Platelet Factor 4 (PF4) And β-Thromboglobulin (BTG) In Atherosclerosis And Diabetes Mellitus

Abstract

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.

Detection of Prethrombotic States in Patients with Atherosclerotic Lesions

“…PF4 was increased in some studies in diabetics, especially in those with macroangiopathy, 115,197,198 whereas other investigators 113,190,196,199,200 found no difference between PF4 values of controls and diabetics with or without angiopathy.…”

“…97 ' 115 ' 185 " 195 In patients with microangiopathy even higher BTG levels were observed. 97, 186,189,195,196 BTG levels were reduced 5 to 8 weeks after initiation of antidiabetic treatment in patients with recently detected diabetes. 97 No positive correlation was found between high BTG values in diabetics and Hb A1 .…”