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P-032 Selected aspects of the antithrombotic prophylaxis in pregnant women with congenital thrombophilias
Abstracts / Thrombosis Research 131, Suppl. 1 (2013) S71–S103
Methods: 810 pregnant women with higher risk for VTE were included in the ETHiG study. 560 women had miscarriages in the history. The risk stratification in 3 groups was done according to Bauersachs et al. [1]: 225 low-risk patients, 469 high-risk patients, 116 very high-risk patients. Risk factors for early and late losses as well stillbirth were analysed. Results: In this risk population maternal age was no risk factor for nonrecurrent miscarriage but for recurrent pregnancy loss (RPL) (RR 2.41 [1.73–3.37] for age > 35 years). A thrombophilia was to detect in 59% of all pregnancies. VTE risk stratification was not associated with the history of pregnancy losses. Conclusion: The elevated VTE risk alone is not associated with higher risks for a pregnancy loss. Thrombophilic risks for thrombembolic events underlie possible an other pathopyhsiological regulation as their association to pregnancy complications. References: [1] Bauersachs et al. Thromb Haemost 2007; 98: 1237–1245.
P-032 Selected aspects of the antithrombotic prophylaxis in pregnant women with congenital thrombophilias T. Kvasniˇcka Thrombotic Center, General Teaching Hospital, Prague, Czech republic Venous thromboembolism (VTE) is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Women with a prior VTE, a family history of VTE, certain clinical risk factors and thrombophilia are at considerably increased risk for pregnancyrelated. Heritable thrombophilias are also important co-determinants of VTE risk in pregnancy. The mechanisms through which pregnancy and hormonal therapies increase VTE risk have not been definitively established, but hormonal effects on levels of coagulation and anticoagulation factors likely play a role. Venous compression and injury also contribute to increased risk during pregnancy and the puerperium. Antithrombotic prophylaxis during pregnancy are mainly based on low-molecular-weight heparin (LMWH). This paper discusses, on the set of pregnant women (n=2039) observed in Thrombotic Center, General Teaching Hospital in Prague, Czech republic, with several gene mutations (A→G5O6 mutation of factor V, n=759, 39% and G→20210 polymorphism of prothrombin, n=259, 12.7%) the indications, times and modalities for the use of LMWH, during pregnancy (puerperium), together with their side-effects, and maternal and fetal contraindications. Conclusions: Subcutaneous LMWHs have a growing role in prophylaxis and treatment of VTE during pregnancy. They are safe, can be administered during breastfeeding and a single-day administration for VTE prophylaxis is effective. Actually, some agreement exists about LMWH treatment in “very high” and “high” thrombotic risk pregnant women. Only preliminary data are available about “moderate” and “low” thrombotic risk pregnant women.
P-033 Sex specific risk factors for VTE recurrence. Long term follow-up, analysis of a single cohort of patients D. Theocharidou, E. Papadakis, A. Banti, A. Karagianni, V. Papageorgiou, V. Papadopoulos, K. Tsimirika, S. Efraimidou, G. Kaltsounis, E. Georgiou, A. Kioumi Hemostasis Unit-Hematology Dept, Papageorgiou Hospital, Thessaloniki, Greece Objectives: Individual risk of recurrent VTE affects patient’s management and might differ among men and women, as long as men have about 50% higher risk of recurrent VTE than women. However, the cofounding factors of this event still remain to be clarified. The aim of this study is to evaluate whether there are gender related risk factors of VTE recurrence. Methods: To achieve this goal among 346 patients, who had already had an episode of TE, we evaluated 194 patients: 86 (44.3%) men and 108 (55.7%) women with a mean age of 40.10 years, who met the following criteria 1. Didn’t receive at first indefinite anticoagulation 2. Had at least completed 2 years of follow up after discontinuation of anticoagulation 3. Continued their follow up at our clinic. Based on previously published data we tried to define whether the fol-
S85
lowing variables are high risk factors for VTE recurrence in our male and female populations: age of diagnosis, thrombophilic factors (FVLeiden, FII, HCY, VIII, AT, PrC, PrS, PAI1, Lp(a), XII), the presence of unprovoked VTE episode and VTE location (DVT, PE, CNS Thrombosis). Women who developed peripartum and hormone related VTE were not included at the unprovoked VTE group. Results: Table 1 shows the number of episodes the patients suffered in relation to their gender. Men showed statistically significantly higher relapse rates in correlation to women, p=0.038. Moreover, development of an unprovoked VTE episode, FVLeiden homozygous p=0.036 and VTE location (CNS has the lowest risk of recurrence) showed statistical significant relation to VTE recurrence at the whole population, p=0.029, 0.036, 0.05 respectively. Moreover, men and women, who developed provoked VTE (surgery, travel, or pregnancy related etc) didn’t show any significant difference concerning their recurrence rates. Focusing on female gender, 23 women developed peripartum thrombosis and 21 during hormonal therapy. On a univariate model high levels of Lp(a), presence of AFS and FVLeiden homozygous showed to be strongly associated to VTE recurrence p=0.020, 0.014 and 0.050, respectively. Moreover, CNS thrombosis shows to have negative association to recurrence p=0.001. AFS and FV Leiden homozygous positive and CNS negative association to VTE recurrence were also confirmed on a multivariable model p=0.01, 0.022 and 0.007, respectively. Focusing on relapsing population, there has been no significant difference among mean diagnosis age of men (42.93 years) and women (37.97 years). Table 1. VTE episodes and gender No. of episodes 1 2 3
≥4
Men (%)
Women (%)
Sum
44 (38.60) 33 (55.93) 7 (43.75) 2 (40)
70 (61.40) 26 (44.07) 9 (56.25) 3 (60)
114 59 16 5
Conclusions: All hypotheses that have been proposed to explain this discrepancy between men and women at recurrence rates are under debate. For example, we hereby do not present any significant difference among men and women concerning the age of primary VTE episode. Furthermore, comparative studies reveal more possible explanations. Nevertheless, gender should be taken into account for risk stratification of VTE recurrence, given the lately supported facts that men have 50% higher risk of recurrence and women are more prone to bleeding disorders during anticoagulation.
P-034 Clinical characteristics of the first thrombosis process among young women and those over 45 years M. Kovac 1,2 , G. Mitic 3 , Z. Mikovic 4 , V. Mandic 4 , L. Rakicevic 5 , V. Djordjevic 5 , D. Radojkovic 5 1 Faculty of Medicine, University of Belgrade, Serbia; 2 Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade; 3 Institute of Laboratory Medicine, Clinical Center of Vojvodina, University Medical School Novi Sad, Novi Sad; 4 Gynaecology and Obstetrics Clinic Narodni Front, University of Belgrade, Belgrade; 5 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade Objective: The study was conducted in order to investigate the clinical characteristics of the first venous thromboembolism (VTE) among young women and those over 45 years. Method: From 1998 till 2012, all Serbian women tested to thrombophilia presence were included in the study (414 young women and 200 aged over 45 years). Results: Proximal DVT is the most frequent among young women, while distal DVT is the most frequent in the older group. The most common reported risk for VTE was pregnancy and puerperium observed in 52.4% of young women, while, 24.8% of them developed VTE without any particular reason. Among women of age over 45, the VTE developed without any particular reason in 39%, while in 23% of them malignant diseases were the most important risk factors. Prothrombin G20210A mutation, deficiency of natural inhibitors or combined thrombophilia, were more frequent among young women compared with the older, p=0.009, p=0.0003, respectively p=0.0006. Contrary, the presence of FVL mutation was equally
Methods: 810 pregnant women with higher risk for VTE were included in the ETHiG study. 560 women had miscarriages in the history. The risk stratification in 3 groups was done according to Bauersachs et al. [1]: 225 low-risk patients, 469 high-risk patients, 116 very high-risk patients. Risk factors for early and late losses as well stillbirth were analysed. Results: In this risk population maternal age was no risk factor for nonrecurrent miscarriage but for recurrent pregnancy loss (RPL) (RR 2.41 [1.73–3.37] for age > 35 years). A thrombophilia was to detect in 59% of all pregnancies. VTE risk stratification was not associated with the history of pregnancy losses. Conclusion: The elevated VTE risk alone is not associated with higher risks for a pregnancy loss. Thrombophilic risks for thrombembolic events underlie possible an other pathopyhsiological regulation as their association to pregnancy complications. References: [1] Bauersachs et al. Thromb Haemost 2007; 98: 1237–1245.
P-032 Selected aspects of the antithrombotic prophylaxis in pregnant women with congenital thrombophilias T. Kvasniˇcka Thrombotic Center, General Teaching Hospital, Prague, Czech republic Venous thromboembolism (VTE) is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Women with a prior VTE, a family history of VTE, certain clinical risk factors and thrombophilia are at considerably increased risk for pregnancyrelated. Heritable thrombophilias are also important co-determinants of VTE risk in pregnancy. The mechanisms through which pregnancy and hormonal therapies increase VTE risk have not been definitively established, but hormonal effects on levels of coagulation and anticoagulation factors likely play a role. Venous compression and injury also contribute to increased risk during pregnancy and the puerperium. Antithrombotic prophylaxis during pregnancy are mainly based on low-molecular-weight heparin (LMWH). This paper discusses, on the set of pregnant women (n=2039) observed in Thrombotic Center, General Teaching Hospital in Prague, Czech republic, with several gene mutations (A→G5O6 mutation of factor V, n=759, 39% and G→20210 polymorphism of prothrombin, n=259, 12.7%) the indications, times and modalities for the use of LMWH, during pregnancy (puerperium), together with their side-effects, and maternal and fetal contraindications. Conclusions: Subcutaneous LMWHs have a growing role in prophylaxis and treatment of VTE during pregnancy. They are safe, can be administered during breastfeeding and a single-day administration for VTE prophylaxis is effective. Actually, some agreement exists about LMWH treatment in “very high” and “high” thrombotic risk pregnant women. Only preliminary data are available about “moderate” and “low” thrombotic risk pregnant women.
P-033 Sex specific risk factors for VTE recurrence. Long term follow-up, analysis of a single cohort of patients D. Theocharidou, E. Papadakis, A. Banti, A. Karagianni, V. Papageorgiou, V. Papadopoulos, K. Tsimirika, S. Efraimidou, G. Kaltsounis, E. Georgiou, A. Kioumi Hemostasis Unit-Hematology Dept, Papageorgiou Hospital, Thessaloniki, Greece Objectives: Individual risk of recurrent VTE affects patient’s management and might differ among men and women, as long as men have about 50% higher risk of recurrent VTE than women. However, the cofounding factors of this event still remain to be clarified. The aim of this study is to evaluate whether there are gender related risk factors of VTE recurrence. Methods: To achieve this goal among 346 patients, who had already had an episode of TE, we evaluated 194 patients: 86 (44.3%) men and 108 (55.7%) women with a mean age of 40.10 years, who met the following criteria 1. Didn’t receive at first indefinite anticoagulation 2. Had at least completed 2 years of follow up after discontinuation of anticoagulation 3. Continued their follow up at our clinic. Based on previously published data we tried to define whether the fol-
S85
lowing variables are high risk factors for VTE recurrence in our male and female populations: age of diagnosis, thrombophilic factors (FVLeiden, FII, HCY, VIII, AT, PrC, PrS, PAI1, Lp(a), XII), the presence of unprovoked VTE episode and VTE location (DVT, PE, CNS Thrombosis). Women who developed peripartum and hormone related VTE were not included at the unprovoked VTE group. Results: Table 1 shows the number of episodes the patients suffered in relation to their gender. Men showed statistically significantly higher relapse rates in correlation to women, p=0.038. Moreover, development of an unprovoked VTE episode, FVLeiden homozygous p=0.036 and VTE location (CNS has the lowest risk of recurrence) showed statistical significant relation to VTE recurrence at the whole population, p=0.029, 0.036, 0.05 respectively. Moreover, men and women, who developed provoked VTE (surgery, travel, or pregnancy related etc) didn’t show any significant difference concerning their recurrence rates. Focusing on female gender, 23 women developed peripartum thrombosis and 21 during hormonal therapy. On a univariate model high levels of Lp(a), presence of AFS and FVLeiden homozygous showed to be strongly associated to VTE recurrence p=0.020, 0.014 and 0.050, respectively. Moreover, CNS thrombosis shows to have negative association to recurrence p=0.001. AFS and FV Leiden homozygous positive and CNS negative association to VTE recurrence were also confirmed on a multivariable model p=0.01, 0.022 and 0.007, respectively. Focusing on relapsing population, there has been no significant difference among mean diagnosis age of men (42.93 years) and women (37.97 years). Table 1. VTE episodes and gender No. of episodes 1 2 3
≥4
Men (%)
Women (%)
Sum
44 (38.60) 33 (55.93) 7 (43.75) 2 (40)
70 (61.40) 26 (44.07) 9 (56.25) 3 (60)
114 59 16 5
Conclusions: All hypotheses that have been proposed to explain this discrepancy between men and women at recurrence rates are under debate. For example, we hereby do not present any significant difference among men and women concerning the age of primary VTE episode. Furthermore, comparative studies reveal more possible explanations. Nevertheless, gender should be taken into account for risk stratification of VTE recurrence, given the lately supported facts that men have 50% higher risk of recurrence and women are more prone to bleeding disorders during anticoagulation.
P-034 Clinical characteristics of the first thrombosis process among young women and those over 45 years M. Kovac 1,2 , G. Mitic 3 , Z. Mikovic 4 , V. Mandic 4 , L. Rakicevic 5 , V. Djordjevic 5 , D. Radojkovic 5 1 Faculty of Medicine, University of Belgrade, Serbia; 2 Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade; 3 Institute of Laboratory Medicine, Clinical Center of Vojvodina, University Medical School Novi Sad, Novi Sad; 4 Gynaecology and Obstetrics Clinic Narodni Front, University of Belgrade, Belgrade; 5 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade Objective: The study was conducted in order to investigate the clinical characteristics of the first venous thromboembolism (VTE) among young women and those over 45 years. Method: From 1998 till 2012, all Serbian women tested to thrombophilia presence were included in the study (414 young women and 200 aged over 45 years). Results: Proximal DVT is the most frequent among young women, while distal DVT is the most frequent in the older group. The most common reported risk for VTE was pregnancy and puerperium observed in 52.4% of young women, while, 24.8% of them developed VTE without any particular reason. Among women of age over 45, the VTE developed without any particular reason in 39%, while in 23% of them malignant diseases were the most important risk factors. Prothrombin G20210A mutation, deficiency of natural inhibitors or combined thrombophilia, were more frequent among young women compared with the older, p=0.009, p=0.0003, respectively p=0.0006. Contrary, the presence of FVL mutation was equally