Wybrane czynniki krzepnięcia we krwi chorych z tętniakami aorty brzusznej

Background: Tissue factor (TF), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor A (VEGF-A) present in vascular structures take part in blood coagulation and in organ revascularisation. The concentration of thrombin–antithrombin complexes (TAT) in blood of patients with abdominal aortic aneurysms (AAA) reflects thrombin-generation. Aim: To determine the concentration of TF, TFPI, VEGF-A and TAT complexes in blood of patients with AAA and to consider if these factors after clot formation can play a role in the pathogenesis of abdominal aortic aneurysms. Methods: Forty eight patients (43 men and 5 women) in the age of 59–80 (mean 72) years with AAA were examined. The blood was drawn in the morning to 3.2% natrium citrate in proportion 9:1. The concentration of TF, TFPI, VEGF-A and TAT complexes were measured in plasma with commercial kits using enzyme immunoassay. Results: In plasma of patients with AAA the mean concentration of TF was elevated almost twice and TAT complexes were three times higher compared with controls. But the mean levels of TFPI and VEGF-A were similar as in control group. Conclusions: Increased concentrations of TF and TAT complexes indicate on high thrombin-generation, hypercoagulability and formation in abdominal aortic aneurysm of intraluminal thrombus, which can induce proteolytic processes in aortic wall.Wstęp: Czynnik tkankowy (TF), jego inhibitor (TFPI) i naczyniowo-śródbłonkowy czynnik wzrostu A (VEGF-A) są obecne w strukturach naczyń krwionośnych i biorą udział w procesie krzepnięcia krwi oraz unaczynieniu narządów. Metodą ilustrującą trombinogenezę jest oznaczanie stężenia kompleksów trombina–antytrombina (TAT). Cel: Celem pracy była ocena stężenia TF, TFPI, VEGF-A i kompleksów TAT we krwi chorych z tętniakami aorty brzusznej i próba odpowiedzi na pytanie, czy czynniki te, odpowiedzialne za wytworzenie przyściennego zakrzepu, mogą uczestniczyć w patogenezie tętniaków aorty. Metody: Badaniem objęto 48 pacjentów z tętniakami aorty brzusznej, w tym 43 mężczyzn i 5 kobiet w wieku 59–80 (śr. 72) lat. Krew do badań pobierano z żyły łokciowej do 3,2-procentowego roztworu cytrynianu sodu w proporcji 9:1. W osoczu krwi oznaczano stężenia TF, TFPI, VEGF-A i kompleksów TAT metodami immunoenzymatycznymi przy użyciu komercyjnych zestawów. Wyniki: W osoczu chorych z tętniakami aorty brzusznej stwierdzono prawie 2-krotnie wyższe średnie stężenia TF i ok. 3-krotnie większe stężenia kompleksów TAT w porównaniu z grupą kontrolną. Natomiast średnie wartości TFPI i VEGF-A były podobne jak w grupie kontrolnej. Wnioski: Podwyższone stężenia TF i kompleksów TAT świadczą o zwiększonej generacji trombiny, nadkrzepliwości krwi i wytworzeniu w obrębie tętniaków aorty brzusznej przyściennych zakrzepów, prawdopodobnie wywołujących procesy proteolityczne w ścianie aorty

Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass

Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. Methods: In the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study. Patients with advanced peripheral artery disease (PAD) requiring above-the-knee femoropopliteal bypass surgery without available autologous graft options had undergone implantation with the HAV, a bioengineered human tissue replacement blood vessel. The patients who completed the 24-month primary portion of the study will be evaluated for ≤10 years after implantation. The present mid-term analysis was performed at the 6-year milestone (72 months) for patients followed up for 24 to 72 months. Results: HAVs were implanted in 20 patients at three sites in Poland. Seven patients had discontinued the study before completing the 2-year portion of the study: four after graft occlusion had occurred and three who had died of causes deemed unrelated to the conduit, with the HAV reported as functional at their last visit. The primary results at 24 months showed primary, primary assisted, and secondary patency rates of 58%, 58%, and 74%, respectively. One vessel had developed a pseudoaneurysm deemed possibly iatrogenic; no other signs of structural failure were reported. No rejections or infections of the HAV occurred, and no patient had required amputation of the implanted limb. Of the 20 patients, 13 had completed the primary portion of the study; however, 1 patient had died shortly after 24 months. Of the remaining 12 patients, 3 died of causes unrelated to the HAV. One patient had required thrombectomy twice, with secondary patency achieved. No other interventions were recorded between 24 and 72 months. At 72 months, five patients had a patent HAV, including four patients with primary patency. For the entire study population from day 1 to month 72, the overall primary, primary assisted, and secondary patency rate estimated using Kaplan-Meier analysis was 44%, 45%, and 60% respectively, with censoring for death. No patient had experienced rejection or infection of the HAV, and no patient had required amputation of the implanted limb. Conclusions: The infection-resistant, off-the-shelf HAV could provide a durable alternative conduit in the arterial circuit setting to restore the lower extremity blood supply in patients with PAD, with remodeling into the recipient’s own vessel over time. The HAV is currently being evaluated in seven clinical trials to treat PAD, vascular trauma, and as a hemodialysis access conduit. : Clinical Relevance: Patients with peripheral artery disease who require surgical revascularization need options when autologous grafts are not available. The human acellular vessel (HAV) has been demonstrated to have characteristics similar to those of autologous vessels in terms of resistance to infection, mechanics, and a very low risk of rejection. Safety and performance were evaluated for ≤6 years after implantation of an HAV in a femoropopliteal position. Overall, the secondary patency rate estimated using the Kaplan-Meier method was 60% at 72 months, with 45% primary patency. No infection or rejection episodes had occurred with the HAV conduits. These data have demonstrated the durability of the HAV and suggest the occurrence of cellular remodeling by the host