Thrombin activity and platelet microparticle formation are increased in type 2 diabetic platelets: a potential correlation with caspase activation.

Diabetics suffer from many complications including a prothrombotic condition. Activated platelet membrane provides an anchor, phosphatidylserine, for the attachment of the prothrombinase complex, which allows increased thrombin formation. This study aimed to further elucidate the interrelationship between coagulation proteins and activated platelets in type 2 diabetic blood. We found that there was a significant increase (30 x) in thrombin activity in the type 2 diabetic (ZDF) blood as compared to age-matched (ZL) controls (p<0.001). There was also a significant increase in the number of platelet microparticles in the type 2 diabetic rat compared to the lean control (p<0.001). Further, there were significant increases in caspase-3, -6, and -8 activities in the type 2 diabetic rats as compared to the lean controls (p<0.05). The combination of increased thrombin activity, increased PMP formation and increased caspase activity may contribute to the hypercoagulability of the diabetic blood. These results give more insight into the mechanisms underlying the interrelationship between diabetic platelets and coagulation proteins causing a prothrombotic condition in this patient population at increased risk from thromboembolic events.

[1]  C. Byrne,et al.  Activated protein C resistance: effect of platelet activation, platelet-derived microparticles, and atherogenic lipoproteins. , 1999, Blood.

[2]  D. Green,et al.  Calpain functions in a caspase-independent manner to promote apoptosis-like events during platelet activation. , 1999, Blood.

[3]  E. Passaro,et al.  Apoptosis: programmed cell death. , 1998, Archives of surgery.

[4]  E. Verrier,et al.  Endothelial cell injury in cardiovascular surgery: ischemia-reperfusion. , 1996, The Annals of thoracic surgery.

[5]  M. Carr Diabetes mellitus: a hypercoagulable state. , 2001, Journal of diabetes and its complications.

[6]  E. Remold-O’Donnell,et al.  HEMOSTASIS , THROMBOSIS , AND VASCULAR BIOLOGY Role of Caspase in a Subset of Human Platelet Activation Responses , 1999 .

[7]  D. Kuter,et al.  The mechanism of apoptosis in human platelets during storage , 2000, Transfusion.

[8]  A. Tedgui,et al.  Apoptosis as a Determinant of Atherothrombosis , 2001, Thrombosis and Haemostasis.

[9]  M. Wojtukiewicz,et al.  Platelet activation and its role in thrombin generation in platelet-induced thrombin generation time. , 2000, Thrombosis research.

[10]  A. Sobol,et al.  The role of platelets in diabetes-related vascular complications. , 2000, Diabetes research and clinical practice.

[11]  M. Nishikawa,et al.  Significance of chemokines and activated platelets in patients with diabetes , 2000, Clinical and experimental immunology.

[12]  A. Saraste,et al.  Morphologic and biochemical hallmarks of apoptosis. , 2000, Cardiovascular research.

[13]  G. FitzGerald,et al.  Prothrombinase Acceleration by Oxidatively Damaged Phospholipids* , 2000, The Journal of Biological Chemistry.

[14]  P. Walsh Roles of Platelets and Factor XI in the Initiation of Blood Coagulation by Thrombin , 2001, Thrombosis and Haemostasis.

[15]  M. Bennett,et al.  Thrombin generation by apoptotic vascular smooth muscle cells. , 1997, Blood.

[16]  G. Salvesen,et al.  Caspases: Intracellular Signaling by Proteolysis , 1997, Cell.