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Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Research Article

Outcomes of Anticoagulant Therapy with Low-Molecular-Weight Heparin (LMWH) and Warfarin for Thromboangiitis Obliterans (TAO)

Author(s): Jiangping Gao*, Liuhuan Huang and Jianli Wang

Volume 19 , Issue 6 , 2021

Published on: 18 January, 2021

Page: [655 - 662] Pages: 8

DOI: 10.2174/1570161119666210118125424

Price: $65

Abstract

Background: Thromboangiitis obliterans (TAO) is a chronic, non-atherosclerotic, progressive inflammatory vascular disease affecting the small- and medium-size arteries and veins of the extremities.

Objective: To evaluate whether long-term anticoagulation with low-molecular-weight heparin (LMWH) and warfarin is beneficial for treating the inflammation and symptoms associated with TAO.

Methods: Patients with TAO who underwent anticoagulation as the mainstay of treatment were included in this prospective study. Rest pain relief and healing of trophic lesions (as the primary and secondary endpoint) were investigated at Day 14 and after 6 months of follow-up. High sensitivity C-reactive protein (hsCRP), monocyte count, and ankle-brachial index (ABI) were recorded, and the difference was compared before and after 2-week anticoagulation. The Chi-square test was used to compare the difference between anticoagulant and aspirin groups (based on the literature).

Results: From 2014 to 2019, 18 patients were included. Only 1 patient with wet gangrene received endo-therapy for a failing stent at the start of treatment. After ~14 days, 12 of 13 (92%) patients showed complete ulcer healing, and 17 of 18 (94%) patients showed complete relief from rest pain. Monocyte-counts and hsCRP levels decreased significantly (p<0.001) after a 2-week period of anticoagulation with LMWH. The mean follow-up was 2.6 years (range 0.5-5 years). At 6 months, all patients showed relief of rest pain and complete healing of trophic lesions. All endpoints were significantly improved compared with the aspirin group (p<0.01), and no rest pain or ulcer/gangrene recurred during follow-up.

Conclusion: Anticoagulant therapy may alleviate the inflammation and symptoms of TAO.

Keywords: Thromboangiitis obliterans, Buerger's disease, inflammation, anticoagulation, high-sensitivity C-reactive protein, critical limb ischaemia.

[1]
Olin JW. Thromboangiitis obliterans (Buerger’s disease). N Engl J Med 2000; 343(12): 864-9.
[http://dx.doi.org/10.1056/NEJM200009213431207] [PMID: 10995867]
[2]
Papa MZ, Rabi I, Adar R. A point scoring system for the clinical diagnosis of Buerger’s disease. Eur J Vasc Endovasc Surg 1996; 11(3): 335-9.
[http://dx.doi.org/10.1016/S1078-5884(96)80081-5] [PMID: 8601245]
[3]
Olin JW, Shih A. Thromboangiitis obliterans (Buerger’s disease). Curr Opin Rheumatol 2006; 18(1): 18-24.
[http://dx.doi.org/10.1097/01.bor.0000198000.58073.aa] [PMID: 16344615]
[4]
Sugimoto M, Miyachi H, Morimae H, et al. Fate of ischemic limbs in patients with Buerger’s disease based on our 30-year experience: does smoking have a definitive impact on the late loss of limbs? Surg Today 2015; 45(4): 466-70.
[http://dx.doi.org/10.1007/s00595-014-0904-6] [PMID: 24845736]
[5]
Kim DH, Ko YG, Ahn CM, et al. Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease. J Vasc Surg 2018; 67(6): 1769-77.
[http://dx.doi.org/10.1016/j.jvs.2017.09.020] [PMID: 29157680]
[6]
Ye K, Shi H, Qin J, et al. Outcomes of endovascular recanalization versus autogenous venous bypass for thromboangiitis obliterans patients with critical limb ischemia due to tibioperoneal arterial occlusion. J Vasc Surg 2017; 66(4): 1133-1142.e1.
[http://dx.doi.org/10.1016/j.jvs.2017.03.425] [PMID: 28697938]
[7]
Esmon CT. The interactions between inflammation and coagulation. Br J Haematol 2005; 131(4): 417-30.
[http://dx.doi.org/10.1111/j.1365-2141.2005.05753.x] [PMID: 16281932]
[8]
Borensztajn K, Peppelenbosch MP, Spek CA. Factor Xa: at the crossroads between coagulation and signaling in physiology and disease. Trends Mol Med 2008; 14(10): 429-40.
[http://dx.doi.org/10.1016/j.molmed.2008.08.001] [PMID: 18774340]
[9]
van der Poll T, de Boer JD, Levi M. The effect of inflammation on coagulation and vice versa. Curr Opin Infect Dis 2011; 24(3): 273-8.
[http://dx.doi.org/10.1097/QCO.0b013e328344c078] [PMID: 21330919]
[10]
Tanaka K. Pathology and pathogenesis of Buerger’s disease. Int J Cardiol 1998; 66(Suppl. 1): S237-42.
[http://dx.doi.org/10.1016/S0167-5273(98)00174-0] [PMID: 9951825]
[11]
Piazza G, Creager MA. Thromboangiitis obliterans. Circulation 2010; 121(16): 1858-61.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.942383] [PMID: 20421527]
[12]
Feistritzer C, Wiedermann CJ. Effects of anticoagulant strategies on activation of inflammation and coagulation. Expert Opin Biol Ther 2007; 7(6): 855-70.
[http://dx.doi.org/10.1517/14712598.7.6.855] [PMID: 17555371]
[13]
Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26(3): 517-38.
[http://dx.doi.org/10.1016/S0741-5214(97)70045-4] [PMID: 9308598]
[14]
Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 45(Suppl. S): S5-S67.
[http://dx.doi.org/10.1016/j.jvs.2006.12.037] [PMID: 17223489]
[15]
Shionoya S. Diagnostic criteria of Buerger’s disease. Int J Cardiol 1998; 66(Suppl. 1): S243-5.
[http://dx.doi.org/10.1016/S0167-5273(98)00175-2] [PMID: 9951826]
[16]
Małecki R, Zdrojowy K, Adamiec R. Thromboangiitis obliterans in the 21st century--a new face of disease. Atherosclerosis 2009; 206(2): 328-34.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.01.042] [PMID: 19269635]
[17]
Dimmick SJ, Goh AC, Cauzza E, et al. Imaging appearances of Buerger’s disease complications in the upper and lower limbs. Clin Radiol 2012; 67(12): 1207-11.
[http://dx.doi.org/10.1016/j.crad.2012.04.005] [PMID: 22784658]
[18]
Fujii Y, Soga J, Nakamura S, et al. Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger’s disease): relationship between corkscrew type and prevalence of ischemic ulcers. Circ J 2010; 74(8): 1684-8.
[http://dx.doi.org/10.1253/circj.CJ-09-0878] [PMID: 20534945]
[19]
Kaptoge S, Di Angelantonio E, Lowe G, et al. Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375(9709): 132-40.
[http://dx.doi.org/10.1016/S0140-6736(09)61717-7] [PMID: 20031199]
[20]
Ridker PM. C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol 2007; 49(21): 2129-38.
[http://dx.doi.org/10.1016/j.jacc.2007.02.052] [PMID: 17531663]
[21]
Ridker PM, Cook N. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation 2004; 109(16): 1955-9.
[http://dx.doi.org/10.1161/01.CIR.0000125690.80303.A8] [PMID: 15051634]
[22]
Neumann FJ, Ott I, Marx N, et al. Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity. Arterioscler Thromb Vasc Biol 1997; 17(12): 3399-405.
[http://dx.doi.org/10.1161/01.ATV.17.12.3399] [PMID: 9437185]
[23]
Herbert JM, Savi P, Laplace MC, Lale A. IL-4 inhibits LPS-, IL-1 beta- and TNF alpha-induced expression of tissue factor in endothelial cells and monocytes. FEBS Lett 1992; 310(1): 31-3.
[http://dx.doi.org/10.1016/0014-5793(92)81139-D] [PMID: 1526281]
[24]
Poitevin S, Cochery-Nouvellon E, Dupont A, Nguyen P. Monocyte IL-10 produced in response to lipopolysaccharide modulates thrombin generation by inhibiting tissue factor expression and release of active tissue factor-bound microparticles. Thromb Haemost 2007; 97(4): 598-607.
[http://dx.doi.org/10.1160/TH06-11-0622] [PMID: 17393023]
[25]
Leroyer AS, Isobe H, Lesèche G, et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol 2007; 49(7): 772-7.
[http://dx.doi.org/10.1016/j.jacc.2006.10.053] [PMID: 17306706]
[26]
Shantsila E, Lip GY. Monocytes in acute coronary syndromes. Arterioscler Thromb Vasc Biol 2009; 29(10): 1433-8.
[http://dx.doi.org/10.1161/ATVBAHA.108.180513] [PMID: 19229072]
[27]
Basavaraj MG, Sovershaev MA, Egorina EM, et al. Circulating monocytes mirror the imbalance in TF and TFPI expression in carotid atherosclerotic plaques with lipid-rich and calcified morphology. Thromb Res 2012; 129(4): e134-41.
[http://dx.doi.org/10.1016/j.thromres.2011.11.044] [PMID: 22178066]
[28]
Gratchev A, Sobenin I, Orekhov A, Kzhyshkowska J. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology 2012; 217(5): 476-82.
[http://dx.doi.org/10.1016/j.imbio.2012.01.008] [PMID: 22325375]
[29]
Nasir K, Guallar E, Navas-Acien A, Criqui MH, Lima JA. Relationship of monocyte count and peripheral arterial disease: results from the National Health and Nutrition Examination Survey 1999-2002. Arterioscler Thromb Vasc Biol 2005; 25(9): 1966-71.
[http://dx.doi.org/10.1161/01.ATV.0000175296.02550.e4] [PMID: 15976323]
[30]
Gao JP, Huang LH, Wang JL. Perioperative changes of peripheral monocyte cells in patients with atherosclerosis obliteration. Chin J Vasc Surg 2018; 3: 95-100.
[31]
Magri D, Vasilas P, Muto A, et al. Elevated monocytes in patients with critical limb ischemia diminish after bypass surgery. J Surg Res 2011; 167(1): 140-50.
[http://dx.doi.org/10.1016/j.jss.2009.06.014] [PMID: 19854451]
[32]
Fiessinger JN, Schäfer M. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. The TAO Study. Lancet 1990; 335(8689): 555-7.
[http://dx.doi.org/10.1016/0140-6736(90)90346-7] [PMID: 1689791]
[33]
Klein-Weigel PF, Bimmler M, Hempel P, et al. G-protein coupled receptor auto-antibodies in thromboangiitis obliterans (Buerger’s disease) and their removal by immunoadsorption. Vasa 2014; 43(5): 347-52.
[http://dx.doi.org/10.1024/0301-1526/a000372] [PMID: 25147011]
[34]
Olin JW. Thromboangiitis obliterans: 110 years old and little progress made. J Am Heart Assoc 2018; 7(23)
[http://dx.doi.org/10.1161/JAHA.118.011214] [PMID: 30571606]
[35]
Tang J, Gan S, Zheng M, Jiang Y, Feng Y, Miao J. Efficacy of endovascular radiofrequency ablation for thromboangiitis obliterans (Buerger’s Disease). Ann Vasc Surg 2017; 42: 78-83.
[http://dx.doi.org/10.1016/j.avsg.2016.11.012] [PMID: 28341508]
[36]
Fazeli B, Rezaee SA. A review on thromboangiitis obliterans pathophysiology: thrombosis and angiitis, which is to blame? Vascular 2011; 19(3): 141-53.
[http://dx.doi.org/10.1258/vasc.2010.ra0045] [PMID: 21652666]
[37]
Cacione DG, Baptista-Silva JC, Macedo CR. Pharmacological treatment for Buerger’s disease. Cochrane Database Syst Rev 2016; 2
[PMID: 26828199]
[38]
Bozkurt AK, Köksal C, Demirbas MY, et al. Turkish Buerger’s Disease Research Group. A randomized trial of intravenous iloprost (a stable prostacyclin analogue) versus lumbar sympathectomy in the management of Buerger’s disease. Int Angiol 2006; 25(2): 162-8.
[PMID: 16763533]
[39]
Oral iloprost in the treatment of thromboangiitis obliterans (Buerger's disease): a double-blind, randomised, placebo-controlled trial. The European TAO study group. Eur J Vasc Endovasc Surg 1998; 15: 300-7.
[40]
Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg 2006; 44(4): 732-9.
[http://dx.doi.org/10.1016/j.jvs.2006.06.023] [PMID: 16926085]
[41]
Akar AR, Durdu S, Baran C. Letter by Akar et al. regarding article, “Effect of autologous bone-marrow cell transplantation on ischemic ulcer in patients with Buerger’s disease”. Circ J 2008; 72(4): 684.
[http://dx.doi.org/10.1253/circj.72.684] [PMID: 18362447]
[42]
Patwa JJ, Krishnan A. Buerger’s Disease (Thromboangiitis obliterans)- management by Ilizarov’s technique of horizontal distraction. A retrospective study of 60 cases. Indian J Surg 2011; 73(1): 40-7.
[http://dx.doi.org/10.1007/s12262-010-0186-1] [PMID: 22211037]
[43]
Maslowski L, McBane R, Alexewicz P, Wysokinski WE. Antiphospholipid antibodies in thromboangiitis obliterans. Vasc Med 2002; 7(4): 259-64.
[http://dx.doi.org/10.1191/1358863x02vm452oa] [PMID: 12710840]
[44]
Jorge VC, Araújo AC, Noronha C, Panarra A, Riso N, Vaz Riscado M. Buerger's disease (Thromboangiitis obliterans): a diagnostic challenge. BMJ Case Rep 2011.
[45]
Maclean PS, Tait RC, Rumley A, McMahon AD, Lowe GD. Anticoagulation with warfarin downregulates inflammation. J Thromb Haemost 2003; 1(8): 1838-9.
[http://dx.doi.org/10.1046/j.1538-7836.2003.t01-1-00372.x] [PMID: 12911602]
[46]
Downing LJ, Strieter RM, Kadell AM, Wilke CA, Greenfield LJ, Wakefield TW. Low-dose low-molecular-weight heparin is anti-inflammatory during venous thrombosis. J Vasc Surg 1998; 28(5): 848-54.
[http://dx.doi.org/10.1016/S0741-5214(98)70060-6] [PMID: 9808852]
[47]
Busch G, Seitz I, Steppich B, et al. Coagulation factor Xa stimulates interleukin-8 release in endothelial cells and mononuclear leukocytes: implications in acute myocardial infarction. Arterioscler Thromb Vasc Biol 2005; 25(2): 461-6.
[http://dx.doi.org/10.1161/01.ATV.0000151279.35780.2d] [PMID: 15550696]
[48]
Branch KR, Probstfield JL, Eikelboom JW, et al. Rivaroxaban with or without aspirin in patients with heart failure and chronic coronary or peripheral artery disease. Circulation 2019; 140(7): 529-37.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.039609] [PMID: 31163978]
[49]
Connolly SJ, Eikelboom JW, Bosch J, et al. COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018; 391(10117): 205-18.
[http://dx.doi.org/10.1016/S0140-6736(17)32458-3] [PMID: 29132879]
[50]
Junqueira DR, Zorzela LM, Perini E. Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev 2017; 4(4)
[http://dx.doi.org/10.1002/14651858.CD007557.pub3] [PMID: 28431186]

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