Spontaneous whole blood platelet aggregation, hematological variables and complications in insulin-dependent diabetes mellitus: The Pittsburgh Epidemiology of Diabetes Complications Study

The role of platelet aggregation in the pathogenesis of diabetes complications remains unclear despite a number of reports suggesting associations in univariate analyses. The Pittsburgh Epidemiology of Diabetes Complications Study is a prospective study initiated in 1985 to determine risk factors for the development of complications in insulin-dependent diabetes mellitus (IDDM). This report focuses on the cross-sectional correlation between platelet count and aggregation and IDDM complications, in 563 participants aged 18 years and older seen at baseline. Spontaneous whole blood platelet aggregation (SWBPA) and other hematological variables [hematocrit, total platelet count (TPC), red blood cell count (RBC), fibrinogen and white blood cell count (WBC)] were evaluated as risk factors for IDDM complications (nephropathy, neuropathy, and retinopathy) in the baseline cross-sectional data of the Pittsburgh Epidemiology of Diabetes Complications Study. SWBPA was determined by a method based on the percentage fall in platelet count after shaking a fresh citrated blood sample kept at 37°C. Subjects with chronic aspirin use or on dialysis were excluded from analysis. An increased TPC was observed in subjects with overt nephropathy (291.4 ± 65.1 versus 261.2 ± 64.9, p < 0.001) compared with subjects without nephropathy. Similar results were found for proliferative retinopathy. The association with nephropathy (but not with retinopathy) persisted in multivariate analyses. Significantly increased platelet aggregation by shaking method was also found in subjects with proliferative retinopathy when compared with subjects with background retinopathy (9.6 ± 8.5 versus 8.3 ± 5.0, p < 0.05), and for those with neuropathy when compared with subjects without (9.7 ± 7.6 versus 7.4 ± 4.8, p < 0.01), in males aged 18 years and older. SWBPA was not, however, independently associated with either complication in multivariate analyses nor with overt nephropathy. We conclude that although SWBPA is associated with neuropathy and proliferative retinopathy in these cross-sectional data, statistical significance was lost in multivariate analysis because of multiple weak links with other potential risk factors including duration of disease, blood pressure, lipid profile, and other hematological variables. The true role of SWBPA in the incidence and progression of complications will be more fully determined by the longitudinal follow-up of this group of subjects.