Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation

Homocysteine may have an effect on risk of cardiovascular disease by stimulating procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis. However, data in humans of such effects are sparse. In this intervention study, we examined the effect of homocysteine lowering by B-vitamin supplementation on prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin complex (TAT), and fibrin degradation products (D-dimer). The study comprised 118 healthy volunteers, 50 with homocysteine > 16 mumol/L and 68 with homocysteine < or = 16 mumol/L, who were randomized to placebo or high-dose B-vitamin supplements (5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks. Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the B-vitamin group compared to the placebo group, no effect on F1 + 2 and TAT concentrations was observed. A 10.4% reduction was observed for D-dimer (p = 0.08). In conclusion, it appears that in healthy subjects homocysteine reduction by B-vitamin supplementation has a modest beneficial effect on clotting activation.     

No effect of folic acid supplementation in the course of 1 year on haemostasis markers and C-reactive protein in older adults

Elevated homocysteine levels are associated with an increased cardiovascular disease (CVD) risk, but the underlying mechanism is still unclear. High homocysteine might affect the endothelium, and consequently lead to impaired haemostasis. In a randomized placebo controlled trial among 276 older adults with plasma total homocysteine concentrations above 13 mM at screening, we investigated the effect of homocysteine lowering by folic acid supplementation (0.8 mg/day) for 1 year on markers of endothelial function (von Willebrand factor), coagulation (tissue factor, factor VIIa, fragments 1+2), and fibrinolysis (fibrin degradation products, tissue-type plasminogen activator), and inflammation (C-reactive protein). Despite a 24% reduction in plasma homocysteine concentration and four-fold increase in serum folate concentration in the folic acid group compared to the placebo group, there was no clear change in any of the haemostasis markers, nor CRP. Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by one-year folic acid supplementation does not influence haemostasis markers.     

Effects of vitamin therapy on plasma total homocysteine,endothelial injury markers,and fibrinolysis in stroke patients

Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B₆ (100 mg), and B₁₂ (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke. Copyright © 2002 by National Stroke Association     

The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs

Patients on antiepileptic drugs (AEDs) may have elevated levels of plasma total homocysteine (p-tHcy). The aim of this study was to assess the effect of B-vitamin supplementation on the levels of p-tHcy and markers of endothelial activation and lipid peroxidation. A total of 33 adult patients on AEDs were identified with either fasting (Group 1, n=23) or post methionine load (PML) (Group 2, n=10) hyperhomocysteinemia. Subjects were supplemented with B-vitamins for 30 days: folic acid 0.4 mg, pyridoxine 120 mg and riboflavin 75 mg per day. After supplementation, serum folate and pyridoxal phosphate had increased, while fasting and PML p-tHcy had decreased (P<0.0001) by 36 and 26%, respectively. Prior to supplementation, the Group 1 patients had elevated levels of P-selectin and von Willebrand factor (vWF) (P=0.05 and 0.03, respectively). After supplementation, the levels of intercellular cell adhesion molecules had decreased (P=0.01) and E-selectin decreased nonsignificantly (P=0.07). However, the levels of vascular cell adhesion molecules had increased (P<0.0001), while lipid peroxidation were unchanged. In conclusion, the combined supplementation with folic acid, pyridoxine and riboflavin reduced fasting and PML hyperhomocysteinemia in patients on AEDs. Patients with fasting hyperhomocysteinemia had elevated levels of P-selectin and vWF, which may indicate an increased risk of cardiovascular disease. Furthermore, B-vitamin supplementation influenced endothelial activation, although the clinical implication is uncertain.     

Determination of plasminogen activator inhibitor (PAI) activity of human plasma after dilution in a PAI-depleted plasma

A simple and discriminating assay for the determination of the fast-acting plasminogen activator inhibitor (PAI) activity in human plasma is described. The method is based on the inhibition of purified tissue plasminogen activator (tPA) by plasma diluted with a PAI-depleted plasma and the subsequent measurement of residual tPA in the presence of CNBr-fibrinogen fragments, purified plasminogen and a plasmin sensitive chromogenic substrate CBS 10.65. This assay does not require any acidification step, and allows PAI determination directly on plasma. Since dilutions are made in PAI-depleted plasma, all the serine-protease inhibitors, except PAI, are kept constant in their effect on the assay. Thus, any detectable degree of inhibition can only be ascribed to PAI. Under these conditions, parallel titration curves of tPA are obtained in plasma and the values of PAI are reproducible when measured at different dilutions. The PAI levels of 31 normal volunteers ranged from 0.3 to 8.7 IU/ml (mean: 3.5 IU/ml). After venous occlusion, variations of PAI were associated with the release of tPA. A marked increase of PAI levels was observed in the post-operative period and in pregnancy. In this case both PAI-1 and PAI-2 related activities were measured. Due to its simplicity, the assay can be easily used for the screening of patients with thrombotic diseases.     

Acute effects of retinoids on fibrinolysis before and after venous occlusion in healthy humans

The effects of acitretin and etretinate on the fibrinolytic system have been investigated in a double-blind, placebo-controlled cross-over study in twelve healthy volunteers. Euglobulin fibrinolytic activity, euglobulin clot lysis time, tissue-type plasminogen activator (t-PA) activity and antigen concentration in plasma were measured before and after 10 min of venous occlusion (VO), three hours after ingestion of the compounds. The plasminogen activator inhibitor (PAI) activity was also measured in each session before fibrinolysis stimulation. None of the parameters studied was significantly affected by the two retinoids in comparison with placebo. Our study demonstrates that a single oral dose of 100 mg of etretinate or acitretin, investigated 3 hours after drug administration does not significantly influence the fibrinolytic system in vivo in humans. This observation does not exclude an effect of retinoids after prolonged intake.     

Plasminogen Activation Without Changes in tPA and PAI-1 in Response to Subcutaneous Administration of Ancrod

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of ischemic stroke. The therapeutic effect is ascribed to a lowering of plasma fibrinogen. Thirty-two healthy volunteers received subcutaneous ancrod at doses of 1.0, 1.5 and 2.0 IU/kg body weight or placebo. Blood samples were drawn before the injection and at various time points until 96 h after the injection. Ancrod leads to the formation of desAA-fibrin, which serves as cofactor in tissue plasminogen activator activity (tPA)-induced plasminogen activation. Unchanged concentrations of prothrombin fragment F1.2 and thrombin–antithrombin complex (TAT) indicate that fibrin formation occurs independent of thrombin. Plasmin generation is independent of an increase in tPA activity or changes in plasminogen activator inhibitor-1 (PAI-1) concentration in plasma. Subcutaneous injection of ancrod leads to a generalized fibrino(geno)lytic response caused solely by providing tPA with soluble fibrin as its cofactor in plasminogen activation. Maximal plasmin activity is present 12 h after subcutaneous injection.     

Increased blood fibrinolytic activity after physical exercise: comparative study in individuals with different sporting activities and in patients after myocardial infarction taking part in a rehabilitation sports program

The activation of fibrinolysis during bicycle ergometry was studied in two pairs of age-matched groups. Group A: 18 healthy male competitive athletes (23 +/- 3.5 years of age, mean +/- SD), Group B: 18 healthy male volunteers (25.7 +/- 2.7) not engaged in any sports, Group C: 17 healthy male volunteers (50.6 +/- 7.7) regularly practicing sports, and Group D: 18 male survivors from myocardial infarction (MI-patients, 54.2 +/- 7.9) who took part in a rehabilitation sports program. Before ergometry, healthy participants with regular sporting activities showed significantly lower plasma plasminogen activator inhibitor capacities (PAI cap) than the members of the respective age-matched control groups: Group A 13.9 +/- 2.6 AU/ml, Group B 18.5 +/- 5.5, p less than 0.005; Group C 15.2 +/- 2.9, Group D 20.7 +/- 5.5, p less than 0.05. During ergometry the release of tPA antigen did not differ significantly between the age-matched groups, however, tissue plasminogen activator (tPA) activities after ergometry were higher in groups presenting lower pre-test PAI cap values. Group A 5.5 +/- 6.4 AU/ml, Group B 1.1 +/- 2.9 AU/ml, p less than 0.05; Group C 2.9 +/- 3.3, Group D 0.2 +/- 0.7, p less than 0.05. Levels of the fibrin split product (D-dimer) did not change in any of the groups. This investigation indicates that (1) regular vigorous sporting activities enhance blood fibrinolysis by reducing blood PAI cap in healthy individuals, (2) rehabilitation sport is not capable of reducing blood PAI cap in MI-patients to values measured in age matched healthy individuals regularly practicing sports and (3) the activation of fibrinolysis during physical exercise has no systemic fibrinolytic effect.     

Fibrinolytic activity in Chinese patients with diabetes or hyperlipidemia in comparison with healthy controls

Plasma tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were determined before and after the venous occlusion test (VOT) in 3 groups of patients with mean age about 60 years: 29 diabetic patients (D group), 8 hyperlipidemic patients (H group) and 19 healthy controls (C group). In the D and H groups, the mean of morning tPA was significantly higher than that of the C group, but the means of PAI were not significantly different among the 3 groups. ELT was significantly shortened and tPA was markedly increased after the VOT in all 3 groups whereas PAI had not significantly changed. In conclusion, high tPA activity and good fibrinolytic response without significant change of PAI activity were found in the diabetic and hyperlipidemic patients, and no definite impairment of the fibrinolytic activity could be found in the Chinese patients with diabetes and hyperlipidemia. This might be one of the reasons why the Chinese has low incidence of thromboembolic diseases.     

Coagulation and fibrinolysis during laparoscopic cholecystectomy

Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood samples drawn on admission, on four occasions during operation as well as 2 hours after operation and on the first postoperative day in 50 patients undergoing elective LC were analyzed for prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), D-dimer (DD), fibrin degradation products (FbDP), tissue-type plasminogen activator (tPA) activity and antigen, and plasminogen activator inhibitor (PAI) activity and antigen. F1+2, SF, DD, and FbDP levels increased significantly after LC. Differences between pre- and postoperative PAI and tPA levels were not significant apart from a transient increase in tPA antigen levels. tPA activity was significantly increased during operation.     

Tissue plasminogen activator and plasminogen activator inhibitor in patients with acute ischemic stroke: relation to stroke etiology

Recent studies suggest that high plasma levels of tissue-type plasminogen activator (tPA) and its inhibitor (plasminogen activator inhibitor-1, PAI-1) are markers of an increased risk of atherothrombotic ischemic events such as stroke and myocardial infarction. In this prospective study, we measured tPA antigen, PAI-1 antigen and activity, as well as tPA/PAI-1 complex in patients with acute stroke. Stroke subtypes were classified according to the TOAST criteria. From 132 consecutively screened patients, 89 (100%) were enrolled in this study, including 42 patients (47%) with large artery atherosclerosis (LAA), 32 (36%) with small vessel occlusion (SVO), and 15 (17%) with cardioembolism (CE). Nineteen age-matched neurologic patients without manifestations of cerebrovascular disease served as control subjects (CS). Patients with acute stroke had significantly higher plasma levels of tPA antigen (p < 0.001), PAI-1 antigen (p < 0.05) and PAI activity (p < 0.05) than patients in the control group. t-PA antigen, PAI activity and tPA/PAI-1 complex levels were similar regardless of stroke etiology. Only PAI-1 antigen was lower in patients with cardioembolic stroke than in stroke patients with LAA (p < 0.05). Plasma tPA antigen, PAI-1 antigen, and PAI activity are significantly increased in patients with acute ischemic stroke. Except for PAI-1 antigen, this increase appears not to be related to the underlying stroke etiology.     

Plasma fibrinolytic activity after ingestion of omega-3 fatty acids in human subjects

Plasma fibrinolytic activity was measured in human volunteers after 30 day periods of ingestion of a fish oil product (Max Vita) containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and a wheat germ oil product containing alpha linolenic acid. Compliance was confirmed by significant increases in plasma levels of EPA and DHA and by significant falls in serum triglyceride levels. Platelet aggregation in platelet rich plasma and in whole blood was not altered significantly by fish oil or wheat germ oil. Neither fish oil or wheat germ oil caused any significant change in tissue plasminogen activator (tPA) or its inhibitor (PAI) measured enzymatically or in tPA antigen measured by an ELISA method. All these analytes (tPA, PAI, and tPA antigen) were measured before and after venous compression.

There was no evidence of enhanced fibrinolytic activity after ingestion of omega-3 fatty acids in fish oil or in wheat germ oil.     

Heparin and fibrinolysis--comparison of subcutaneous administration of unfractionated and low molecular weight heparin

The effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration. In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti-Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, alpha 2-antiplasmin, fibrin(ogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin. It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.     

Relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies

Endothelial cell activation or damage is believed to play a key role in preeclampsia (PE) and may underlie the hemostatic changes observed in this syndrome. The aim of this study was to evaluate a relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies. We measured the plasma levels of tissue plasminogen activator (tPA) antigen and of plasminogen activator inhibitor type 1 (PAI-1) antigen, both markers of hemostatic and endothelial function, and fibrin fragment D-dimer. Maternal blood from uncomplicated (n = 42) and PEc pregnancies (n = 44) were collected before delivery, and umbilical cord blood (UCB) immediately after delivery.In preeclamptic cases, UCB presented significantly higher tPA values and significantly lower PAI-1/tPA ratio. Preeclamptic women also presented significantly higher tPA, as well as PAI-1 values, when compared with normal pregnant women; no significant difference was found for D-dimer. In preeclamptic women, proteinuria (a marker of PE severity) correlated positively and significantly with tPA and PAI-1 antigen levels. An inverse relationship between maternal tPA antigen levels and fetal birth weigh in PE was also observed.Our data show that the hemostatic maternal disturbances observed in preeclamptic women have similarities with the UCB circulation, and that endothelial dysfunction is the most plausible underlying cause. Moreover, maternal hemostatic disturbances seem to be associated with the severity of PE. Further studies are needed to strength the values of tPA and PAI-1 as markers of severity in PE.     

Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women

We compared the effects of oral estradiol (2 mg), transdermal estradiol (50 microg), and placebo on measures of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in 27 postmenopausal women at baseline and after 2 and 12 weeks of treatment. Oral and transdermal estradiol induced similar increases in serum free estradiol concentrations. Oral therapy increased the plasma concentrations of factor VII antigen (FVIIag) and activated factor VII (FVIIa), and the plasma concentration of the prothrombin activation marker prothrombin fragment 1+2 (F1+2). Oral but not transdermal estradiol therapy significantly lowered plasma plasminogen activator inhibitor-1 (PAI-1) antigen and tissue-type plasminogen activator (tPA) antigen concentrations and PAI-1 activity, and increased D-dimer concentrations, suggesting increased fibrinolysis. The concentration of soluble E-selectin decreased and serum C-reactive protein (CRP) increased significantly in the oral but not in the transdermal or placebo groups. In the oral but not in the transdermal or placebo estradiol groups low-density-lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein (a) concentrations decreased while high-density-lipoprotein (HDL) cholesterol, apolipoprotein AI and apolipoprotein All concentrations increased significantly. LDL particle size remained unchanged. In summary, oral estradiol increased markers of fibrinolytic activity, decreased serum soluble E-selectin levels and induced potentially antiatherogenic changes in lipids and lipoproteins. In contrast to these beneficial effects, oral estradiol changed markers of coagulation towards hypercoagulability, and increased serum CRP concentrations. Transdermal estradiol or placebo had no effects on any of these parameters. These data demonstrate that oral estradiol does not have uniformly beneficial effects on cardiovascular risk markers and that the oral route of estradiol administration rather than the circulating free estradiol concentration is critical for any changes to be observed.     

Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400 IU/day (group B), vitamin C 2g/day plus vitamin E 800 IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.     

Amyloid beta soluble forms and plasminogen activation system in Alzheimer’s disease: Consequences on extracellular maturation of brain‐derived neurotrophic factor and therapeutic implications

Soluble oligomeric forms of amyloid beta (Aβ) play an important role in causing the cognitive deficits in Alzheimer’s disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain‐derived neurotrophic factor (BDNF) is synthesized as a precursor (pro‐BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro‐BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin‐dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor‐1 (PAI‐1), the natural inhibitor of tissue‐type plasminogen activator (tPA). Therefore, tPA/PAI‐1 system represents an important regulator of extracellular BDNF/pro‐BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble Aβ forms based on the effects on tPA/PAI‐1 system and on the consequence of an altered conversion from pro‐BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.     

Effects of folic acid supplementation on inflammatory and thrombogenic markers in chronic smokers. A randomised controlled trial

INTRODUCTION: Cigarette smoking may induce pro-inflammatory and pro-thrombotic changes. It is not known whether these abnormalities are caused at least partly by increased homocysteine levels. We investigated whether lowering homocysteine by folic acid supplementation might reduce the plasma concentration of inflammatory and thrombogenic markers in chronic smokers. MATERIAL AND METHODS: Twenty-four healthy cigarette smokers (age 37.8+/-2.5 years, mean+/-SEM) were randomly assigned to 4 weeks of folic acid 5 mg/day or placebo. The following parameters were measured before and after treatment: (1) markers of inflammation (C-reactive protein, CRP, and white cell count, WCC); (2) blood coagulation screen (Activated Partial Thromboplastin time Ratio, APTR, and International Normalized Ratio, INR); (3) pro-thrombotic markers (fibrinogen, factor VIII coagulant activity, VIII:C, von Willebrand factor, vWF, and D-dimer). RESULTS: Folic acid induced a significant reduction in homocysteine (10.8+/-0.6 vs. 8.2+/-0.5 micromol/l, p<0.001), plasma fibrinogen (3.15+/-0.14 vs. 2.87+/-0.14 g/l, p<0.05), and D-dimer (102+/-44 vs. 80+/-26 microg/l, p<0.05) concentrations. By contrast, no significant changes were observed in CRP (2.2+/-0.7 vs. 1.7+/-0.7 mg/l), WCC (7.2+/-0.5 vs. 6.8+/-0.5 10(9) cells/l), APTR (0.91+/-0.02 vs. 0.93+/-0.02), INR (0.92+/-0.01 vs. 0.91+/-0.01), vWF (103+/-8 vs. 102+/-9 U/dl), and VIII:C (120+/-8 vs. 107+/-8 U/dl) levels. Changes in folic acid plasma concentrations were significantly and negatively correlated with changes in fibrinogen (r=-0.48, p=0.01) but not with changes in D-dimer (r=-0.15, p=0.5) levels. Changes in plasma homocysteine concentrations did not correlate with changes in either fibrinogen or D-dimer. No significant changes in homocysteine, inflammatory and thrombogenic markers were observed in the placebo group. CONCLUSIONS: Short-term folic acid supplementation had no significant effects on inflammatory markers but induced a significant reduction in plasma fibrinogen and D-dimer concentrations in healthy chronic smokers. Thus, folic acid might have an anti-thrombotic effect in this high-risk group independent of the homocysteine lowering effect.     

Effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator and plasminogen activator inhibitor

Short-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20-30 and 45-55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.