Plasma lipid fatty acids and platelet function in insulin-dependent diabetic patients

Platelet function, estimated from plasma beta-thromboglobulin (beta-TG, ng/ml), is frequently altered in insulin-dependent diabetics (IDDs). As several factors may affect beta-TG, we studied respectively in 15 IDDs, the roles played by: (i) diabetic control evaluated from glycosylated haemoglobin (HbA1); (ii) plasma C-peptide and pancreatic glucagon; (iii) plasma lipids and the relative percentages of fatty acids in total plasma lipids. Plasma beta-TG did not correlate significantly with the first 3 parameters. However, beta-TG was correlated: (i) positively with plasma triglycerides (P less than 0.01), cholesterol (P less than 0.02), phospholipids (P less than 0.05) and total plasma lipids (P less than 0.01) and the percentage of oleic acid (C18 : 1 omega 9) in plasma lipids (P less than 0.01); (ii) negatively with the percentage of linoleic acid (C18 : 2 omega 6) in plasma lipids (P less than 0.02). No correlation was found between beta-TG and the percentages of the other saturated (C16 : 0, C18 : 0), monounsaturated (C16 : 1 omega 7) and polyunsaturated fatty acids (C18 : 3 omega 6, C20 : 3 omega 6 and C20 : 4 omega 6). The present results indicate that beta-TG in IDDs can be markedly improved by all dietary and therapeutic measures which lower plasma lipids and increase the percentage of the linoleic acid in the body.     

Platelet activation during thrombolysis and percutaneous transluminal coronary angioplasty in the acute phase of myocardial infarction

To clarify the mechanism of recanalization and reocclusion in thrombolysis and percutaneous transluminal coronary angioplasty (PTCA), the plasma concentrations of beta-thromboglobulin (beta-TG), thromboxane B2 (TXB2) and platelet aggregation adenosine diphosphate (ADP) (2 microM/ml, collagen 2 micrograms/ml) were assessed in 11 normal subjects and in 19 patients with acute myocardial infarction whose infarct-related vessels were recanalized by thrombolysis and/or PTCA. In patients with acute myocardial infarction, the plasma concentrations of beta-TG and TXB2 were significantly higher than those in normal subjects (beta-TG: 128 +/- 132 ng/ml vs 38 +/- 17 ng/ml, TXB2: 131 +/- 154 pg/ml vs 36 +/- 18 pg/ml). Collagen-induced platelet aggregation decreased significantly in patients with acute myocardial infarction; whereas, ADP-induced platelet aggregation showed no significant difference. Infarct-related vessels recanalized by thrombolysis (seven patients: group 1) and PTCA (seven patients: group 2) were patent on the follow-up angiograms. Infarct-related vessels were reoccluded in five patients immediately after PTCA or during the follow-up angiography (group 3). Beta-TG and TXB2 did not change before and after recanalization in groups 1 and 2, but increased significantly after recanalization in group 3 (beta-TG: 155 +/- 185 ng/ml----269 +/- 233 ng/ml, TXB2: 104 +/- 87 pg/ml----169 +/- 91 pg/ml). Platelet aggregation did not differ significantly among the three groups. We concluded that platelets are not activated during thrombolysis and/or PTCA in cases without reocclusion, while platelets are markedly activated during PTCA in cases with reocclusion. Thus, it is suggested that platelet activation plays an important role in the mechanism of reocclusion.     

Plasma levels of beta-thromboglobulin and platelet factor 4 in relation to the venous platelet concentration

The plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were determined in patients with various hematologic malignancies, and the results were related to simultaneously determined venous platelet counts. All studied patients were in a steady state. The plasma beta-TG concentrations were determined on 69 occasions and the values ranged from 0 to 82 ng/ml. In 33 instances, the venous platelet count was <25 x 10 (9/1) and in two thirds of these samples beta-TG was undedectable. The highest values for plasma beta-TG were found in patients with the highest venous platelet counts. A highly significant correlation (r=0.77, p <0.001) between the values for plasma beta-TG and venous platelet count was present. The plasma concentrations for PF-4 ranged from 0 to 50 ng/ml. Similarly, there was a highly significant relationship (r=0.78, p<0.001) between the values for PF-4 and venous platelet concentration. We conclude, if the plasma levels of beta-TG and PF-4 are used as markers of platelet activation in vivo, it is necessary to simultaneously consider the platelet concentration in the collected blood.     

Long-term diet modification and platelet activity

Platelet activity was assessed in a sub-sample of 56 participants in the MRC Diet and Reinfarction Trial (DART). Men whose diets contained a high ratio of polyunsaturated to saturated fatty acids (a P:S ratio of greater than 0.5) showed reduced secondary platelet aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP), and diminished platelet aggregation to ADP in whole blood. A trend of reduced secondary platelet aggregation to ADP with increasing dietary eicosapentaenoic acid was noted, but this was not statistically significant. The results of this study and the MRC Diet and Reinfarction Trial suggest a mediatory role for platelet activity in the relationship between diet and ischaemic heart disease.     

Plasma beta-thromboglobulin values in thrombocytopenic patients with acute leukemia

Plasma beta-thromboglobulin (beta-TG) levels were measured in 14 healthy subjects and in 20 acute leukemia (AL) patients, newly diagnosed, with highly variable values for venous platelet counts. For healthy subjects the plasma beta-TG levels ranged 12-38 (mean 17) ng/ml. In this group of patients with AL, a highly significant positive correlation (P < 0.001) between the values for plasma beta-TG and venous platelet count was present. During a thrombocytopenic period, the plasma beta-TG concentraton was measured in nine of the AL patients immediately before and 10 to 12 hours after platelet transfusion therapy. Fourteen platelet transfusions were administered when the patient's highest temperature of the day was < 38.5 degrees C, and 18 when the highest temperature of the day was greater than or equal to 38.5 degrees C. The mean pre-transfusion and post-transfusion beta-TG values for the 14 platelet transfusions were 7 +/- 2 and 20 +/- 5 ng/ml, respectively. The corresponding means for the 18 transfusions given to febrile patients were 5 +/- 2 ng/ml and 11 +/- 2 ng/ml, respectively. Of the pretransfusion values, 11/14 and 14/18 were below the control range. We conclude that the plasma beta-TG values are considerably lower in thrombocytopenic patients than in subjects with normal platelet counts. Further work should provide reference values for plasma beta-TG over a wide range of venous platelet counts.     

Platelet activation indices and apolipoproteins in hypertensive patients

We have studied the platelet activation indices beta-thromboglobulin (beta-TG and platelet factor 4(PF4), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and apolipoprotein (A1, A2, B, C2, C3, E) profiles of 22 untreated essential hypertensive subjects (WHO stages 1 and 2) and 22 controls, to see if there might be some causal relationship between lipoprotein abnormalities and greater platelet activation. The results showed the patients had both greater platelet activation than the controls, as demonstrated by higher plasma beta-TG levels (P less than 0.01) and lower apolipoprotein A2 levels (P less than 0.05). However there were no significant correlations between the platelet activation indices and the plasma levels of apolipoproteins, lipoproteins or lipids in either group.     

Evidence for the Platelet Specificity of β-Thromboglobulin and Studies on its Plasma Concentration in Healthy Individuals

The concentration of normal human platelet beta-thromboglobulin (beta-TG) was measured in various washed organ samples by a radioimmunoassay. As only trace amounts were detected, beta-TG appears to be a platelet specific protein. Assay of beta-thromboglobulin in plasma samples from 180 normal individuals gave a range of 10--65 mg/ml. In the 10 subjects studied, plasma beta-TG concentration was related to platelet lifespan but not to turnover. The plasma beta-TG concentration rose with increasing age but did not correlate with the whole blood platelet count or the percentage of megathrombocytes. These results provide further substantial evidence that measurement of plasma beta-TG concentration is useful for assessing the participation of platelets in various disease processes.     

Increased platelet activity in patients with isolated coronary artery ectasia

BACKGROUND: The common coexistence with coronary artery disease has led to the suggestion that coronary artery ectasia (CAE) is a variant of coronary artery disease. The mechanisms, however, responsible for CAE formation during the atherosclerotic process and the exact clinical significance are not well known. In this study, we aimed to investigate platelet activity in patients with isolated CAE by using specific markers of platelet activation as P-selectin, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). METHODS: Thirty-two patients with isolated CAE without significant stenosis and 30 control participants with angiographically normal coronary arteries were included in this study. According to the angiographic definition used in the Coronary Artery Surgery Study, a vessel is considered to be ectasic when its diameter is > or = 1.5 times that of the adjacent normal segment in segmental ectasia. Plasma P-selectin, beta-TG and PF4 levels were measured in all patients and control participants using enzyme-linked immunosorbent assay method. RESULTS: Patients with isolated CAE were detected to have significantly higher levels of plasma P-selectin, beta-TG and PF4 in comparison with control participants with angiographically normal coronary arteries (P-selectin: 248+/-46 vs. 154+/-32 ng/ml, respectively, P<0.001; beta-TG: 51+/-19 vs. 21+/-9 ng/ml, respectively, P<0.001; PF4: 58+/-23 vs. 33+/-11 ng/ml, respectively, P<0.001). CONCLUSION: In conclusion, we have shown for the first time that patients with isolated CAE have raised levels of plasma P-selectin, beta-TG and PF4 compared with control participants with angiographically normal coronary arteries, suggesting increased platelet activation in patients with CAE.     

Platelet aggregation and thromboxane A2 production after adrenergic stimulation in young healthy humans

The effects of adrenergic stimulation on platelet aggregation (platelet aggregation ratio; PAR), beta-thromboglobulin (beta-TG) release and plasma thromboxane B2 (TxB2) levels were investigated in 25 healthy young volunteers. Adrenergic stimulation induced by cold application was checked by evaluating the changes in the calculated vascular resistance in the forearm. A prompt increase in platelet aggregates and plasma beta-TG and TxB2 concentrations was observed after adrenergic stimulation. PAR changed from resting values of 0.97 +/- 0.05 to 0.75 +/- 0.08 (p less than 0.001) at the end of cold application. At the same time, beta-TG plasma concentration increased from 32.09 +/- 19.64 to 135.48 +/- 37.97 ng/ml (p less than 0.001) and TxB2 plasma levels changed from 0.49 +/- 0.24 to 0.99 +/- 0.39 pmol/ml (p less than 0.001). TxB2 levels, but not PAR and beta-TG concentration came back to the resting values at the end of the observation period (10 min). Aspirin, as the lysine acetylsalicylate equivalent to 5 mg/kg i.v. of acetylsalicylic acid, although able to completely inhibit platelet cyclooxygenase failed to inhibit the plasma TxB2 increase induced by adrenergic stimulation. This strongly suggests that the increase in plasma TxB2 following adrenergic stimulation is of extraplatelet origin. Also beta-TG and PAR changes were not affected by aspirin administration.     

Plasma fatty acids and lipoproteins in type 2 diabetic patients

BACKGROUND: The dyslipidemia of type 2 diabetic patients is characterized by high VLDL, abnormal LDL composition and low HDL cholesterol concentrations. The aim of this study was to establish whether the type of dietary fats affects LDL size and density and HDL cholesterol concentrations in these patients. METHODS: Plasma phospholipid fatty acid composition, which reflects the type of dietary fatty acids, was quantified by gas chromatography. LDL relative flotation (LDL-Rf), a measure of LDL particle size and density, was determined by single vertical spin density gradient ultracentrifugation in 97 type 2 diabetic patients. RESULTS: By linear regression analysis of the data, plasma fatty acids were associated neither with LDL-cholesterol levels nor with LDL-Rf. The HDL cholesterol concentrations were negatively related with saturated fatty acids (r = -0.23; p = 0.02) but positively related with monounsaturated fatty acids (r = +0.20; p = 0.00). Furthermore, higher HDL concentrations were associated with large and buoyant LDL particles (HDL cholesterol vs LDL-Rf: r = +0.47; p = 0.00). In the multiple regression analysis, the LDL-Rf was significantly related both to triglycerides (beta coefficient = -0.55, p = 0.000) and HDL cholesterol (beta coefficient = 0.19, p = 0.034) concentrations. In a stepwise regression analysis including both triglycerides and HDL cholesterol, triglycerides alone explained the 43.0% of the LDL-Rf variability. CONCLUSIONS: A reduction of the dietary saturated fats and an increment of monounsaturated fats might increase HDL cholesterol concentrations in type 2 diabetic patients. Modifications of LDL composition might be expected from interventions aimed to reduce plasma triglycerides.     

Platelet functions in relation to diet and serum lipids in British farmers.

Coagulation and platelet aggregation induced by thrombin, ADP, adrenaline, and collagen were studied in three contrasted groups, each of 20 to 22 middle-aged male farmers. Serum lipids were similar in the three groups. In the west of Scotland group, however, platelet reactivity was significantly greater than in the east of Scotland. This was associated with a dietary intake, evaluated by three different techniques, higher in saturated fat but also lower in polyunsaturated fat and alcohol. Platelet function in the southern England group also correlated with dietary fats and in addition inversely with calcium intake. On an individual basis in the 63 farmers, all the platelet function tests were significantly correlated with the intake of saturated fat regulated by that of calcium and alcohol. The dietary effects on platelets appear to be mediated by the fatty acid composition of plasma lipids and of platelet phospholipids. In that fraction, the fatty acids 20:3 omega 9, 22:3 omega 9 and 20:4 were the most closely related to the platelet function tests. the trienoic acid 20:3 omega 9, identified with essential fatty acid deficiency, was also correlated with the intake of saturated fat and calcium. In this study, platelet functions were more dependent upon the dietary factors associated with coronary heart disease such as saturated fats, calcium, and alcohol than upon serum lipids.     

Nifedipine in the treatment of Raynaud's phenomenon. Evidence for inhibition of platelet activation

Platelet activation has been reported to occur in patients with Raynaud's phenomenon; however, the effect of calcium channel blockers and thromboxane synthetase inhibitors has not been previously studied. The effect of two drugs that potentially inhibit platelet activation were studied: nifedipine, a calcium channel blocker, and dazoxiben, a specific thromboxane synthetase inhibitor. Two platelet-specific proteins released during platelet activation, beta-thromboglobulin and platelet factor 4, were measured during a double-blind clinical trial of these two drugs in patients with Raynaud's phenomenon. The plasma beta-thromboglobulin level was significantly elevated in the patient population (53.8 +/- 7.6 ng/ml) during the placebo period compared with that in a normal control population (27.0 +/- 3.1 ng/ml) (p less than 0.01). The plasma platelet factor 4 level was 8.7 +/- 2.2 ng/ml in the patients compared with 6.5 +/- 1.0 ng/ml in the normal subjects (p = NS). These findings indicate the presence of in vivo platelet activation in patients with Raynaud's phenomenon. Nifedipine lowered the levels of beta-thromboglobulin to near the normal range (33.4 +/- 4.6 ng/ml). The inhibition of platelet activation by nifedipine was associated with clinical improvement in Raynaud's phenomenon with fewer and less intense episodes. Beta-thromboglobulin was not lowered by dazoxiben (58.1 +/- 9.0 ng/ml) compared with the placebo. The reduction of beta-thromboglobulin levels by nifedipine indicates that in vivo platelet activation was inhibited by this agent. Since this was associated with a reduced frequency of attacks, it is not clear whether this was a direct effect of the drug on platelet activation, leading to decreased frequency of vasospasm, or an effect on vascular smooth muscle leading to decreased vasospasm and a secondary decrease in platelet activation.     

Dietary interventions in north Karelia, Finland and south Italy. Modification of thromboxane B2 formation in platelets of male subjects only

The effects of dietary interventions, based on changes of total fat, saturated fatty acids and cholesterol contents and of the polyunsaturated/saturated (P/S) fatty acid ratio of the diet, were studied in normal male and female subjects, living in North Karelia, Finland, and South Italy. In North Karelia the increase of P/S ratio (from 0.15 to 1.2) of the diet for a 6-week period resulted in reduced thromboxane B2 (TxB2) production by collagen-stimulated platelets only in male subjects, whereas plasma total, LDL and HDL cholesterol were reduced in both sexes. After a 6-week return to the original diet, plasma lipid levels were restored in all subjects. In the South Italy study, changes in platelet TxB2 production were observed only after return to the original diet in male subjects. Total and LDL cholesterol were significantly increased during the dietary intervention and returned toward baseline levels after switch back to the original diet. These data indicate that the increase of the P/S ratio in the diet reduces platelet TxB2 formation only in men.     

Beta-thromboglobulin and platelets in unstable angina

BACKGROUND. Atheromatous plaque rupture is the main cause of platelet activation in ischaemic heart disease (IHD). Platelet activation is manifested by a release into circulation of the components of granules, including beta-thromboglobulin (beta-TG) - a marker of platelet activation in vivo. The platelet count (PLT), mean platelet volume (MPV) and the proportion of large platelets (L(PLT)) are indirect platelet activation markers. Data in literature on the role of these markers in patients with unstable angina are discordant. AIM. To assess plasma concentration of beta-TG, PLT, MPV and LPLT in patients with unstable angina before and during standard pharmacological therapy. METHODS. The study group consisted of 54 patients (19 females and 35 males) with unstable angina who were divided into two groups: Group A - 45 patients with a history of angina, and group B - nine patients with a new onset unstable angina. beta-TG and platelet activation markers were measured at baseline (groups A and B) and after 8-10 days of standard medical therapy for unstable angina (group B). The control group consisted of 26 healthy subjects (13 females and 13 males). RESULTS. The mean beta-TG concentration in groups A (16.2 IU/ml) and B (19.7 IU/ml - before and 21.8 IU/ml - after treatment) was significantly (p<0.05) higher than in controls (10.6 IU/ml). In patients with unstable angina, the PLT and MPV values were not affected by therapy and were similar to those obtained in controls, whereas the LPLT value was significantly higher than in controls. CONCLUSIONS. Concentrations of beta-TG and L(PLT) are increased in patients with unstable angina due to platelet activation. The introduction of standard medical treatment for unstable angina did not significantly change beta-TG and platelet activation markers.     

Comparative effect of fish oil feeding and other dietary fatty acids on plasma lipoproteins, biliary lipids, and hepatic expression of proteins involved in reverse cholesterol transport in the rat

BACKGROUND: While elevated plasma high-density lipoprotein (HDL) levels has been associated to a reduction in cardiovascular risk, dietary fish oils rich in omega-3 polyunsaturated fatty acids (PUFAs) may protect against this disease. The protective effect of HDL is associated to its participation in the reverse cholesterol transport pathway. On the other hand, omega-3 PUFAs decrease plasma HDL levels compared to other fatty acids, which may suggest an effect on reverse cholesterol transport. AIM: In this work, the effect of dietary fish oil on the fatty acid composition of hepatic membranes, plasma lipoprotein cholesterol profile, biliary lipids, and the expression of proteins involved in reverse cholesterol transport, was compared to other dietary oils having a different degree of fatty acid unsaturation. METHODS: Male rats were fed a semi synthetic diet containing fish oil (omega-3), sunflower oil (omega-6), olive oil (omega-9) or coconut oil (saturated). Hepatic membrane fatty acid composition, plasma cholesterol levels, lipoprotein cholesterol profile, biliary lipids, hepatic mRNA levels for lecithin cholesterol acyltransferase, hepatic lipase, apo E, and apo A-I, and hepatic protein levels of the scavenger receptor class B type I, caveolin-1, and the ATP binding cassette transporter A1 were analyzed. Plasma apo A-I and apo E protein levels were also evaluated. RESULTS: Compared to the other diets, omega-3 PUFAs significantly changed omega-3/omega-6 fatty acid ratio of hepatic membranes, caused a reduction of plasma total and HDL cholesterol, and selectively increased biliary cholesterol secretion. No modification in the expression levels of lecithin cholesterol acyltransferase, hepatic lipase, apo A-I and apo E mRNA was observed. Hepatic scavenger receptor class B type I, caveolin-1, and the ATP binding cassette transporter A1 protein levels were also not affected. Plasma apo A-I, but not apo E, was reduced. CONCLUSIONS: These results show that dietary omega-3 PUFAs reduce plasma HDL cholesterol and increase biliary cholesterol without concomitant modifications in the expression of key genes and proteins involved in reverse cholesterol transport. These findings suggest that functional changes in the activity of these proteins as consequence of the incorporation of omega-3 PUFAs into hepatic membranes and plasma lipoproteins may underlie the effect of fish oil feeding on plasma and hepatic cholesterol metabolism in the rat.     

Increased blood coagulation and platelet activation in patients with infective endocarditis and embolic events

BACKGROUND: Inflammation-induced procoagulant changes and alterations in platelet activity appear to play an important role in thromboembolic complications of infective endocarditis (IE). HYPOTHESIS: The aim of this study was to investigate systemic coagulation activity, fibrinolytic capacity, and platelet activation in patients with IE with and without embolic events by measuring the plasma levels of prothrombin fragment 1+2 (PF1+2), thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor-1 (PAI-1), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF4), respectively. METHODS: The study included 76 consecutive patients (female = 55, male = 21, mean age 26 years, range 8-64 years) with definite IE according to the Duke criteria; of these, 13 (17.1%) had embolic events. RESULTS: Plasma concentrations of PF1+2 (3.2 +/- 1.3 vs. 1.7 +/- 0.7 and 1.4 +/- 0.7 nmol/l, p < 0.001, respectively) and TAT (7.3 +/- 1.5 vs. 2.9 +/- 1.2 and 2.2 +/- 1.1 ng/ml, p < 0.001, respectively) were elevated in patients with embolic events compared with patients without embolic events and control subjects. Similarly, patients with embolic events had increased plasma levels of beta-TG (63.3 +/- 10.9 vs. 33.1 +/- 11.6 and 19.1 +/- 10.6 ng/ml, p < 0.001, respectively) and PF4 (106.0 +/- 28.7 vs. 50.3 +/- 16.7 and 43.0 +/- 15.8 ng/ml, p < 0.001, respectively) compared with those without embolic events and the control group. Embolic patients also had higher PAI-1 levels than nonembolic patients and healthy subjects (14.4 +/- 6.4 vs. 8.6 +/- 5.9 and 5.4 +/- 4.3 ng/ml, p = 0.002, respectively). CONCLUSION: Patients with IE and with subsequent thromboembolism have increased systemic coagulation activation, enhanced platelet activity/damage, and impaired fibrinolysis. The resulting imbalance produces a sustained hypercoagulable state, which contributes to the increased risk of thromboembolic events in this particular group.     

Platelet fatty acids and function in two distinct regions of Belgium: relationship to age and dietary habits

We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD). In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids. While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects. When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups. In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity. The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.     

Plasma beta-thromboglobulin and platelet factor 4 concentrations in patients with atrial fibrillation

The clinical significance of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) levels were evaluated in 26 patients with atrial fibrillation (af) complicated by valvular heart disease (VHD), 73 patients with af but without valvular heart disease and 57 normal subjects. The beta-TG level was significantly higher in af patients without VHD than in normal subjects (49.4 +/- 35.8 ng/ml vs 31.2 +/- 14.0 ng/ml, p less than 0.01) and in af patients with VHD than in normals (64.1 +/- 52.8 ng/ml vs 31.2 +/- 14.0 ng/ml, p less than 0.01). Af patients with or without VHD tended to show high levels of PF4 compared with normals (af patients without VHD: 34.1 +/- 45.5 ng/ml, af patients with VHD: 18.6 +/- 27.2 ng/ml, normals: 11.6 +/- 8.2 ng/ml). There was no correlation between beta-TG levels and age in af patients without VHD or in normals. There was also no correlation between beta-TG levels and heart rate in af patients without VHD. The activation of platelets was suggested in patients with atrial fibrillation on the basis of increased levels of platelet releasing substances, especially in those with VHD. The high levels of beta-TG and PF4 in patients with atrial fibrillation may be one explanation for the high incidence of thromboembolism in these patients, indicating the necessity of antiplatelet therapy.     

Evidence that platelet density depends on the alpha-granule content in platelets

The relation between platelet buoyant density and beta-thromboglobulin (beta-TG), a marker for platelet alpha-granule content, was assessed by three independent approaches. (1) Platelets were separated on iso- osmolar discontinuous Stractan density gradients into five fractions, ranging in density from 1.061 g/ml to 1.091 g/ml (20 degrees C). The beta-TG content (mean +/- SD, n = 17) increased with the platelet density from 27.8 +/- 8.6 micrograms beta-TG/10(9) cells (20% less- dense platelets) up to 65.6 +/- 15.5 micrograms beta-TG/10(9) cells (15% most-dense platelets). (2) Activation of platelets in platelet- rich plasma with thrombin, adenosine diphosphate, collagen, or epinephrine resulted in a decreased density of the platelets. This was only seen when there was simultaneous secretion of beta-TG. (3) The less-dense and the more-dense platelet fractions, after isolation by density gradient centrifugation, were separately treated with thrombin. After complete degranulation, the density distribution of the originally less-dense and more-dense platelets were identical and were much narrower than the density distribution of resting platelets.     

Defective platelet aggregation and increased platelet turnover in patients with myelofibrosis and other myeloproliferative diseases

In 9 patients with myeloproliferative diseases (MPD) (6 with myelofibrosis, MF, 1 with Ph1 positive chronic granulocytic leukaemia, CGL, 1 with primary eosinophilia, PE, 1 with pre-leukaemia syndrome, preL) collagen, epinephrine, and ADP-induced aggregation, N-ethylmaleimide-induced malondialdehyde (MDA) production, beta-thromboglobulin (beta-TG) plasma levels, and platelet turnover were studied. Collagen-induced aggregation was found to be normal in 7 patients, absent in 1, and reduced in 1. In all but 3 patients, aggregation with ADP was markedly reduced. Epinephrine-induced aggregation was decreased in 7 patients. No difference was found between mean MDA production in MPD (3.21 +/- 0.50 nmol/10(9) PLTs) and in control group of 21 normal subjects (3.04 +/- 0.26 nmol/10(9) PLTs). Mean beta-TG levels were significantly higher (P less than 0.01) in MPD patients (165.00 +/- 28.29 ng/ml) than in healthy controls (81.76 +/- 14.63 ng/ml). Mean platelet production half-time was significantly shorter in MPD (2.48 +/- 0.24 d) than in the control group (3.43 +/- 0.17 d), after adjustment for age by covariance analysis (P less than 0.005). Our data do not indicate an abnormal prostaglandin synthesis and are consistent with the hypothesis that a disseminated intravascular platelet aggregation might take place in MPD patients.