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S Coccheri

Publications and source records attributed to S Coccheri.

At least 19 recordsLinked to original sources
PubMed1997

Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial.

A randomized, double-blind multicenter trial was performed to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) (LU 47311, Clivarine) and standard unfractionated heparin for the prophylaxis of postoperative venous thromboembolism. Altogether 1351 patients scheduled to undergo abdominal surgery were included. Main outcome measures included the incidence of thromboembolic events (deep vein thrombosis, pulmonary embolism, or both) and bleeding complications, including wound hematoma. A total of 655 patients received 1750 anti-Xa IU of LMWH plus a placebo injection daily; 677 patients received 5000 IU of unfractionated heparin (UFH) twice a day. Both drugs were found to be equally effective, as 4.7% of patients in the LMWH group and 4.3% in the UFH group developed postoperative thromboembolic complications. However, the incidence of bleeding complications was significantly reduced in the LMWH group: 55 (8.3%) patients in the LMWH group and 80 (11.8%) in the UFH group developed bleeding complications, a relative risk (RR) of 0.70 (95% CI 0.51-0.97;p = 0.03); wound hematoma occurred in 29 (4.4%) of the LMWH group compared with 55 (7.7%) in those in the UFH group for an RR of 0.57 (95% CI 0.37-0.88;p = 0.01). This study confirmed that a very low dose of 1750 anti-Xa IU daily of this new LMWH is as effective as 10,000 IU of UFH for preventing postoperative deep vein thrombosis. At this dose its administration is associated with a significant reduction in the risk of bleeding including wound hematoma.

Adult↗
PubMed1997

Comparison of new rapid methods for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients.

Eighty-seven outpatients consecutively admitted to the emergency unit of our hospital with clinically suspected first deep vein thrombosis (DVT) of a leg had D-dimer levels measured by the following recently introduced fast methods: VIDAS (bioMerieux), LPIA (Mitsubishi), Nephelotex (Biopool), Nycocard (Nycomed) and Instant.I.A. (Diagnostica Stago). A latex agglutination test (Minutex, Biopool) was also performed and a classical ELISA (Gold EIA, Agen) used as reference. Venography was performed in all patients, with DVT diagnosed in 42 (37 proximal). All the new methods can be adopted in emergency situations, since they are suited for individual tests, are rapid and the reagents ready to use. All the methods proved to have a good interassay reproducibility. The new D-dimer and latex agglutination tests showed negative (88-96%) and positive (63-81%) predictive values similar to those of ELISA (92% and 71%, respectively), though the still wide confidence intervals suggest larger patient population series be investigated. As regards clinical application, the use of these tests to rule out DVT should be tested in prospective clinical follow-up trials where anticoagulation is withheld in subjects with negative non-invasive reliable vascular tests and normal D-dimer levels.

Biological Assay↗
PubMed1997

Hyperhomocyst(e)inemia and a common methylenetetrahydrofolate reductase mutation (Ala223Val MTHFR) in patients with inherited thrombophilic coagulation defects.

To assess whether certain abnormalities of the sulfated amino acid metabolism are associated with the occurrence of thromboembolic events in patients with inherited thrombophilic conditions, the levels of homocyst(e)ine, before or after methionine load, and the presence of the Ala223Val substitution in the 5,10-methylenetetrahydrofolate reductase (MTHFR) were evaluated in 119 subjects with a congenital single thrombophilic condition (type I deficiency of antithrombin n = 10, protein C n = 24, protein S n = 16; activated protein C resistance due to factor V Leiden mutation n = 69). Sixty-three subjects had experienced at least one documented thrombotic event, while the remaining 56 subjects were still free from any thrombotic symptom. Our results show that (1) high homocyst(e)ine levels, either in fasting condition or after methionine load, were not more frequent in subjects with inherited thrombophilic alterations (14.4%) than in normal control subjects (10% by definition) and (2) the frequency of hyperhomocyst(e)inemia was similar in thrombophilic subjects, who already have (14.3%) or have not (14.6%) experienced thrombotic events. As regards the MTHFR mutation, the homozygous condition was present in 23.2% of the thrombophilic patients versus 17.5% in the control subjects, a nonsignificant difference. The mutation was slightly more frequent in those thrombophilic subjects who had suffered a thrombotic episode (25.5%) versus those with no thrombosis (20.8%), with odds ratios of 1.61 (confidence interval (CI) = 0.58-4.52) and 1.24 (CI = 0.42-3.43), respectively. These differences were also nonsignificant. It is concluded that in subjects with inherited thrombophilias, a condition of hyperhomocyst(e)inemia "per se" is not a factor increasing the risk of thrombosis. The risk enhancement conferred by the MTHFR mutation, if any, seems to be slight or limited, and its significance could be ascertained only in a large multicenter trial.

Adult↗
PubMed1997

Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators.

BACKGROUND AND PURPOSE: The results of a large prospective randomized trial have shown the efficacy of oral anticoagulation in the secondary prevention of major vascular events in patients with nonrheumatic atrial fibrillation (NRAF); less well established is the role of antiplatelet agents. The present study compared the effects of indobufen, a reversible inhibitor of platelet cyclooxygenase, with those of warfarin in this setting. METHODS: A total of 916 patients with NRAF and a recent (< or = 15 days) cerebral ischemic episode were admitted to this multicenter, randomized study, during which they were treated with either indobufen (100 or 200 mg BID) or warfarin (to obtain an international normalized ratio of 2.0 to 3.5) for 12 months. The two groups (462 on indobufen and 454 on warfarin) were well balanced in terms of their main baseline characteristics. The primary outcome of the study was the combined incidence of nonfatal stroke (including intracerebral bleeding), pulmonary or systemic embolism, nonfatal myocardial infarction, and vascular death. RESULTS: At the end of follow-up, the incidence of primary outcome events was 10.6% in the indobufen group (95% confidence interval, 7.7% to 13.5%) and 9.0% in the warfarin group (95% confidence interval, 6.3% to 11.8%), with no statistically significant difference between treatments. The frequency of noncerebral major bleeding complications was low: only four cases (0.9%) of gastrointestinal bleeding were observed, all of them in the warfarin group. CONCLUSIONS: We conclude that, within the limitations of its design, this study may help the medical community in devising appropriate antithrombotic strategies for NRAF patients for whom oral anticoagulants are contraindicated or do not represent a feasible approach to treatment.

Adult↗
PubMed1997

[Hemorrhagic complications of oral anticoagulant therapy: results of a prospective multicenter study ISCOAT (Italian Study on Complications of Oral Anticoagulant Therapy)].

BACKGROUND: To assess the incidence of bleeding complications during oral anticoagulant therapy (OAT) in a population of patients representative of daily practice in Italian anticoagulation clinics. METHODS DESIGN: prospective, inception-cohort, multicentre. SETTING: Thirty-four anticoagulation clinics federated in the Italian Federation of Anticoagulation Clinics. PATIENTS: 2745 consecutive patients, included from beginning of their first OAT course. Most patients were aged between 60 and 79 y (57.8%), with 8% being > or = 80 y. Venous thromboembolism was the most frequent indication for OAT (one third of all the patients), followed by non ischemic heart disease which mainly included atrial fibrillation (16.8% of patients). Warfarin (in 63.8% of patients) and acenocoumarol were the only anticoagulant drugs used. The targeted anticoagulation intensity was low (INR < or = 2.8) in 71% of patients and high (INR > 2.8) in the remainder. OUTCOMES: Fatal, major and minor bleeding events. Thrombotic events were also recorded, though not analyzed in the present report. FINDINGS: During the 2011 patient-years (pt-y) of follow-up, 153 bleeding complications (7.6% pt-y) were recorded--5 fatal (all cerebral haemorrhages, 0.25% pt-y), 23 major (1.1% pt-y) and 125 minor (6.2% pt-y). The rate of events did not vary according to sex, coumarin type, size of enrolling centre or targeted therapeutic range; it was higher in older patients (10.5% pt-y in those aged > or = 70 y, relative risk--RR--1.75, p < 0.001), in cases where indication for anti-coagulant treatment was peripheral and/or cerebrovascular disease (12.5% pt-y; RR 1.80, p < 0.01) and during the first 90 days of treatment (11% pt-y, RR 1.75, p < 0.001). One fifth of bleeding events occurred at a very low anticoagulation intensity (INR < 2; the category rate being 7.7% pt-y); the rate was 4.8% pt-y in the 2.0-2.9 INR category, reaching 9.5% pt-y, 40.5% pt-y and 200% pt-y in the 3-4.4, 4.5-6.9 and > or = 7 INR categories respectively (RR for INR levels > 4.5 = 7.91, p < 0.0001). CONCLUSIONS: The overall rate of bleeding events recorded in the present study was much lower than that recorded in other (including recent) observational and experimental studies. The risk of bleeding increased in the following cases: age > 70 y; arterial vascular disease as indication for OAT; first 3 months of treatment; INR values > or = 4.5. OAT has become safer in recent years, particularly if monitored in special anticoagulation clinics. Caution should be exercised when prescribing OAT in elderly patients and the intensity anticoagulation levels should be closely monitored to minimize incidental periods of overanticoagulation.

Aged↗
PubMed1997

Assessment of mental ability in elderly anticoagulated patients: its reduction is associated with a less satisfactory quality of treatment.

Mental capacity was assessed in 311 apparently self-sufficient patients (> or = 60 years of age, 170 men) under stabilised oral anticoagulant treatment (OAT) by administering the Hodkinson's Abbreviated Mental Test (AMT). The international normalized ratios (INR) recorded during the 3 months before and the 3 after the data of test administration were examined by the INR-Day software program. The percentage of time spent within, below or above the intended therapeutic range was calculated in patients who scored abnormally at AMT, and compared with matched controls with normal AMT results. Forty patients [12.9%; 28 women (19.8%) and 12 men (7.1%), P < 0.0011] had abnormal AMT results; the rate seemed to increase with age. Most of these patients (35, 75%) had only elementary education. Patients with abnormal AMT results spent more time outside the intended therapeutic ranges than 40 matched controls (20.9% of the observed time vs 13.7%, P < 0.0001; odds ratio 1.68, CI 1.53-1.84). Unsuspected reduction of mental ability or attention levels was found in a number of elderly patients receiving OAT; these patients presented longer periods of either under- or over-anticoagulation and were, therefore, exposed to a higher risk of thrombotic or bleeding complications. Anticoagulation clinics would be advised to assess mental abilities in elderly patients before starting OAT.

Aged↗
PubMed1997

Thrombotic events during oral anticoagulant treatment: results of the inception-cohort, prospective, collaborative ISCOAT study: ISCOAT study group (Italian Study on Complications of Oral Anticoagulant Therapy).

The paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.5 per 100 patient years) were recorded in 67 patients: 20 fatal (1%), 39 major (1.9%) and 11 minor (0.6%). 34/70 events occurred within the first 90 days of treatment (relative risk - at multivariate analysis - of < or =90 days vs. >90 = 20.6, C.I. 12.7-33.5; p <0.0001). The risk was higher in patients aged > or =70 y (1.62, C.I. 1.0-2.61; p <0.05), and when indication for anticoagulant treatment was peripheral/cerebral arterial disease (1.84, C.I. 1.01-3.36; p <0.05). The frequency of thrombotic events was 17.5% when international normalised ratio (INR) levels were < 1.5, decreasing to 2.3% for INRs within the 2-2.99 category (relative risk of INRs <2.0 vs. > or =2 = 1.88, C.I. 1.16-3.07; p <0.05). The recorded rate of thrombotic events was lower than that reported in the few available studies. A greater risk should be expected during the first 90 days of treatment, when anticoagulation levels are <2.0 INR, in patients > 70 years and in those with cerebrovascular/peripheral arterial disease.

Administration, Oral↗
PubMed1997

[Deep venous thrombosis. Evaluation of a non-invasive diagnostic procedure based on compression ultrasonography and measurement of D-dimer plasma levels].

BACKGROUND: Clinical diagnosis of deep venous thrombosis (DVT) of the leg is unreliable. An accurate diagnosis is important for therapeutic decision since anticoagulant treatment, though potentially dangerous, is useless in case of a false positive diagnosis, whereas a false negative diagnosis may lead to withdrawal of an extremely necessary anticoagulation. Contrast venography is still recognized as the gold standard method for the diagnosis of DVT, but in recent years a variety of accurate non-invasive methods has been developed. The ultrasound compression sonography (CUS) is considered a simple non invasive test highly sensitive and specific for proximal DVT in symptomatic outpatients, though non adequately sensitive and specific for isolated calf DVT. Plasma D-dimer levels (DD, fibrin degradation products) have a high negative predictive value for DVT. The aim of this study, performed in outpatients with suspected leg DVT, was to validate, versus venography, a non-invasive, easy to perform and fast diagnostic procedure based on a combination of CUS and D-dimer test. End points of the procedure were: confirmation or exclusion of proximal DVT; suspicion of isolated calf DVT in which case the test would be repeated in a few days to detect any possible proximalization of thrombosis. MATERIALS AND METHODS: Sixty-eight consecutive outpatients, 37 male, with clinically suspected first episode of leg DVT were eligible and examined with CUS, DD test and venography. RESULTS: The results showed that the diagnostic procedure under examination has a high sensibility and specificity for DVT. CONCLUSIONS: It can thus be recommended as routine diagnostic procedure in symptomatic outpatients with suspected DVT reserving venography special cases only.

Ambulatory Care Facilities↗
PubMed1996

Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy.

BACKGROUND: Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics. METHODS: In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories. FINDINGS: 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001). INTERPRETATION: We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

Acenocoumarol↗
PubMed1996

Effect of diets containing different amounts of precursor and derivative fatty acids on serum TXB2.

Dietary precursor and derivative polyunsaturated fatty acids influence metabolic parameters, such as eicosanoid synthesis. We have studied the effect of dietary intakes of lipids containing different amounts of precursor and derivative fatty acids (olive oil, olive-blackcurrant-fish oil mixture, blackcurrant-fish oil mixture, MCT (medium chain triglycerides)-soyabean oil mixture) on serum thromboxane B2 (TXB2) in four groups of rats. Plasma fatty acid composition showed differences related to dietary intakes. TXB2 levels were similar in all conditions except in the group receiving the mixture of olive-blackcurrant-fish oils which showed lower values.

Animals↗
PubMed1996

Activated protein C resistance: a comparison between two clotting assays and their relationship to the presence of the factor V Leiden mutation.

Resistance to the anticoagulant effect of activated protein C (APC resistance), a frequent abnormality in patients with a history of venous thrombosis, is known to be due, in the large majority of cases, to the presence of an abnormal factor V: the factor V Leiden. It is reasonable to surmise that screening for this abnormality should be performed with a clotting method for APC resistance, before submitting the patients with abnormal results to DNA analysis. The present study was performed on 216 individuals enrolled at the Bologna centre, of which 189 were unrelated patients with a history of juvenile venous thromboembolism and 27 were relatives with or without thrombosis. APC resistance was first measured in Bologna by a standard commercial method and then, in Leiden, by an in-house method: DNA analysis was performed in those cases in which at least one of the clotting methods was abnormal. The data obtained confirm the good performance and the optimal positive predictive value for the Leiden mutation (100%) of the Leiden in-house clotting method. Performance of the commercial method was less satisfactory but markedly improved by expressing the data in relation to the values simultaneously obtained with a normal plasma pool. Even with optimal data expression, however, the positive predictive value of the commercial method, versus DNA analysis, did not exceed 88%. It is concluded that further standardization of the commercial method here evaluated is necessary before it can be widely adopted for the screening of APC resistance and prediction of the presence of factor V Leiden.

Blood Coagulation Tests↗
PubMed1996

A prostacyclin-sparing effect of indobufen vs. aspirin.

Indobufen ((+/-)-2-[p-(1-oxo-2-insoindolinyl)-phenyl]-butyric acid, indo) is a drug inhibiting platelet function by a reversible block of the arachidonic acid metabolism at the level of cyclooxygenase. Since tolerability profile of such drugs is mostly linked to extra-platelet cyclooxygenase inhibition, we prospectively evaluated the extent of platelet and extra-platelet cyclooxygenase inhibition by in vivo administration of indo in comparison with ASA. We assessed the effects of the two drugs on the ex vivo generation of TXB2 and 6-keto-PGF1 alpha in whole blood, as indices of the production of TXA2 and PGI2 (prostacyclin), respectively, either after spontaneous clotting at 37 degrees C for 1 h (Study 1) or after the addition of 2 micrograms/ml collagen (Study 2). Generation of 6-keto-PGF1 alpha in whole blood is a mixed index of platelet and extra-platelet cyclooxygenase activity, deriving from both platelet and white blood cell arachidonic acid metabolization. Fifteen patients with ischemic heart disease and baseline serum TXB2 levels > 300 ng/ml were allocated to receiving one single administration of either indobufen 200 mg (n = 6) or aspirin 500 mg (n = 9). Whole blood prostanoid generation was assessed at 0, 1, 2, 4, 6, 8, 12 and 24 h after drug administration (Study I). Ten healthy male volunteers were allocated to a double-blind, randomized crossover comparison of indo 200 mg b.i.d. vs. ASA 300 mg/d for 7 days (Study 2). Prostanoid generation and whole blood platelet aggregation were performed before and at the end of each study period (Day 0 and Day 7). At each time-point after single dose administration (Study 1), indobufen caused less % inhibition of whole blood 6-keto-PGF1 alpha than of TXB2. At 2 h, TXB2 was reduced to a similar extent after ASA (98 +/- 4%) and indo (97 +/- 6%) (p = N.S.), while inhibition of 6-keto-PGF1 alpha was clearly different ( > 98% after ASA, 81 +/- 2.5% after indo, p < 0.01). After one week of ASA or indo (Study 2) the maximum extent of whole blood platelet aggregation was similarly inhibited (from 17.2 +/- 1.4 ohms to 3.6 +/- 1.3 ohms with ASA; from 18.3 +/- 1.0 ohms to 1.6 +/- 0.7 ohms with indo (p ASA vs. indo = N.S.). Despite equal inhibition of whole blood TX production after collagen (from 49.0 +/- 4.3 ng/ml to 1.1 +/- 0.6 ng/ml with ASA, from 49.8 +/- 1.3 ng/ml to 1.4 +/- 0.6 ng/ml with indo), again, however, 6-keto-PGF1 alpha production was less affected by indo than by ASA (from 409 +/- 30 pg/ml to 37 +/- 13 pg/ml with ASA, inhibition = 91%; from 396 +/- 35 to 318 +/- 40 with indo, inhibition = 20%). These differential effects of indo and ASA might lead to a better platelet selectivity, tolerability and benefit/risk profile of indo vs. ASA, which are worthy of further assessment.

Adult↗
PubMed1996

Defibrotide as a possible anti-ischemic drug.

Defibrotide is a polydeoxyribonucleotide extracted from mammalian organs (porcine) and prepared by controlled depolymerization, resulting in a single-stranded deoxyribonucleotide with a mean molecular weight of 15 to 30 kDa. Early studies of experimental pharmacology in different animal species (1981-1986) were focused on an antithrombotic effect in arteries, veins, and the microcirculation, attributed to a dose-dependent activation of fibrinolysis. More recently, a number of new data have raised interest in an "anti-ischemic" action of the substance, as suggested by its evident protective effect in different models of tissue and organ ischemia. Protection from myocardial ischemia was demonstrated in different experimental models, and several ischemic features, such as heart muscle contracture, loss of high-energy substrates, decline in beta-adrenergic receptor sensitivity, and drop in infarct-related blood flow, were successfully prevented. Similar protective effects were observed during liver and kidney ischemia and in different types of experimental shock. The mechanisms involved in the anti-ischemic properties of defibrotide have been investigated in studies of experimental and human pharmacology. The substance has been shown to modulate arachidonic acid metabolism by enhancing the production and release of prostacyclin and prostaglandin E2 from tissues and whole blood, and inhibiting leukotriene B4 generation in leukocytes. Furthermore, an effect of defibrotide on activation of polymorphonuclear leukocytes and their incorporation into thrombi was described. Favorable effects on blood rheology were also reported. In summary, defibrotide deserves attention for therapeutic trials in clinical conditions characterized by organ or tissue ischemia.

Animals↗