Thromboembolic risk in children with nephrotic syndrome.

The in vivo activation of the hemostatic system was evaluated in 14 children (4-13 years old) with nephrotic syndrome at different stages of the disease. The blood platelet count, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), fibrinogen, the coagulation inhibitors antithrombin III and protein C (ATIII:Ag and PC:Ag), and D-dimers were determined. Platelet number was significantly higher at the onset of the disease than in the next stages (p less than 0.05). beta-TG, PF4 and fibrinogen were significantly increased as compared with controls at the onset (p less than 0.001) and decreased progressively during the course of the disease without reaching the control values. Blood coagulation inhibitors behaved differently; PC was higher in patients than in controls at all stages (p less than 0.05) whereas ATIII values were significantly decreased at the onset (p less than 0.05), but increased during the course the disease (p less than 0.01). No changes were observed in the D-dimer plasma levels. These data suggest that the thrombotic risk in nephrotic syndrome is particularly evident at the onset of the disease, and appears to be due mainly to changes in platelet number and function, and to increased fibrinogen levels rather than to alterations of plasma anticoagulant factors.     

Fibrin formation and platelet aggregation in patients with acute myocardial infarction: effects of intravenous and subcutaneous low-dose heparin

Fibrinopeptide A (FPA) and beta thromboglobulin (BTG) were measured in 42 patients with acute myocardial infarction (AMI) allocated on admission to one of three groups: 14 patients received a heparin bolus injection of 5000 IU intravenously followed by a 2-hour intravenous infusion (830 IU/hr) (group 1), 14 patients received a heparin bolus of 5000 IU subcutaneously (group 2), and the remaining 14 patients received no anticoagulant treatment (group 3). In group 1 the initially elevated FPA level of 5.8 +/- 1.8 ng/ml dropped to 2.0 +/- 1.5 ng/ml 30 minutes after the intravenous heparin bolus injection of 5000 IU (p less than 0.001) and returned to normal (1.9 +/- 0.8 ng/ml) in 8 of 14 patients. The initially elevated BTG level of 64 +/- 21 ng/ml did not change significantly during intravenous heparin treatment, whereas there was a rapid but only transitory increase in platelet factor 4, (PF4) from 25 +/- 9 to 74 +/- 16 ng/ml (p less than 0.01) after the intravenous heparin bolus. In group 2 the initial FPA of 5.0 +/- 2.3 ng/ml was similarly elevated as in group 1 and dropped to 2.7 +/- 1.7 and 3.3 +/- 1.5 ng/ml 2 and 4 hours after 5000 IU subcutaneously (p less than 0.05), whereas 6 and 8 hours after subcutaneous heparin bolus the mean FPA levels were 4.2 +/- 1.7 and 5.5 +/- 2.0 ng/ml and no more significantly different from the initial FPA values. BTG and PF4 did not change significantly after the subcutaneous heparin bolus. In group 3 the initially elevated mean FPA level of 4.9 +/- 2.4 ng/ml did not change significantly during the first 8 hours after admission, whereas the FPA level 24 hours after admission was 8.4 +/- 3.9 ng/ml and higher than the initial value (p less than 0.01). We conclude that heparin may reduce the elevated FPA level in plasma found in patients with AMI; however, neither subcutaneous nor intravenous heparin in a dosage frequently used is sufficient to consistently normalize the elevated rate of fibrin formation found in these patients.     

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.     

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.     

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.     

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 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.     

Platelet activation in the lung after antigen challenge in a model of allergic asthma.

The purpose of this study was to investigate whether platelets are activated and release their products in the human lung after antigen challenge. Using subsegmental antigen challenge as a model of asthma, bronchoalveolar lavage fluids from ragweed-allergic asthmatic subjects were assayed for the alpha granule products, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), prior to challenge (baseline) and at 5 min and 19 h after challenge with ragweed antigen. Airway segments challenged with normal saline were used as controls. Five minutes after antigen challenge, levels of platelet products in BAL fluid were not elevated from baseline or normal saline control levels. However, 19 h after antigen challenge, a 10-fold increase in platelet products in BAL fluids was found. The mean PF4 levels increased from baseline and saline control values of less than 1.0 to 7.2 ng/ml (p less than 0.05) 19 h after antigen challenge. beta-TG increased from baseline and control levels of less than 1.0 to 6.6 ng/ml (p less than 0.05). Elevations in PF4 and beta-TG were highly correlated with each other (r = 0.98, p less than 0.0001). Levels of platelet products during the 19-h response correlated with albumin, with kinins, with the prostaglandins 6-keto-PGF1 alpha, PGE2, and PGF2 alpha, and with the eosinophil-derived proteins, eosinophil-derived neurotoxin and eosinophil peroxidase. We conclude that platelet activation in the lung is a feature of the late inflammatory response to antigen challenge and that platelets may play an important role in allergic inflammation and asthma.     

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.     

Aggressive antiplatelet therapy before coronary stent implantation in acute coronary syndrome with essential thrombocythemia--a case report

A 52-year-old man was admitted to the hospital because of unstable angina pectoris. Coronary angiography revealed severe stenosis at a proximal site of the left anterior descending artery. Essential thrombocythemia (ET) was diagnosed on the basis of findings of marked thrombocytosis (106 x 10(4)/microL) and an increased number of immature megakaryocytes in the bone marrow. Because hyperaggregability of platelets was demonstrated by an ex vivo platelet aggregation assay and by elevated plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), antiplatelet therapy with aspirin and ticlopidine and cytoreduction therapy with hydroxyurea were started. This combination treatment resulted in a decrease in the platelet count to less than 60 x 10(4)/microL and decreases in plasma levels of both beta-TG and PF4 to almost normal values. Percutaneous coronary angioplasty and stenting were then performed successfully without thrombotic complications. These findings suggest that combination therapy with antiplatelet and cytoreduction agents before catheter intervention is useful for the prevention of thrombotic complications in patients with acute coronary syndrome associated with essential thrombocythemia.     

Deep vein thrombosis and related platelet changes after total hip replacement

Postoperative changes related to platelets and their correlation with the incidence of deep venous thrombosis (DVT) were studied in 30 patients undergoing total hip replacement. Levels of platelet count, platelet-crit, mean platelet volume, spontaneous platelet aggregation, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured before operation and on the 1st, 3rd and 7th postoperative days. DVT was detected by 125I-fibrinogen leg scanning in 11 of the patients. After the operation there was a significant and progressive increase (p less than 0.01) in PF4 and beta-TG, and the presence of circulating platelet aggregates was demonstrated. Platelet count levels and platelet-crit were decreased on the 1st and 3rd postoperative days followed by recovery on the 7th day. The changes observed following total hip replacement were not related to the development of postoperative DVT.     

Raised plasma concentrations of platelet factor 4 (PF4) in Crohn's disease.

Plasma platelet factor 4 (PF4), secreted by the platelets, is an index of platelet aggregation and thromboembolic risk. The authors assessed PF4 in 20 patients with Crohn's disease (ileitis in 13 patients, ileocolitis in seven) and in 20 healthy volunteers. Disease activity was low (Crohn's Disease Activity Index less than 150) in 11 patients and high in nine. Radioimmunoassay of PF4 using Abbott's Kit was performed on one sample of plasma from each subject (nv less than or equal to 0.324 nmol/ml), (nv less than or equal to 10 ng/ml). A significantly higher concentration of PF4 was found in Crohn's disease patients: 4.625 +/- 1.1 nmol/ml (142.5 +/- 36 ng/ml) than in the control group: 0.189 +/- 0.07 nmol/ml (5.6 +/- 4.8 ng/ml) (Z = 5.396, p less than 0.0001). No correlation was present between PF4 levels and activity, the site of disease, or medical treatment with or without prednisone.     

Effect of heparin on the in vivo release and clearance of human platelet factor 4

Intravenous injection of heparin (100 U/kg) into normal volunteers resulted in an increase of platelet factor 4 (PF4) level in platelet- poor plasma from a mean value of 18.1 +/- 6.6 ng/ml before the injection to 257.9 +/- 68.3 ng/ml at 5 min after injection. PF4 antigen isolated from "postheparin plasma" by adsorption on heparin-agarose and elution with 2.0 M NaCl and "authentic PF4" isolated from human platelets showed identical patterns of migration as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Material released by washed human platelets was injected intravenously into rats. The clearance of PF4 followed a biphasic exponential pattern. The half-lives (T1/2) for the fast and slow components for control rats were 1.2 and 17.1 min. Heparin significantly extended the half-life of human PF4 in rat circulation. The clearance of PF4 injected together with heparin followed a single component model with a half-life of 27.6 min. Administration of heparin to rats that had been previously injected with human platelet releasate resulted in a 30-fold increase of plasma PF4 level in their circulation. The clearance of PF4 from the circulation of these rats (T1/2 = 45 min) fitted a single component model. We propose that PF4 is originally secreted by platelets into circulation and subsequently bound reversibly to vascular sites from which it can be released back into the circulation by heparin. The fast component of PF4 clearance that is abolished by heparin may reflect binding of this protein to the endothelial cells.     

Effect of heparin on in vivo platelet factor 4 (PF4) release and platelet aggregation after aspirin administration

We studied the release in vivo of platelet specific proteins platelet factor 4 (PF4) and β-thromboglobulin (βTG), and confirmed that only PF4 is released, after heparin intravenous administration. A good correlation was found between platelet count and PF4 and this seems at variance with the idea that the source of released PF4 is vascular endothelium rather than platelets; however, such a possibility cannot be excluded. Although platelet function was blocked by aspirin injection heparin was still able to induce the release of PF4 and exerted a potentiating effect on platelet aggregation induced by ADP and collagen.     

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.     

Antithrombin III supplementation reduces heparin requirement and platelet loss during hemodialysis of patients with fulminant hepatic failure

Previous studies have shown that antithrombin III levels are low in fulminant hepatic failure, and heparin kinetics are abnormal, making control of heparinization difficult during hemodialysis of these patients who are at risk of bleeding. In this study, we have performed a controlled, randomized trial of antithrombin III supplementation on heparin activity, occurrence of bleeding and the platelet count and activation during hemodialysis in 24 patients with fulminant hepatic failure. The treated group of 12 patients was given 3,000 units of antithrombin III before hemodialysis. Antithrombin III supplementation was shown to normalize antithrombin III levels during hemodialysis (prelevels: 0.22 +/- 0.03 U/ml S.E.; at 1 hr 0.99 +/- 0.06 U/ml; p less than 0.001; control prelevels: 0.24 +/- 0.03 U/ml; at 1 hr 0.23 +/- 0.04 U/ml). Total heparin usage was significantly decreased by antithrombin III supplementation (median 5,200 U; range = 2,000 to 13,000) as compared with the control group (median 10,200 U; range = 5,000 to 16,500; p less than 0.005). Blood heparin level (antifactor Xa activity) after the initial bolus was significantly greater in the antithrombin III-supplemented subjects (0.40 +/- 0.07 U/ml compared with 0.22 +/- 0.05 U/ml in the control group; p less than 0.05). The significant reduction in platelet count observed in the control patients (18% +/- 6% at 1 hr; p less than 0.05) did not occur in antithrombin III patients (6% +/- 4% at 1 hr), which was reflected by a lower release of the platelet-specific protein beta-thromboglobulin. Two of 12 patients in both groups showed minor bleeding around vascular access sites during the first hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet aggregation and P-selectin levels during exercise treadmill test in patients with ischaemic heart disease

INTRODUCTION: Coronary artery disease (CAD) is associated with higher platelet activation sometimes despite aspirin use. There are conflicting data concerning platelet activation course during physical exercise in patients on aspirin with CAD. AIM: To assess platelet activation pattern during physical exercise in patients with CAD. METHODS: The study included 35 patients (20 men, 15 women) aged 64.7+/-10 years with CAD (CCS II) on aspirin treatment (75 mg daily) and a control group of 10 healthy subjects adjusted for age and gender. Treadmill testing was performed using the Bruce protocol. Platelet aggregation was measured with optical aggregation with the agonists ADP (10 microM), collagen (2 microg/ml) and arachidonic acid (0.5 mg/ml) before and at peak exercise; P-selectin platelet and soluble expression (basal and after stimulation with thrombin) was assessed with cytofluorometry before, at peak exercise and 1 hour after. RESULTS: There were no differences in collagen and ADP aggregation between patients and the control group. There was a significant increase of ADP aggregation at peak exercise in the control group (p <0.05). There was a positive correlation between platelet aggregation before exercise and at peak exercise with ADP (r=+0.86) and with collagen (r=+0.61). There was no difference in soluble P-selectin concentration between patients and the control group. Platelet P-selectin expression without stimulation with thrombin 1 hour after exercise was significantly higher in patients than in the control group (p <0.05). CONCLUSIONS: 1. Physical exercise does not intensify platelet aggregation in patients with CAD on 75 mg aspirin daily. 2. Despite taking aspirin, platelet activation measured with the expression of platelet P-selectin increases and there is further intensification during exercise testing. 3. The concentration of soluble P-selectin in patients with CAD does not reflect the expression of platelet P-selectin.     

Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy.

To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82 +/- 2% and 79 +/- 2%, respectively, compared with 51 +/- 8% for t-PA alone (P less than 0.05) and 50 +/- 4% for t-PA plus aspirin (p less than 0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p less than 0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5 +/- 0.6 versus 12.1 +/- 2.0 versus 12.6 +/- 2.2 versus 10.0 +/- 0.8 minutes, respectively; p less than 0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p less than 0.01 by t test; p less than 0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.     

Plasma beta-thromboglobulin to platelet factor 4 ratios as indices of vascular complications in essential hypertension

The ratio of the plasma level of beta-thromboglobulin (beta-TG) to platelet factor 4 (PF-4) which is regarded as a most reliable indicator of platelet activation in vivo, was followed in 52 subjects at various stages of essential hypertension according to the WHO classification. These comprised 30 cases at stage I, 19 cases at stage II and three cases at stage III, and 20 age-matched normotensive control subjects. The observed beta-TG:PF-4 ratio in the hypertensive patients was 4.59 +/- 0.20, which was significantly higher than the value of 3.13 +/- 0.19 recorded in the normotensive control subjects. According to the WHO classification, beta-TG:PF-4 ratios in hypertensive patients at stages I, II and III were 3.93 +/- 0.19, 5.31 +/- 0.35 and 6.56 +/- 0.12, respectively. The beta-TG:PF-4 ratio revealed a tendency of platelet activation to increase with advanced progress of hypertensive vascular lesions. These results suggest that the abnormal platelet function observed in patients with essential hypertension plays an important role in the development of hypertensive vascular complications.     

Plasma markers of platelet and polymorphonuclear leukocyte activation in young adults with acute myocardial infarction

Our goal was to evaluate some plasma markers of platelet and polymorphonuclear leukocyte (PMN) activation in a group of young adults with acute myocardial infarction (AMI) at the initial stage and after three months. We enrolled 49 AMI subjects aged<45 years and examined plasmatic levels of platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), elastase and myeloperoxidase (MPO) using ELISA methods. PF4 and beta-TG were increased, compared to control subjects, both at the initial stage and after 3 months. In control subjects and in AMI patients, at both times of observation, there was a significant and positive correlation between the two platelet parameters, while no correlation was present between each parameter and platelet count. In AMI patients there was an increase in elastase levels in comparison with the control group; this increase was evident at the initial stage and after 3 months. There was no difference in MPO levels between control subjects and AMI patients. In control subjects and in AMI patients there was a significant and positive correlation between elastase and MPO level, whereas no relationship was found between each marker and PMN count. Our data show that in young AMI patients the discharge treatment including antiplatelet drugs did not modify platelet activation and suggest the association of molecules able to inhibit PMN activation to the conventional therapy of these AMI patients.