Abstract

ISTH07A1_SYM-S-001: Contact View [SYM-S-001] CONTROVERSIAL ISSUES REGARDING THROMBOPROPHYLAXIS IN SURGICAL PATIENTS O.E. Dahl. International Surgical Thrombosis Forum, Thrombosis Research Institute, London, United Kingdom North American surgeons have declared mistrust to the ACCP Guideline Committee and their recommended surgical thromboprophylaxis. Screening studies on asymptomatic DVT in selected patients, citation of old studies with high VTE rates, lack of information on side effects and extrapolation to the general surgical population are controversies of concern. Recent epidemiological studies on elective major joint operated patients have shown an overall mortality of about 0.2%, highest close to surgery, decreasing by time and dominated by vascular deaths. Thrombin driven arterial and venous complications like microembolism syndrome (fat embolism), MI, stroke, DIC; ARDS, SIRS, septicaemias and VTE are seen from the time of the trauma/surgery and for a long time afterwards. Old and comorbide non-selected orthopaedic patients have an increased mortality that persists after the operation. By controlling the underlying thrombin driven process with chemical compounds, general vascular death seems to be reduced in the same proportion as fatal PE [1]. A paradigm shift has started, driven by new scientific knowledge and the surgeons demand for clinically relevant studies and guidelines. Focus has shifted from venous thrombosis that was a frequent and serious clinical complication several decades ago, via screening studies on asymptomatic DVT to studies that take into account all thrombin driven vascular complications, the main cause of peri and postoperative mortality and morbidity. A challenge to scientists and the industry to catch up and respond on this demand and design studies that mirror the wide span of reallife vascular complications related to trauma and surgery in order to apply the best available therapy for each individual patient. Reference: 1. Dahl OE et al Fatal Vascular Outcomes Following Major Orthopaedic Surgery Thromb Haemost 2005; 93: 860-6. Dahl OE. CONTROVERSIAL ISSUES REGARDING THROMBOPROPHYLAXIS IN SURGICAL PATIENTS. J Thromb Haemost 2007; 5 Supplement 2: SYM-S-001 Date: Sunday, July 8, 2007 Session Info: Symposium: Thrombotic disorders Room: Plenary Hall file:///E|/working/jaymehra/Symposium%20Thrombotic%20...rs/Abstract%20ISTH07A1_SYM-S-001%20Contact%20View.htm [1/16/2014 7:07:33 PM] Abstract ISTH07A1_SYM-S-002: Contact ViewISTH07A1_SYM-S-002: Contact View [SYM-S-002] THROMBOPROPHYLAXIS IN ACUTELLY ILL MEDICAL PATIENTS: WHO, WHEN AND HOW P. Mismetti, S. Laporte. Thrombosis Research Group EA3065-CIE3, University Jean Monnet, Saint-Etienne, France Thrombophylaxis in acutely ill medical patients should be considered in every hospitalized patient since: – venous thromboembolic (VTE) risk is very significant in this field. Indeed, without any thrombophylaxis, the risk of asymptomatic DVT systematically detected between day 7 to day 14 is approximately equal to 50% in ischemic stroke, 25% in myocardial infarction, and 20% in heart and respiratory failures or severe sepsis; – approximately 75% of patients presented with an acute VTE event did not have any surgical procedures in the previous 3 months; – anticoagulants have been shown to be safe and effective with about a 60% risk reduction in both asymptomatic and symptomatic VTE [Mismetti et al. Thromb Haemost 2000; Dentali et al. Ann Intern Med 2007]. Apart from the risk due to a specific disease, the VTE risk highly depends on specific patient risk factors such as advanced age, previous VTE, underlying cancer, renal insufficiency. However analysis of individual data has shown that the thromboprophylactic effect of heparins does not seem to be modified by these patient risk factors. On the contrary, bleeding risk associated with heparins seems to depend on specific patient risk factors. In this way, a careful analysis of patient risk factors should be of interest to optimize thrombophylaxis. This was supported by the implementation of a VTE risk analysis based on an electronic expert system [Kucher et al. N Engl J Med 2005]. Indeed the systematic use of this system has resulted in an improvement in the rate of thrombophylaxis prescriptions resulting in a significant decrease in symptomatic VTE. Once the need for thromboprophylaxis has been evaluated, the optimal treatment should be discussed based on new available data in terms of: – the drugs themselves, unfractionated heparins (UFH), low-molecular-weight heparins (LMWH), or fondaparinux; – dose regimen, e.g. 5000 IU bid or tid of UFH; – treatment duration, e.g. 7 to 14 days or 28 to 35 days of LMWH. Mismetti P, Laporte S. THROMBOPROPHYLAXIS IN ACUTELLY ILL MEDICAL PATIENTS: WHO, WHEN AND HOW. J Thromb Haemost 2007; 5 Supplement 2: SYM-S-002 Date: Sunday, July 8, 2007 Session Info: Symposium: Thrombotic disorders Room: Plenary Hall file:///E|/working/jaymehra/Symposium%20Thrombotic...Abstract%20ISTH07A1_SYM-S-002%20Contact%20View.htm (1 of 2) [1/16/2014 7:07:33 PM] Abstract ISTH07A1_SYM-S-003: Contact ViewISTH07A1_SYM-S-003: Contact View [SYM-S-003] OBESITY, METABOLIC SYNDROME, AND VENOUS THROMBOEMBOLISM M.C. Alessi, I. Juhan-Vague. Lab. Hematology, Inserm U626, Faculty of medicine, Marseilles, France Idiopathic venous thromboembolism (VTE) is associated with atherosclerosis more frequently than expected. These two conditions may share a common risk factor. The Metabolic Syndrome (MetS) is of current interest as a common antecedent. The MetS, a concurrence of abdominal fat, disturbed glucose and insulin metabolism, mild dyslipidemia (high triglycerides and low HDL cholesterol levels), mild inflammation, and hypertension has been strongly associated with subsequent development of type 2 diabetes and arterial disease. The physiopathology of this syndrome is complex. An integrated vision would be that, in response to excess energy intake, the subcutaneous adipose tissue would not play its storage role any more, a status that would orientate fat accumulation in visceral territories, leading to lipotoxic and inflammatory responses. Although obesity per se has been accused of being a risk factor for VTE, little is known about the contribution of visceral obesity. Recently, case control studies observed that waist circumference and the related dyslipidemia showed association with idiopathic VTE. The MetS affects the thrombogenicity of circulating blood. Apart from its effect on platelets, a procoagulant and hypofibrinolytic state has been clearly identified, mainly underlain by the inflammatory state, dyslipidemia, and liver fat accumulation that accompany the MetS. Among hemostasis disturbances, the strong rise in the inhibitor of plasminogen activator type 1 plasma level is the most documented abnormality implicating the participation of the oxidative stress and inflammatory state developed during the MetS. Endothelial dysfunction is also a central feature. Moreover, secretion products of fat tissues (adipokines) are now thought to have direct modulating effects on the vascular and the circulating cells. In support of these data, the MetS, may predispose to atherosclerosis as well as to VTE. Further studies are needed to establish this association. Alessi MC, Juhan-Vague I. OBESITY, METABOLIC SYNDROME, AND VENOUS THROMBOEMBOLISM. J Thromb Haemost 2007; 5 Supplement 2: SYM-S-003 Date: Sunday, July 8, 2007 Session Info: Symposium: Thrombotic disorders Room: Plenary Hall file:///E|/working/jaymehra/Symposium%20Thrombotic%20...rs/Abstract%20ISTH07A1_SYM-S-003%20Contact%20View.htm [1/16/2014 7:07:34 PM] Abstract ISTH07A1_SYM-S-004: Contact ViewISTH07A1_SYM-S-004: Contact View [SYM-S-004] PROGRESS AND HURDLES IN NOVEL GENETIC THERAPIES FOR HEMOPHILIA K.A. High. Pediatrics, University of PA and Howard Hughes Medical Institute, Philadelphia, United States The goal of gene transfer for genetic diseases such as hemophilia is to achieve long-term expression of the donated gene at levels high enough to result in phenotypic improvement. Multiple gene transfer strategies have resulted in longterm "cures" in mouse models of hemophilia. Success in the large animal model of hemophilia has been restricted to only three approaches: retroviral transduction of liver in the neonatal period (while hepatocytes are still rapidly dividing), and delivery of adeno associated viral (AAV) vectors to either skeletal muscle or liver. Translation of these strategies to the clinic has not yet achieved the dual goals of long term expression and therapeutic levels; AAV-mediated gene transfer to skeletal muscle has resulted in long-term expression, but at subtherapeutic levels, and AAV-mediated gene transfer to liver has resulted in therapeutic levels, but only short-term expression. Problems uncovered in the course of the clinical studies, as well as potential solutions, will be reviewed and discussed. Novel strategies for gene correction, and other molecular approaches to gene defects, will be briefly discussed. High KA. PROGRESS AND HURDLES IN NOVEL GENETIC THERAPIES FOR HEMOPHILIA. J Thromb Haemost 2007; 5 Supplement 2: SYM-S-004 Date: Sunday, July 8, 2007 Session Info: Symposium: Haemorrhagic disorders Room: Room A/B file:///E|/working/jaymehra/Symposium%20Haemorrhagic%...rs/Abstract%20ISTH07A1_SYM-S-004%20Contact%20View.htm [1/16/2014 7:07:30 PM] Abstract ISTH07A1_SYM-S-005: Contact ViewISTH07A1_SYM-S-005: Contact View [SYM-S-005] IMPROVED THERAPEUTIC AGENTS FOR HEMOPHILIA P. Lollar. Pediatrics, Emory University, Atlanta, United States The hemophilia community has witnessed a continuing evolution of therapeutic replacement products since the advent of cryoprecipitate in 1964. Current plasma-derived and recombinant products have an excellent safety profile with respect to infectious risk. Recent years have witnessed the emergence of B domain – deleted and full-length factor VIII (fVIII) products with reduced amounts of anima