy as fetal loss syndrome, fetal growth retardation syndrome, intrauterine fetal death, abruptio placenta, preeclampsia and recurrent abortions. We determined different manifestations in the APS and assessed whether these clinical situations are due to the presence of antiphospholipid antibodies. Materials and methods: During 2000–2012 we observed more than 836 patients with different obstetric and gynecological complications and APS (recurrent miscarriage, preeclampsia, placental thrombosis, fetal growth retardation, metabolic syndrome, infertility, venous and arterial thrombosis, hypopituitarism Sheehans syndrome, failure of IVF, HRT, oral contraceptives). Results: The presence of autoantibodies to various phospholipids and phospholipid-binding proteins (antibodies to beta-2-glycoprotein I, annexin V, prothrombin and to the antiphospholipid subtypes) has been identified in 64% of cases. In women with history of obstetric complications and circulation of APA fetal loss was found in 33.5% of cases, pre-eclampsia 17.2%, thrombosis and placenta abruption 44%, stroke 2.2%, IVF 35.7%. In 71.5% APS was associated with genetic thrombophilia. Conclusions: The presence of antiphospholipid antibodies rather than any single genetic abnormality appears to signal an increased thromboembolic risk in patients. Treatment (anticoagulants, antioxidants, vitamins group B, folic acid, hepatoprotectors) would be necessary in patients APS and successful pregnancy rates of 70% or more can be achieved with appropriate treatment. Laboratory testing for aPL and antibodies to phospholipidbinding proteins has routinely to be recommended in the patients with suspected thrombophilia and attentive clinical care is required for best outcomes.
P-057 IVF – Genetic and acquired thrombophilia D.K. Khizroeva, V.O. Bitsadze, N. Makatsariya, N. Stuleva I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: IVF failure has recently been associated not only with embryo quality or endometrial receptivity but with thrombophilia.
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Materials and methods: We examined 75 patients after IVF failure. Among them – 55 after repeated IVF, and 20 pregnant women after IVF who received anticoagulant therapy at the period of planning of pregnancy. All of them had complicated obstetric history and venous thrombosis. Control group consisted of 75 healthy pregnant women. All patients were tested for acquired and inherited thrombophilia and hemostasis parameters Results: The prevalence of thrombophilia was found in all 75 patients with IVF failure and consisted 90%. The incidence of genetic thrombophilia was 44.4%. MTHFR mutation was found in 41%, prothrombin gene mutation – 9%, Factor V Leiden mutation – 8%, PAI-I gene polymorphism – 69%, t-PA – 34%. 42.1% had circulation of antiphospholipid antibodies, 47% – anti-b2-GP I antibodies, 24% – anti-annexin V antibodies, and 8% – antibodies to prothrombin. Hyperhomocysteinemia was found in 54%. Multigenic thrombophilia was revealed in 74.6%, combination of genetic thrombophilic mutations and circulation of APA was identified in 57%. All women with pregnancy after IVF who received therapy from the fertile cycle and during all pregnancy (LMWH, antioxidants, aspirin, folic acid, natural progesterone, vitamins group B) were delivered with healthy newborn. Comments:: These data suggest that thrombophilia may play a role in the genesis of IVF failure, especially in cases of multigenic and combined thrombophilia. Since thrombophilia has been diagnosed antithrombotic therapy should be evaluated in patients with thrombophilia and IVF failure.
P-058 Antiphospholipid antibodies and progesterone deficiency D.K. Khizroeva, V.O. Bitsadze, M.D. Andreeva, E. Shakhovskaya I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: As damaging action of antiphospholipid antibodies (aPL) besides thrombotic effects includes throphoblast injury by activated complement, NK cells activation, increase of proinflammatory cytokine production, suppression of hCG production and secondary progesterone insufficiency, the aim of our work was to examine efficiency, safety and influence on pregnancy course and neonatal outcome of natural progesterone therapy for preventing recurrent pregnancy loss (RPL) in patients with antiphospholipid syndrome (APS). Materials and methods: We have observed 105 patients with RPL and APS. Cases were 60 women who besides standart therapy received natural progesterone treatment in doses 400–600 mg daily per vaginally depending on presence or absence clinical signs of threatened abortion since fertile cycle until 20 weeks of gestation. Control group consist of 45 women who received only standart therapy with LMWH and low doses of aspirin. Maternal and fetal outcomes were analyzed. Results: Cases had clinical signs of threatened abortion and preterm delivery rarer (36.4% vs 57.7% vs 15.5%) compared to control. Control group more frequently experienced preeclampsia and uteroplacental deficiency versus cases (15.5% vs 7.3% and 11.1% vs 3.6%). all patients delivered at term. The incidence of caesarean section in cases was 31%, in controls – 35.5%. all babies were of normal weight (3407±266g), but functional tests assessment was higher in cases group. Conclusion: Natural progesterone inclusion in complex therapy of patients with history of RPL associated with APS is pathogenically substantiated. This therapeuric approach results in excellent fetal and maternal outcome. It can be recommended for treatment of patients with APS and RPL and other obstetrical complications.
P-059 LMWH in prophylaxis of repeated complications of multiple pregnancy in women with thrombophilia N. Makatsariya, O. Panfilova, V. Bitsadze I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: Thrombophilia play an important role in obstetric complications, especially in cases of multiple pregnancy. Normal pregnancy is a prothrombotic state and associated with profound alterations in the coagulation and fibrinolytic systems. Materials and methods: We examined 25 patients with multiple pregnancy, thrombophilia and complicated obstetric history. All pregnancies were dichorionic. 13 women were after IVF. These patients were com-
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Abstracts / Thrombosis Research 131, Suppl. 1 (2013) S71–S103
pared with group of 53 women examined retrospectively with multiple pregnancy, thrombophilia (75.4%) and obstetric complications (fetal loss syndrome 45%, antenatal fetal death 30%, IUGR 13%, neonatal death 11%, preeclampsia 60%, severe preeclampsia 8%, abruptio placenta 26%, preterm labor 26%) and did not receive anti-thrombotic therapy. All patients had been examined for the genetic and acquired thrombophilia Results: 40% of patients had circulation of antiphospholipid antibodies, 28% – hyperhomocysteinemia. The incidence of factor V Leiden mutation was 8%, prothrombin gene mutation – 12%. 80% of patients had combined thrombophilia. Anticoagulant therapy was started after first visit to a doctor: 13 women with IVF were cured from preparing to IVF, 8 – from the period of pregnancy planning, 5 – at the beginning of I trimester of pregnancy. All patients received LMWH, folic acid, vitamins B, Omega-3, micronized progesterone. Mild preeclampsia was in 5 patients at term 30–34 weeks of pregnancy. There were no cases of obstetrical complications. Comments: Testing for thrombophilia should be performed in all patients with multiple pregnancy. Since thrombophilia has been diagnosed LMWH therapy and micronized progesterone should be started.
P-060 Prophylaxis of recurrent placental abruptions in multiple pregnancy O. Panfilova, N. Makatsariya Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia Some researches demonstrated the efficiency of anticoagulant treatment in prophylaxis of fetal loss syndrome and placental abruptions in patients with thrombophilia (Gris, 2004), but the question still remains controversial. Materials and methods: Clinical and hemostasiological examination, control of the coagulation parameters. Aims: Evaluation of maternal and fetal outcomes in women with history of abruptio placentae in multiple pregnancy. Method: We analysed 50 cases of pregnancies in patients with history of recurrent placental abruption and thrombophilia in anamnesis All pregnancies were multiple: 30 – after IVF, 20 – physiological multiple pregnancy. All of the patients had inherited or acquired forms of thrombophilia. 18% of the patients had antiphospholipid syndrome, 14% – factor V Leiden mutation, 5% – prothrombin mutation G20210A, 15% – gomozygous forms of polymorphisms, 60% – heterozygous forms of polymorphisms, 35.4% – hyperhomocysteinemia. During preconceptive period and during pregnancy all patients with history of abruption placentae and thrombophilia received treatment with low-molecular-weight heparins under the control of D-dimer, natural progesterone till 24 gestaional weeks, antioxidants, vitamins and folic acid in women with hyperhomocycteinemia. Results: 98% of pregnancies under this treatment were uncomplicated, in all patients caesarean section was performed at 36–37 weeks of gestation, all newborns were alive. Conclusion: Thrombophilia is an important pathogenetic factor of recurrent placental abruption in multiple pregnancy. Treatment with low-molecularweight heparins during preconceptive period, pregnancy and postnatal period is effective in prophylaxis of recurrent placental abruption.
P-061 Biosimilar LMWH Hemapaxan (enoxaparin natrium) in prevention of repeated thromboses at pregnant women with trombophilia V. Bitsadze, O. Panfilova, N. Makatsariya Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: The biosimilar enoxaparin, Hemapaxan, is effective and safe in prevention of repeated thromboses at pregnant women. Materials and methods: We examined 57 patients at the age of 29.4±5.5 years with a history of venous tromboembolism and burdened obstetrical anamnesis. The control group consisted on 60 women with the physiological uncomplicated pregnancy course. Among the patients with tromboembolism 32 patients had deep veins thromboses, 14 – thromboembolism of the pulmonary artery, 11 – thrombosis of atypical localizations (splenic, mesenterial, hepatic, ovarian veins). 82% had burdened obstetrical history
(fetal loss syndrome – in 57%, preeclampsia – in 40%, placental abruption – in 32%). We performed laboratory screening for genetic and acquired thrombophilia. We detected thrombophilic condition in 90% of all cases: in 23.5% – mutation of the factor V Leiden (heterozygous), a prothrombin mutation – in 13.7% (heterozygous). PAI-1 – in 41.2% (homozygous) and in 33.3% – heterozygous. Heterozygous form of MTHFR C677T was found in 52.9%)In 40% of cases hyperhomocysteinemia was detected. Circulation of antiphospholipid cofactors (beta-2 GP-1) was found in 27.5% of patients. Polimorphismes of proinflammatory cytokines were detected in 40% of patients. Both genetic and acquired thrombophilia were detected in 75% of all cases. Results: There was no repeated trombotic complications in patients treated with Hemapaxan. 25 (44%) women were undergone cesarean cection, 32 (56%) women had uncomplicated vaginal delivery. 57 alive newborns were born. Comment: Biosimilar enoxaparin – Hemapaxan – applied in women with repeated thromboses and thrombophilia allowed to prevent repeated thromboses in 100% of cases and improve perinatal outcomes.
P-062 Massive obstetric bleedings and pathology of hemostasis system A.D. Makatsariya Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia The problem of massive obstetric bleedings continues to remain one of the most challenging all over the world. It is the leading reason of maternal mortality worldwide, one of the reasons of disability of patients. Every year more than 150,000 women die because of massive obstetric bleedings (McLintock, 2009). Our personal 25-years experience and the analyse of more than 200 clinical cases allows us to consider that in the absence of rude obstetrical and surgical complications absolut majority of the massive obstetric bleedings are initially coagulopathic, they proceed against a background of undetected coagulopathy. Main risk factors that provoke massive obstetric bleedings are, besides obstetric reasons, hemostasiologic disturbances: 1. (a) Acute forms of DIC; (b) conversion of the chronic form of DIC to the acute or sudden appearance of acute forms – placental abruption, chorioamnionitis, septic shock, heavy preeklampsia, anafilaktoid syndrome of pregnancy (amniotic embolism). 2. The hidden undiagnosed forms of hemorrhagic diathesis – Willebrand disease, thrombocytopathias, taking of medicines influencing on hemostasis, liver diseases (defect of synthesis of coagulation factors and their inhibitors), sudden appearance of inhibitors of coagulation in bloodstream (Factor VIII inhibitor). 3. Absence of adaptive hemostasiological changes that are typical in pregnancy. We suggest that extend laboratory screening for latent coagulopathic disturbances is of high clinical value in correct diagnosis and treatment of massive obstetric bleedings. Mechanical methods of bleeding arrest which are widely used recently cannot be effective without the determination of primary coagulopathic nature of the hemorrhage.
P-063 Clinical significance of detection of genetic and acquired forms of thrombophilia in preoperative period A.V. Vorobiev Faculty of Obstetrics and Gynecology, The First Moscow State Medical Sechenov University, Moscow, Russia Purpose: To define frequency and a spectrum of the congenital and acquired forms of thrombophilia in cancer patients in preoperative period and estimate potential risk of thrombotic complication. Materials and methods: 546 cancer patients before surgery treatment. Group I: 155 cancer patients with thrombotic episodes in the past history. Group II: 391 cancer patients without thrombotic complications in past history. Group III: 137 patients with benign tumors. Results: In group I APA circulation has been found in 55.8%: antibodies to
P-055 The circulating endothelial cells level and coronary heart disease in women O. Sirotkina 1,2 , V. Feoktistova 1 , A. Laskovets 1 , I. Leonova 1 , L. Gaykovaya 1 , S. Boldueva 1 , T. Vavilova 1 1 I.I. Mechnikov North-West State Medical University; 2 B.P. Konstantinov Petersburg Nuclear Physics Institute, St-Petersburg, Russia Objectives: The vascular endothelium plays a pivotal role in blood flow regulation, vascular permeability and thrombogenesis. While endothelial dysfunction is a risk factor for cardiovascular diseases. The aim of our study was to investigate the quantity of circulating endothelial cells (CEC) in women with coronary heart disease (CHD) and in healthy controls. Materials and methods: We examined 41 women with CHD (mean age 51±1) and 50 healthy women (mean age 48±2). Level of CEC was determined in venous blood by flow cytometry using a fluorescently-labeled antibodies specific to CD45 and CD146 as a number of nucleate cells with specified size and positive binding to anti-CD146, but negative binding to anti-CD45. Results: Mean level of CEC in controls was 3.84±0.39 cells/ml (0–12 cells/ml) and in group with CHD – 6.71±1.88 cells/ml (1–78 cells/ml). There were no differences in CEC number between studied groups. However, when we selected the menopausal women with CHD the significant differences were found: the level of CEC was 9.45±3.71 cells/ml and 4.10±0.81 cells/ml in menopausal women and menstrual women groups, respectively (p=0.04). There were no significant differences in CEC number between menopausal women and menstrual women in control group. Conclusion: CEC level in women with CHD varied widely, but was significantly higher among menopausal women compared with menstrual.
P-056 Molecular mechanisms and different clinical manifestations of APS D.K. Khizroeva, V.O. Bitsadze, A.D. Makatsariya I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: Recent studies give evidence of a distinct correlation between APS and such complications during pregnancy as fetal loss syndrome, fetal growth retardation syndrome, intrauterine fetal death, abruptio placenta, preeclampsia and recurrent abortions. We determined different manifestations in the APS and assessed whether these clinical situations are due to the presence of antiphospholipid antibodies. Materials and methods: During 2000–2012 we observed more than 836 patients with different obstetric and gynecological complications and APS (recurrent miscarriage, preeclampsia, placental thrombosis, fetal growth retardation, metabolic syndrome, infertility, venous and arterial thrombosis, hypopituitarism Sheehans syndrome, failure of IVF, HRT, oral contraceptives). Results: The presence of autoantibodies to various phospholipids and phospholipid-binding proteins (antibodies to beta-2-glycoprotein I, annexin V, prothrombin and to the antiphospholipid subtypes) has been identified in 64% of cases. In women with history of obstetric complications and circulation of APA fetal loss was found in 33.5% of cases, pre-eclampsia 17.2%, thrombosis and placenta abruption 44%, stroke 2.2%, IVF 35.7%. In 71.5% APS was associated with genetic thrombophilia. Conclusions: The presence of antiphospholipid antibodies rather than any single genetic abnormality appears to signal an increased thromboembolic risk in patients. Treatment (anticoagulants, antioxidants, vitamins group B, folic acid, hepatoprotectors) would be necessary in patients APS and successful pregnancy rates of 70% or more can be achieved with appropriate treatment. Laboratory testing for aPL and antibodies to phospholipidbinding proteins has routinely to be recommended in the patients with suspected thrombophilia and attentive clinical care is required for best outcomes.
P-057 IVF – Genetic and acquired thrombophilia D.K. Khizroeva, V.O. Bitsadze, N. Makatsariya, N. Stuleva I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: IVF failure has recently been associated not only with embryo quality or endometrial receptivity but with thrombophilia.
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Materials and methods: We examined 75 patients after IVF failure. Among them – 55 after repeated IVF, and 20 pregnant women after IVF who received anticoagulant therapy at the period of planning of pregnancy. All of them had complicated obstetric history and venous thrombosis. Control group consisted of 75 healthy pregnant women. All patients were tested for acquired and inherited thrombophilia and hemostasis parameters Results: The prevalence of thrombophilia was found in all 75 patients with IVF failure and consisted 90%. The incidence of genetic thrombophilia was 44.4%. MTHFR mutation was found in 41%, prothrombin gene mutation – 9%, Factor V Leiden mutation – 8%, PAI-I gene polymorphism – 69%, t-PA – 34%. 42.1% had circulation of antiphospholipid antibodies, 47% – anti-b2-GP I antibodies, 24% – anti-annexin V antibodies, and 8% – antibodies to prothrombin. Hyperhomocysteinemia was found in 54%. Multigenic thrombophilia was revealed in 74.6%, combination of genetic thrombophilic mutations and circulation of APA was identified in 57%. All women with pregnancy after IVF who received therapy from the fertile cycle and during all pregnancy (LMWH, antioxidants, aspirin, folic acid, natural progesterone, vitamins group B) were delivered with healthy newborn. Comments:: These data suggest that thrombophilia may play a role in the genesis of IVF failure, especially in cases of multigenic and combined thrombophilia. Since thrombophilia has been diagnosed antithrombotic therapy should be evaluated in patients with thrombophilia and IVF failure.
P-058 Antiphospholipid antibodies and progesterone deficiency D.K. Khizroeva, V.O. Bitsadze, M.D. Andreeva, E. Shakhovskaya I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: As damaging action of antiphospholipid antibodies (aPL) besides thrombotic effects includes throphoblast injury by activated complement, NK cells activation, increase of proinflammatory cytokine production, suppression of hCG production and secondary progesterone insufficiency, the aim of our work was to examine efficiency, safety and influence on pregnancy course and neonatal outcome of natural progesterone therapy for preventing recurrent pregnancy loss (RPL) in patients with antiphospholipid syndrome (APS). Materials and methods: We have observed 105 patients with RPL and APS. Cases were 60 women who besides standart therapy received natural progesterone treatment in doses 400–600 mg daily per vaginally depending on presence or absence clinical signs of threatened abortion since fertile cycle until 20 weeks of gestation. Control group consist of 45 women who received only standart therapy with LMWH and low doses of aspirin. Maternal and fetal outcomes were analyzed. Results: Cases had clinical signs of threatened abortion and preterm delivery rarer (36.4% vs 57.7% vs 15.5%) compared to control. Control group more frequently experienced preeclampsia and uteroplacental deficiency versus cases (15.5% vs 7.3% and 11.1% vs 3.6%). all patients delivered at term. The incidence of caesarean section in cases was 31%, in controls – 35.5%. all babies were of normal weight (3407±266g), but functional tests assessment was higher in cases group. Conclusion: Natural progesterone inclusion in complex therapy of patients with history of RPL associated with APS is pathogenically substantiated. This therapeuric approach results in excellent fetal and maternal outcome. It can be recommended for treatment of patients with APS and RPL and other obstetrical complications.
P-059 LMWH in prophylaxis of repeated complications of multiple pregnancy in women with thrombophilia N. Makatsariya, O. Panfilova, V. Bitsadze I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: Thrombophilia play an important role in obstetric complications, especially in cases of multiple pregnancy. Normal pregnancy is a prothrombotic state and associated with profound alterations in the coagulation and fibrinolytic systems. Materials and methods: We examined 25 patients with multiple pregnancy, thrombophilia and complicated obstetric history. All pregnancies were dichorionic. 13 women were after IVF. These patients were com-
S92
Abstracts / Thrombosis Research 131, Suppl. 1 (2013) S71–S103
pared with group of 53 women examined retrospectively with multiple pregnancy, thrombophilia (75.4%) and obstetric complications (fetal loss syndrome 45%, antenatal fetal death 30%, IUGR 13%, neonatal death 11%, preeclampsia 60%, severe preeclampsia 8%, abruptio placenta 26%, preterm labor 26%) and did not receive anti-thrombotic therapy. All patients had been examined for the genetic and acquired thrombophilia Results: 40% of patients had circulation of antiphospholipid antibodies, 28% – hyperhomocysteinemia. The incidence of factor V Leiden mutation was 8%, prothrombin gene mutation – 12%. 80% of patients had combined thrombophilia. Anticoagulant therapy was started after first visit to a doctor: 13 women with IVF were cured from preparing to IVF, 8 – from the period of pregnancy planning, 5 – at the beginning of I trimester of pregnancy. All patients received LMWH, folic acid, vitamins B, Omega-3, micronized progesterone. Mild preeclampsia was in 5 patients at term 30–34 weeks of pregnancy. There were no cases of obstetrical complications. Comments: Testing for thrombophilia should be performed in all patients with multiple pregnancy. Since thrombophilia has been diagnosed LMWH therapy and micronized progesterone should be started.
P-060 Prophylaxis of recurrent placental abruptions in multiple pregnancy O. Panfilova, N. Makatsariya Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia Some researches demonstrated the efficiency of anticoagulant treatment in prophylaxis of fetal loss syndrome and placental abruptions in patients with thrombophilia (Gris, 2004), but the question still remains controversial. Materials and methods: Clinical and hemostasiological examination, control of the coagulation parameters. Aims: Evaluation of maternal and fetal outcomes in women with history of abruptio placentae in multiple pregnancy. Method: We analysed 50 cases of pregnancies in patients with history of recurrent placental abruption and thrombophilia in anamnesis All pregnancies were multiple: 30 – after IVF, 20 – physiological multiple pregnancy. All of the patients had inherited or acquired forms of thrombophilia. 18% of the patients had antiphospholipid syndrome, 14% – factor V Leiden mutation, 5% – prothrombin mutation G20210A, 15% – gomozygous forms of polymorphisms, 60% – heterozygous forms of polymorphisms, 35.4% – hyperhomocysteinemia. During preconceptive period and during pregnancy all patients with history of abruption placentae and thrombophilia received treatment with low-molecular-weight heparins under the control of D-dimer, natural progesterone till 24 gestaional weeks, antioxidants, vitamins and folic acid in women with hyperhomocycteinemia. Results: 98% of pregnancies under this treatment were uncomplicated, in all patients caesarean section was performed at 36–37 weeks of gestation, all newborns were alive. Conclusion: Thrombophilia is an important pathogenetic factor of recurrent placental abruption in multiple pregnancy. Treatment with low-molecularweight heparins during preconceptive period, pregnancy and postnatal period is effective in prophylaxis of recurrent placental abruption.
P-061 Biosimilar LMWH Hemapaxan (enoxaparin natrium) in prevention of repeated thromboses at pregnant women with trombophilia V. Bitsadze, O. Panfilova, N. Makatsariya Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: The biosimilar enoxaparin, Hemapaxan, is effective and safe in prevention of repeated thromboses at pregnant women. Materials and methods: We examined 57 patients at the age of 29.4±5.5 years with a history of venous tromboembolism and burdened obstetrical anamnesis. The control group consisted on 60 women with the physiological uncomplicated pregnancy course. Among the patients with tromboembolism 32 patients had deep veins thromboses, 14 – thromboembolism of the pulmonary artery, 11 – thrombosis of atypical localizations (splenic, mesenterial, hepatic, ovarian veins). 82% had burdened obstetrical history
(fetal loss syndrome – in 57%, preeclampsia – in 40%, placental abruption – in 32%). We performed laboratory screening for genetic and acquired thrombophilia. We detected thrombophilic condition in 90% of all cases: in 23.5% – mutation of the factor V Leiden (heterozygous), a prothrombin mutation – in 13.7% (heterozygous). PAI-1 – in 41.2% (homozygous) and in 33.3% – heterozygous. Heterozygous form of MTHFR C677T was found in 52.9%)In 40% of cases hyperhomocysteinemia was detected. Circulation of antiphospholipid cofactors (beta-2 GP-1) was found in 27.5% of patients. Polimorphismes of proinflammatory cytokines were detected in 40% of patients. Both genetic and acquired thrombophilia were detected in 75% of all cases. Results: There was no repeated trombotic complications in patients treated with Hemapaxan. 25 (44%) women were undergone cesarean cection, 32 (56%) women had uncomplicated vaginal delivery. 57 alive newborns were born. Comment: Biosimilar enoxaparin – Hemapaxan – applied in women with repeated thromboses and thrombophilia allowed to prevent repeated thromboses in 100% of cases and improve perinatal outcomes.
P-062 Massive obstetric bleedings and pathology of hemostasis system A.D. Makatsariya Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia The problem of massive obstetric bleedings continues to remain one of the most challenging all over the world. It is the leading reason of maternal mortality worldwide, one of the reasons of disability of patients. Every year more than 150,000 women die because of massive obstetric bleedings (McLintock, 2009). Our personal 25-years experience and the analyse of more than 200 clinical cases allows us to consider that in the absence of rude obstetrical and surgical complications absolut majority of the massive obstetric bleedings are initially coagulopathic, they proceed against a background of undetected coagulopathy. Main risk factors that provoke massive obstetric bleedings are, besides obstetric reasons, hemostasiologic disturbances: 1. (a) Acute forms of DIC; (b) conversion of the chronic form of DIC to the acute or sudden appearance of acute forms – placental abruption, chorioamnionitis, septic shock, heavy preeklampsia, anafilaktoid syndrome of pregnancy (amniotic embolism). 2. The hidden undiagnosed forms of hemorrhagic diathesis – Willebrand disease, thrombocytopathias, taking of medicines influencing on hemostasis, liver diseases (defect of synthesis of coagulation factors and their inhibitors), sudden appearance of inhibitors of coagulation in bloodstream (Factor VIII inhibitor). 3. Absence of adaptive hemostasiological changes that are typical in pregnancy. We suggest that extend laboratory screening for latent coagulopathic disturbances is of high clinical value in correct diagnosis and treatment of massive obstetric bleedings. Mechanical methods of bleeding arrest which are widely used recently cannot be effective without the determination of primary coagulopathic nature of the hemorrhage.
P-063 Clinical significance of detection of genetic and acquired forms of thrombophilia in preoperative period A.V. Vorobiev Faculty of Obstetrics and Gynecology, The First Moscow State Medical Sechenov University, Moscow, Russia Purpose: To define frequency and a spectrum of the congenital and acquired forms of thrombophilia in cancer patients in preoperative period and estimate potential risk of thrombotic complication. Materials and methods: 546 cancer patients before surgery treatment. Group I: 155 cancer patients with thrombotic episodes in the past history. Group II: 391 cancer patients without thrombotic complications in past history. Group III: 137 patients with benign tumors. Results: In group I APA circulation has been found in 55.8%: antibodies to