Differences in thrombus structure and kinetics in patients with type 2 diabetes mellitus after non ST elevation acute coronary syndrome

Girish N Viswanathan, Sally M Marshall, Karthik Balasubramaniam, Juan J Badimon, Azfar G Zaman, Girish N Viswanathan, Sally M Marshall, Karthik Balasubramaniam, Juan J Badimon, Azfar G Zaman

Abstract

Introduction: Despite optimal secondary prevention therapy following non-ST elevation acute coronary syndrome (NSTE-ACS), recurrent thrombotic events are more frequent in patients with type 2 diabetes mellitus (T2DM).

Materials and methods: This exploratory study was aimed to evaluate quantitative and qualitative aspects of thrombus. In 28 patients with and without T2DM treated with aspirin and clopidogrel we assessed thrombus quantity using an ex-vivo chamber, platelet reactivity, thrombus ultrastructure and thrombus kinetics one week after NSTE-ACS.

Results: T2DM was associated with increased thrombus [14861 (8003 to 30161) vs 8908 (6812 to 11996), μ(2)/mm, median (IQR), p=0.045] and platelet reactivity. In addition, diabetic thrombus showed lower visco-elastic tensile strength [(-0.2(-1.7 to 0.7) vs 1.0(-0.9 to 3.3), p=0.044)] and was more resistant to autolysis [(27.8(11.7 to 70.7) vs 78.8(68.5 to109.6) mm/min, p=0.002)]. On SEM, fibrin fibres in diabetes were thinner, with higher lateral interlinkage and mesh-like organisation. Thrombus quantity correlated inversely with thrombus retraction (r=-0.450 p=0.016) but not with platelet reactivity (r=0.153, p=0.544).

Conclusions: Despite optimal antiplatelet therapy, T2DM patients after NSTE-ACS developed increased thrombus of lower tensile strength and slower retraction. SEM revealed loosely arranged fibrin fibres. Our data showed significant differences in the magnitude as well as structural and mechanistic characteristics of thrombus in patients with T2DM.

Keywords: Antiplatelet therapy; Fibrin structure; Non ST elevation acute coronary syndrome; Thrombus kinetics; Type 2 diabetes mellitus; Whole blood thrombus.

Copyright © 2014. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Thrombus of patients from Badimon chamber (left and middle column) after staining with modified Mason trichrome. Platelet rich thrombus was stained in pink with the tunica media of the aortic tissue stained in green. The right column shows the representative images of the thrombus under scanning electron microscopy (SEM) at 3.4X103 times magnification. Diabetic thrombus was increased in quantity occupying a larger surface area over the tunica media. The SEM appearance showed loosely woven thrombus with thinner fibrin fibres and mesh like appearance with less twisted arrangement compared to those without diabetes.
Fig. 2
Fig. 2
Correlation graphs between thrombus area and various parameters. Correlation analysis: a. Serum fibrinogen correlated with thrombus area, r = 0.551, p = 0.002. b. Thrombus retraction or autolysis correlated with thrombus area, r = − 0.450. p = 0.016.

References

    1. Fox C.S., Coady S., Sorlie P.D., D'Agostino R.B., Sr., Pencina M.J., Vasan R.S. Increasing Cardiovascular Disease Burden Due to Diabetes Mellitus: The Framingham Heart Study. Circulation. 2007;115:1544–1550.
    1. Krempf M., Parhofer K.G., Steg P.G., Bhatt D.L., Ohman E.M., Rother J. Cardiovascular event rates in diabetic and nondiabetic individuals with and without established atherothrombosis (from the REduction of Atherothrombosis for Continued Health [REACH] Registry) Am J Cardiol. 2010;105:667–671.
    1. Donahoe S.M., Stewart G.C., McCabe C.H., Mohanavelu S., Murphy S.A., Cannon C.P. Diabetes and Mortality Following Acute Coronary Syndromes. JAMA. 2007;298:765–775.
    1. Anderson J.L., Adams C.D., Antman E.M., Bridges C.R., Califf R.M., Casey D.E., Jr. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50:e1–e157.
    1. Bassand J.-P., Hamm C.W., Ardissino D., Boersma E., Budaj A., Fernandez-Alvez F. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28:1598–1660.
    1. Viswanathan G.N., Marshall S.M., Schechter C.B., Balasubramaniam K., Badimon J.J., Zaman A.G. Thrombus and antiplatelet therapy in type 2 diabetes mellitus. A prospective study after non-ST elevation acute coronary syndrome and a randomised, blinded, placebo-controlled study in stable angina. Thromb Haemost. 2012;108:937–945.
    1. Badimon L., Badimon J.J., Turitto V.T., Vallabhajosula S., Fuster V. Platelet thrombus formation on collagen type I. A model of deep vessel injury. Influence of blood rheology, von Willebrand factor, and blood coagulation. Circulation. 1988;78:1431–1442.
    1. Natarajan A., Marshall S.M., Worthley S.G., Badimon J.J., Zaman A.G. The presence of coronary artery disease increases platelet-dependent thrombosis in patients with type 2 diabetes mellitus. J Thromb Haemost. 2008;6:2210–2213.
    1. Reikvam H., Steien E., Hauge B., Liseth K., Hagen K.G., Størkson R. Thrombelastography. Transfus Apher Sci. 2009;40:119–123.
    1. Rivard G.E., Brummel-Ziedins K.E., Mann K.G., Fan L., Hofer A., Cohen E. Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography. J Thromb Haemost. 2005;3:2039–2043.
    1. Gurbel P.A., Becker R.C., Mann K.G., Steinhubl S.R., Michelson A.D. Platelet Function Monitoring in Patients With Coronary Artery Disease. J Am Coll Cardiol. 2007;50:1822–1834.
    1. Marcucci R., Gori A.M., Paniccia R., Giusti B., Valente S., Giglioli C. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation. 2009;119:237–242.
    1. Angiolillo D.J., Capranzano P., Desai B., Shoemaker S.B., Charlton R., Zenni M.M. Impact of P2Y12 Inhibitory Effects Induced by Clopidogrel on Platelet Procoagulant Activity in Type 2 Diabetes Mellitus Patients. Thromb Res. 2009;124:318–322.
    1. Grant P.J. Diabetes mellitus as a prothrombotic condition. J Intern Med. 2007;262:157–172.
    1. Pieters M., Covic N., Loots du T., van der Westhuizen F.H., van Zyl D.G., Rheeder P. The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects. Thromb Haemost. 2006;96:623–629.
    1. Dunn E.J., Ariëns R.A.S., Grant P.J. The influence of type 2 diabetes on fibrin structure and function. Diabetologia. 2005;48:1198–1206.
    1. Pieters M., Covic N., van der Westhuizen F.H., Nagaswami C., Baras Y., Toit Loots D. Glycaemic control improves fibrin network characteristics in type 2 diabetes - a purified fibrinogen model. Thromb Haemost. 2008;99:691–700.
    1. Alzahrani S.H., Ajjan R.A. Review article: Coagulation and fibrinolysis in diabetes. Diab Vasc Dis Res. 2010;7:260–273.
    1. Ajjan R.A., Standeven K.F., Khanbhai M., Phoenix F., Gersh K.C., Weisel J.W. Effects of Aspirin on Clot Structure and Fibrinolysis Using a Novel In Vitro Cellular System. Arterioscler Thromb Vasc Biol. 2009;29:712–717.
    1. Balasubramaniam K., Viswanathan G.N., Marshall S.M., Zaman A.G. Increased atherothrombotic burden in patients with diabetes mellitus and acute coronary syndrome: a review of antiplatelet therapy. Cardiol Res Pract. 2012;2012:909154.
    1. Angiolillo D.J., Saucedo J.F., DeRaad R., Frelinger A.L., Gurbel P.A., Costigan T.M. Increased Platelet Inhibition After Switching From Maintenance Clopidogrel to Prasugrel in Patients With Acute Coronary Syndromes: Results of the SWAP (SWitching Anti Platelet) Study. J Am Coll Cardiol. 2010;56:1017–1023.
    1. Serebruany V., Pokov I., Kuliczkowski W., Chesebro J., Badimon J. Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease. Thromb Haemost. 2008;100:76–82.
    1. Sambu N., Hobson A., Curzen N. "Short" thrombelastography as a test of platelet reactivity in response to antiplatelet therapy: validation and reproducibility. Platelets. 2011;22:210–216.
    1. Price M.J., Berger P.B., Teirstein P.S., Tanguay J.-F., Angiolillo D.J., Spriggs D. Standard- vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention. JAMA. 2011;305:1097–1105.
    1. Collet J.P., Cuisset T., Range G., Cayla G., Elhadad S., Pouillot C. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012;367:2100–2109.
    1. Hess K., Marx N., Lehrke M. Cardiovascular disease and diabetes: the vulnerable patient. Eur Heart J. 2012;14:B4–B13.
    1. Bhatt D.L. What makes platelets angry: diabetes, fibrinogen, obesity, and impaired response to antiplatelet therapy? J Am Coll Cardiol. 2008;52:1060–1061.
    1. Moreno P.R., Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol. 2004;44:2293–2300.
    1. Wiviott S.D., Braunwald E., Angiolillo D.J., Meisel S., Dalby A.J., Verheugt F.W.A. Greater Clinical Benefit of More Intensive Oral Antiplatelet Therapy With Prasugrel in Patients With Diabetes Mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation. 2008;118:1626–1636.
    1. James S., Angiolillo D.J., Cornel J.H., Erlinge D., Husted S., Kontny F. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J. 2010;31:3006–3016.

Source: PubMed

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