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P24 The use of fondaparinux in pregnancy
S146 Material: we studied 191 women with mean age 33.9 ± 4.8 years that had about 2.9 ± 1.3 fetal loses. Method: We studied all the possible factors of haemostasis that can be implicated for disturbances and also full genetic control. Results: we found 22 women heterozygote and 3 were homozygote for FV-Leiden, 9 women were carriers of the Gp-IIIa mutation and also 3 more women had the FV -HR2 with the GpIIIa homozygote mutation, 8 woman with FII 20210 G>A mutation (including 1 homozygote), 5 more had FII mutation and GpIIIa homozygote mutation, and 4 more had PAI-4G/4G and GpIIIa homozygote mutation, 2 women with the 455G>A mutation of fibrinogen, 25 women with PAI-4G/4G polymorphism. Also 2 more women with protein S, 1 woman with FXII, 1 woman showed plasminogen deficiency, 3 women with antiphospholipid syndrome and 7 women had haemorrhagic diathesis (mainly mild Willebrand disease). Overall in 95 women we found risk factors connected with recurrent fetal losses. From the 191 women we examined 95 were able to have one effective pregnancy with the help of antithrombotic treatment (mMBH mainly innohep, or antiplatelets mainly aspirin) or with DDAVP in order to increase the levels of factor Willebrand. In the other women an effective therapeutic approach was not possible. Comment: The determination of the causes of recurrent fetal losses can help in an effective pregnancy. P23 Incidence of thrombophilic markers in women undergoing assisted reproduction (AR) treatment I. Oborn´ a1 , J. Bˇrezinov´ a1 , V. Krˇ cov´ a2 , H. Fingerov´ a1 , A. Hluˇsí2 , ´ lehlov´ a2 . 1 Dept. of Obstetrics and Gynaecology, L. Slavík2 , J. U 2 Dept. of Haematooncology, Faculty of Medicine, Palack´ y University Olomouc, Czech Republic Introduction: It is known that the most frequent types of inherited thrombophilic disorders (Factor V Leiden and F II prothrombin mutations) can increase the frequency of recurrent or idiopathic fetal loss in the first trimester and the risk of ovarian hyperstimulation syndrome (OHSS), and also decrease the take-home baby rate after IVF. The aim of our study was to estimate the frequency of these and related mutations, and in patients with a proven hereditary thrombophilic risk, to apply appropriate preventive prophylaxis during infertility treatment and ensuing pregnancy. Materials and Methods: We screened patients undergoing infertility treatment for thrombophilic markers (AT III, protein C, protein S, APC resistance, factor II, VIII and plasminogen, LA, ACLA) followed by genotyping of mutations for Factor V Leiden, prothrombin, MTHFR and PAI-I. Personal and family histories of venous and arterial thrombosis, OHSS and repeated implantation failure were evaluated. The obstetric history included the number of spontaneous and missed abortions, fetal deaths, IUGR, pre-eclampsia, HELLP syndrome and placental abruption. Results: 107 infertile women were included in the study. The incidence of thrombophilic risk markers and results of infertility treatment are presented. Conclusions: Thrombophilia may be a cause of recurrent IVF failure. There are at present no guidelines for use, or duration, of thromboprophylaxis during AR treatment. Assessment of relative risk can help ensure appropriate antithrombotic prophylaxis during stimulation and ensuing pregnancy. Thromboprophylaxis may minimize the risk of complications of ovarian hyperstimulation and improve the outcome of pregnancy.
Abstracts selected for Poster Presentation P24 The use of fondaparinux in pregnancy A.M. Winkler, A. Duncan. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA Fondaparinux (Arixtra® ), a synthetic selective inhibitor of activated factor X (fXa), is commonly used as an alternative anticoagulant in patients who develop heparin intolerance; however, the use of fondaparinux in pregnancy is limited in the literature by animal models, few case reports, and no randomized controlled clinical trials. Although it has been shown that transplacental passage can occur resulting in measurable fXa activity in cord blood, no adverse outcomes in pregnancy have been reported. At our institution, ten patients have been successfully treated with fondaparinux during pregnancy for various indications which include but are not limited to thromboprophylaxis, prevention of fetal loss or early onset pre-eclampsia in high risk patients, or for unexplained infertility. These patients are initially started on fondaparinux prior to conception or typically within their first trimester and routinely monitored monthly with anti-Xa activity levels and other markers of coagulation and hemostasis activation including prothrombin fragment 1.2 (PF1.2), thrombin antithrombin complexes (TAT), fibrin monomers, and D-dimers. Patients consistently report less injection site reaction as compared to administration with low molecular heparin, which has increased patient compliance and satisfaction. As a result, we strongly believe that treatment with fondaparinux during pregnancy represents a safe and effective alternative to low molecular weight heparin; however, more research including randomized controlled clinical trials should be advocated to further support our findings. P25 Successful treatment of a fetal alloimmunthrombocytopenia caused by HLA-B7 using immunoadsorbtion onto Protein-A E. Schleussner1 , S. Rummler2 , A. Huebler3 , D. Barz2 . of Obstetrics, 2 Institute for Transfusion Medicine, 3 Department of Neonatology, Friedrich Schiller University Jena, Germany
1 Department
Fetal alloimmune thrombocytopenia (FAIT) due to transplacentally acquired maternal platelet alloantibodies is a rare event. The majority (>75%) of cases are due to fetomaternal incompatibility for the platelet specific alloantigen, HPA-1a, whether human leucocyte antigen (HLA) antibodies can cause FAIT is still controversial. In this case a woman lost after the first uncomplicated pregnancy two children due to severe thrombocytopenia and coagulopathia after preterm birth. Maternal sera were tested for HPA and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phaselinked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis find no HPA, but HLA B7 antibodies (titer 1:512). Typing result show the HLAB7 antigen in the father and first child. During the 4th pregnancy immunoadsorbtion were performed up to three times weekly starting in early pregnancy. An amniocentesis detected maternal HLA-B7 antibodies in the amnion fluid (titer 1:32) and HLA-B7 antigen in the fetal cells. Under this therapy the pregnancy was ongoing without complication up to 34 weeks. By primary caesarean section a healthy eutrophic neonate was born with only mild thrombocytopenia which normalized immediately after immunoglobulin therapy. This is the first report about fetal alloimmunothrombocytopenia caused by HLA-B7 antibodies demonstrating a successful therapeutic approach.
Abstracts selected for Poster Presentation P24 The use of fondaparinux in pregnancy A.M. Winkler, A. Duncan. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA Fondaparinux (Arixtra® ), a synthetic selective inhibitor of activated factor X (fXa), is commonly used as an alternative anticoagulant in patients who develop heparin intolerance; however, the use of fondaparinux in pregnancy is limited in the literature by animal models, few case reports, and no randomized controlled clinical trials. Although it has been shown that transplacental passage can occur resulting in measurable fXa activity in cord blood, no adverse outcomes in pregnancy have been reported. At our institution, ten patients have been successfully treated with fondaparinux during pregnancy for various indications which include but are not limited to thromboprophylaxis, prevention of fetal loss or early onset pre-eclampsia in high risk patients, or for unexplained infertility. These patients are initially started on fondaparinux prior to conception or typically within their first trimester and routinely monitored monthly with anti-Xa activity levels and other markers of coagulation and hemostasis activation including prothrombin fragment 1.2 (PF1.2), thrombin antithrombin complexes (TAT), fibrin monomers, and D-dimers. Patients consistently report less injection site reaction as compared to administration with low molecular heparin, which has increased patient compliance and satisfaction. As a result, we strongly believe that treatment with fondaparinux during pregnancy represents a safe and effective alternative to low molecular weight heparin; however, more research including randomized controlled clinical trials should be advocated to further support our findings. P25 Successful treatment of a fetal alloimmunthrombocytopenia caused by HLA-B7 using immunoadsorbtion onto Protein-A E. Schleussner1 , S. Rummler2 , A. Huebler3 , D. Barz2 . of Obstetrics, 2 Institute for Transfusion Medicine, 3 Department of Neonatology, Friedrich Schiller University Jena, Germany
1 Department
Fetal alloimmune thrombocytopenia (FAIT) due to transplacentally acquired maternal platelet alloantibodies is a rare event. The majority (>75%) of cases are due to fetomaternal incompatibility for the platelet specific alloantigen, HPA-1a, whether human leucocyte antigen (HLA) antibodies can cause FAIT is still controversial. In this case a woman lost after the first uncomplicated pregnancy two children due to severe thrombocytopenia and coagulopathia after preterm birth. Maternal sera were tested for HPA and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phaselinked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis find no HPA, but HLA B7 antibodies (titer 1:512). Typing result show the HLAB7 antigen in the father and first child. During the 4th pregnancy immunoadsorbtion were performed up to three times weekly starting in early pregnancy. An amniocentesis detected maternal HLA-B7 antibodies in the amnion fluid (titer 1:32) and HLA-B7 antigen in the fetal cells. Under this therapy the pregnancy was ongoing without complication up to 34 weeks. By primary caesarean section a healthy eutrophic neonate was born with only mild thrombocytopenia which normalized immediately after immunoglobulin therapy. This is the first report about fetal alloimmunothrombocytopenia caused by HLA-B7 antibodies demonstrating a successful therapeutic approach.