Behçet's syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects.

Behçet's syndrome (BS) is a complex disease with different organ involvement. The vascular one is the most intriguing, considering the existence of a specific group of patients suffering from recurrent vascular events involving the venous and, more rarely, the arterial vessels. Several clinical clues suggest the inflammatory nature of thrombosis in BS, especially of the venous involvement, thus BS is considered a model of inflammation-induced thrombosis. Unique among other inflammatory conditions, venous involvement (together with the arterial one) is currently treated with immunosuppressants, rather than with anti-coagulants. Although many in-vitro studies have suggested the different roles of the multiple players involved in clot formation, in-vivo models are crucial to study this process in a physiological context. At present, no clear mechanisms describing the pathophysiology of thrombo-inflammation in BS exist. Recently, we focused our attention on BS patients as a human in-vivo model of inflammation-induced thrombosis to investigate a new mechanism of clot formation. Indeed, fibrinogen displays a critical role not only in inflammatory processes, but also in clot formation, both in the fibrin network and in platelet aggregation. Reactive oxygen species (ROS)-derived modifications represent the main post-translational fibrinogen alterations responsible for structural and functional changes. Recent data have revealed that neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. Altogether, these new findings may help understand the pathogenetic bases of inflammation-induced thrombosis and, more importantly, may suggest potential targets for innovative therapeutic approaches.

Systemic lupus erythematosus: immunopathogenesis and novel therapeutic targets.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiorgan involvement. SLE presents many genetic and epigenetic associations and the pathogenesis is characterized by a complex network of alterations affecting both adaptative and innate immunity. The disclosure of novel mechanisms of SLE pathogenesis suggested new therapeutic targets, based on interference with the cytokine pathways or on depletion of the immune cells.

Higher uric acid levels are associated with better functional recovery in elderly patients receiving cardiac rehabilitation.

BACKGROUND AND AIMS: Whether uric acid (UA) serves as risk factor for cardiovascular diseases or as antioxidant defense has not yet been completely clarified. In this study we investigated the effects of UA on functional recovery in patients receiving cardiac rehabilitation. METHODS AND RESULTS: 306 patients, 209 men and 97 women, age range 25-87 years (mean 68 ± 11), performed the 6-min walk test (6mWT) before and after the rehabilitation, and the increase in walking distance was considered as the outcome measure of the study. Baseline UA serum levels ranged from 1.0 to 10.9 mg/dL (mean 5.2 ± 1.7). As there was a significant (p = 0.005) age*UA levels interaction, patients were divided into two subgroups, less then 65 years (n. 103, 68 men and 35 women, mean age 56 ± 9) and 65 years or more (n. 203, 141 men and 62 women, mean age 74 ± 5). After adjusting for relevant confounders, higher UA levels remained independent positive predictors of the increase in walking distance in older (p < 0.001) but not in younger patients (p = 0.807). CONCLUSIONS: Our findings show an independent association of higher UA levels with better functional recovery after cardiac rehabilitation selectively in elderly patients, suggesting that higher UA levels might reflect the decline in antioxidant defenses that occurs with advancing age. Future studies aimed at understanding the several contradictions concerning UA should, probably, address the issue within this perspective.

II Italian intersociety consensus statement on antithrombotic prophylaxis in orthopaedics and traumatology: arthroscopy, traumatology, leg immobilization, minor orthopaedic procedures and spine surgery.

Pharmacological prophylaxis for preventing venous thromboembolism (VTE) is a worldwide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures, but few data exist in other fields of orthopaedics and traumatology. Thus, no guidelines or recommendations are available in the literature except for a limited number of weak statements about knee arthroscopy and lower limb fractures. In any case, none of them are a multidisciplinary effort as the one here presented. The Italian Society for Studies on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the Association of Orthopaedic Traumatology of Italian Hospitals (OTODI), together with the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) and the Italian Society of General Medicine (SIMG) have set down easy and quick suggestions for VTE prophylaxis in a number of surgical conditions for which only scarce evidence is available. This inter-society consensus statement aims at simplifying the approach to VTE prophylaxis in the single patient with the goal to improve its clinical application.

Italian intersociety consensus statement on antithrombotic prophylaxis in hip and knee replacement and in femoral neck fracture surgery.

Anticoagulant prophylaxis for preventing venous thromboembolism (VTE) is a worldwide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures (FNF). Different guidelines are available in the literature, with quite different recommendations. None of them is a multidisciplinary effort as the one presented. The Italian Society for Studies on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the association of Orthopaedists and Traumatologists of Italian Hospitals (OTODI), together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) have set down easy and quick suggestions for VTE prophylaxis in hip and knee surgery as well as in FNF treatment. This inter-society consensus statement aims at simplifying the grading system reported in the literature, and its goal is to benefit its clinical application. Special focus is given to fragile patients, those with high bleeding risk, and those receiving chronic antiplatelet (APT) and vitamin K antagonists treatment. A special chapter is dedicated to regional anaesthesia and VTE prophylaxis.

Standardized low-molecular-weight heparin bridging regimen in outpatients on oral anticoagulants undergoing invasive procedure or surgery: an inception cohort management study.

BACKGROUND: Bridging therapy with low-molecular-weight heparin is usually recommended in patients who must stop oral anticoagulants before surgical or invasive procedures. To date, there is no universally accepted bridging regimen tailored to the patient's thromboembolic risk. This prospective inception cohort management study was designed to assess the efficacy and safety of an individualized bridging protocol applied to outpatients. METHODS AND RESULTS: Oral anticoagulants were stopped 5 days before the procedure. Low-molecular-weight heparin was started 3 to 4 days before surgery and continued for 6 days after surgery at 70 anti-factor Xa U/kg twice daily in high-thromboembolic-risk patients and prophylactic once-daily doses in moderate- to low-risk patients. Oral anticoagulation was resumed the day after the procedure with a boost dose of 50% for 2 days and maintenance doses afterward. The patients were followed up for 30 days. Of the 1262 patients included in the study (only 15% had mechanical valves), 295 (23.4%) were high-thromboembolic-risk patients and 967 (76.6%) were moderate- to low-risk patients. In the intention-to-treat analysis, there were 5 thromboembolic events (0.4%; 95% confidence interval, 0.1 to 0.9), all in high-thromboembolic-risk patients. There were 15 major (1.2%; 95% confidence interval, 0.7 to 2.0) and 53 minor (4.2%; 95% confidence interval, 3.2 to 5.5) bleeding episodes. Major bleeding was associated with twice-daily low-molecular-weight heparin administration (high-risk patients) but not with the bleeding risk of the procedure. CONCLUSIONS: This management bridging protocol, tailored to patients' thromboembolic risk, appears to be feasible, effective, and safe for many patients, but safety in patients with mechanical prosthetic valves has not been conclusively established.

Cerebral venous thrombosis treated with enoxaparin in an IUGR neonate with DIC.

BACKGROUND: The case of a term IUGR newborn who presented a cerebral vein thrombosis diagnosed by routine ultrasound brain scan, and confirmed by magnetic resonance imaging and magnetic resonance venography, is reported. A thrombosis of cortical cerebral veins and intracerebral haemorrhage in the right frontal paramedian region was observed. METHODS: Treatment with enoxaparin was started at the initial dose of 0.5 mg/kg subcutaneously every 12 h and then at 1.25 mg/kg per 12 h in order to obtain anti-factor Xa levels between 0.5 and 1.0 U/ml. After hospital discharge, enoxaparin was continued for 2 months with a lower dose (1.8 mg/kg/die). CONCLUSION: Treatment with enoxaparin was effective as demonstrated by a complete "restitutio ad integrum".

Retrievable vena cava filters: key considerations.

Retrievable filters are a new generation of inferior vena cava (IVC) filters and represent an attractive option because they may be either left in place permanently or safely retrieved after a quite long period when they become unnecessary. In this review the currently available literature regarding retrievable IVC filters is summarized and their efficacy and safety is discussed. Moreover, the appropriate indications for their use are reviewed. Retrievable filters are becoming safer and easier to use; in fact the bioengineering research has optimized the technical characteristics of these devices, in order to reduce the incidence of possible complications. However, there are important unresolved issues, including the appropriate maximum implantation time, the possibility to safely and efficaciously remove the filters without being compromised by entrapped clots, and the use of anticoagulation during the implantation and periremoval periods. Large prospective cohort studies or randomized trials are strongly warranted to definitely clarify the beneficial role of these devices.

Atherosclerotic and thrombophilic risk factors in patients with recurrent central retinal vein occlusion.

PURPOSE: Atherosclerotic and thrombophilic risk factors may be causes of central retinal vein occlusion (CRVO). The aim of this study was to evaluate the prevalence of the aforesaid risk factors in patients with recurrent CRVOs and patients with a single episode of CRVO. METHODS: Seventeen patients with recurrent CRVO and 30 with a single episode of CRVO were enrolled. The atherosclerotic risk factors investigated were hypertension, diabetes, smoking, and dyslipidemia. Specific laboratory tests for the following thrombophilic markers were performed: homocystinemia (Hcy), lipoprotein (a), factor VIII, factor II G20210A and factor V G1691A polymorphisms, lupus anticoagulant, anticardiolipin antibodies, plasminogen activator inhibitor-1, and deficit of vitamins B6, B12, and folic acid. A multivariate analysis, adjusted for age, gender, traditional and thrombophilic risk factors, was performed. Statistical significance was set at p

Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients.

BACKGROUND: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. OBJECTIVES AND METHODS: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5'-diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 micromol L(-1) ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients. RESULTS: Cut-off values for identifying RPR were: > or = 54% and > or = 66% for LTA induced by 2 and 10 micromol L(-1) ADP respectively, and > or = 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was > or = 68 s. RPR was detected in 25.1% of patients by 2 mumol L(-1) ADP-induced LTA (ADP-LTA), in 23.2% by 10 micromol L(-1) ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 micromol L(-1) ADP. The correlation was similar but the agreement was better between VerifyNow and 10 micromol L(-1) ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays. CONCLUSIONS: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.

Renal transplant recipients are at high risk for both symptomatic and asymptomatic deep vein thrombosis.

BACKGROUND: Venous thromboembolism (VTE) is one of the thrombotic complications that can occur in patients receiving renal transplantation (RT). The prevalence of VTE in RT patients is, however, undefined. OBJECTIVES: To evaluate the rate of a first episode of VTE in a series of 538 consecutive RT recipients admitted to our institution, the timing of occurrence of the thromboembolic events after transplantation, and the rate of recurrence after thromboprophylaxis withdrawal. Risk factors for recurrence were also evaluated, particularly in relation to the type of the first event (symptomatic or asymptomatic). RESULTS: During follow-up, 47 of 518 patients (28 males, 19 females; 9.1%) developed a first episode of VTE at a median time of 17 months (range 1-165 months) after kidney transplantation. Cancer was associated with the occurrence of VTE (odds ratio 4.8). Seventeen of 43 patients (39.5%) with deep vein thrombosis were asymptomatic and the diagnosis was made during routine ultrasound examination. Twenty-two patients (46.8%) experienced a recurrence of VTE. A relevant rate of recurrence was documented amongst patients with a first episode of both symptomatic (53%) and asymptomatic (23.5%) VTE. CONCLUSION: This study confirms that RT patients are at high risk of symptomatic and asymptomatic VTE and that this risk persists even after several years. Patients who experience VTE are at high risk of recurrence after thromboprophylaxis withdrawal.

OC-15 - Risk factors for cancer development after idiopathic venous thromboembolism.

INTRODUCTION: Idiopathic venous thromboembolism (VTE) is associated with the risk of cancer but the risk factors for cancer development in such patients are still uncertain. AIM: To assess risk factors for the development of cancer after a standard course of anticoagulation in patients with first episode of idiopathic VTE. MATERIALS AND METHODS: Subjects were enrolled in the three large prospective multicentre studies: PROLONG (NEJM 2006) PROLONG II (Blood 2010) and DULCIS (Blood 2014). Women whose index event was hormone related were excluded from the analysis. The development of cancer was recorded during a 2-year follow-up. RESULTS: 1,805 patients were enrolled (M/F: 510/453), mean age: 62, median: 67; range:18-87 years). Cancer developed in 55 patients (3% ; 1.7% pt-years) of whom 15 (2.0%; 1.1% pt-years) had PE with or without DVT and 40 (3.8%; 2.1% pt-years) had DVT without PE (p=0.03). The development of cancer was associated with DVT without PE (HR:1.8; 95% CI: 1.1-3.3) and age >65 (HR: 2.5; 95%: 1.3-4.9). Among patients with DVT, with or without PE, the development of cancer was associated with the presence of residual vein obstruction>4mm (RVO) at compression ultrasound (HR: 1.8, 95% CI: 1.1-3.3) and age>65 (HR: 2.8; 95% CI: 1.3-6.2). CONCLUSIONS: Age>65 years, DVT without PE and the presence of RVO are significantly associated with the risk of developing cancer after a first episode of idiopathic VTE over a two-year follow-up.

Erythrocyte oxidative stress is associated with cell deformability in patients with retinal vein occlusion.

Essentials Retinal vein occlusion (RVO), characterized by blood hyperviscosity, has an unclear pathogenesis. We aimed to find out if hemorheological profile is altered by oxidative stress in RVO patients. Red blood cell (RBC) oxidative stress is associated to whole blood viscosity and RBC deformability. Reactive oxygen species alter RBC membrane rigidity, playing a key role in RVO pathogenesis. SUMMARY: Background Retinal vein occlusion (RVO) is characterized by vision loss resulting from hypoperfusion and hypoxia of the retina. RVO pathogenesis is not yet fully understood, although blood hyperviscosity has been observed. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to microvascular perfusion and oxygen delivery. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Objectives To determine whether erythrocytes from RVO patients show signs of oxidative stress, and whether this condition can modify the hemorheologic profile in these patients. Patients and Methods We analyzed the entire hemorheologic profile and erythrocyte oxidative stress - reactive oxygen species (ROS) production and membrane lipid peroxidation - in 128 RVO patients and 128 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results In RVO patients, erythrocyte oxidative stress was present and positively correlated with whole blood viscosity and erythrocyte deformability. Multivariate linear regression analysis after adjustment for age, cardiovascular risk factors, medications, leukocyte number and mean corpuscular volume indicated that erythrocyte-derived ROS and erythrocyte lipid peroxidation were significantly and positively correlated with erythrocyte membrane viscosity and deformability. Moreover, in vitro experiments demonstrated that ROS have a key role in erythrocyte membrane fluidity. Conclusions Our findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of RVO, and pave the way to new therapeutic interventions.

Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss.

BACKGROUND: In recent years there has been a significant increase in the diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with an incidence of 20 of 100,000 people affected every year. No clear causes for this disease have been found thus far, but cochlear ischemia has been hypothesized in patients in whom an infectious episode or acoustic neurinoma have been excluded. OBJECTIVES: The aim of this case-control study was to investigate a number of acquired and inherited thrombophilic risk factors [antithrombin, protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy); lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to cardiovascular risk factors in patients with idiopathic SSHL (ISSHL). PATIENTS AND METHODS: We investigated 155 patients (67 male/88 female; age: 55 (range 19-79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms, and 155 controls (67 male/88 female; age 54 (range 19-78 years). Fasting Hcy levels were significantly higher in patients than in controls [11.6 (6.7-60) micromol/L vs. 8.7 (5.0-24) micromol/L] as well as PAI-1 levels [19 (2-95) mg/dL vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%) patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no patient was a deficiency of physiological clotting inhibitors antithrombin, protein C and protein S found. No significant differences between patients and controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11-695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant G20210A (3.8% vs. 3.2%). RESULTS AND CONCLUSIONS: Independent risk factors for ISSHL at the multivariate analysis (adjusted for age, sex and the traditional cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0-15.3); cholesterol levels within the second and third tertiles (with respect to the first tertile): T2 = OR 4.8 (95% CI 1.9-12.6)/T3 = OR 19 (95% CI 7-50.1); PAI-1 and Hcy levels within the third tertile (with respect to the first tertile): OR 20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1 levels and anticardiolipin antibodies are associated with ISSHL, so indirectly supporting the hypothesis of a vascular occlusion in the pathogenesis of the disease.

Venous thromboembolism in renal transplant recipients: high rate of recurrence.

Few data are available on the incidence of venous thromboembolism occurring in renal transplant recipients and optimal duration of oral anticoagulant therapy after thrombotic episode. Our study was performed to evaluate the risk of thrombosis recurrence in patients developing a first episode. Among 484 renal transplant patients 34 (7%) developed a first thromboembolism and were referred to the Thrombosis Centre: 28 patients (group 1) were prospectively studied, after stopping anticoagulants. Group 1 was compared with a group of 84 patients without an history of renal disease who had suffered from a first thrombotic episode and were matched for age, sex, and type of thrombotic event (group 2). During follow-up, 14/28 group 1 patients and 8/84 group 2 patients experienced thrombotic recurrence (P = .0001). Our data outline the high risk of recurrence in renal transplant recipients. Strategies for recurrence prevention are needed taking into account the high bleeding risk of anticoagulants in renal transplant patients.

Homocysteine-lowering therapy and carotid intima-media thickness in renal transplant recipients.

The aim of this study was to document, in hyperhomocysteinemic renal transplant recipients, the effect of vitamin supplementation on carotid intima-media thickness (cIMT). Fifty-six hyperhomocysteinemic stable renal transplant recipients were randomly assigned to either vitamin supplementation (group A) or placebo treatment (group B). All patients underwent high-resolution B mode ultrasound to measure IMT of common carotid arteries before and after 6 months of vitamin supplementation. In group A, cIMT significantly decreased after treatment, whereas no significant changes were observed in group B. In conclusion, our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on an early sign of atherosclerosis in a group of renal transplant recipients.

Effect of n-3 polyunsaturated fatty acid intake on phospholipid fatty acid composition in plasma and erythrocytes.

To characterize the time course of plasma and red blood cell (RBC) changes after n-3 polyunsaturated fatty acid (PUFA) supplementation, 20 healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 PUFA ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 mo, followed by a 3-mo washout period. Fatty acids of plasma and RBC phospholipid fractions were analyzed at 0, 2, and 4 mo of treatment and at 1, 2, and 3 mo of washout. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were marked after 2 mo with differences among different fractions of plasma and RBCs in further accumulation up to 4 mo. During the first and second months of the washout, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 mo of washout, only minor alterations were still detectable with respect to pretreatment values. These data confirm the complex relations among different fatty acid pools after n-3 PUFA supplementation.

Lipoprotein (a) and anticardiolipin antibodies are risk factors for clinically relevant restenosis after elective balloon percutaneous transluminal coronary angioplasty.

Recent reports have shown the importance of new risk factors for cardiovascular disease. We investigated the relationship between Lp(a), fibrinolytic parameters and anticardiolipin antibodies (aCL) and the occurrence of clinical recurrence owing to restenosis after elective balloon percutaneous transluminal coronary angioplasty (PTCA) without stenting. In 167 patients, undergoing PTCA, Lp(a) plasma levels, aCL, euglobulin lysis time (ELT), plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) plasma levels were evaluated before the procedure. During follow-up 29 patients underwent clinical recurrence due to restenosis. Lp(a) levels were significantly higher in patients with restenosis in comparison to those without (P<0.05); an earlier restenosis was observed in patients with Lp(a) values >450 mg/L. Kaplan-Meier survival estimate showed an earlier occurrence of restenosis in patients with base-line Lp(a)>300 mg/l associated with aCL positivity. High Lp(a) plasma levels play a role in the occurrence of clinical recurrence due to restenosis after elective balloon PTCA without stenting; the association with aCL accelerates the development of restenosis.

Activation of the immune system and coronary artery disease: the role of anti-endothelial cell antibodies.

On the basis of the role of immuno-mediated inflammation in atherosclerosis we investigated, (1) the prevalence of anti-endothelial cell antibodies (AECA) in ischaemic heart disease (IHD); (2) if beta2-glycoprotein I (beta2-GPI) was the target antigen of AECA; (3) the relationship between AECA, tissue factor (TF) and tissue factor pathway inhibitor (TFPI). In 93 consecutive IHD patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and 105 controls AECA were detected by ELISA on human umbilical vein endothelial cells (HUVEC). AECA positive sera were evaluated for anti-beta2-GPI antibodies by ELISA. TF and TFPI plasma levels were assessed by ELISA. Twelve of 93 (12.9%) IHD patients and only one of 105 controls (0.95%) were AECA positive. The prevalence of AECA was higher in unstable angina (UA) than in effort angina (EA) (P=0.01). Three of 12 AECA positive sera resulted positive for anti-beta2-GPI and showed a marked decrease in EC-binding when tested on HUVEC cultured in serum-free medium. The binding was restored by the addition of beta2-GPI. TF and TFPI levels were similar in AECA positive and AECA negative patients. The rate of angiographically documented clinical recurrences was 66.7% in the AECA positive and 14.8% in the AECA negative group (P=0.0004) with a significant relationship between restenosis and AECA (P<0.0001), unchanged by the inclusion of cardiovascular risk factors in the regression model. Our results suggest a 'role' for AECA in the immune-mediated inflammation in UA beta2-GPI is not the only AECA target antigen. AECA are not responsible for high TF and TFPI levels. The high rate of clinical recurrences after PTCA, confirmed by angiography, in AECA positive patients is in line with such a role and suggests further large-scale 'ad hoc' studies.