Abstracts / Thrombosis Research 130 (2012) S100–S202
C0331 ADAMTS-13 and the platelets activity of the microcoagulation of the blood at the PAI-1 polyporfism Maria Matveeva1, Ekaterina Shelest1, Ludmila Popova1, Lev Patrushev2, Igor Bokarev1 1 I.M. Sechenov First Moscow State Medical University, Hospital therapy 1 - Lenskaya street, 15, Moscow, Russia; 2Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia Background: It is possible, that the polymorphism in the gene for PAI-1 is a thrombophilia. There is proved influence of polymorphismsin the gene for PAI-1 on platelet activity of the blood microcoagulation. It is known that VWFs activate platelets contact with the vessel walls and influenced by ADAMTS-13. The aim of this study was to examine dependence of platelet activation at the people with this mutation from the activity of enzyme ADAMTS-13. Methods: The study included 14 practically healthy people with a mutation in the gene of PAI-1, among them 6 men and 8 women. The age was from 23 to 63 years (middle age 36,3 years). All of them had an increased level of β-thromboglobulin. The activity of ADAMTS-13 was measured by ELISA method, Technoclone. The control group included 13 practically healthy people (2 men and 11 women) with a mutation in the gene of PAI-1 with normal level of β-thromboglobulin. Results: All of investigated people in two groups had a normal level of ADAMTS-13. Comment: The result of our study shows the independence of platalets activity from ADAMTS-13. It is possibile that the polymorphism in the gene for PAI-1 has a direct effect on platelets. To determine the exact mechanism of the influence of this mutation on the platelets part of the microcoagulation further studies are required. doi:10.1016/j.thromres.2012.08.240
C0320 Oral anticoagulation in atrial fibrillation, the patients and physicians experiences of the consultation: A qualitative study Christian Borg Xuereb1, Rachel L. Shaw1, Gregory Y.H. Lip2, Deirdre A. Lane2 1 Aston University, School of Life and Health Sciences - Aston University, Birmingham, B4 7ET, UK; 2University of Birmingham, Centre for Cardiovascular Sciences - City Hospital, Birmingham, B18 7QH, UK Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF), however it is still underutilized and sometimes refused by patients. This project was divided in two inter-related studies. Study 1 explored the experiences that influence prescription of OAC by physicians. Study 2 explored the experiences which influence patients' decisions to accept, decline or discontinue OAC. Methods: Semi-structured individual interviews were conducted in both studies. In Study 1four sub-groups of physicians (n = 16) experienced with OAC in AF were interviewed: consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. In Study 2 three sub-groups of patients (n = 11) diagnosed with AF were interviewed; those who accepted, refused, and who discontinued warfarin. Results: Study 1: Two over-arching themes emerged from doctors' experiences: (1) communicating information and (2) challenges with OAC prescription for AF. Physicians still adopt a paternalistic approach to decision-making. They should instead motivate patients to take part in treatment discussions and choices should reflect the
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patient's needs and concerns. Physician education should focus more on communication skills, individualised care and time-management as these are critical for patient adherence. Continuous OAC education for AF should adopt a multi-disciplinary approach. Further, interpreters should also be educated on medical communication skills. Study 2: Three over-arching themes comprised patients' experiences: (1) the initial consultation, (2) life after the consultation, and (3) patients' reflections. Patient education during the initial consultation was critical in increasing patient's knowledge of OAC. On-going patient education is imperative to maintain adherence. Patients valued physicians' concern for their needs during decision-making. Patients who had experience of stroke were more receptive to education aimed towards stroke risk reduction rather than bleeding risk. Patients' perceptions of warfarin are also influenced by the media. Comment: Qualitative research is crucial in exploring barriers to treatment as it provides an excellent insight into patients' experiences of healthcare. A patient-centred approach should be adopted and incorporated into physicians' education. Education and patient involvement in the decision-making process is essential to promote treatment acceptance and long-term adherence. doi:10.1016/j.thromres.2012.08.241
C0192 Efficacy and safety of fondaparinux in the treatment of pulmonary embolism provoked by romiplostin: A case report Dimitriy Arioli1, Emanuele Negri1, Alessia Tieghi2, Annamaria Casali1, Maria Cristina Leone1, Francesca Pileri3, Francesco Merli2, Ido Iori1 1 Arcispedale Santa Maria Nuova Reggio Emilia, Internal Medicine, Thrombosis and Haemostasis Centre - Viale Risorgimento 80, Italy; 2 Arcispedale Santa maria Nuova Reggio Emilia, Haematology - Viale Risorgimento 80, Italy; 3Policlinico di Modena, Internal Medicine - Via del Pozzo 71, Italy Background: In daily clinical practice it's frequent to treat hemorrhagic complications of anticoagulant and/or antiaggregant therapy. The recent introduction of thrombopoietin mimetic drugs in the treatment of immune thrombocytopenic purpura (=ITP) has been associated with the development of provoked venous thromboembolism in a small, but not trascurable, minority of patients (1%). The treatment of thromboembolic events in patients with a low base line platelet count will represent a new real therapeutic challenge. Methods: We report the case of a 74 years old man with a twenty years history of ITP who presented to our emergency department for acute respiratory insufficiency (PO2 60 mmHg, PCO2 33.7 mmHg, Sat 92.3%). Apart from past splenectomy due to the hematologic disease, the patient was previously healthy and due to the recurrence of ITP (platelet count b 10 × 10 (9)/l), refractory to standard therapy, He was started on the thrombopoietin receptor agonist, Romiplostim, (2 mcg/kg by subcutaneous injection once weekly) three weeks before. A chest CT revealed bilateral pulmonary embolism while compressive ultrasonography showed bilateral distal vein thrombosis and the patient was then hospitalized. At admission platelet count was 655 × 10 (9)/l and Fondaparinux 7,5 mg/day was immediately started and continued for four weeks. Then Fondaparinux 5 mg/day was continued for other eight weeks. Results: Romiplostim was discontinued immediately after the thromboembolic event, however, the patient\'s platelet count consistently remained above 50 × 10(9)/L for all the duration of anticoagulant treatment. No hemorrhagic events happened during the complete cycle of Fondaparinux therapy and four weeks after the discontinuation of
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Abstracts / Thrombosis Research 130 (2012) S100–S202
anticoagulant drug a Chest CT confirmed the complete resolution of the pulmonary embolism. Comment: With the widespread use of thrombopoietin mimetic drugs for ITP provoked thromboembolic events will appear especially in older patients. Due to its pharmacokinetics (once daily regimen) and pharmacodynamics (possibility of daily modulation of its dose, very low risk of Heparin Induced Thrombocytopenia) profile, a short course (3– 6 months) of Fondaparinux therapy could represent an attractive and safe chance in this frail class of patients. A International Register on the outcomes of this adverse events could help to clarify the best treatment option. doi:10.1016/j.thromres.2012.08.242
C0182 Dysregulated micrornas related to angiogenesis expression in endometrial cancer Luis Andrés Ramón1, Aitana Braza-Boils1, Juan Gilabert-Estellés2, Juan Gilabert Aguilar3, Melitina Chirivella Casanova4, Francisco España Furió1, Amparo Estellés1 1 Hospital Universitario La Fe, Research Center - Av. Campanar, 21.46009, Valencia, Spain; 2Hospital Universitario Dr PesetGynecology Service C/ Gaspar Aguilar, 90. 46017, Valencia, Spain; 3Hospital Arnau de VilanovaGynecology Service - C/ San Clemente, 12. 46015, Valencia, Spain; 4Hospital Universitario La Fe, Anatomopathology Service Av. Campanar, 21.46009, Valencia, Spain Background: Endometrial cancer is the most common malignancy of the female genital tract. microRNAs (miRNAs) are small noncoding RNAs that function as posttranscriptional regulators of gene expression and may be up-regulated or down-regulated in various tumor types. Angiogenesis is important for the progress of malignant tumors, including endometrial cancer. Among those miRNAs with altered expression in endometrial cancer, we selected those that regulate angiogenic factors, named angiomiRs. Objective: To analyze several miRNAs related to angiogenesis, vascular endothelial growth factor-A (VEGF-A, angiogenic factor) and thrombospondin-1 (TSP-1, antiangiogenic factor) in endometrial cancer in comparison with control endometrium, as well as the association of these parameters with tumor severity in women with endometrial cancer. Methods: RNA from tissue samples was analyzed with the GeneChip miRNA 2.0 Array platform (Affymetrix). TaqMan qRT-PCR was used to assess the expression of the selected miRNAs related to angiogenesis (miR-15b, -16, -17-5p, -20a, -21, -125a, -200b, -210, -214*, -221, -222 and 424) and qRT-PCR using SYBR Green for VEGF-A and TSP-1 mRNA. Protein levels were quantified by ELISAs. Results: Eight miRNAs (miR-15b, miR-17-5p, miR-20a, miR-125a, miR214*, miR-221, miR-222 and miR-424) were significantly down-regulated and two miRNAs (miR-200b and miR-210) were significantly up-regulated in endometrial cancer in comparison to control endometrium. A significant increase in VEGF-A mRNA and protein expression and in TSP-1 protein levels (Pb 0.01) was observed in endometrial cancer. Moreover, significant inverse correlations between VEGF-A protein levels and miR-20a, miR125a, miR-214*, miR-221, miR-222 and miR-424 were detected. In contrast, a positive correlation was observed between VEGF-A and miR200b and miR-210. Furthermore, stage IB endometrial cancer showed higher VEGF-A protein levels and lower miR-222 in comparison to stage IA. Comment: A dysregulated expression of miRNAs related to angiogenesis and an increase in VEGF-A levels was observed in endometrial cancer in comparison to control endometrium. These results suggest that the angiogenic mechanisms implicated in endometrial cancer can be modulated, directly or indirectly, by several miRNAs. (FIS PI080185, PI0110091,
RECAVA RD06/0014/0004, AP-141/11, PROMETEO/2011/027, Becario FETH 2010, 2011 and Fund Investigación Hospital La Fe). doi:10.1016/j.thromres.2012.08.243
C0207 Factor V Leiden G1691 to a mutation is a prevalent genetic thrombotic risk factor for recurrent pregnancy loss in Tunisian patients Raida Karray-Bradai1, Khemais Benhaj1, Haykel Trabelsi2, Mourad Chaari2, Mohamed Guermazi2, Choumous Kallel21Centre de biotechnologie de Sfax, Laboratoire de valorisation de la biomasse et production des proteins chez les eucaryotes - centre de biotechnologie de Sfax, route sidi Mansour km. 6, Tunisa; 2Complex hospitalo-universitaire Habib Bourguiba de Sfax, Tunisia - Route Alain Sfax, Tunisa Background: Recurrent pregnancy loss (RPL) is one of the most common obstetrical complications. It occurs in 0.5 - 1% of total pregnancies. RPL is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. It has multiple etiologies, such as endocrine, anatomic, genetic, hematological and immunological causes. Thrombotic/inflammatory processes are often observed at the maternal-fetal interface as the final pathological assault in many cases of RPL. Methods: 91 patients from the university hospital complex Habib Bourguiba of Sfax in the south of Tunisia with RPL were studied. Genomic DNA was extracted from blood cells using salting out technique. Allele-specific polymerase chain reaction (AS-PCR) analysis was used for determination of factor V Leiden G1691® A mutation, prothrombin gene G20210® A mutation and TNFa gene G-308® A polymorphism. Results: Of 91 patients with RPL, 25 had G1691® A factor V Leiden mutation (27.47%) compared to an average of 5.8% in control population in Tunisia as determined in three recent pulished studies. The prothrombin gene G20210® A mutation was not detected in any of our patient group. While the allelic frequencies of TNFa G-308® A polymorphism didn't show any statistically significant difference between that of our RPL patients group (13%) and the average of Tunisian control population in five published studies (13.4%). Comment: Our results show that among three genetic thrombotic/ inflammatory risk factors studied, the G1691® A factor V Leiden mutation could be retained as a prevalent genetic thrombotic risk factor for recurrent pregnancy loss in Tunisian patients. doi:10.1016/j.thromres.2012.08.244
C0211 Activation and balance of coagulation in pregnant women treated with low-molecular weight heparin, administered in therapeutic or preventive dosage Barbara Krevel, Mojca Bozic, Sasa Smid, Matija Kozak University Medical Centre Ljubljana, Department for Vascular Diseases Zaloska 7, Slovenia Background: Pregnancy itself is a risk factor for venous thromboembolism (VTE). Besides changes in coagulation-anticoagulation balance resulting from alterations in hormone status, venous flow disturbances and some congenital factors are also involved. In our study we wanted to assess the coagulation balance in women treated due to previous or current VTE in comparison to heatlhy pregnant women.We measured as markers of activated coagulation prothrombin fragment F1+ 2,