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OC-04 Gender aspects of fibrin clot structure in patients with type 1 diabetes mellitus
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Abstracts / Thrombosis Research 131, Suppl. 1 (2013) S71–S103
OC-04 Gender aspects of fibrin clot structure in patients with type 1 diabetes mellitus
OC-06 Effects of low-molecular-weight heparin within the Uteroplacental Unit
S. Tehrani 1 , N.H. Wallen 1 , G. Elgue 1 , K. Majeed 1 , P. Henriksson 2 , A. Ågren 3 , U. Adamson 1 , P.-E. Lins 1 , G. Jörneskog 1 , A. Antovic 1 1 Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; 2 Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital; 3 Coagulation Unit, Haematology Centre, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
S.K. Ismail 1 , L. Norris 2 , L. Kelly 1 , J.R. Higgins 1 1 1Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland; 2 Coagulation Research Laboratory, Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James’ Hospital, Dublin 8, Ireland
Background: Mortality rate from cardiovascular disease (CVD) before the age of 40 years is increased in type 1 diabetes mellitus (DM), especially in women.Patients with type 1 DM have tighter fibrin clot associated with CVD. Aim: To investigate fibrin clot structure in patients with type 1 DM in relation to gender as well as to other risk factors of importance for development of CVD. Material and methods: 232 age and sex matched patients (age 45±13; diabetes duration 23±15 years) (101 females) without history of CVD were included. Fibrin clot structure was assessed by determination of the permeability coefficient Ks. Results: Ks did not differ between men and women with type 1 DM (10.5±4.0 vs 10.9±3.8 cm2 ×10−9 , p=0.3, respectively), while premenopausal women (<50 years) had as tight fibrin clot as men at the same age (Ks 11.7±4.1 vs 11.4±4.2 cm2 ×10−9 , respectively, p=0.3). Ks was strongly related to P-fibrinogen (r=−0.6, p<0.001), HbA1c (r=−0.3; p<0.0001), age (r=−0.3; p<0.001) and S-triglycerides (r=−0.21 p<0.05) in all patients, with similar correlations in men and women. In a multivariate analysis including P-fibrinogen, HbA1c, S-triglycerides and age as independent variables, P-fibrinogen was significantly (p<0.0001) correlated to the dependent variable Ks (r=−0.42). When adjusted for fibrinogen concentration ANCOVA analysis showed that age (p<0.0001) and HbA1c (p<0.0001) explained 20% of the remaining variation in Ks. Comment: To the best of our knowledge this is this is the largest study investigating gender differences in fibrin clot properties in patients with type 1 DM. Premenopausal women with type 1 DM have as tight fibrin clot as men at the same age. This can partly explain why the protective effect of female gender on CVD is abolished in type 1 DM.
OC-05 Pregnancy and labour in patients with history of arterial thrombosis A.D. Makatsariya, V.O. Bitsadze, S.V. Akinshina, D.K. Khizroeva, Z.K. Gadaeva I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: Arterial thrombosis is a rare event, however, when it occurs especially during pregnancy, may have devastating consequence, is life threatening and there may be implications for management of the patient and delivery. Materials and methods: we observed 67 patients with history of arterial thrombotic complications and 60 healthy pregnant women. 1st subgroup – 20 patients with history of arterial thrombosis and all of them were enrolled into the study from the fertile cycle or from the beginning of pregnancy. 2nd – 17 patients who applied from the II or III trimesters and therapy was started after their admission. Results: Analysis of risk factors in patients showed that stroke was associated with severe medical conditions: hypertension (27.1%), metabolic syndrome (37.3%), systemic diseases (16.7%), the presence of prosthetic valves (6.8%), inadequate anticoagulation, past history of thromboembolic complications (21.7%), oral contraceptive use (3.4%), septic complications and others. Thrombophilia was detected in 88.2%, including fibrinolysis defects – 76.5%, FV Leiden (+/−) – 21.6% prothrombin +/− 11.7%, MTHFR 29.4%, APA – 41.2%, hyperhomocysteinemia – 19%. The treatment during the pregnancy was LMWH, antioxidants, folic acid,vitamins B, aspirin in patients with APS and platelet hyperactivity, natural progesterone. Most of the patients were delivered via caesarean section. All patients were delivered at term and all babies were alive. In the second group moderate to severe obstetrics complications were noted. Conclusion: in women with the history of arterial thrombosis who received therapy from the fertile cycle/I trimester there were no cases of severe obstetric complications. In group of women who got treatment from II/III trimesters there was high frequency of obstetric complications.
Background: Perturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications in thrombophilic women. Low-molecular-weight heparin (LMWH) may be effective in altering local thrombin production in the uteroplacental compartment. Aim: We determined the effects of LMWH (tinzaparin) on the peripheral, uteroplacental and fetal circulation and on haemostatic gene and antigen expression in placental tissue. Method: Eight women on antenatal LMWH prophylaxis (tinzaparin 75 IU/kg) due to moderate risk of VTE undergoing caesarean section (CS) and a control group of 15 healthy pregnant women undergoing CS had venous blood taken from the peripheral and uterine vein before delivery of placenta. Simultaneously, cord venous blood and placental biopsy was collected. Tissue factor pathway inhibitor (TFPI), thrombin antithrombin (TAT) and endogenous thrombin potential (ETP) were measured. Real-time PCR and ELISA were used to quantify mRNA and protein expression of TFPI and TF in placental tissue. Results: TAT levels within uterine vein are significantly higher compared to maternal peripheral circulation in both the control group (P<0.0001) and LMWH group (P<0.02). In the LMWH group, TAT is reduced compared with controls in the uterine vein (P<0.001).ETP and TFPI within uterine circulation is reduced significantly in the LMWH group (P<0.05) and (P<0.02) respectively. Down-regulation of placental TFPI and TFPI2 mRNA expression was also found (p<0.05). Placental TF mRNA expression in LMWH group showed a non significant increase compared to control and this is replicated in placental TF antigen expression. Conclusion: TAT is reduced in uteroplacental circulation in thrombophilic women on LMWH prophylaxis and this is mirrored by decreased ETP in uteroplacental circulation. LMWH may be effective in reducing in-vivo thrombin production in the uteroplacental circulation of thrombophilic women.
OC-07 Inhibitor of PAI-1 prevents abortion in CBA/J x DBA/2 mice model M. Odeh 1,2 , S.B. Haroush 1 , E. Palzur 3 , A.A.-R. Higazi 4 , J. Bornstein 1,2 1 Department of Obstetrics and Gynecology, Western Galilee Hospital, Nahariya and 2 Bar Ilan Univesity, Galilee Faculty of Medicine, Safed; 3 Eliachar Research Laboratory, Western Galilee Hospital, Nahariya; 4 Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem, Israel Background: Hypercoagulability plays an important role in recurrent abortion. A plasminogen activator inhibitor (PAI-1) antagonist was developed that binds to tissue Plasminogen activator (tPA) and inhibits its interaction with PAI-1, thereby increasing fibrinolysis. Our purpose in this study is to examine if PAI-1 antagonist administration in recurrent abortion in mice model of CBA/J (Females) X DBA/2 (Males) mating reduces abortion rate. Methods: CBA/J female and DBA/2 male mice (purchased from Harlan Laboratories, Israel) were mated. Pregnancy day 0.5 was determined by the presence of a vaginal plug. CBA/J pregnant mice were euthanized on day 14.5. Resorbed and normal fetoplacental units were scored and the proportion of resorbed fetuses was evaluated: R% = 100 Re/(Re+F) (Re: the number of resorbed embryos; F: the number of viable ones). The control group consisted of two subgroups: group1a non-treated pregnant mice, group 1b was treated by an intra-peritoneal injection of saline and the study group (group2) was treated twice daily with an intra-peritoneal injection of the antagonist (1mg/kg). Results: The R% in group 1a (8 mice) was 29.1% (16 out of 55). In group 1b (6 mice) the R% was 28.9% (11 out of 38). The combined R% in the 2 control groups 1a and 1b was 29.0% (27out of 93). In group 2 (8 mice) the R% was 14.5% (8 out of 55). The difference was statistically significant (P=0.041). Conclusions: The administration of the antagonist significantly reduced the abortion rate in mice model. This treatment modality may in the future be applied to humans.
Abstracts / Thrombosis Research 131, Suppl. 1 (2013) S71–S103
OC-04 Gender aspects of fibrin clot structure in patients with type 1 diabetes mellitus
OC-06 Effects of low-molecular-weight heparin within the Uteroplacental Unit
S. Tehrani 1 , N.H. Wallen 1 , G. Elgue 1 , K. Majeed 1 , P. Henriksson 2 , A. Ågren 3 , U. Adamson 1 , P.-E. Lins 1 , G. Jörneskog 1 , A. Antovic 1 1 Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; 2 Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital; 3 Coagulation Unit, Haematology Centre, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
S.K. Ismail 1 , L. Norris 2 , L. Kelly 1 , J.R. Higgins 1 1 1Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland; 2 Coagulation Research Laboratory, Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James’ Hospital, Dublin 8, Ireland
Background: Mortality rate from cardiovascular disease (CVD) before the age of 40 years is increased in type 1 diabetes mellitus (DM), especially in women.Patients with type 1 DM have tighter fibrin clot associated with CVD. Aim: To investigate fibrin clot structure in patients with type 1 DM in relation to gender as well as to other risk factors of importance for development of CVD. Material and methods: 232 age and sex matched patients (age 45±13; diabetes duration 23±15 years) (101 females) without history of CVD were included. Fibrin clot structure was assessed by determination of the permeability coefficient Ks. Results: Ks did not differ between men and women with type 1 DM (10.5±4.0 vs 10.9±3.8 cm2 ×10−9 , p=0.3, respectively), while premenopausal women (<50 years) had as tight fibrin clot as men at the same age (Ks 11.7±4.1 vs 11.4±4.2 cm2 ×10−9 , respectively, p=0.3). Ks was strongly related to P-fibrinogen (r=−0.6, p<0.001), HbA1c (r=−0.3; p<0.0001), age (r=−0.3; p<0.001) and S-triglycerides (r=−0.21 p<0.05) in all patients, with similar correlations in men and women. In a multivariate analysis including P-fibrinogen, HbA1c, S-triglycerides and age as independent variables, P-fibrinogen was significantly (p<0.0001) correlated to the dependent variable Ks (r=−0.42). When adjusted for fibrinogen concentration ANCOVA analysis showed that age (p<0.0001) and HbA1c (p<0.0001) explained 20% of the remaining variation in Ks. Comment: To the best of our knowledge this is this is the largest study investigating gender differences in fibrin clot properties in patients with type 1 DM. Premenopausal women with type 1 DM have as tight fibrin clot as men at the same age. This can partly explain why the protective effect of female gender on CVD is abolished in type 1 DM.
OC-05 Pregnancy and labour in patients with history of arterial thrombosis A.D. Makatsariya, V.O. Bitsadze, S.V. Akinshina, D.K. Khizroeva, Z.K. Gadaeva I.M. Sechenov First Moscow State Medical University, Moscow, Russia Background: Arterial thrombosis is a rare event, however, when it occurs especially during pregnancy, may have devastating consequence, is life threatening and there may be implications for management of the patient and delivery. Materials and methods: we observed 67 patients with history of arterial thrombotic complications and 60 healthy pregnant women. 1st subgroup – 20 patients with history of arterial thrombosis and all of them were enrolled into the study from the fertile cycle or from the beginning of pregnancy. 2nd – 17 patients who applied from the II or III trimesters and therapy was started after their admission. Results: Analysis of risk factors in patients showed that stroke was associated with severe medical conditions: hypertension (27.1%), metabolic syndrome (37.3%), systemic diseases (16.7%), the presence of prosthetic valves (6.8%), inadequate anticoagulation, past history of thromboembolic complications (21.7%), oral contraceptive use (3.4%), septic complications and others. Thrombophilia was detected in 88.2%, including fibrinolysis defects – 76.5%, FV Leiden (+/−) – 21.6% prothrombin +/− 11.7%, MTHFR 29.4%, APA – 41.2%, hyperhomocysteinemia – 19%. The treatment during the pregnancy was LMWH, antioxidants, folic acid,vitamins B, aspirin in patients with APS and platelet hyperactivity, natural progesterone. Most of the patients were delivered via caesarean section. All patients were delivered at term and all babies were alive. In the second group moderate to severe obstetrics complications were noted. Conclusion: in women with the history of arterial thrombosis who received therapy from the fertile cycle/I trimester there were no cases of severe obstetric complications. In group of women who got treatment from II/III trimesters there was high frequency of obstetric complications.
Background: Perturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications in thrombophilic women. Low-molecular-weight heparin (LMWH) may be effective in altering local thrombin production in the uteroplacental compartment. Aim: We determined the effects of LMWH (tinzaparin) on the peripheral, uteroplacental and fetal circulation and on haemostatic gene and antigen expression in placental tissue. Method: Eight women on antenatal LMWH prophylaxis (tinzaparin 75 IU/kg) due to moderate risk of VTE undergoing caesarean section (CS) and a control group of 15 healthy pregnant women undergoing CS had venous blood taken from the peripheral and uterine vein before delivery of placenta. Simultaneously, cord venous blood and placental biopsy was collected. Tissue factor pathway inhibitor (TFPI), thrombin antithrombin (TAT) and endogenous thrombin potential (ETP) were measured. Real-time PCR and ELISA were used to quantify mRNA and protein expression of TFPI and TF in placental tissue. Results: TAT levels within uterine vein are significantly higher compared to maternal peripheral circulation in both the control group (P<0.0001) and LMWH group (P<0.02). In the LMWH group, TAT is reduced compared with controls in the uterine vein (P<0.001).ETP and TFPI within uterine circulation is reduced significantly in the LMWH group (P<0.05) and (P<0.02) respectively. Down-regulation of placental TFPI and TFPI2 mRNA expression was also found (p<0.05). Placental TF mRNA expression in LMWH group showed a non significant increase compared to control and this is replicated in placental TF antigen expression. Conclusion: TAT is reduced in uteroplacental circulation in thrombophilic women on LMWH prophylaxis and this is mirrored by decreased ETP in uteroplacental circulation. LMWH may be effective in reducing in-vivo thrombin production in the uteroplacental circulation of thrombophilic women.
OC-07 Inhibitor of PAI-1 prevents abortion in CBA/J x DBA/2 mice model M. Odeh 1,2 , S.B. Haroush 1 , E. Palzur 3 , A.A.-R. Higazi 4 , J. Bornstein 1,2 1 Department of Obstetrics and Gynecology, Western Galilee Hospital, Nahariya and 2 Bar Ilan Univesity, Galilee Faculty of Medicine, Safed; 3 Eliachar Research Laboratory, Western Galilee Hospital, Nahariya; 4 Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem, Israel Background: Hypercoagulability plays an important role in recurrent abortion. A plasminogen activator inhibitor (PAI-1) antagonist was developed that binds to tissue Plasminogen activator (tPA) and inhibits its interaction with PAI-1, thereby increasing fibrinolysis. Our purpose in this study is to examine if PAI-1 antagonist administration in recurrent abortion in mice model of CBA/J (Females) X DBA/2 (Males) mating reduces abortion rate. Methods: CBA/J female and DBA/2 male mice (purchased from Harlan Laboratories, Israel) were mated. Pregnancy day 0.5 was determined by the presence of a vaginal plug. CBA/J pregnant mice were euthanized on day 14.5. Resorbed and normal fetoplacental units were scored and the proportion of resorbed fetuses was evaluated: R% = 100 Re/(Re+F) (Re: the number of resorbed embryos; F: the number of viable ones). The control group consisted of two subgroups: group1a non-treated pregnant mice, group 1b was treated by an intra-peritoneal injection of saline and the study group (group2) was treated twice daily with an intra-peritoneal injection of the antagonist (1mg/kg). Results: The R% in group 1a (8 mice) was 29.1% (16 out of 55). In group 1b (6 mice) the R% was 28.9% (11 out of 38). The combined R% in the 2 control groups 1a and 1b was 29.0% (27out of 93). In group 2 (8 mice) the R% was 14.5% (8 out of 55). The difference was statistically significant (P=0.041). Conclusions: The administration of the antagonist significantly reduced the abortion rate in mice model. This treatment modality may in the future be applied to humans.