TY - JOUR
T1 - Differences in thrombus structure and kinetics in patients with type 2 diabetes mellitus after non ST elevation acute coronary syndrome
AU - Viswanathan, Girish N.
AU - Marshall, Sally M.
AU - Balasubramaniam, Karthik
AU - Badimon, Juan J.
AU - Zaman, Azfar G.
N1 - Funding Information:
Dr Azfar G Zaman was supported by a Clinical Research Leave Fellowship from the British Heart Foundation, UK (FS/033/07) . The BHF funded the study and study specific investigations were supported by the Northumberland, Tyne and Wear Comprehensive Local Research Network ( UKCRN 7338 , National Institute of Health Research, UK). We acknowledge the support from the staff at the Clinical Research Facility and departments of Haematology and Clinical Pathology, Newcastle-upon-Tyne Hospital NHS Foundation Trust . We thank Mrs Heather Cook and Ms Annette Lane, Institute of Cellular Medicine, Newcastle University for sample preparation and storage. We express our gratitude to Dr Kath White and the staff of the EM Research Services, Newcastle University, Newcastle upon Tyne.
PY - 2014/5
Y1 - 2014/5
N2 - 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), μ2/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.
AB - 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), μ2/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.
KW - Antiplatelet therapy
KW - Fibrin structure
KW - Non ST elevation acute coronary syndrome
KW - Thrombus kinetics
KW - Type 2 diabetes mellitus
KW - Whole blood thrombus
UR - http://www.scopus.com/inward/record.url?scp=84898800722&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2014.01.033
DO - 10.1016/j.thromres.2014.01.033
M3 - Article
C2 - 24582462
AN - SCOPUS:84898800722
SN - 0049-3848
VL - 133
SP - 880
EP - 885
JO - Thrombosis Research
JF - Thrombosis Research
IS - 5
ER -