Influence of thrombophilic factors on patency of peripheral arterial bypasses in patients with PAOD

Eine wichtige Therapieoption bei fortgeschrittener peripherer arterieller Verschlusskrankheit (pAVK) stellt die Bypassoperation dar. Mit dieser prospektiven Untersuchung wollten wir dazu beitragen zu klären, ob das Vorliegen thrombophiler Risikofaktoren, insbesondere von Antiphospholipid- Antikörpern, einen Einfluss auf die Funktionsdauer der Bypässe hat und zu einer erhöhten Verschlussrate beiträgt. Methodik: Zwischen 2005 und 2007 wurde bei 55 konsekutiv eingeschlossenen Patienten mit pAVK der unteren Extremitäten im Stadium IIb bis IV nach Fontaine, die sich einer elektiven peripheren Bypassoperation unterzogen, präoperativ eine breite Thrombophiliediagnostik durchgeführt. Diese umfasste die Bestimmung von Antithrombin, Protein C, Protein S, Faktor-V-Leiden-Mutation, Prothrombinmutation, Faktor VIII, Lipoprotein(a), Plasminogenaktivatorinhibitor (PAI), Lupus-Antikoagulans, Cardiolipin-Antikörper, Beta-2-Glykoprotein-Antikörper und Homocystein. Die Untersuchung des Lupusantikoagulans, der Cardiolipin- und Beta-2-Glykoprotein- Antikörper wurde 3, 12 und 24 Monate postoperativ wiederholt. Anhand klinischer Kriterien, der standardisierten Gehstrecke und des Knöchel-Arm- Indexes erfolgte die Beurteilung der Bypassfunktion. Die Diagnose eines Verschlusses wurde mittels farbcodierter Duplexsonografie oder Angiografie gestellt. Ergebnisse: 49 Patienten (89,1%) erhielten einen Bypass aus Polytetrafluorethylen (PTFE), darunter ein kombinierter PTFE-/Venenbypass. Bei 6 Patienten (10,9%) wurden autologe Venenbypässe angelegt. In dem 24 Monate betragenden Beobachtungszeitraum kam es bei 14 Patienten (25,5%) zum Bypassverschluss, darunter ein Frühverschluss innerhalb von 30 Tagen postoperativ. Das Vorliegen mindestens eines thrombophilen Risikofaktors wurde bei 63,4% der Patienten ohne Bypassverschluss und bei 64,3% der Patienten mit Bypassverschluss nachgewiesen. Wir fanden keine Hinweise darauf, dass Antiphopholipid-Antikörper wie Lupusantikoagulans und Cardiolipin-Antikörper durch das Verwenden von PTFE als Gefäßersatz induziert werden. Bei den Patienten mit Nachweis von Antiphospholipid-Antikörpern traten Bypassverschlüsse nicht signifikant häufiger auf als bei den Patienten ohne Thrombophilie. Schlussfolgerung: Ein Einfluss thrombophiler Risikofaktoren auf die Funktionsdauer arterieller Rekonstruktionen konnte in dieser Untersuchung weder sicher nachgewiesen noch völlig ausgeschlossen werden. Dies betrifft sowohl das Vorliegen einer Thrombophilie insgesamt als auch das Vorliegen einzelner Thrombophilieparameter. Die Aussagekraft der vorliegenden Studie ist durch die kleine Fallzahl begrenzt. Zudem wird die Rate der Bypassverschlüsse durch viele Faktoren beeinflusst, unter anderem das Erkrankungsstadium, die Qualität des arteriellen Ein- und Abstromes, die Progression der Arteriosklerose in der betroffenen Gefäßregion, die Auswahl des Materials für den Gefäßersatz und die verwendete gerinnungshemmende Medikation. Die Ergebnisse der bisherigen Untersuchungen zum Einfluss der Thrombophilie auf die Bypassverschlussrate sind widersprüchlich, wobei allerdings große, prospektive Studien fehlen.Bypass implantation is an important therapeutic option in patients with advanced peripheral arterial occlusive disease (PAOD). This prospective study was conducted in order to evaluate if thrombophilia (hypercoagulability), especially the presence of antiphospholipid antibodies, influences bypass graft patency and contributes to an increased occlusion rate. Methods: Between the years 2005 and 2007 fifty-five patients with PAOD stage IIb to IV (Fontaine classification) who underwent elective bypass graft surgery were consecutively included and a broad range of laboratory parameters indicating thrombophilia (hypercoagulability), were measured preoperatively, including the following: antithrombin, protein C, protein S, factor V Leiden mutation, prothrombin mutation, factor VIII, lipoprotein(a), plasminogen activator inhibitor (PAI), lupusanticoagulant, cardiolipin-antibodies, beta-2 -glycoprotein-antibodies and homocystein. Postoperatively, measurement of lupusanticoagulant, cardiolipin-antibodies and beta-2-glycoprotein-antibodies was repeated after 3, 12 and 24 months. Bypass graft function was assessed by clinical features, doppler-derived ankle-brachial index and standardized measurement of the walking distance. Occlusion of the bypass graft was diagnosed by duplex ultrasonography or angiography. Results: 49 patients (89.1%) received PTFE (polytetrafluoroethylene) bypass grafts, one of them a combined venous/PTFE bypass graft. In six patients (10.9%) autologous venous bypasses were implanted. During the observational period of 24 months, bypass occlusion occurred in 14 patients (25.5%), one of which was as an early occlusion within 30 days after surgery. Presence of at least one indicator of hypercoagulability was found in 63.4% of the patients with patent bypass grafts and in 64.3% of the patients with occlusion of the bypass graft. Our results did not support the thesis that the use of PTFE induces antiphospholipid antibodies such as lupusanticoagulant and cardiolipin antibodies. In patients with antiphospholipid antibodies bypass occlusion rate was not significantly increased in comparison with patients without thrombophilia. Conclusion: In this study, an influence of hypercoagulability on the duration of arterial bypass graft patency could neither be proved nor be completely excluded. This refers to thrombophilia in general as well as to single laboratory values indicating thrombophilia. The significance of the results is limited by the small number of cases. Apart from that, the occlusion rate of arterial bypass grafts is influenced by many factors, for example the severity of PAOD, the quality of arterial blood inflow and outflow, progression of arteriosclerosis in the vascular area concerned, the choice of material for the bypass graft and the concomitant antithrombotic medication. The results of former studies investigating the influence of thrombophilia on bypass occlusion rate are contradictive, but large prospective studies have not yet been conducted

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479