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C0073 Clinical manifestation in hereditary thrombophilias and managenemt of thrombosis, pregnancy and delivery
Abstracts / Thrombosis Research 130 (2012) S100–S202
C0073 Clinical manifestation in hereditary thrombophilias and managenemt of thrombosis, pregnancy and delivery Ivo Elezovic1, Darko Antic1, Predrag Miljic1, Mirjana Mitrovic2, Valentina Djordjevic3, Ljudmila Stojanovic4, Olivera Markovic4, Mirjana Kovac5 1 Medical Faculty University of Belgrade, Clinic of Haematology Clinical Center of Serbia - Koste Todorovica 2, 11000 Belgrade, Serbia; 2Clinic of Haematology Clinical Center of Serbia - Koste Todorovica 2, 11000 Belgrade, Serbia; 3Institute of Molecular Genetics and Genetic Engineering - Vojvode Stepe 444, 11000, Belgrade, Serbia; 4Clinical Hospital Center Bezanijska Kosa - 11000 Belgrade, Serbia; 5Institute of Blood Transfusion, Belgrade, Serbia - Svetog Save 39, 11000 Belgrade, Serbia Background: Patients with thrombosis have hereditary or acquired hypercoagulable states, which contribute to development of thrombosis or other manifestation as miscarriages and fetal complications. The aim of this study is to investigate incidence, localization and trigger mechanisms of thrombosis, rethrombosis, as well miscarriages, and treatment in hereditary thrombophili. Methods: Antithrombin, protein C, protein S, factor XII, resistance to activated protein C or factor V Leiden, prothrombin 20210, polymorphism C677T of methylene-tetrahydrofolate reductase, PAI-1 4 G and antiphospholipid antibodies were measured at patients with thrombosis, miscarriages or fetal complications. Results: Hereditary thrombophilias were diagnosed in 544 patients, (381 female, 163 male), with deficiency of antithrombin (25), protein C (17), protein S (23), and factor XII (25), resistance to activated protein C or factor V Leiden (174), prothrombin 20210 (44), polymorphism C677T of methylene-tetrahydrofolate reductase (348), and PAI-1 4 G (21). One hundred twenty one patients (22.2%) have two or more hereditary thrombophilias. Acquired antiphospholipid antibodies (APA) were detected in 112 patients (20.67%) with hereditary thrombophilias. Our group consisted of highly selected patients: 317 with (average 1.84) thrombosis, 185 with miscarriages (26/185 with thrombosis), and 67 without event (12.3%). Patients with hereditary thrombophilias developed first thrombosis at the median age of 33.5 years, and they had 585 thrombotic events with (96) 16.4% of arterial thrombosis. Thromboses were associated with surgery, trauma or immobilization (63), pregnancy or delivery (55), smoking (34), malignancy (9), infections (21), air travel/seating (15), oral contraceptives (10) and disrupt of anticoagulant therapy (2). When diagnosis of hereditary thrombophilia was established all patients with two or more venous thromboembolisms were treated with long-term anticoagulant therapy. Patients with arterial thrombosis were treated with low doses of aspirin (50-75 mg) and two patients died. 185/381 women (48.5%) with thrombophilia had 474 miscarriages (average 2.6 (range 1–9), with APA 2.3, without APA 2.6). Forty-two women with thrombophilia (14/42 with two or more thrombophilias and 5 with APA) had 47 successful delivered (7 with APA) after prophylactic treatment with LMWH and folic acid at woman with MTHFR during pregnancy and 4–6 weeks after. Comment: Prophylactic long-term anticoagulant therapy is effective in patients with hereditary thrombophilia and recurrent venous thrombosis. Prophylactic anticoagulant therapy during pregnancy, delivery, and 4–6 weeks after is recommended in woman with inherited thrombophilia and previously recurrence miscarriages, or unsuccessful in vitro fertilisation, or thrombosis.
doi:10.1016/j.thromres.2012.08.084
S133
C0086 High sensitivity of the global CIP assay for hereditary thrombophilia Orsolya Tóth1, Jacqueline Conard2, Hajna Losonczy1, Barbara Réger1, Marianne S. Andresen3, Marie-Hélene Horellou4, Réka Mózes5, Ulrich Abildgaard6 1 University of Pécs, Ist Department of Medicine, Haematology - Ifjúság u. 13., 7624 Pécs, Hungary; 2Hotel Dieu University Hospital, University Paris-DescartesHaematology - 1 Place du Parvis Notre-Dame, 75004 Paris, France; 3University of Oslo and Oslo University Hospital, Research Institute of Internal Medicine, Haematology, Rikshospitalet - PB 4950 Nydalen, 0424 Oslo, Norway; 4Hotel Dieu University Hospital, University Paris-DescartesHaematology - 1 Place du Parvis Notre-Dame, 75004 Paris, France; 5University of Pécs, Ist Department of Medicine, Haematology Ifjúság str. 13., 7624 Pécs, Hungary; 6Oslo University Hospital, Department of Haematology - PB 4950 Nydalen, 0424 Oslo, Norway Background: Deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), homozygous factor V Leiden (FVL) or prothrombin (FII) G20210A mutations and combined abnormalities confer a high risk of first venous thromboembolism (VTE), a significantly increased risk of recurrent VTE, and increased total morbidity in pregnancy. Screening for this high risk group is indicated in young patients with unprovoked VTE or with familial VTE. The heterozygous FVL and FII G20210A mutations confer moderately increased risk of a first VTE and a low risk of recurrent VTE. Screening for this low risk group is controversial and recommended on an individual basis only. The low risk types are absent in Asian and African populations. The Coagulation Inhibitor Potential (CIP) assay monitors fibrin formation and measures the inhibition of coagulation in presence of pentasaccharide and Protac. In a pilot study, CIP performed better than the Calibrated Automated Thrombin generation (CAT) and the ProC Global assays in discriminating 21 persons with high risk hereditary thrombophilia from healthy controls. Methods: The CIP assay was performed in 207 healthy controls and in 135 patients (pts) with hereditary thrombophilia. High risk thrombophilia was present in 80 pts: deficiencies of AT (n = 13), PC (n = 9), PS (n = 13); homozygous FVL (n = 9) or FII 20210 mutation (n = 7) and combined types (n = 29), and low risk thrombophilia in 55 pts: heterozygous FVL (n = 32) or FII G20210A (n = 23). Results: In all high risk groups and in the heterozygous FVL group, median CIP values were significantly abnormal. Median CIP values were 59.3 U for healthy controls, 6.4 U for single high risk, 0.8 U for combined types, and 16.5 U for low risk thrombophilia. Sensitivity was 100% and specificity 77% for detection of all types except heterozygous FII mutation. The best performance by ROC analysis was a sensitivity 91% and specificity 88%. Vitamin K antagonist medication reduced its sensitivity. The CIP assay may be run on a conventional automated analyzer with inexpensive reagents. Comment: The CIP assay may have a higher sensitivity for hereditary thrombophilias than other global assays and may be a useful single screening test for thrombophilia. In Western populations, negativity of the test excludes hereditary thrombophilia except the lowest risk heterozygous FII mutation. In populations lacking the low risk mutations studies are needed to examine its clinical usefulness for routine screening after VTE. doi:10.1016/j.thromres.2012.08.085
C0025 Venous thromboembolism and factor V Leiden: Enigma or paradox Francisco Gabriel1, Olga Portolés2, Manuel Labiós1, C. Rodriguez3, E. Cisneros4, J.R. Vela5, M.J. Nuñez6
C0073 Clinical manifestation in hereditary thrombophilias and managenemt of thrombosis, pregnancy and delivery Ivo Elezovic1, Darko Antic1, Predrag Miljic1, Mirjana Mitrovic2, Valentina Djordjevic3, Ljudmila Stojanovic4, Olivera Markovic4, Mirjana Kovac5 1 Medical Faculty University of Belgrade, Clinic of Haematology Clinical Center of Serbia - Koste Todorovica 2, 11000 Belgrade, Serbia; 2Clinic of Haematology Clinical Center of Serbia - Koste Todorovica 2, 11000 Belgrade, Serbia; 3Institute of Molecular Genetics and Genetic Engineering - Vojvode Stepe 444, 11000, Belgrade, Serbia; 4Clinical Hospital Center Bezanijska Kosa - 11000 Belgrade, Serbia; 5Institute of Blood Transfusion, Belgrade, Serbia - Svetog Save 39, 11000 Belgrade, Serbia Background: Patients with thrombosis have hereditary or acquired hypercoagulable states, which contribute to development of thrombosis or other manifestation as miscarriages and fetal complications. The aim of this study is to investigate incidence, localization and trigger mechanisms of thrombosis, rethrombosis, as well miscarriages, and treatment in hereditary thrombophili. Methods: Antithrombin, protein C, protein S, factor XII, resistance to activated protein C or factor V Leiden, prothrombin 20210, polymorphism C677T of methylene-tetrahydrofolate reductase, PAI-1 4 G and antiphospholipid antibodies were measured at patients with thrombosis, miscarriages or fetal complications. Results: Hereditary thrombophilias were diagnosed in 544 patients, (381 female, 163 male), with deficiency of antithrombin (25), protein C (17), protein S (23), and factor XII (25), resistance to activated protein C or factor V Leiden (174), prothrombin 20210 (44), polymorphism C677T of methylene-tetrahydrofolate reductase (348), and PAI-1 4 G (21). One hundred twenty one patients (22.2%) have two or more hereditary thrombophilias. Acquired antiphospholipid antibodies (APA) were detected in 112 patients (20.67%) with hereditary thrombophilias. Our group consisted of highly selected patients: 317 with (average 1.84) thrombosis, 185 with miscarriages (26/185 with thrombosis), and 67 without event (12.3%). Patients with hereditary thrombophilias developed first thrombosis at the median age of 33.5 years, and they had 585 thrombotic events with (96) 16.4% of arterial thrombosis. Thromboses were associated with surgery, trauma or immobilization (63), pregnancy or delivery (55), smoking (34), malignancy (9), infections (21), air travel/seating (15), oral contraceptives (10) and disrupt of anticoagulant therapy (2). When diagnosis of hereditary thrombophilia was established all patients with two or more venous thromboembolisms were treated with long-term anticoagulant therapy. Patients with arterial thrombosis were treated with low doses of aspirin (50-75 mg) and two patients died. 185/381 women (48.5%) with thrombophilia had 474 miscarriages (average 2.6 (range 1–9), with APA 2.3, without APA 2.6). Forty-two women with thrombophilia (14/42 with two or more thrombophilias and 5 with APA) had 47 successful delivered (7 with APA) after prophylactic treatment with LMWH and folic acid at woman with MTHFR during pregnancy and 4–6 weeks after. Comment: Prophylactic long-term anticoagulant therapy is effective in patients with hereditary thrombophilia and recurrent venous thrombosis. Prophylactic anticoagulant therapy during pregnancy, delivery, and 4–6 weeks after is recommended in woman with inherited thrombophilia and previously recurrence miscarriages, or unsuccessful in vitro fertilisation, or thrombosis.
doi:10.1016/j.thromres.2012.08.084
S133
C0086 High sensitivity of the global CIP assay for hereditary thrombophilia Orsolya Tóth1, Jacqueline Conard2, Hajna Losonczy1, Barbara Réger1, Marianne S. Andresen3, Marie-Hélene Horellou4, Réka Mózes5, Ulrich Abildgaard6 1 University of Pécs, Ist Department of Medicine, Haematology - Ifjúság u. 13., 7624 Pécs, Hungary; 2Hotel Dieu University Hospital, University Paris-DescartesHaematology - 1 Place du Parvis Notre-Dame, 75004 Paris, France; 3University of Oslo and Oslo University Hospital, Research Institute of Internal Medicine, Haematology, Rikshospitalet - PB 4950 Nydalen, 0424 Oslo, Norway; 4Hotel Dieu University Hospital, University Paris-DescartesHaematology - 1 Place du Parvis Notre-Dame, 75004 Paris, France; 5University of Pécs, Ist Department of Medicine, Haematology Ifjúság str. 13., 7624 Pécs, Hungary; 6Oslo University Hospital, Department of Haematology - PB 4950 Nydalen, 0424 Oslo, Norway Background: Deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), homozygous factor V Leiden (FVL) or prothrombin (FII) G20210A mutations and combined abnormalities confer a high risk of first venous thromboembolism (VTE), a significantly increased risk of recurrent VTE, and increased total morbidity in pregnancy. Screening for this high risk group is indicated in young patients with unprovoked VTE or with familial VTE. The heterozygous FVL and FII G20210A mutations confer moderately increased risk of a first VTE and a low risk of recurrent VTE. Screening for this low risk group is controversial and recommended on an individual basis only. The low risk types are absent in Asian and African populations. The Coagulation Inhibitor Potential (CIP) assay monitors fibrin formation and measures the inhibition of coagulation in presence of pentasaccharide and Protac. In a pilot study, CIP performed better than the Calibrated Automated Thrombin generation (CAT) and the ProC Global assays in discriminating 21 persons with high risk hereditary thrombophilia from healthy controls. Methods: The CIP assay was performed in 207 healthy controls and in 135 patients (pts) with hereditary thrombophilia. High risk thrombophilia was present in 80 pts: deficiencies of AT (n = 13), PC (n = 9), PS (n = 13); homozygous FVL (n = 9) or FII 20210 mutation (n = 7) and combined types (n = 29), and low risk thrombophilia in 55 pts: heterozygous FVL (n = 32) or FII G20210A (n = 23). Results: In all high risk groups and in the heterozygous FVL group, median CIP values were significantly abnormal. Median CIP values were 59.3 U for healthy controls, 6.4 U for single high risk, 0.8 U for combined types, and 16.5 U for low risk thrombophilia. Sensitivity was 100% and specificity 77% for detection of all types except heterozygous FII mutation. The best performance by ROC analysis was a sensitivity 91% and specificity 88%. Vitamin K antagonist medication reduced its sensitivity. The CIP assay may be run on a conventional automated analyzer with inexpensive reagents. Comment: The CIP assay may have a higher sensitivity for hereditary thrombophilias than other global assays and may be a useful single screening test for thrombophilia. In Western populations, negativity of the test excludes hereditary thrombophilia except the lowest risk heterozygous FII mutation. In populations lacking the low risk mutations studies are needed to examine its clinical usefulness for routine screening after VTE. doi:10.1016/j.thromres.2012.08.085
C0025 Venous thromboembolism and factor V Leiden: Enigma or paradox Francisco Gabriel1, Olga Portolés2, Manuel Labiós1, C. Rodriguez3, E. Cisneros4, J.R. Vela5, M.J. Nuñez6