Time course of changes in in vitro platelet function and plasma von willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag) in the diabetic rat.
The relationship between platelet abnormalities and vessel wall changes in diabetes is not known. We have examined the time course of alterations in in vitro platelet function and endothelial damage, as assessed by measurement of plasma levels of von Willebrand factor (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag), in streptozotocin-induced diabetic rats. Platelet aggregation and the platelet release reaction in response to ADP, thrombin, and collagen were measured in suspensions of washed platelets prepared from rats 3, 7, 14, or 28 days after induction of diabetes and in control animals. Platelets from diabetic animals showed enhanced aggregation response to ADP as early as 3 days after induction of diabetes and became hyperresponsive to thrombin after 7 days, compared to control platelets. Thrombin-induced release of serotonin was greater in platelets from diabetic animals at 14 days. Collagen-induced responses were not different at any time studied. VIIIR:WF was determined by ristocetin-induced platelet agglutination time in gel-filtered platelets, and VIIIR:Ag was determined by immunoelectrophoretic technique. VIIIR:WF and VIIIR:Ag were significantly enhanced in plasma from rats at 28 days after induction of diabetes and VIIIR:Ag was enhanced in plasma from rats at 14 days after induction of diabetes, but at the earlier times studied, neither were different from values in plasma from control-treated rats. Changes in VIIIR:WF and VIIIR:Ag therefore occurred later than the changes in platelet function. Plasma cholesterol concentrations were not significantly different at any of the times studied, but plasma triglyceride concentrations were significantly increased at 3 days and remained increased with further durations of diabetes. This may have contributed to the observed platelet and vessel wall changes. If these in vitro alterations reflect in vivo behavior, then platelet alterations occur before vessel wall changes and therefore do not appear to be a consequence of such changes in experimental diabetes mellitus.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000032:analysis*; D001779:Blood Coagulation Factors / Q000032:analysis*; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000503:physiopathology; D005169:Factor VIII / Q000032:analysis / Q000276:immunology*; D008297:Male; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis*
D000941:Antigens; D001779:Blood Coagulation Factors; D001786:Blood Glucose; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D005169:Factor VIII; D002784:Cholesterol; D013917:Thrombin