Semin Thromb Hemost 2013; 39(05): 477-488
DOI: 10.1055/s-0033-1343888
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prothrombotic Changes in Diabetes Mellitus

Olivier Morel
1   Unité de recherche EA 7293 Stress vasculaire et tissulaire en Transplantation, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
2   Pôle d'activité médico-chirurgicale, Cardio-Vasculaire des Hôpitaux, Universitaires de Strasbourg, Strasbourg, France
,
Laurence Jesel
1   Unité de recherche EA 7293 Stress vasculaire et tissulaire en Transplantation, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
2   Pôle d'activité médico-chirurgicale, Cardio-Vasculaire des Hôpitaux, Universitaires de Strasbourg, Strasbourg, France
,
Malak Abbas
3   Plateforme de Recherche et d'Analyses en Sciences de l'Environnement, Ecole Doctorale des Sciences et Technologies, Université Libanaise, Hadath, Beirut, Lebanon, Beyruth, Lebanon
,
Nicolas Morel
4   Pôle d'Urgences, CHU Bordeaux, Bordeaux, France
› Author Affiliations
Further Information

Publication History

Publication Date:
29 April 2013 (online)

Abstract

Although our understanding of vascular pathology has greatly improved in recent years, the cellular and molecular mechanisms underlying the enhanced thrombotic propensity in type 2 diabetes mellitus (T2DM) remain incompletely characterized. Detrimental interactions between activated vascular cells (i.e., platelets, leukocytes, endothelial cells) and the vulnerable atheromatous plaque are a major determinant of the increased atherothrombotic burden in T2DM patients. Endothelial damage and accelerated senescence, impairment of the endothelial progenitor cell repair system, plaque neovascularization and inflammation, decreased clearance of detrimental molecules within the plaque, and increased expression of matrix metalloproteinases may collectively contribute to intraplaque hemorrhage and subsequent rupture. Notably, recent data demonstrates the central importance of the tissue factor-microparticle–mediated pathway in diabetic thrombophilia and cardiovascular complications. Acting as detrimental amplifiers of various biological responses (including thrombogenicity and plaque remodeling), microparticles have also emerged as a key marker of global vascular damage in T2DM patients. Available evidence suggests that targeting the tissue factor-microparticle pathway may be a promising approach for reducing the burden of the atherosclerotic complications of diabetes.

 
  • References

  • 1 Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339 (4) 229-234
  • 2 Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation 2010; 121 (17) 1896-1903
  • 3 Wattanakit K, Lutsey PL, Bell EJ , et al. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost 2012; 108 (3) 508-515
  • 4 Vazzana N, Ranalli P, Cuccurullo C, Davì G. Diabetes mellitus and thrombosis. Thromb Res 2012; 129 (3) 371-377
  • 5 Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009; 53 (5, Suppl): S35-S42
  • 6 Morel O, Kessler L, Ohlmann P, Bareiss P. Diabetes and the platelet: toward new therapeutic paradigms for diabetic atherothrombosis. Atherosclerosis 2010; 212 (2) 367-376
  • 7 Tschoepe D, Roesen P, Esser J , et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost 1991; 17 (4) 433-438
  • 8 Guthikonda S, Alviar CL, Vaduganathan M , et al. Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease. J Am Coll Cardiol 2008; 52 (9) 743-749
  • 9 Morel O, Hugel B, Jesel L , et al. Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. Thromb Haemost 2004; 91 (2) 345-353
  • 10 Kakouros N, Rade JJ, Kourliouros A, Resar JR. Platelet function in patients with diabetes mellitus: from a theoretical to a practical perspective. Int J Endocrinol 2011; 2011: 742719
  • 11 Hernández Vera R, Vilahur G, Ferrer-Lorente R, Peña E, Badimon L. Platelets derived from the bone marrow of diabetic animals show dysregulated endoplasmic reticulum stress proteins that contribute to increased thrombosis. Arterioscler Thromb Vasc Biol 2012; 32 (9) 2141-2148
  • 12 Santilli F, Formoso G, Sbraccia P , et al. Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus. J Thromb Haemost 2010; 8 (4) 828-837
  • 13 Yngen M, Ostenson CG, Li N, Hjemdahl P, Wallén NH. Acute hyperglycemia increases soluble P-selectin in male patients with mild diabetes mellitus. Blood Coagul Fibrinolysis 2001; 12 (2) 109-116
  • 14 Vaidyula VR, Rao AK, Mozzoli M, Homko C, Cheung P, Boden G. Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. Diabetes 2006; 55 (1) 202-208
  • 15 Randriamboavonjy V, Pistrosch F, Bölck B , et al. Platelet sarcoplasmic endoplasmic reticulum Ca2+-ATPase and mu-calpain activity are altered in type 2 diabetes mellitus and restored by rosiglitazone. Circulation 2008; 117 (1) 52-60
  • 16 Morel O, Toti F, Jesel L, Freyssinet JM. Mechanisms of microparticle generation: on the trail of the mitochondrion!. Semin Thromb Hemost 2010; 36 (8) 833-844
  • 17 Morel O, Jesel L, Freyssinet JM, Toti F. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 2011; 31 (1) 15-26
  • 18 Assert R, Scherk G, Bumbure A, Pirags V, Schatz H, Pfeiffer AF. Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro. Diabetologia 2001; 44 (2) 188-195
  • 19 De Cristofaro R, Rocca B, Vitacolonna E , et al. Lipid and protein oxidation contribute to a prothrombotic state in patients with type 2 diabetes mellitus. J Thromb Haemost 2003; 1 (2) 250-256
  • 20 Chappey O, Dosquet C, Wautier MP, Wautier JL. Advanced glycation end products, oxidant stress and vascular lesions. Eur J Clin Invest 1997; 27 (2) 97-108
  • 21 Thomas G, Skrinska V, Lucas FV, Schumacher OP. Platelet glutathione and thromboxane synthesis in diabetes. Diabetes 1985; 34 (10) 951-954
  • 22 Davì G, Catalano I, Averna M , et al. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 1990; 322 (25) 1769-1774
  • 23 Queen LR, Ji Y, Goubareva I, Ferro A. Nitric oxide generation mediated by beta-adrenoceptors is impaired in platelets from patients with Type 2 diabetes mellitus. Diabetologia 2003; 46 (11) 1474-1482
  • 24 Ferreira IA, Eybrechts KL, Mocking AI, Kroner C, Akkerman JW. IRS-1 mediates inhibition of Ca2+ mobilization by insulin via the inhibitory G-protein Gi. J Biol Chem 2004; 279 (5) 3254-3264
  • 25 Ferreira IA, Mocking AI, Feijge MA , et al. Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 2006; 26 (2) 417-422
  • 26 Falcon C, Pfliegler G, Deckmyn H, Vermylen J. The platelet insulin receptor: detection, partial characterization, and search for a function. Biochem Biophys Res Commun 1988; 157 (3) 1190-1196
  • 27 Singla A, Antonino MJ, Bliden KP, Tantry US, Gurbel PA. The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J 2009; 158 (5) e1-e6
  • 28 Geisler T, Anders N, Paterok M , et al. Platelet response to clopidogrel is attenuated in diabetic patients undergoing coronary stent implantation. Diabetes Care 2007; 30 (2) 372-374
  • 29 Vivas D, García-Rubira JC, Bernardo E , et al. Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study (“Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo”). Heart 2011; 97 (10) 803-809
  • 30 Angiolillo DJ, Bernardo E, Ramírez C , et al. Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment. J Am Coll Cardiol 2006; 48 (2) 298-304
  • 31 Morel O, El Ghannudi S, Hess S , et al. The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: roles of white blood cell count and body weight. Thromb Haemost 2012; 108 (2) 338-348
  • 32 Gaborit B, Frère C, Cuisset T, Alessi MC, Dutour A. Enhanced post-clopidogrel platelet reactivity in diabetic patients is independently related to plasma fibrinogen level but not to glycemic control. J Thromb Haemost 2009; 7 (11) 1939-1941
  • 33 Mangiacapra F, Patti G, Peace A , et al. Comparison of platelet reactivity and periprocedural outcomes in patients with versus without diabetes mellitus and treated with clopidogrel and percutaneous coronary intervention. Am J Cardiol 2010; 106 (5) 619-623
  • 34 Erlinge D, Varenhorst C, Braun OO , et al. Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 2008; 52 (24) 1968-1977
  • 35 Geisler T, Mueller K, Aichele S , et al. Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions. Clin Res Cardiol 2010; 99 (11) 743-752
  • 36 Sanchez PL, Morinigo JL, Pabon P , et al. Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome. Heart 2004; 90 (3) 264-269
  • 37 Vaidyula VR, Boden G, Rao AK. Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects. Platelets 2006; 17 (8) 577-585
  • 38 Sage AT, Holtby-Ottenhof S, Shi Y, Damjanovic S, Sharma AM, Werstuck GH. Metabolic syndrome and acute hyperglycemia are associated with endoplasmic reticulum stress in human mononuclear cells. Obesity (Silver Spring) 2012; 20 (4) 748-755
  • 39 Dasu MR, Devaraj S, Jialal I. High glucose induces IL-1beta expression in human monocytes: mechanistic insights. Am J Physiol Endocrinol Metab 2007; 293 (1) E337-E346
  • 40 Venugopal SK, Devaraj S, Yang T, Jialal I. Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha. Diabetes 2002; 51 (10) 3049-3054
  • 41 Gawlowski T, Stratmann B, Stirban AO, Negrean M, Tschoepe D. AGEs and methylglyoxal induce apoptosis and expression of Mac-1 on neutrophils resulting in platelet-neutrophil aggregation. Thromb Res 2007; 121 (1) 117-126
  • 42 Ling L, Shen Y, Wang K , et al. Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization. PLoS ONE 2012; 7 (11) e50739
  • 43 Moreno PR, Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol 2004; 44 (12) 2293-2300
  • 44 Rubenstein DA, Maria Z, Yin W. Glycated albumin modulates endothelial cell thrombogenic and inflammatory responses. J Diabetes Sci Tech 2011; 5 (3) 703-713
  • 45 Otsuka A, Azuma K, Iesaki T , et al. Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat thoracic aorta. Diabetologia 2005; 48 (12) 2667-2674
  • 46 Vogl-Willis CA, Edwards IJ. High glucose-induced alterations in subendothelial matrix perlecan leads to increased monocyte binding. Arterioscler Thromb Vasc Biol 2004; 24 (5) 858-863
  • 47 Moreno PR, Murcia AM, Palacios IF , et al. Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Circulation 2000; 102 (18) 2180-2184
  • 48 Burke AP, Kolodgie FD, Zieske A , et al. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol 2004; 24 (7) 1266-1271
  • 49 Tabas I, Seimon T, Arellano J , et al. The impact of insulin resistance on macrophage death pathways in advanced atherosclerosis. Novartis Found Symp 2007; 286: 99-109 , discussion 109–112, 162–163, 196–203
  • 50 Purushothaman KR, Purushothaman M, Muntner P , et al. Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content: implication for plaque progression in diabetic atherosclerosis. Vasc Med 2011; 16 (2) 103-108
  • 51 Pandolfi A, De Filippis EA. Chronic hyperglycemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications. Genes Nutr 2007; 2 (2) 195-208
  • 52 Olson FJ, Strömberg S, Hjelmgren O, Kjelldahl J, Fagerberg B, Bergström GM. Increased vascularization of shoulder regions of carotid atherosclerotic plaques from patients with diabetes. J Vasc Surg 2011; 54 (5) 1324-1331 , e5
  • 53 Moreno PR, Purushothaman M, Purushothaman KR. Plaque neovascularization: defense mechanisms, betrayal, or a war in progress. Ann N Y Acad Sci 2012; 1254: 7-17
  • 54 Levy AP, Purushothaman KR, Levy NS , et al. Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype: implications for the response to intraplaque hemorrhage and plaque vulnerability. Circ Res 2007; 101 (1) 106-110
  • 55 Osende JI, Badimon JJ, Fuster V , et al. Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control. J Am Coll Cardiol 2001; 38 (5) 1307-1312
  • 56 Davì G, Gennaro F, Spatola A , et al. Thrombin-antithrombin III complexes in type II diabetes mellitus. J Diabetes Complications 1992; 6 (1) 7-11
  • 57 Wasty F, Alavi MZ, Moore S. Distribution of glycosaminoglycans in the intima of human aortas: changes in atherosclerosis and diabetes mellitus. Diabetologia 1993; 36 (4) 316-322
  • 58 Borcea V, Morcos M, Isermann B , et al. Influence of ramipril on the course of plasma thrombomodulin in patients with diabetes mellitus. Vasa 1999; 28 (3) 172-180
  • 59 Fujiwara Y, Tagami S, Kawakami Y. Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy. J Atheroscler Thromb 1998; 5 (1) 21-28
  • 60 Isermann B, Vinnikov IA, Madhusudhan T , et al. Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis. Nat Med 2007; 13 (11) 1349-1358
  • 61 Hernestål-Boman J, Norberg M, Jansson JH , et al. Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study. Cardiovasc Diabetol 2012; 11: 152
  • 62 Tripodi A, Branchi A, Chantarangkul V , et al. Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay. J Thromb Thrombolysis 2011; 31 (2) 165-172
  • 63 Tsimerman G, Roguin A, Bachar A, Melamed E, Brenner B, Aharon A. Involvement of microparticles in diabetic vascular complications. Thromb Haemost 2011; 106 (2) 310-321
  • 64 Jung KH, Chu K, Lee ST , et al. Risk of macrovascular complications in type 2 diabetes mellitus: endothelial microparticle profiles. Cerebrovasc Dis 2011; 31 (5) 485-493
  • 65 Bogdanov VY, Osterud B. Cardiovascular complications of diabetes mellitus: the tissue factor perspective. Thromb Res 2010; 125 (2) 112-118
  • 66 Ichikawa K, Yoshinari M, Iwase M , et al. Advanced glycosylation end products induced tissue factor expression in human monocyte-like U937 cells and increased tissue factor expression in monocytes from diabetic patients. Atherosclerosis 1998; 136 (2) 281-287
  • 67 Boden G, Vaidyula VR, Homko C, Cheung P, Rao AK. Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: effects of insulin and glucose. J Clin Endocrinol Metab 2007; 92 (11) 4352-4358
  • 68 Morel O, Toti F, Hugel B , et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26 (12) 2594-2604
  • 69 Morel O, Pereira B, Averous G , et al. Increased levels of procoagulant tissue factor-bearing microparticles within the occluded coronary artery of patients with ST-segment elevation myocardial infarction: role of endothelial damage and leukocyte activation. Atherosclerosis 2009; 204 (2) 636-641
  • 70 Falati S, Liu Q, Gross P , et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197 (11) 1585-1598
  • 71 Lacroix R, Dignat-George F. Microparticles: new protagonists in pericellular and intravascular proteolysis. Semin Thromb Hemost 2013; 39 (1) 33-39
  • 72 Lozito TP, Tuan RS. Endothelial cell microparticles act as centers of matrix metalloproteinsase-2 (MMP-2) activation and vascular matrix remodeling. J Cell Physiol 2012; 227 (2) 534-549
  • 73 Ettelaie C, Su S, Li C, Collier ME. Tissue factor-containing microparticles released from mesangial cells in response to high glucose and AGE induce tube formation in microvascular cells. Microvasc Res 2008; 76 (3) 152-160
  • 74 Chahed S, Leroyer AS, Benzerroug M , et al. Increased vitreous shedding of microparticles in proliferative diabetic retinopathy stimulates endothelial proliferation. Diabetes 2010; 59 (3) 694-701
  • 75 Steppich BA, Braun SL, Stein A , et al. Plasma TF activity predicts cardiovascular mortality in patients with acute myocardial infarction. Thromb J 2009; 7: 11
  • 76 Porto I, Biasucci LM, De Maria GL , et al. Intracoronary microparticles and microvascular obstruction in patients with ST elevation myocardial infarction undergoing primary percutaneous intervention. Eur Heart J 2012; 33 (23) 2928-2938
  • 77 Sinning JM, Losch J, Walenta K, Böhm M, Nickenig G, Werner N. Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. Eur Heart J 2011; 32 (16) 2034-2041
  • 78 Nozaki T, Sugiyama S, Koga H , et al. Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am Coll Cardiol 2009; 54 (7) 601-608
  • 79 Chen J, Chen S, Chen Y , et al. Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse: possible implications in cerebral ischemic damage. Am J Physiol Endocrinol Metab 2011; 301 (1) E62-E71
  • 80 Curtis AM, Zhang L, Medenilla E , et al. Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population. Cytometry B Clin Cytom 2010; 78 (5) 329-337
  • 81 Chen Y, Feng B, Li X, Ni Y, Luo Y. Plasma endothelial microparticles and their correlation with the presence of hypertension and arterial stiffness in patients with type 2 diabetes. J Clin Hypertens (Greenwich) 2012; 14 (7) 455-460
  • 82 Pirro M, Schillaci G, Bagaglia F , et al. Microparticles derived from endothelial progenitor cells in patients at different cardiovascular risk. Atherosclerosis 2008; 197 (2) 757-767
  • 83 Feng B, Chen Y, Luo Y, Chen M, Li X, Ni Y. Circulating level of microparticles and their correlation with arterial elasticity and endothelium-dependent dilation in patients with type 2 diabetes mellitus. Atherosclerosis 2010; 208 (1) 264-269
  • 84 Koga H, Sugiyama S, Kugiyama K , et al. Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2005; 45 (10) 1622-1630
  • 85 Huang PH, Huang SS, Chen YH , et al. Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria. J Hypertens 2010; 28 (8) 1655-1665
  • 86 Wiviott SD, Braunwald E, Angiolillo DJ , et al; TRITON-TIMI 38 Investigators. 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 (16) 1626-1636
  • 87 James S, Angiolillo DJ, Cornel JH , et al; PLATO Study Group. 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 (24) 3006-3016
  • 88 Wang TH, Bhatt DL, Fox KA , et al; CHARISMA Investigators. An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial. Eur Heart J 2007; 28 (18) 2200-2207
  • 89 Gerrits AJ, Koekman CA, Yildirim C, Nieuwland R, Akkerman JW. Insulin inhibits tissue factor expression in monocytes. J Thromb Haemost 2009; 7 (1) 198-205
  • 90 Henriksson CE, Hellum M, Haug KB , et al. Anticoagulant effects of an antidiabetic drug on monocytes in vitro. Thromb Res 2011; 128 (5) e100-e106
  • 91 Nomura S, Omoto S, Yokoi T , et al. Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin level in patients with type 2 diabetes mellitus. Int J Gen Med 2011; 4: 539-545
  • 92 Esposito K, Maiorino MI, Di Palo C , et al. Effects of pioglitazone versus metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes—a randomized controlled trial. Diabetes Obes Metab 2011; 13 (5) 439-445
  • 93 Tramontano AF, O'Leary J, Black AD, Muniyappa R, Cutaia MV, El-Sherif N. Statin decreases endothelial microparticle release from human coronary artery endothelial cells: implication for the Rho-kinase pathway. Biochem Biophys Res Commun 2004; 320 (1) 34-38
  • 94 Sommeijer DW, Joop K, Leyte A, Reitsma PH, ten Cate H. Pravastatin reduces fibrinogen receptor gpIIIa on platelet-derived microparticles in patients with type 2 diabetes. J Thromb Haemost 2005; 3 (6) 1168-1171
  • 95 Tehrani S, Mobarrez F, Antovic A , et al. Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia. Thromb Res 2010; 126 (3) e225-e231
  • 96 Nomura S, Inami N, Shouzu A , et al. The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients. Platelets 2009; 20 (1) 16-22
  • 97 Koh KK, Quon MJ, Han SH, Ahn JY, Lee Y, Shin EK. Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. Atherosclerosis 2007; 194 (1) 230-237
  • 98 Diamant M, Tushuizen ME, Abid-Hussein MN , et al. Simvastatin-induced endothelial cell detachment and microparticle release are prenylation dependent. Thromb Haemost 2008; 100 (3) 489-497
  • 99 Morel O, Jesel L, Hugel B , et al. Protective effects of vitamin C on endothelium damage and platelet activation during myocardial infarction in patients with sustained generation of circulating microparticles. J Thromb Haemost 2003; 1 (1) 171-177
  • 100 Nomura S, Shouzu A, Omoto S , et al. Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes. J Atheroscler Thromb 2009; 16 (2) 83-90
  • 101 Morel O, Luca F, Grunebaum L , et al. Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles. Int J Obes (Lond) 2011; 35 (12) 1479-1486
  • 102 Cheng V, Kashyap SR, Schauer PR, Kirwan JP, McCrae KR. Restoration of glycemic control in patients with type 2 diabetes mellitus after bariatric surgery is associated with reduction in microparticles. Surg Obes Relat Dis 2011;
  • 103 Shimazu T, Inami N, Satoh D , et al. Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients. J Thromb Thrombolysis 2009; 28 (4) 429-435