thromboxane-b2 and Hyperlipoproteinemia-Type-II

Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.

Topics: Adenosine Diphosphate; Adult; Alprostadil; beta-Thromboglobulin; Blood Platelets; Cholesterol, LDL; Collagen; Diet; Endothelial Cells; Epoprostenol; Female; Humans; Hyperlipoproteinemia Type II; Male; Medicine, Traditional; Opuntia; Plants, Medicinal; Platelet Adhesiveness; Platelet Aggregation; Platelet Count; Platelet Factor 4; Thromboxane B2

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival (111 In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159+/-14 hours to a mean of 164+/-12 hours (p=0.025), whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL (p=0.003) in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9) platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandin I2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (-2.9%), low density lipoprotein cholesterol (-3.5%), and triglycerides (-12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.

Topics: Blood Platelets; Cell Survival; Combined Modality Therapy; Diet; Diet Records; Diet, Fat-Restricted; Double-Blind Method; Eicosapentaenoic Acid; Epoprostenol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Fish Oils; gamma-Linolenic Acid; Humans; Hyperlipoproteinemia Type II; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Lipoproteins; Male; Malondialdehyde; Oenothera biennis; Plant Oils; Platelet Activation; Thromboxane B2

Platelet function parameters were studied in type II hyperlipoproteinemics in relation to baseline and drug-induced changes in serum cholesterol levels. There were no significant differences between 28 type II hyperlipoproteinemics and 19 normal subjects in baseline values for platelet aggregation, thromboxane generation, sensitivity to prostacyclin, plasma platelet factor 4 or beta-thromboglobulin. Eleven of the hyperlipoproteinemic patients were treated with a combination of the cholesterol-lowering drugs probucol and colestipol. The drug treatment resulted in statistically significant lowering of serum total and low-density lipoprotein (LDL)-cholesterol levels (30% reduction of mean LDL-cholesterol, p less than 0.01); however, there was no significant change in any of the platelet function parameters after the drug treatment compared with placebo. These results provide evidence against a relationship between serum cholesterol levels and in vitro platelet function.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Platelets; Cholesterol, LDL; Epoprostenol; Female; Humans; Hyperlipoproteinemia Type II; Hypolipidemic Agents; In Vitro Techniques; Lipids; Male; Middle Aged; Platelet Aggregation; Platelet Factor 4; Thromboxane B2

Patients with familial hypercholesterolemia (type IIa) were given 30 ml cod liver oil (CLO) as dietary supplement daily for 6 weeks. The effects on platelets, bleeding time, coagulation and blood and platelet lipids were examined. The major findings were a reduced collagen-induced platelet aggregation and a decrease in thrombin-stimulated thromboxane B2 generation in platelets in vitro. The primary bleeding time was not significantly prolonged. Statistically significant increase in eicosapentaenoic acid/arachidonic acid ratios in the main platelet phospholipids were also observed. These changes did not correlate with any of the changes in platelet behavior observed after CLO intake. The serum total and HDL cholesterol and triglycerides were not altered during the trial.

Topics: Adult; Bleeding Time; Blood Coagulation; Cod Liver Oil; Epoprostenol; Female; Fish Oils; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Platelet Aggregation; Thromboxane B2

Platelet phospholipid composition was analyzed before and after extracorporeal removal of low density lipoproteins (LDL) by LDL apheresis in six patients with familial hypercholesterolemia. Elevated levels of total plasma cholesterol and the portion of plasma cholesterol carried by LDL were reduced by 56 and 66% after LDL apheresis. Platelet cholesterol contents remained unaffected. While the phosphatidylcholine (PC):sphingomyelin (SM) ratio in plasma lipoproteins was increased by 22% following apheresis, the same parameter was lowered by 14% in platelets. LDL apheresis induced decreases in the percentages of distinct molecular species containing arachidonic acid in platelet diacyl subgroups of PC, phosphatidylinositol (PI) and phosphatidylserine (PS) as well as in alkenylacyl (plasmalogen) phosphatidylethanolamine (PE). Directly after apheresis, the percentages of molecular species with arachidonic acid of diacyl PC, diacyl PI and alkenylacyl PE were reduced by 20, 23 and 8%, respectively. Two days after the procedure, total arachidonic acid of diacyl PC, diacyl PS and alkenylacyl PE was lowered by 11, 20 and 8%. Overall, the amount of phospholipid bound arachidonic acid was reduced by 16% after apheresis (from 79.1 to 66.4 nmol/10(8) platelets). The results are thus in agreement with previous data indicating decreased phospholipid bound arachidonic acid in red blood cells after apheresis (Engelman B. Bräutigam C, Kulschar R et al. Biochim Biophys Acta 1994:1196:154). Urinary 2,3-dinor thromboxane B2, an estimate of platelet thromboxane A2 (TXA2) production, tended to be decreased following the procedure. The percentage change in the TXA2 metabolite was positively related to the magnitude of change induced by apheresis in phospholipid bound arachidonic acid. In summary, the results suggest that in patients with hypercholesterolemia, the level of plasma LDL is an important determinant of the arachidonic acid content of several platelet phospholipids.

Topics: Adult; Arachidonic Acid; Blood Component Removal; Blood Platelets; Humans; Hyperlipoproteinemia Type II; Immunosorbent Techniques; Lipoproteins, LDL; Male; Middle Aged; Phospholipids; Thromboxane A2; Thromboxane B2

Platelets from familial hypercholesterolaemia type IIa patients are hyperreactive and produce increased amounts of thromboxane A2. These modifications of platelet function may play an important role in the occurrence of premature atherosclerosis. One approach to the prevention of the thromboembolic complications of atherosclerosis is the use of antiplatelet agents which depress platelet function. Ridogrel, a combined thromboxane synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor blocker inhibits platelet aggregation. This study was designed to investigate the in vitro effect of ridogrel on platelet function in normocholesterolaemic and familial hypercholesterolaemia type IIa subjects. In citrated platelet rich plasma ridogrel significantly inhibited platelet aggregation and thromboxane A2 production in response to collagen, ADP and arachidonic acid stimulation. In washed platelets ridogrel significantly decreased aggregation and serotonin release. Ridogrel significantly increased cAMP levels in response to thrombin stimulation. In conclusion, ridogrel at low concentrations significantly inhibited the in vitro function of platelets in a dose dependant manner in both normocholesterolaemic subjects and familial hypercholesterolaemia IIa subjects.

Topics: Adult; Blood Platelets; Enzyme Inhibitors; Humans; Hyperlipoproteinemia Type II; In Vitro Techniques; Middle Aged; Pentanoic Acids; Platelet Aggregation Inhibitors; Pyridines; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Many studies have found that familial hypercholesterolemia, a hyperlipoproteinemia associated with premature atherosclerosis, is characterized by enhanced platelet aggregation. This study was undertaken to measure the urinary excretion of the two main urinary thromboxane B2 (TXB2) metabolites (2, 3-dinor-TXB2 and 11-dehydro-TXB2) in 20 patients affected by familial hypercholesterolemia treated for one month with 40 mg/day of pravastatin (10 patients) in comparison to 10 normocholesterolemic subjects. After a run-in period, the type II A patients showed total cholesterol levels (296 +/- 32 mg/dL) significantly higher (P < 0.001) than those of control subjects (155 +/- 46 mg/dL). The urinary concentrations of 11-dehydro-TXB2 and 2,3-dinor-TXB2 also significantly differed (P < 0.001) between control group (1,463 +/- 1,440 and 386 +/- 447 pg/mg urinary creatinine) and treated patients (3,536 +/- 2,112 and 914 +/- 572 pg/mg urinary creatinine). At baseline there was a positive correlation between total cholesterol (TC) levels and urinary TXB2 metabolite concentrations (2,3-dinor-TXB2 r = 0.61, P < 0.02; 11-dehydro-TXB2, r = 48, P < 0.05), but not between low-density-lipoprotein cholesterol (LDL-C) and the urinary compounds. At the end of a four-week treatment. TC and LDL-C had decreased significantly from the baseline levels, by 27% and 30% in the fluvastatin group (P < 0.01) and by 23% and 31% in the pravastatin group (P < 0.01), with no significant difference between the two groups. After the two treatments with HMG-CoA reductase inhibitors, there was no statistically significant reduction of the urinary metabolite levels. In addition, the positive correlation seen at baseline between TC and TXB2 metabolites was no longer present. In accord with previous studies, we found a significant correlation between TC levels and TXB2 metabolites concentrations in type II A hypercholesterolemic patients. Although, short-term treatment with two statins reduced TC levels, it did not change the thromboxane metabolite excretion.

Topics: Anticholesteremic Agents; Cholesterol; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Indoles; Lipids; Male; Middle Aged; Pravastatin; Thromboxane B2

Increased platelet aggregability has been shown in hypercholesterolemia, and stirring-induced spontaneous aggregation in whole blood is increased in insulin-dependent diabetes mellitus (DM). We have determined spontaneous aggregation in citrated (10 mM) whole blood, from 27 primary dyslipidemic patients (DYS; 14F, 13M), 16 male non-insulin-dependent DM (NIDDM) patients, and 17 normolipidemic controls (N; 6F, 11M), using platelet counting to quantify aggregation. Spontaneous aggregation was significantly higher, both in the female DYS group (median 30% [interquartile range 25,50], P < 0.005) and the NIDDM group (33% [25,41], P < 0.005), than in the N group (17% [12,27]), but did not differ significantly in the male DYS group (23% [10,33]). Similar results were obtained in the presence of indomethacin (25 mumol/l) to prevent artefactual thromboxane (TX) A2 formation, indicating that increased spontaneous aggregation was TXA2-independent. Interestingly, increased spontaneous aggregation appeared to be independent of serum cholesterol and triglyceride concentrations, as well as age and sex per se. We conclude that spontaneous platelet aggregation was increased both in female primary dyslipidemic patients and NIDDM patients, but not in male DYS patients. The clinical significance of increased spontaneous platelet aggregability is that it may favour shear-induced aggregation which may occur at critical arterial stenoses in vivo leading to thrombus formation.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Hematocrit; Humans; Hyperlipoproteinemia Type II; Male; Platelet Aggregation; Platelet Count; Sex Factors; Thromboxane B2

In continuation of investigations on primary hyperlipidaemias, we determined serum thromboxane (TX) B2 and prostaglandin (PG) F2 alpha after standardized blood clotting in patients without hyperlipidaemia and without (group 1, n = 11) or with coronary heart disease (CHD; group 2, n = 5), in patients with familial combined hyperlipoproteinaemia and without (group 3, n = 4) or with CHD (group 4, n = 5), as well as in patients with familial hypercholesterolaemia and CHD (group 5, n = 5). TXB2 was detected by gas chromatography and PGF2 alpha by means of radioimmunoassay. The TXB2 level did not differ significantly between the groups, but there was a tendency to higher values in hyperlipidaemia, while in group 5 the level tended to decrease with rising serum LDL-cholesterol and in group 3 it tended to increase with rising serum apolipoprotein B. The PGF2 alpha level was significantly lower in group 4 than in groups 1 and 3. It showed in group 5 a negative correlation with serum LDL-cholesterol and in group 3 a positive correlation with serum triglycerides.

Topics: Adult; Aged; Apolipoproteins A; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Dinoprost; Female; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Lipids; Male; Middle Aged; Thromboxane B2; Triglycerides

A group of 22 subjects with type IIA hypercholesterolaemia (mean serum cholesterol = 8.3 +/- 0.3 mmol/l) were sex, age and weight matched with 22 control subjects (mean serum cholesterol = 4.5 +/- 0.1 mmol/l). Diastolic blood pressure was significantly higher in hypercholesterolaemic subjects (79.2 +/- 1.4 mm Hg) than in control subjects (71.9 +/- 1.4 mm Hg). While the high cholesterol group had 52% greater thromboxane production in clotted whole blood than controls this difference was not significant, and the platelet aggregation and serotonin secretion response to doses of collagen, ADP and arachidonic acid were similar between the 2 groups. Polymorphonuclear leukocyte (PMN) chemiluminescence (used as a measure of reactive oxygen species production) in response to low doses of the chemotactic-peptide FMLP and opsonized zymosan was significantly greater in high cholesterol subjects compared to their matched controls. The production of platelet activating factor (PAF) by calcium ionophore (2.5 micrograms) stimulated PMN isolated from hypercholesterolaemic subjects (11.5 +/- 1.4 ng/10(6) cells) was significantly greater than PAF production by cells from the control group (8.3 +/- 1.0 ng/10(6) cells). Leukotriene B4 release by PMN in response to calcium ionophore did not differ between the 2 groups. These data suggest a degree of leukocyte activation in hypercholesterolaemic subjects compared to controls with normal cholesterol. In addition, plasma levels of lyso-PAF were higher in high cholesterol subjects (317 +/- 21 ng/ml) compared to their matched controls (271 +/- 18 ng/ml) perhaps indicating increased plasma acetylhydrolase activity in subjects with raised cholesterol levels. Recently described biological activity for lyso PAF suggests a possible role for this substance in atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Diphosphate; Adult; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Calcimycin; Collagen; Fatty Acids; Female; Humans; Hyperlipoproteinemia Type II; Leukotriene B4; Lipids; Luminescent Measurements; Male; Neutrophils; Platelet Activating Factor; Platelet Aggregation; Serotonin; Thromboxane B2

The effect of lowering total serum cholesterol and low-density lipoprotein (LDL) cholesterol on platelet function, thromboxane formation and platelet sensitivity against PGI2 was studied in platelet-rich plasma ex vivo. Additionally, PGI2 receptors were determined in membrane preparations of these platelets. Twelve patients suffering from familial hyperlipoproteinemia type IIa (FH) were treated for 8 months with simvastatin (20-40 mg/day) and compared with 10 untreated FH patients and 10 untreated normocholesterolemic subjects. Compared with those of healthy controls, platelets of untreated FH patients were hyperreactive, as shown by an enhanced aggregation response and release of ATP and thromboxane after stimulation by collagen (0.3-5 micrograms/ml) and ADP (0.3-10 micrograms/ml). Simvastatin reduced the total and LDL serum cholesterol towards control levels while HDL cholesterol remained unchanged. This was accompanied by a significant decrease of platelet aggregation, thromboxane formation and ATP secretion being no more different from normocholesterolemic controls. In addition, the reduced platelet sensitivity against prostacyclin (aggregation, stimulation of cAMP formation) in untreated FH patients was improved to normal values by simvastatin. This was associated with a significant elevation of the reduced prostacyclin binding sites and might be explained by an improved access of prostacyclin to its receptors at platelet membranes. These data demonstrate that the reduction of total and LDL serum cholesterol by simvastatin results in a normalization of platelet function by (i) reduction of platelet hyperreactivity and (ii) improvement of the sensitivity against prostacyclin towards normal via enhanced PGI2-binding sites.

Topics: Adenosine Triphosphate; Adult; Aged; Anticholesteremic Agents; Blood Platelets; Cyclic AMP; Epoprostenol; Humans; Hyperlipoproteinemia Type II; Iloprost; Lipids; Lovastatin; Middle Aged; Platelet Aggregation; Receptors, Epoprostenol; Receptors, Prostaglandin; Simvastatin; Thromboxane B2

An increased susceptibility of platelets to aggregation induced by various agents and a higher production of active arachidonate metabolism have been described in type IIa hypercholesterolemia. This study was designed to evaluate whether changes in platelet function could be observed in hypercholesterolemic patients after synvinolin therapy. Administration of synvinolin to 12 type IIa hypercholesterolemic patients for 24 weeks had a lipid lowering effect and resulted in a marked reduction of platelet aggregation and thromboxane formation induced by collagen and arachidonate. Maximum response was achieved at 4-8 weeks and lipid lowering effects at 2 weeks. This finding indicates that platelet changes cannot be explained by a direct effect of synvinolin on platelets, and the antiplatelet response may therefore depend on platelet membrane lipid composition changes, particularly in the platelet cholesterol content of platelet membranes, following substantial reductions of total plasma cholesterol and LDL-cholesterol.

Topics: Aged; Anticholesteremic Agents; Female; Humans; Hyperlipoproteinemia Type II; Lovastatin; Male; Middle Aged; Platelet Aggregation; Simvastatin; Thromboxane B2

The effect of lowering total plasma and low density lipoprotein (LDL) cholesterol in heterozygous familial hypercholesterolaemia type IIa (FH) on platelet function, thromboxane (TX) formation and platelet sensitivity against iloprost, a stable prostacyclin mimetic, was studied in platelet-rich plasma ex vivo. Seven FH patients were treated with cholestyramine (12 g day 1) for 8-11 months and were compared with eight untreated FH patients and 11 healthy control subjects. In comparison with platelets from healthy controls, platelets from untreated FH patients exhibited a significantly increased aggregation response and TX formation, and a reduced reactivity against inhibition of platelet aggregation by prostacyclin. Treatment with cholestyramine for 8-11 months resulted in a 21% reduction in total serum and LDL-cholesterol. This was not accompanied by any change in platelet hyperreactivity or TX formation. However, cholestyramine treatment normalized the platelet reactivity of FH patients against iloprost, being no more different from healthy controls. It is concluded that reduction in plasma cholesterol by cholestyramine results in normalization of the reduced platelet sensitivity against prostacyclin. This might contribute to beneficial effects of cholestyramine treatment in preventing thromboembolic complications of atherosclerosis.

Topics: Blood Platelets; Cardiovascular Agents; Cholestyramine Resin; Epoprostenol; Humans; Hyperlipoproteinemia Type II; Iloprost; Male; Platelet Aggregation; Thromboxane B2

Platelets play an essential role in the pathogenesis of atherosclerosis; by impedance method we valued in whole blood platelet aggregation induced by collagen in 40 healthy subjects and in 40 type II and type IV hyperlipemic subjects. Meanwhile by radioimmunoassay we dosed thromboxane B2, a stable product of thromboxane A2, released by platelets during activation, in 7 healthy subjects and 25 hyperlipemic subjects. The statistical investigation put in evidence that at higher plasmatic levels of cholesterol, triglycerides and LDL correspond a greater platelet sensitivity to the aggregating agent, while the opposite happens to higher levels of HDL. The dosage of thromboxane B2 put in evidence a moderate increase in hyperlipemic as to healthy subjects, probably pointing to a state of platelet activity.

Topics: Adult; Female; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Male; Middle Aged; Platelet Aggregation; Radioimmunoassay; Thromboxane B2

The formation of the major metabolic products of endogenous arachidonic acid (AA) via cyclooxygenase and lipoxygenase pathways in platelets from normal and type IIA hypercholesterolemic subjects was evaluated. 12-Hydroxyeicosatetraenoic acid (12-HETE) and thromboxane B2(TXB2) were determined by selected ion monitoring (SIM) after extraction and purification of collagen stimulated platelet-rich plasma (PRP). The levels of both arachidonic acid metabolites in the non-stimulated PRP of control and type IIA subjects were below the detection limit of the method, rising significantly after collagen stimulation. Both 12-HETE and TXB2 levels in collagen-stimulated PRP samples from the patients were significantly higher than levels in controls (P less than 0.001). In view of the key role of 12-HETE in mediating smooth muscle cell migration and proliferation and in stimulating macrophage activity, these data may provide information for the understanding of the elevated incidence of thrombosis and atheromatous lesion in patients with type IIA hypercholesterolemia.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adult; Arachidonic Acid; Arachidonic Acids; Arteriosclerosis; Blood Platelets; Female; Humans; Hydroxyeicosatetraenoic Acids; Hyperlipoproteinemia Type II; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Cholesterol; Epoprostenol; Humans; Hydroxyeicosatetraenoic Acids; Hyperlipoproteinemia Type II; Membrane Fluidity; Platelet Aggregation; Thromboxane B2

It is generally accepted that in hyperlipoproteinemia (HLP) the vascular prostacyclin formation is diminished. We wondered, whether HLP is also associated with changes in platelet sensitivity to antiaggregatory prostaglandins. Therefore, we examined the platelet sensitivity to the prostaglandins PGI2 and PGD2 as well as plasma thromboxane B2 (TXB2)-levels in 24 patients with HLP type IIa, IIb and IV. We found a marked decrease of platelet sensitivity to PGI2 in all the patients examined, which was more pronounced in type IIb than in types IIa and IV. Platelet sensitivity to PGD2 showed no difference in the hyperlipemic patients. Plasma TXB2-levels were significantly increased in comparison to a control group, the changes being most pronounced in patients with type IV HLP. Platelet half-life was significantly shortened in the HLP-patients. This in-vivo platelet function parameter was found to be reduced in patients with type IIa HLP to the greatest extent. Our findings suggest that platelet deposition in HLP is promoted not only by diminished vascular PGI2-formation, but also by decreased sensitivity of the platelets to antiaggregatory prostaglandins. The high TXB2-levels and the shortened platelet half-life reflect the in-vivo activated platelet population in these patients.

Topics: Adult; Aged; Blood Platelets; Epoprostenol; Female; Half-Life; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Hyperlipoproteinemias; In Vitro Techniques; Male; Middle Aged; Platelet Aggregation; Prostaglandin D2; Prostaglandins D; Thromboxane B2

Platelet aggregation induced by collagen, ADP and epinephrine, was monitored in 150 type-II patients (115 type IIA and 35 type IIB) and compared with a reference group of normolipidaemic controls; in addition, malondialydehyde formation and thromboxane B2 were examined in a subsample of the type-IIA patients. Threshold aggregatory concentrations were significantly lower in the whole group of type-II patients for all three aggregating agents; no difference in terms of aggregatory response was detected between platelets from type-IIA and -IIB patients. Only 56% of type-II patients, however, exceeded the 95th percentile of the threshold aggregatory concentrations in controls. The formation of malondialdehyde in platelet-rich plasma stimulated with thrombin and collagen, was significantly higher in platelets from type-IIA patients. The production of thromboxane B2 by platelets, from endogenous arachidonic acid in type-IIA patients, was significantly higher and exceeded the highest level found in controls.

Topics: Adolescent; Adult; Aged; Arachidonic Acids; Blood Platelets; Cholesterol; Collagen; Female; Humans; Hyperlipoproteinemia Type II; In Vitro Techniques; Male; Malondialdehyde; Middle Aged; Platelet Aggregation; Thromboxane B2; Thromboxanes

Seventeen subjects with hypercholesterolemia (type IIa) were compared with 11 normocholesterolemic family members (controls) with similar dietary habits. The type IIa subjects had a shorter bleeding time. Beta-thromboglobulin in plasma and thromboxane B2 and malondialdehyde released from platelets before and after stimulation with collagen or thrombin were similar. No differences in platelet sensitivity to adenosine diphosphate, thrombin or collagen were observed. Gel-filtered platelets from type IIa subjects had a tendency to spontaneous aggregation and lower procoagulant activity. Platelet sensitivity to prostacyclin was slightly higher in type IIa subjects. No differences in a series of coagulation parameters were observed between the groups. This study has shown some deviations from normal in platelets from subjects with familial hypercholesterolemia. These changes may contribute to the increased tendency to occlusive vascular diseases in such subjects.

Topics: Adult; Beta-Globulins; Bleeding Time; Blood Coagulation; Collagen; Epoprostenol; Female; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Malondialdehyde; Middle Aged; Platelet Aggregation; Thrombin; Thromboxane B2

In 13 type II hyperlipidemics (10 males and 3 females; mean age 50.2 +/- 10.6 years), in 10 type IV hyperlipidemics (7 males and 3 females; mean age 51 +/- 13.3 years) and in 23 healthy age- and sex-matched controls, the following parameters were measured: plasma cholesterol; plasma TG; plasma C-HDL; VLDL, separated in a preparative ultracentrifuge; C-LDL; Apo B, with immunoelectrophoretic method; platelet sensitivity to prostacyclin; TXB2 formation in PRP; TXB2 in serum. This study provides evidence for: 1. Reduced platelet sensitivity to prostacyclin, more evident in type II hyperlipidemia that provides an additional mechanism involved in increased platelet aggregation found in type II hyperlipidemia. 2. Enhanced TXB2 formation in PRP after thrombin stimulation (664.65 +/- 142.18 pmol/10(8) platelets) only in type II hyperlipidemics and such enhanced formation was positively correlated to C-LDL (r = 0.53; p less than 0.05) and to Apo B (r = 0.62; p less than 0.05); serum TXB2 formation rate was also increased in type II hyperlipidemia.

Topics: Adult; Aged; Blood Platelets; Cholesterol; Dose-Response Relationship, Drug; Epoprostenol; Female; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Male; Middle Aged; Platelet Aggregation; Prostaglandins; Thromboxane B2; Thromboxanes