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C0284 Does a tight fibrin clot in premenopausal women with type 1 diabetes explain the lack of gender difference in cardiovascular disease?
S122
Abstracts / Thrombosis Research 130 (2012) S100–S202
Women's health
C0167 Pregnancy and labor in patients with history of ischemic stroke Alexander Makatsariya, Viktoriya Bitsadze, Dzhamilya Khizroeva, Svetlana Akinshina I.M. Sechenov First Moscow State Medical University, Obstetrics and Gynecology - Zemlyanoi Val, 62, Russia Background: Arterial thrombosis is uncommon in pregnancy but may have devastating consequences. The incidence of ischemic stroke associated with pregnancy is estimated to be about 4.2 to 210 per 100 000 deliveries. Mortality level is very high and is 8-26%. Events occur most frequently in the III trimester of pregnancy or postpartum. Pregnancy is a kind of an essential spontaneous screening test for the risk of early stroke in women and augments the risk of stroke in 3-13%. Methods: We observed 59 patients with history of arterial thrombotic complications and 60 healthy pregnant women. Among 59 women 4 of them had stroke and VTE, 3 had myocardial infarction, 2 patients – acute arterial cerebral thromboembolism and thrombosis of prosthetic heart valves. Some women had history of stroke and ileo-femoral thrombosis and splenic infarction and thrombosis occurred in different other localizations (n = 16, 27.1%) including combination of ischemic stroke and retinal thrombosis, deep vein thrombosis, Takayasu syndrome and renal thrombosis, subclavian artery thrombosis, avascular necrosis of the femoral head and reoccurred cerebral thromboembolism in patients with catastrophic antiphospholipid syndrome. I subgroup consists of 20 patients with history of arterial thrombosis. All these women were enrolled into the study from the fertile cycle or from the beginning of pregnancy andd therapy was started early. II subgroup accepted 17 patients from II or III trimesters of pregnancy and therapy was started after their admission. Thrombosis was associated with pregnancy in 17 women (28.8%). The remaining 22 patients with arterial thrombosis had thromboembolic complications during current pregnancy. All included patients had been examined for the hemostasis system abnormalities. Results: Risk factors included SLE, vasculitis, metabolic syndrome, hypertonic diseases, cardiac arrhythmia, the presence of prosthetic heart valves, inadequate anticoagulant therapy, open foramen ovale, intake of OC, surgery interventions, septic complications, vertebrobasilar abnormalities. The examination demonstrated the high frequency of genetic and acquired froms of thrombophilia and high level of resistance to protein C in patients with arterial thrombotic events. Different forms of thrombophilia were present in 88.2% of patients. Multigenic thrombophilia was recorded in 84,3% of patients, fibrinolytic defects in 76.5% patients, APA in 41.2%, and hyperhomocysteinemia in 19.6%. Comment: The revelation of the multigenic thrombophilia, fibrinolytic defects and APA circulation indicates an essential role of thrombophilia in the genesis of thrombotic complications. Early pathogenic anticoagulant therapy with LMWH, antiaggregant drugs, antioxidants, vitamins group B from the fertile cycle when a women start to plan a pregnancy allows prevent reoccurred thrombotic events, severe obstetric complications and improve perinatal outcomes.
doi:10.1016/j.thromres.2012.08.057
C0284 Does a tight fibrin clot in premenopausal women with type 1 diabetes explain the lack of gender difference in cardiovascular disease? Aleksandra Antovic1, Nils Håkan Wallèn1, Graciela Elgue1, Koteiba Majeed1, Peter Henriksson2, Anna Ågren2, Ulf Adamson1, Per-Eric Lins1, Gun Jörneskog1 1 Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; 2Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Sweden Background: The risk of dying from cardiovascular disease (CVD) before the age of 40 years is markedly increased in subjects with type 1 diabetes mellitus (DM) and even more pronounced in women with type 1 DM compared to those without diabetes. Patients with type 1 DM have a tight and less permeable 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 in these patients. Methods: 232 age and sex matched patients (131 males; age 45 ± 13; diabetes duration 23 ± 15 years) were included. 149 (64%) subjects had retinopathy, while none had any history of CVD. Fibrin clotstructurewas assessed by determination of the permeability coefficient Ks. Turbidimetry clotting/lysis assay was performed to further explore the fibrin polymerization rate, clot density and fibrinolysis. Results: Ks did not differ between men and women with type 1 DM (10.5 ± 4.0 vs 10.9 ± 3.8 cm2x10-9, p = 0.3, respectively), while premenopausal women (b50 years) had as tight fibrin clot as men at the same age (Ks 11.7 ± 4.1 vs11.4 ± 4.2cm2x10-9, respectively, p = 0.3). Furthermore, women with type 1 DM had worse metabolic control (HbA1c 7.2 ± 1.4% vs 6.8 ± 1.2%, p b 0.05) despite a lower BMI (24.1 ± 4.5 vs 25.5 ± 3.6 kg/m2 in men; p b 0.01). No gender differences were found regarding P-fibrinogen levels or other fibrin clot characteristics, even when adjusted for P-fibrinogen. Ks was strongly related to P-fibrinogen (r = −0.6, p b 0.001), HbA1c (r = −0.3; p b 0.0001), age (r = − 0.3; p b 0.001) and S-triglycerides (r = −0.21 p b 0.05) in all patients, with similar correlations in men and women. No significant correlations were seen between Ks and other investigated biochemical variables. In a multivariate analysis including P-fibrinogen, HbA1c, S-triglycerides and age as independent variables, P-fibrinogen was significantly (pb 0.0001) correlated to the dependent variable Ks (r= −0.42). When adjusted for fibrinogen concentration ANCOVA analysis showed that age (pb 0.0001) and HbA1c (pb 0.0001) explained 20% of the remaining variation in Ks. Comment: This is the largest study so far, 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 and a worse metabolic control. This can partly explain why the protective effect of female gender on CVD is abolished in type 1 DM.
doi:0.1016/j.thromres.2012.08.058
C0298 Differential risk factors for pregnancy related deep vein thrombosis and pulmonary embolism' results from a population-based case–control study Astrid Bergrem1, Anders E.A. Dahm2, Anne Flem Jacobsen3, Leiv Sandvik4, Per Morten Sandset1
Abstracts / Thrombosis Research 130 (2012) S100–S202
Women's health
C0167 Pregnancy and labor in patients with history of ischemic stroke Alexander Makatsariya, Viktoriya Bitsadze, Dzhamilya Khizroeva, Svetlana Akinshina I.M. Sechenov First Moscow State Medical University, Obstetrics and Gynecology - Zemlyanoi Val, 62, Russia Background: Arterial thrombosis is uncommon in pregnancy but may have devastating consequences. The incidence of ischemic stroke associated with pregnancy is estimated to be about 4.2 to 210 per 100 000 deliveries. Mortality level is very high and is 8-26%. Events occur most frequently in the III trimester of pregnancy or postpartum. Pregnancy is a kind of an essential spontaneous screening test for the risk of early stroke in women and augments the risk of stroke in 3-13%. Methods: We observed 59 patients with history of arterial thrombotic complications and 60 healthy pregnant women. Among 59 women 4 of them had stroke and VTE, 3 had myocardial infarction, 2 patients – acute arterial cerebral thromboembolism and thrombosis of prosthetic heart valves. Some women had history of stroke and ileo-femoral thrombosis and splenic infarction and thrombosis occurred in different other localizations (n = 16, 27.1%) including combination of ischemic stroke and retinal thrombosis, deep vein thrombosis, Takayasu syndrome and renal thrombosis, subclavian artery thrombosis, avascular necrosis of the femoral head and reoccurred cerebral thromboembolism in patients with catastrophic antiphospholipid syndrome. I subgroup consists of 20 patients with history of arterial thrombosis. All these women were enrolled into the study from the fertile cycle or from the beginning of pregnancy andd therapy was started early. II subgroup accepted 17 patients from II or III trimesters of pregnancy and therapy was started after their admission. Thrombosis was associated with pregnancy in 17 women (28.8%). The remaining 22 patients with arterial thrombosis had thromboembolic complications during current pregnancy. All included patients had been examined for the hemostasis system abnormalities. Results: Risk factors included SLE, vasculitis, metabolic syndrome, hypertonic diseases, cardiac arrhythmia, the presence of prosthetic heart valves, inadequate anticoagulant therapy, open foramen ovale, intake of OC, surgery interventions, septic complications, vertebrobasilar abnormalities. The examination demonstrated the high frequency of genetic and acquired froms of thrombophilia and high level of resistance to protein C in patients with arterial thrombotic events. Different forms of thrombophilia were present in 88.2% of patients. Multigenic thrombophilia was recorded in 84,3% of patients, fibrinolytic defects in 76.5% patients, APA in 41.2%, and hyperhomocysteinemia in 19.6%. Comment: The revelation of the multigenic thrombophilia, fibrinolytic defects and APA circulation indicates an essential role of thrombophilia in the genesis of thrombotic complications. Early pathogenic anticoagulant therapy with LMWH, antiaggregant drugs, antioxidants, vitamins group B from the fertile cycle when a women start to plan a pregnancy allows prevent reoccurred thrombotic events, severe obstetric complications and improve perinatal outcomes.
doi:10.1016/j.thromres.2012.08.057
C0284 Does a tight fibrin clot in premenopausal women with type 1 diabetes explain the lack of gender difference in cardiovascular disease? Aleksandra Antovic1, Nils Håkan Wallèn1, Graciela Elgue1, Koteiba Majeed1, Peter Henriksson2, Anna Ågren2, Ulf Adamson1, Per-Eric Lins1, Gun Jörneskog1 1 Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; 2Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Sweden Background: The risk of dying from cardiovascular disease (CVD) before the age of 40 years is markedly increased in subjects with type 1 diabetes mellitus (DM) and even more pronounced in women with type 1 DM compared to those without diabetes. Patients with type 1 DM have a tight and less permeable 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 in these patients. Methods: 232 age and sex matched patients (131 males; age 45 ± 13; diabetes duration 23 ± 15 years) were included. 149 (64%) subjects had retinopathy, while none had any history of CVD. Fibrin clotstructurewas assessed by determination of the permeability coefficient Ks. Turbidimetry clotting/lysis assay was performed to further explore the fibrin polymerization rate, clot density and fibrinolysis. Results: Ks did not differ between men and women with type 1 DM (10.5 ± 4.0 vs 10.9 ± 3.8 cm2x10-9, p = 0.3, respectively), while premenopausal women (b50 years) had as tight fibrin clot as men at the same age (Ks 11.7 ± 4.1 vs11.4 ± 4.2cm2x10-9, respectively, p = 0.3). Furthermore, women with type 1 DM had worse metabolic control (HbA1c 7.2 ± 1.4% vs 6.8 ± 1.2%, p b 0.05) despite a lower BMI (24.1 ± 4.5 vs 25.5 ± 3.6 kg/m2 in men; p b 0.01). No gender differences were found regarding P-fibrinogen levels or other fibrin clot characteristics, even when adjusted for P-fibrinogen. Ks was strongly related to P-fibrinogen (r = −0.6, p b 0.001), HbA1c (r = −0.3; p b 0.0001), age (r = − 0.3; p b 0.001) and S-triglycerides (r = −0.21 p b 0.05) in all patients, with similar correlations in men and women. No significant correlations were seen between Ks and other investigated biochemical variables. In a multivariate analysis including P-fibrinogen, HbA1c, S-triglycerides and age as independent variables, P-fibrinogen was significantly (pb 0.0001) correlated to the dependent variable Ks (r= −0.42). When adjusted for fibrinogen concentration ANCOVA analysis showed that age (pb 0.0001) and HbA1c (pb 0.0001) explained 20% of the remaining variation in Ks. Comment: This is the largest study so far, 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 and a worse metabolic control. This can partly explain why the protective effect of female gender on CVD is abolished in type 1 DM.
doi:0.1016/j.thromres.2012.08.058
C0298 Differential risk factors for pregnancy related deep vein thrombosis and pulmonary embolism' results from a population-based case–control study Astrid Bergrem1, Anders E.A. Dahm2, Anne Flem Jacobsen3, Leiv Sandvik4, Per Morten Sandset1