Coagulation Factor Activity and Hemostatic Markers of Endothelial Dysfunction in Patients with Peripheral Arterial Disease

Roman E Kalinin, Igor A Suchkov, Nina D Mzhavanadze, Olga N Zhurina, Emma A Klimentova, Vladislav O Povarov, Roman E Kalinin, Igor A Suchkov, Nina D Mzhavanadze, Olga N Zhurina, Emma A Klimentova, Vladislav O Povarov

Abstract

Purpose: We aimed to evaluate the impact of intrinsic coagulation factors and hemostatic markers of endothelial dysfunction on complications in patients with atherosclerotic peripheral arterial disease (PAD).

Materials and methods: This prospective study enrolled 120 PAD patients at Fontaine stages 2b to 3 who underwent open surgical, endovascular, or conservative treatment. Coagulation factors (FVIII, FIX, and FXI) and endothelial hemostatic markers, including von Willebrand factor (vWF) activity and level, soluble endothelial protein C receptor, and plasminogen activator inhibitor-1 (PAI-1) levels, were assessed.

Results: At 3 months after open bypass grafting, activity of FVIII significantly increased from a median of 175% to 233% (P<0.001). At 3 months after endovascular treatment, the activities of FVIII, FIX, and FXI significantly increased from medians of 157%, 180%, and 156% to 184%, 218%, and 181%, respectively (P<0.05). Six patients with increased FVIII activity developed bypass graft thrombosis. Four patients in the endovascular group and three patients in the conservative treatment group with increased activity of vWF developed myocardial infarction (P=0.049). The subjects who developed restenosis had increased vWF activity (P=0.023) and decreased nitric oxide metabolite levels (P=0.003). Three subjects who received conservative treatment and developed PAD progression at 12 months had increased PAI-1 activity (P=0.028).

Conclusion: Patients with advanced PAD had a hypercoagulable status, and performance of open or endovascular revascularization was associated with further hypercoagulability. Increased activity of coagulation factors and altered levels of hemostatic markers of endothelial dysfunction were associated with PAD complications such as graft thrombosis, myocardial infarction, disease progression, and restenosis.

Keywords: Endovascular procedures; Hemostasis; Peripheral arterial disease; Thrombosis; Vascular endothelium.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Changes of coagulation factors and hemostatic markers in group A patients (open bypass grafting). vWF, von Willebrand factor; PAI-1, plasminogen activator inhibitor type 1; sEPCR, soluble endothelial protein C receptor.
Fig. 2
Fig. 2
Changes of coagulation factors and hemostatic markers after endovascular treatment in group B patients (endovascular treatment). vWF, von Willebrand factor; PAI-1, plasminogen activator inhibitor type 1; sEPCR, soluble endothelial protein C receptor.

References

    1. Singh P, Harper Y, Oliphant CS, Morsy M, Skelton M, Askari R, et al. Peripheral interventions and antiplatelet therapy: role in current practice. World J Cardiol. 2017;9:583–593. doi: 10.4330/wjc.v9.i7.583.
    1. Katsanos K, Al-Lamki SA, Parthipun A, Spiliopoulos S, Patel SD, Paraskevopoulos I, et al. Peripheral stent thrombosis leading to acute limb ischemia and major amputation: incidence and risk factors in the aortoiliac and femoropopliteal arteries. Cardiovasc Intervent Radiol. 2017;40:351–359. doi: 10.1007/s00270-016-1513-0.
    1. Sana TR, Janatpour MJ, Sathe M, McEvoy LM, McClanahan TK. Microarray analysis of primary endothelial cells challenged with different inflammatory and immune cytokines. Cytokine. 2005;29:256–269. doi: 10.1016/j.cyto.2004.11.003.
    1. Mohan Rao LV, Esmon CT, Pendurthi UR. Endothelial cell protein C receptor: a multiliganded and multifunctional receptor. Blood. 2014;124:1553–1562. doi: 10.1182/blood-2014-05-578328.
    1. Delvaeye M, Conway EM. Coagulation and innate immune responses: can we view them separately? Blood. 2009;114:2367–2374. doi: 10.1182/blood-2009-05-199208.
    1. Doolittle RF. Coagulation in vertebrates with a focus on evolution and inflammation. J Innate Immun. 2011;3:9–16. doi: 10.1159/000321005.
    1. Sanders YV, Eikenboom J, de Wee EM, van der Bom JG, Cnossen MH, Degenaar-Dujardin ME, et al. Reduced prevalence of arterial thrombosis in von Willebrand disease. J Thromb Haemost. 2013;11:845–854. doi: 10.1111/jth.12194.
    1. Zanolini D, Merlin S, Feola M, Ranaldo G, Amoruso A, Gaidano G, et al. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A. Haematologica. 2015;100:881–892. doi: 10.3324/haematol.2014.123117.
    1. Hoffman M, Pawlinski R. Hemostasis: old system, new players, new directions. Thromb Res. 2014;133 Suppl 1:S1–S2. doi: 10.1016/j.thromres.2014.03.001.
    1. Monroe DM, Hoffman M. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol. 2006;26:41–48. doi: 10.1161/01.ATV.0000193624.28251.83.
    1. Kotschy D, Kotschy M, Socha P, Masłowski L, Kwapisz J, Żuk N, et al. Tissue factor and other hemostatic parameters in patients with advanced peripheral artery disease after endovascular revascularization - search for hemostatic factors which indicate restenosis. Adv Clin Exp Med. 2015;24:93–98. doi: 10.17219/acem/38160.
    1. Srámek A, Kriek M, Rosendaal FR. Decreased mortality of ischaemic heart disease among carriers of haemophilia. Lancet. 2003;362:351–354. doi: 10.1016/S0140-6736(03)14021-4.
    1. Johansson K, Jansson JH, Johansson L, Bylesjö I, Nilsson TK, Eliasson M, et al. Factor XII as a risk marker for hemorrhagic stroke: a prospective cohort study. Cerebrovasc Dis Extra. 2017;7:84–94. doi: 10.1159/000468994.
    1. Kalinin RE, Suchkov IA, Pshennikov AS. [Correction of endothelial dysfunction as a component in treatment for atherosclerosis obliterans of lower-limb arteries] Angiol Sosud Khir. 2014;20:17–22. Russian.
    1. Kalinin RE, Suchkov IA, Nikiforov AA, Phennikov AS. Dynamics of some biochemical parameters in patients with peripheral occlusive arterial disease at different periods following reconstructive surgery. I.P. Pavlov Rus Med Biol Her. 2012;20:41–44. doi: 10.17816/PAVLOVJ2012142-45.
    1. Kalinin RE, Suchkov IA, Pshennikov AS, Slepnev AA. [L-arginine efficiency in treatment for lower limbs arteries atherosclerosis and in prevention of reconstruction zone restenosis] Bull Ivanovo Med Acad. 2013;18:18–21. Russian.
    1. Vischer UM. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost. 2006;4:1186–1193. doi: 10.1111/j.1538-7836.2006.01949.x.
    1. Costa C, Alves M, Durão D, Leal M, Monteiro I. Elevated factor VIII in a patient with acute coronary syndrome. Rev Port Cardiol. 2014;33:181.e1–181.e4. doi: 10.1016/j.repce.2013.09.012.
    1. Lazarenko VA, Bobrovkaya EA, Khruslov MV, YukhanovaI YU. [Assessment of fibrinolytic activity in patients with peripheral arterial disease before and after reconstructive procedures] Thromb Hemost Rheol. 2017;69:55–59. Russian.
    1. Zhalyalov AS, Balandina AN, Kuprash AD, Srivastava A, Shibeko AM. The overview of fibrinolysis system contemporary concepts and of its disorders diagnostic methods. Pediatr Hematol Oncol Immunopathol. 2017;16:69–82. doi: 10.24287/1726-1708-2017-16-1-69-82.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir