Effects of selective LDL-apheresis and pravastatin therapy on platelet function in familial hypercholesterolaemia.
Platelet function was studied in 10 patients with familial hypercholesterolaemia, following lipid-lowering treatment with selective LDL-apheresis and with the HMG-CoA reductase inhibitor pravastatin. Platelet function was assessed before, and 2, 5 and 14 days after LDL-apheresis, and before and after 4 weeks of pravastatin therapy. Both treatments significantly reduced total- and LDL-cholesterol, whereas LDL-apheresis also reduced VLDL-cholesterol. Lp(a)-levels were reduced by LDL-apheresis and elevated by pravastatin treatment. Pravastatin therapy significantly enhanced platelet aggregability in vivo, as measured by ex vivo filtragometry. Plasma serotonin levels also increased. Other markers of in vivo activation of platelets, i.e. beta-thromboglobulin in plasma and urine, and 11-dehydro-thromboxane B2 in urine were unaltered. Adenosine diphosphate-induced platelet aggregation in vitro remained unchanged during pravastatin therapy, and the platelet volume distribution was not affected. LDL-apheresis reduced the mean platelet volume, as well as the percentage of large platelets, whereas the percentage of small platelets increased. Other measures of platelet function in vivo or in vitro were, however, unaltered following LDL-apheresis. Thus, pravastatin therapy enhances certain aspects of platelet aggregability in vivo, whereas a single treatment with selective LDL-apheresis does not consistently affect platelet aggregability during resting conditions. These results do not support the concept that reduction of LDL-cholesterol improves platelet function in hypercholesterolaemic patients, at least not in the short-term. However, the reduction of platelet volume after LDL-apheresis may be beneficial for patients receiving this therapy regularly.
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
A
A
Bröijersén
M
M
Eriksson
P T
PT
Larsson
O
O
Beck
L
L
Berglund
B
B
Angelin
P
P
Hjemdahl
D000328:Adult; D001781:Blood Component Removal; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003131:Combined Modality Therapy; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000628:therapy*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D017035:Pravastatin / Q000627:therapeutic use*; D013997:Time Factors
D008055:Lipids; D008077:Lipoproteins, LDL; D017035:Pravastatin