Platelet-dependent thrombin generation in patients with hyperlipidemia.
OBJECTIVE
We evaluated coagulability as determined by platelet-dependent thrombin generation in hypercholesterolemic patients before and after treatment with pravastatin and in hypertriglyceridemic patients to investigate the usefulness of coagulability as an index of atherosclerosis and to determine the importance of treating hyperlipidemia.


BACKGROUND
An understanding of the interaction between platelets and the plasma coagulation system is important for clarifying the mechanism of the procoagulant process.


METHODS
We assessed coagulability in 58 patients with hypercholesterolemia (serum total cholesterol level > or = 220 mg/dl, age 56.5 +/- 1.5 years [mean +/- SEM]), 37 patients with hypertriglyceridemia (serum triglyceride level > or = 200 mg/dl, age 59.5 +/- 1.7 years), 13 patients with hypercholesterolemia plus hypertriglyceridemia (age 51.4 +/- 3.1 years) and 75 normal subjects (age 52.2 +/- 1.7 years). We also studied platelet-dependent thrombin generation in patients with hypercholesterolemia before and after treatment with pravastatin. Calcium chloride was added to 0.5 ml of platelet-rich plasma (150 x 10(9)/liter) to initiate coagulation. Ten microliters of the sample was transferred into 90 microliters of 3.8% sodium citrate at 10-min intervals for 30 min. A chromogenic substrate, S-2238, was added to each sample, and absorbance was measured spectrophotometrically at a wavelength of 405 nm to determine thrombin generation.


RESULTS
Platelet-dependent thrombin generation was increased in patients with hypercholesterolemia and patients with hypercholesterolemia plus hypertriglyceridemia (p < 0.01) compared with patients with hypertriglyceridemia and control subjects. Treatment with pravastatin normalized thrombin generation.


CONCLUSIONS
Hypercholesterolemia, but not hypertriglyceridemia, was associated with increased platelet-dependent thrombin generation. Pravastatin normalized the generation of thrombin.
Aoki
I
I
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Aoki
N
N
Kawano
K
K
Shimoyama
K
K
Maki
A
A
Homori
M
M
Yanagisawa
A
A
Yamamoto
M
M
Kawai
Y
Y
Ishikawa
K
K
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D017270:Lipoprotein(a) / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D017035:Pravastatin / Q000627:therapeutic use*; D011453:Prostaglandins / Q000096:biosynthesis; D013917:Thrombin / Q000096:biosynthesis* / Q000187:drug effects
D000924:Anticholesteremic Agents; D017270:Lipoprotein(a); D010743:Phospholipids; D011453:Prostaglandins; D013917:Thrombin; D017035:Pravastatin