Platelets were obtained from patients with various
hyperlipidemias [type II, type V,
lecithin-cholesterol acyltransferase (
LCAT) deficiency] and hypolipidemias (
abetalipoproteinemia,
Tangier disease) to ascertain relationships among plasma
lipids, platelet
lipids,
thrombin binding and
thrombin-induced platelet aggregation, and to compare these data with those previously obtained on stimulus-response coupling in platelets following in vitro modification of membrane microviscosity. Washed platelets were studied for their ability to bind 125I-thrombin in the range of 10(-10) to 10(-6) mol/L (10 mU/mL to 100 U/mL) and to aggregate with
thrombin at concentrations less than 10(-9) mol/L (100 mU/mL). The values for binding and aggregation in eight patients from six kindred with
familial hypercholesterolemia, taken as a group, fell in the low normal range. If divided into two groups, patients with overt
cardiovascular disease bound normal amounts of
thrombin but were more responsive to it, whereas patients without overt
cardiovascular disease bound lower amounts of
thrombin but gave an aggregation response in the normal range. These results suggest that platelet hyperresponsiveness in
familial hypercholesterolemia arises from an alteration in the coupling mechanism between
thrombin binding and response such that platelets from patients with
familial hypercholesterolemia are able to respond with lower receptor occupancy than is the case with normal platelets.
Thrombin binding and aggregation were within normal ranges for platelets from
abetalipoproteinemia patients (N = 4) and
type V hyperlipoproteinemia (N = 2), although in the latter case the response appeared to be less at very low
thrombin concentrations (less than 30 mU/mL).
Thrombin binding was elevated in
Tangier disease (N = 3) but with lower responsiveness at lower
thrombin concentrations.
Thrombin binding was also elevated in
LCAT deficiency (N = 2), and one patient showed increased and another showed decreased aggregation responses. In general, increased plasma
cholesterol levels resulted in increased stimulus-response coupling (type II), whereas increased
triglyceride levels resulted in decreased coupling (type V, Tangier), and there was no apparent alteration in the coupling mechanism with overall reduction in plasma
lipid levels as in
abetalipoproteinemia.