Palumbo, P J

Mayo Clinic, Mayo Foundation, Rochester, MinnesotaPlatelets are believed to play an important role in the pathogenesis of atherosclerosis and thrombotic occlusive arterial disease. As part of a prospective study of peripheral occlusive arterial disease in diabetes mellitus, platelet survival half-life (PS) was determined in years 1 and 2 from the disappearance pattern of 51cr-labeled platelets obtained by measuring radioactivity in serial samples over 8 days in four groups of patients age 50-70. Using computer assisted least-square analysis, a single exponent is fitted to the data and half-life determined.Groups included (1) normal subjects (NC); (2) subjects with clinical and objective evidence (transcutaneous doppler ultrasound and treadmill exercise) of peripheral arterial occlusive disease (AS0); (3) subjects with diabetes mellitus without AS0 (DM); (A) subjects with both diabetes mellitus and AS0 (DM+AS0). 112 subjects were tested in year 1 and 75 of these were available for retesting in year 2.In year 1, there is a difference in the distribution of platelet survival (PS) for the four groups (p=.002). PS is significantly short in groups AS0 and DM+AS0 compared with controls (NC), Year 2 values for PS (75 subjects) were compared to year 1. Using the t test on mean differences PS for each group was not significantly different year 2 vs year 1; mean percent differences year 2 vs year 1 were 1.2% (NC), 0.2% (ASO), 3.2% (DM), and -9.3% (9-3% lower than year 1 for DM+ ASO).Platelet survival half-life (PS) does distinguish popula tion groups and is reproducible when repeated.

Distinguishing between in vitro and in vivo release of platelet specific proteins has led to problems in interpretation of clinical studies with PF4, and with BTG.As part of a prospective study of peripheral occlusive arterial disease in diabetes mellitus PF4 and BTG were measured together by specific radioimmunoassay in four groups of subjects age 50-70 years. Groups included (1) 106 normal subjects (NC); (2) 126 with clinical and objective evidence (transcutaneous doppler ultrasound and treadmill exercise) of peripheral arterial occlusive disease (ASO); (3) 244 with diabetes mellitus without ASO and (4) 101 with both diabetes mellitus and ASO.PF4 did not distinguish among the four groups: NC vs ASO p=. 18, NC vs DM p=.52, NC vs DM+ASO p=.73, NC vs all diabetics p=.61, and NC vs all ASO p=.46. However, BTG did distinguish the groups with vascular disease from NC: NC vs ASO p=.02, NC vs DM+ASO p<.001, NC vs DM p=.32, DM vs DM+ASO p<.01, all ASO vs all nonASO p<.001.Normal range for PF4 is 0-13 ng/ml with a median of 3.0 ng/ml, a mean of 3.0 ng/ml, and SD 1.97. Normal range for BTG is 14-46 ng/ml with a median of 26 ng/ml, a mean of 27.2 ng/ml, and SD 10.3. When PF4 and BTG are correlated (all groups included) r=.41 p<.001.PF4 and BTG levels should be performed together. When done together low PF4 levels support the absence of in vitro platelet release due to sample collection and handling. BTG levels are significantly increased in subjects with peripheral arterial disease, supporting the active role of platelets in thrombotic occlusive arterial disease.

To determine comparative rates of development and progression of peripheral occlusive arterial disease, 110 healthy nondiabetic control subjects, 112 patients with peripheral occlusive arterial disease (POAD), 240 patients with diabetes mellitus (DM), and 100 patientswith diabetes mellitus and peripheral occlusive arterialdisease (DM + POAD) were studied over 4 yr with noninvasive techniques. The presence of peripheral occlusive arterial disease was determined by postexercise ankle-brachial index (ABI) values; progression of peripheral occlusive arterial disease was determined by the rate of change in postexercise ABI. Patients who underwent peripheral arterial reconstructive surgery or amputation were also classified as having progression of their peripheral occlusive arterial disease. On this basis, follow-up revealed that peripheral occlusive arterial disease developed and therefore progressed in 1 (1%) of the control group and 22 (9%) of the DM. Peripheral occlusive arterial disease progressed in 31 (28%) of the POAD and 26 (26%) of the DM + POAD. The presence of peripheral occlusive arterial disease predisposes to progression of disease, and peripheral occlusive arterial disease is more likely to develop in diabetic patients who do not have peripheral occlusive arterial disease than in nondiabetic control subjects. However, the presence of diabetes mellitus in patients with peripheral occlusive arterial disease does not seem to increase the risk of progression.