Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease

Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infarction. The underlying mechanisms of this increased mortality remain unclear. This study investigated the hypothesis that patients suffering from ischemic heart disease (IHD) and depression concurrently may have abnormal platelet activation resulting in an increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured in young healthy control subjects, in nondepressed patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups. This increase was not related to age, gender, racial difference, aspirin use, or severity of cardiac disease. This finding suggests that in depressed patients with IHD there is greater platelet activation, and may indicate an increased risk of thrombotic complications.     

Spontaneous platelet aggregation in arterial insufficiency: mechanisms and implications

To investigate the clinical implications and mechanisms of spontaneous platelet aggregation (SPA) in man, 150 normal subjects, 22 patient controls and 130 patients with vascular insufficiency were studied. SPA was negative in normal subjects and patient controls whereas it was positive in 36 of 66 (54%) patients with transient ischemic attacks, 6 of 32 (19%) patients with stable angina, 7 of 10 (70%) patients with acute myocardial infarction and 11 of 14 (80%) patients with acute peripheral arterial insufficiency. The SPA was inhibited with aspirin in vivo, and inhibited competitively in vitro by low concentrations of aspirin, 2-chloroadenosine, prostaglandin E1 or apyrase but only by high concentrations of heparin or hirudin. Addition of platelet-poor plasma from patients with positive SPA did not cause normal platelets to aggregate. Treatment of patients who had acute peripheral arterial insufficiency with aspirin and dipyridamole prevented SPA with notable clinical improvement of the ischemic changes.     

The young platelet population in children with cyanotic congenital heart disease

Some morphological, biochemical and functional parameters of platelet population in children with cyanotic congenital heart disease (CCHD) were studied by making comparisons of the normal platelet population in both CCHD patients and controls. The mean volume of the platelets from cyanotic patients was greater than from normals. The platelet size distribution curves demonstrated a shift towards larger than normal size in the case of CCHD. The mean protein content, as well as the mean PF3 content of platelets was increased in CCHD. Following addition of kaolin, PF3 release was more rapid and of shorter duration with platelets from CCHD patients as compared to normal platelets. They also released more PF3 than did normal platelets. After addition of ADP, collagen, or adrenalin, platelets of CCHD patients were more responsive than similarly treated platelets from normals. Platelets from CCHD showed an increased initial rate of aggregation and greater maximum aggregation. These data suggested that the platelet population of CCHD patients consists of larger, younger and functionally more active platelets than does the platelet population of normals.     

Effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls

The effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls were investigated. Platelet function was studied at rest, and during mental stress (colour word test), or after exercise (bicycle ergometry), in 113 angina patients (21 on aspirin) and 50 matched controls. Platelet function was assessed by filtragometry ex vivo (reflecting platelet aggregability), by measuring platelet secretion (beta-thromboglobulin and platelet factor 4 levels in plasma), and by Born aggregometry in vitro. At rest, platelet function did not differ between patients and controls. Exercise increased platelet aggregability and secretion similarly in both groups. Aspirin did not attenuate the platelet activating effect of exercise despite inhibition at rest. Mental stress increased heart rate, blood pressure and plasma catecholamines, but platelet responses were highly variable. However, mental stress tended to shorten filtragometry readings in patients but not in controls (P < 0.05 between the groups); plasma beta-thromboglobulin showed a similar difference between patients and controls (P < 0.05 between the groups; aspirin-treated patients included). Physical exercise activates platelets in patients with stable angina pectoris and healthy controls. Aspirin is not an effective inhibitor of exercise-induced platelet aggregation. Platelet responses to mental stress are variable, but more pronounced in angina patients.     

Steam-sterilizable, fluorescence lifetime-based sensing film for dissolved carbon dioxide

Heparin-induced thrombocytopenia (HIT) is a common adverse effect of heparin therapy that carries a risk of serious thrombotic events. This condition is caused by platelet aggregation, which is mediated by anti-heparin/platelet factor 4 antibodies. Sera from patients with HIT in the presence of platelets, induced the expression of E-selectin, VCAM, ICAM-1 and tissue factor and the release of IL1beta, IL6, TNFalpha and PAI-1 by human umbilical vein endothelial cells (HUVECs) in vitro and initiated platelet adhesion to activated HUVECs. These effects which occurred in a time-dependent manner were significant in the first 1-2 h of incubation and reached a maximum after 6 to 9 h. The GP IIb-1IIa receptor antagonist SR121566A which has been shown to block platelet aggregation induced by a wide variety of agonists including HIT serum/heparin, reduced in a dose-dependent manner the HIT serum/heparin-induced, platelet mediated expression and release of the above mentioned proteins. The IC50 for inhibition of HIT serum/ heparin-induced platelet dependent HUVEC activation by SR121566A was approximately 10-20 nM. ADP, but not serotonin release, also appeared to be involved as apyrase and ATPgammaS blocked platelet-dependent, HIT serum/heparin-induced cell surface protein expression and cytokine release by HUVECs. Increased platelet adherence to HIT serum/heparin-activated HUVECs was inhibited by SR121566A and, to a lesser extent, by apyrase and ATPgammaS, showing that platelet activation and release was at the origin of the HIT serum/heparin-induced expression of these proteins by HUVECs. Thus, sera from patients with HIT induced the expression of adhesive and coagulation proteins and the release of cytokines by HUVECs through the activation of platelets which occurred in a GP IIb-IIIa-dependent manner, a process that could be selectively blocked by SR121566A.     

Clopidogrel inhibition of stent, graft, and vascular thrombogenesis with antithrombotic enhancement by aspirin in nonhuman primates

BACKGROUND: A recent study showed that clopidogrel reduces thrombo-occlusive complications in patients with symptomatic atherosclerosis more effectively than aspirin. METHODS AND RESULTS: The effects of clopidogrel and aspirin have been compared, singly and in combination, for measurements of 111In-labeled platelets and 125I-labeled fibrin deposition in baboon models of arterial thrombosis and related to platelet aggregation and expression of activation epitopes induced by ADP, collagen, and thrombin receptor agonist peptide (TRAP) and to template bleeding times (BTs). Low-dose oral clopidogrel (0.2 mg. kg-1. d-1) produced cumulative (1) intermediate decreases in 111In-platelet and 125I-fibrin deposition for segments of prosthetic vascular graft, deployed endovascular metallic stents, and endarterectomized aorta (P<0.009 in all cases); (2) elimination of ADP-induced platelet aggregation (P<0.001); (3) modest inhibition of collagen-induced platelet aggregation (P<0.01); (4) no reduction in TRAP-induced platelet aggregation; and (5) minimal prolongation of BTs (P=0.03). High-dose oral clopidogrel (>/=2 mg/kg) produced the same effects within 3 hours. The effects of clopidogrel dissipated over 5 to 6 days. Aspirin 10 mg. kg-1. d-1 alone did not decrease 111In-platelet and 125I-fibrin deposition on segments of vascular graft but detectably decreased 111In-platelet and 125I-fibrin accumulation on stents (P<0.01), minimally inhibited ADP- and collagen-induced platelet aggregation (P<0.05 in both cases), and minimally prolonged BTs (P=0.004). Within 3 hours of aspirin administration, the antithrombotic effects of acute high-dose or chronic low-dose clopidogrel were substantially enhanced, and BTs were modestly prolonged without inhibiting platelet aggregation induced by TRAP (P<0.001 in all cases compared with clopidogrel alone). CONCLUSIONS: Clopidogrel produces irreversible, dose-dependent, intermediate reduction in thrombosis that is substantially enhanced by the addition of aspirin. The effects of combining aspirin and clopidogrel need to be evaluated in patients at risk of vascular thrombosis.     

Platelet coagulant activities and serum lipids in transient cerebral ischemia

To determine whether platelets play a part in the pathogenesis of transient cerebrovascular ischemia, we studied 22 patients with transient ischemia, 18 control patients and 38 normal subjects. Platelet aggregation and [14C]-serotonin release by ADP, epinephrine and collagen were normal in all patients, as were plasma coagulation assays, except for shortened partial thromboplastin times in the patients with transient ischemia. Platelet coagulant activities concerned with initiation and early stages of intrinsic coagulation were increased two to three times in 12 patients with transient ischemic attacks with normal serum lipids and normal in the 10 others with Type IV hyperlipoproteinemia. These results indicate an association between platelet coagulant hyperactivity and transient ischemic attacks in a group of patients with normal serum lipids.     

In vivo platelet and T-lymphocyte activities during pulmonary tuberculosis

Platelets have been suggested to play a role in the inflammatory response, including defence against bacteria. The aims of this study were to determine in vivo platelet activity during the clinical course of pulmonary tuberculosis and to investigate whether or not there is a correlation between the magnitude of platelet activation and the extent of the pulmonary disease. T-lymphocyte activity was also analysed in the patients. Platelet factor-4 (PF4) and soluble interleukin-2 receptor-alpha (sIL-2Ralpha) concentrations were used as markers of platelet and T-lymphocyte activation, respectively. Twenty-five patients with pulmonary tuberculosis were studied. Fifteen healthy subjects served as a control group. The levels of both sIL-2Ralpha (3,000+/-1,948 pg x mL(-1)) and PF4 (103.1+/-6.7 IU x mL(-1)) were significantly higher in the patients with tuberculosis than in the control group (984+/-360 pg x mL(-1) and 78.2+/-23.9 IU x mL(-1), respectively) (Mann-Whitney U-test, p<0.001 for both comparisons). The plasma PF4 levels were found to be well correlated with the extent of pulmonary lesions on chest radiography (the Spearman's bivariate correlation analysis, r=0.65, p<0.001). However, sIL-2Ralpha concentrations did not correlate with the extent of disease. In conclusion, it has been suggested that platelet and T-lymphocyte activation occurs during pulmonary tuberculosis. The good correlation between platelet activation and the extent of pulmonary tuberculosis might be ascribed to a pathophysiological role of platelets in pulmonary tuberculosis.     

Salutary effects of aspirin in coronary artery disease are not limited to its platelet inhibitory effects

Aspirin is widely used in the treatment and prevention of coronary artery disease (CAD). However, other platelet inhibitory agents, which inhibit platelet activation, have not been found to be effective or as effective as aspirin. The discrepancy between the efficacy of these compounds and aspirin suggests that the therapeutic efficacy of aspirin may not be limited to its platelet inhibitory effect. In this review, the basis for a unique place for aspirin in the therapy of patients with CAD is discussed. The author believes that the nonplatelet-mediated effects of aspirin could be more important than the platelet inhibitory effect, or at least may complement the platelet inhibitory effects of aspirin in patients with acute myocardial ischemia and in others undergoing intracoronary procedures.     

Differential expression of platelet activation markers in aspirin-sensitive asthmatics and normal subjects

BACKGROUND: Activation of platelets and expression of adhesion molecules (e.g. CD62P and CD63) which mediate interactions between platelets and other cells may be important in the pathogenesis of aspirin-sensitive asthma. OBJECTIVE: To determine the expression of CD62P and CD63 on platelets from aspirin-sensitive asthmatic (ASA+), aspirin-tolerant asthmatic (ASA-) and normal subjects and to assess the modulatory effect of aspirin on platelet CD62P and CD63 expression following stimulation with either platelet-activating factor (PAF), arachidonic acid (AA) or collagen (COL). METHODS: Platelet-rich plasma was obtained from 10 ASA+, 10 ASA- and 10 normal control subjects, and expression of CD62P and CD63 was measured by flow cytometry. Platelets were stimulated with PAF (10, 80 nM), AA (0.1, 1 mM) or COL (80, 800 micrograms/mL) with or without aspirin (concentration range 0.4-4 mg/mL). RESULTS: In the absence of aspirin, CD62P expression induced by AA and COL was greater in ASA+ patients compared with control subjects (P < 0.001) while CD62P expression with PAF, AA and COL was reduced in ASA- when compared with ASA+ and control subjects (P < 0.001). CD63 expression with PAF and AA was reduced in both ASA+ and ASA- patients compared with control subjects (P < 0.001). Aspirin inhibited the expression of both CD62P and CD63 after agonist stimulation. Greater inhibition of CD62P expression was observed in ASA+ compared with ASA- patients (P < 0.001) and normal subjects (P < 0.05) while greater inhibition of CD63 expression was observed in normal subjects compared with both ASA+ and ASA- patients (P < 0.05). In ASA+ patients and normal subjects, stimulation with PAF and COL resulted in only one platelet population while in contrast with 1 mM AA two populations were observed. CONCLUSIONS: Enhanced AA- and collagen-induced platelet CD62P expression in ASA+ patients compared with normal subjects and greater inhibition by aspirin of CD62P expression in ASA+ may be relevant to the pathogenesis of this syndrome. Reduced expression of CD62P and CD63 in platelets of ASA- patients following stimulation with PAF and AA may also have implications for the role of platelets and these mediators in the pathogenesis of other forms of asthma.     

Method of quantitative measurement of human platelet aggregation in clinical practice

We examined the quantitative measurement of platelet aggregation in 20 volunteers and 89 patients with ischemic heart disease (IHD). Subjects in whom platelet aggregation was induced by an adenosine diphosphate (ADP and an epinephrine solution were clearly divided into two groups: "normal" and "accentuated". We chose the maximum aggregation time for the ADP solution and the maximum transmission rate for the epinephrine solution for the quantitative measurement of platelet aggregation. The results were as follows. The maximum aggregation time with a 1.0 microM ADP solution in the normal group of 13 volunteers was 0.71 +/- 0.12 min, (mean +/- SD), in 50 IHD patients it was 0.91 +/- 0.49 min, in the "accentuated" group of 7 volunteers it was 5.34 +/- 1.18 min, in 39 IHD patients it was 6.01 +/- 1.22 min. The maximum light transmission rate with a 0.1 microM epinephrine solution in the normal group of 14 volunteers was 8.04 +/- 4.14%, in 52 IHD patients it was 13.74 +/- 5.75%, in the "accentuated" group of 6 volunteers it was 76.33 +/- 9.91%, and in 37 IHD patients it was 77.26 +/- 13.39%. The difference between the "normal" and "accentuated" groups was statistically significant (p < 0.001), with the ADP and with the epinephrine solution. Next, we examine the effect of antiplatelet therapy (dipyridamole and aspirin) on 15 patients selected from among those with IHD who had accentuated platelet aggregation when the ADP solution was added. Their maximum aggregation time was 5.98 +/- 1.24 min, and their maximum platelet aggregation rate when the epinephrine solution was added was 78.90 +/- 11.60% (10 patients), 20.00 +/- 3.24% (5 patients). After the therapies, the maximum aggregation time in 10 patients was 0.94 +/- 0.21 min (return to normal condition), and in 5 patients it was 5.90 +/- 1.09 min (not effective). The maximum platelet aggregation rate in 10 patients was 14.11 +/- 5.88% (normal condition), and in 5 patients it was 75.00 +/- 9.51% (not effective). Finally, we examined the long term effects of various antiplatelet drugs. Most of the patients in whom platelet aggregation was accentuated got well.     

Platelet hyperactivation in patients with essential thrombocythemia is not associated with vascular endothelial cell damage as judged by the level of plasma thrombomodulin, protein S, PAI-1, t-PA and vWF

The occurrence of thrombotic events remains an important clinical problem in Essential Thrombocythemias (ET). Thus, hemostatic, fibrinolytic and vascular status was investigated in 16 patients (5 males and 11 females) with ET. Among them five presented thromboses in their past history. Platelet hyperactivation, as evidenced by a mean three-fold increase in plasma betathromboglobulin (beta TG), was observed in 13 among 16 patients; surprisingly this activation was present even when the platelet count was normal (in two patients) or subnormal, below 600 x 10(9)/l (in 11 patients). The mean value was 104 +/- 57 IU/ml significantly different from that of normal controls (35 +/- 16.5 IU/ml) (p < 0.001). An artefactual in vitro platelet activation was ruled out by the concomitant measurement of platelet factor 4 (PF4). D-dimers fibrin degradation products (D-Di FDP) were normal in all patients. Vascular endothelial cell function parameters were not markedly modified. The mean value of plasma thrombomodulin (TM) was found slightly but not significantly increased (60.1 +/- 4.9 ng/ml versus 49.1 +/- 10.0 ng/ml in controls). The values of plasma TM correlated neither with that of the platelet count nor with that of plasma beta TG or plasma PF4. The mean values of plasma protein S, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA) were normal and were not correlated neither with that of plasma TM nor with that of plasma beta TG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men

Some epidemiological observations indicate that 1 to 2 weekly servings of fish prevent ischemic heart disease (IHD). This might be explained by an effect of the very-long-chain n-3 polyunsaturated fatty acids (n-3 VLCPUFA) of fish oil on lipid metabolism and/or the hemostatic system, both involved in IHD development. We studied the effect of incorporating natural fish oil (4 g daily equivalent to 0.91 g n-3 VLCPUFA and corresponding to one to two weekly servings of fatty fish) into the diet in a 4-week parallel, randomized, and double-blind trial of 47 healthy males aged 29 to 60 years. Sunflower oil was used as placebo. The fish oil had no significant effect on plasma lipids, apolipoproteins, lipoprotein(a), blood coagulation FVII, fibrinogen, endogenous fibrinolysis, beta-thromboglobulin, von Willebrand factor, glucose, or insulin in fasting blood samples. In nonfasting samples (n = 19), fish oil was associated with an approximately 30% decline in plasma triglycerides (P < .02) and a 9% decline in FVII protein (P < .05), whereas FVII coagulant activity and fibrinolysis were unaffected. In conclusion, our findings indicate that lowering of postprandial triglycerides is the only n-3 VLCPUFA effect that could contribute to primary prevention of IHD in healthy middle-aged men as assessed by currently measurable lipid and hemostatic risk markers.     

Increased fraction of circulating activated platelets in acute and previous cerebrovascular ischemia

Determination of circulating activated platelets may be helpful to estimate the prognosis and to stratify therapies in arterial vascular disorders including stroke. We used flow cytometry and phase contrast microscopy to study whether the fraction of platelets expressing p-selectin and CD63 and the fraction of platelets with shape change are increased in patients with acute and previous cerebrovascular ischemia. The proportion of platelets expressing activation dependent antigens was higher in patients with acute (n = 24; p-selectin: 8.23 +/- 4.21%; CD63: 3.53 +/- 2.53%) and with previous cerebrovascular ischemia (n = 46; 3.86 +/- 1.98%; 2.80 +/- 1.79%) as compared to age- and sex-matched control subjects (n = 35; 2.17 +/- 0.96%; 1.79 +/- 0.75%; p < or = 0.005, respectively). In patients with previous ischemia, there was no difference between treatment with aspirin (n = 25) or phenprocoumon (n = 21). Hypertension, diabetes mellitus and smoking were not associated with increased antigen expression (analysis of variance). The fraction of discoid platelets and platelet counts were not significantly different between groups. Our results indicate increased expression of platelet neoantigens in acute and to a less degree in previous cerebrovascular ischemia. Ongoing platelet activation after cerebrovascular ischemia despite therapy with aspirin or phenprocoumon indicates that new anti-platelet drugs may be of benefit for these patients. Flow cytometry appears to be a useful tool to assess platelet function in cerebrovascular ischemia.     

Aspirin in essential thrombocythemia: status quo and quo vadis

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis in essential thrombocythemia (ET) has become an important issue. The rationale for its use in ET comes from the observation that arterial thrombosis and platelet-mediated microcirculatory disturbances are the major causes of morbidity and mortality in ET. Experimental data have shown persistently elevated levels of thromboxane A2 (TXA2) in ET patients probably reflecting an enhanced in vivo platelet activation. Increased TXA2 biosynthesis and platelet activation in vivo in ET are selectively suppressed by repeated low doses of aspirin. ET-related symptoms such as erythromelalgia, transient neurologic and ocular disturbances are sensitive to aspirin. However, the benefit of low-dose aspirin is still uncertain in the primary prevention of thrombosis in ET. Furthermore, aspirin may unmask a latent bleeding diathesis frequently present in ET which may result in severe hemorrhagic complications. Thus, aspirin is contraindicated in ET patients with a bleeding history or a very high platelet count (> 1500 x 10(9)/L) leading to the acquisition of von Willebrand factor deficiency. If indicated, aspirin is presently used in the widely accepted low-dose regimen of 100 mg daily. However, an optimal effective dose has not yet been established. To further evaluate the efficacy and safety of aspirin in ET, prospective clinical trials are needed.     

Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM patients

Platelets participate in the atherothrombotic complications of diabetes. Recent data demonstrate that platelet reactivity can be modulated via cell-cell interactions with erythrocytes and neutrophils. In this study, platelet reactivity was evaluated in 30 IDDM patients. We used an analytical procedure that permits an independent evaluation of platelet activation (granule release, eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell-free releasates) after platelet stimulation with collagen in the presence or absence of other blood cells. The interaction between platelets and erythrocytes (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT, betaTG, TXA2 release) and recruitment in both patients and control subjects. The erythrocyte enhancement of platelet TXA2 synthesis and recruitment was significantly higher in the patients, while no differences were detected in platelet granule release. The elevated platelet recruitment in the IDDM patients was found to be due to 1) increased susceptibility of diabetic platelets to the prothrombotic effect of erythrocytes and 2) the greater response of diabetic platelets to their own cell-free releasate. Patients with poor metabolic control (elevated HbA1c) or longer evolution time had an even greater platelet recruitment. The presence of microalbuminuria is not related to the platelet recruitment. Since platelet recruitment is an essential step in thrombus growth, its enhancement may favor thrombotic complications in IDDM.     

Psychological stress and platelet activation: Differences in platelet reactivity in healthy men during active and passive stressors.

Blood platelets have been found to play a major role in the pathogenesis of coronary artery disease. This study examined the effects of active and passive stressors on platelet function and assessed the possible effects of perceived control on platelet reactivity to stress. Heart rate, blood pressure, catecholamine levels, and platelet factor 4 (PF 4) were assessed in 55 healthy males during resting baseline (25 min), 7-min stressor/task periods, and recovery (60 min). Results showed significant increases in PF 4 during the stressor/task periods for both active and passive stressor groups. Psychological stress involving both active and passive participation had a direct effect on platelet activation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in bone tissue of women under condition of 120 days antiorthostatic hypokinesia

A comparative analysis was carried out between the hair content of basic trace metals in patients with atherosclerosis, ischemic heart disease (IHD) and findings from their immunogrammes. Close correlation was found out between changes in concentrations of Mn, Cu, Fe, Si, Zn, Ca and processes of activation of basic leucocyte populations characteristic of IHD course and alterations in humoral immune response peculiar to the above patients. Conclusions were reached about presence of the aforementioned changes in the pathogenesis of atherosclerosis, IHD.     

Effect of different dialysis membranes on platelet function. A tool for biocompatibility evaluation

Intradialytic coagulative and platelet activation, one of the main consequences of blood-membrane contact, was studied in a group of 5 RDT patients with a comparative evaluation of 3 different dialytic membranes: Cuprophan (CU), Polysulfone (PS) and Cellulose Triacetate (CT). Each patient underwent 5 consecutive dialysis sessions with the above mentioned membranes. Intradialytic platelet activation was studied through a morpho-functional evaluation between the mean platelet volume (MPV) and Serotonin (S), beta-Thromboglobulin (beta-TG) and Platelet Factor 4 (PF4) serum levels. These determinations were made before HD (time 0) and after 30', 120', and 240'. We also checked the intradialytic status of thrombogenesis and fibrinolysis determining aPTT, thrombin time, fibrinogen, antithrombin III (AT III), alpha-2 antiplasmin and plasminogen, at the same time intervals. All membranes tested (CU, PS, CT) caused appreciable intradialytic platelet activation, above all after 15' and at the end of dialysis sessions, more marked for CU than PS or CT. In particular MPV showed a decrease throughout the session (-5% at 30' and -9% at 240') while S, beta TG and PF4 peripheral blood levels showed a significant increase at the same intervals with CU membrane. Lastly coagulative and fibrinolytic parameters showed no significant differences among any of the membranes tested.