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Biomedical subjects

S Coccheri

Publications and source records attributed to S Coccheri.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1994

Acute and chronic effects of a new low molecular weight dermatan sulphate (Desmin 370) on blood coagulation and fibrinolysis in healthy subjects.

The acute and chronic effects on blood coagulation and fibrinolysis of a new molecular weight dermatan sulphate (Desmin 370) have been investigated in a double blind, placebo-controlled cross over study in 12 healthy volunteers. The compound (100 and 200 mg) was injected IM and the expected heparin cofactor II potentiating effect, reflecting dermatan sulphate activity, peaked after 2 h and was still detectable after 9 h. Surprisingly for this type of compound, a substantial increase in anti-Xa activity also appeared and lasted up to 12 h in the absence of a significant change in aPTT. The bovine-thrombin time was not changed, while human-thrombin times were slightly, albeit non-significantly, prolonged. The activity of t-PA was increased 6h after the higher dose, but the overall pattern of fibrinolytic activities did not suggest any important change after drug treatment in comparison to placebo. No residual or cumulative effect on any of the investigated parameters was detectable 24 h after the injection on the 4th and 8th days during repeated daily administration. Parallel in vitro and in vivo investigations showed that the unexpected anti-Xa effect was not attributable to contamination by traces of low molecular weight heparin. Desmin 370, a low molecular weight dermatan sulphate that potentiates heparin cofactor II and also inhibits Factor Xa, deserves clinical evaluation as an antithrombotic agent.

Adolescent↗
PubMed1994

[Prevention and treatment of deep venous thrombosis: prevention of pulmonary embolism].

Deep vein thrombosis (DVT), if not properly treated, may be complicated by pulmonary embolism in about 50% of the cases within 3 months. Therefore, effective prevention of pulmonary embolism relies on three cornerstones: correct prophylaxis, early diagnosis, and correct treatment of DVT. In prophylaxis of DVT, low-dose heparin is effective in preventing postoperatory DVT and pulmonary embolism in medium risk operations, and also in "medical" DVT. In high risk operations and patients, personalized low-dose heparin, oral anticoagulants and especially low-molecular weight heparins have been used. The available controlled trials demonstrate that the low-molecular weight heparins are especially efficacious and also cost-effective in high risk situations as elective hip surgery. Validated techniques for early diagnosis of DVT are phlebography and, in symptomatic proximal DVT, also venous echotomography. Therapy of overt DVT is usually performed with infusional or subcutaneous heparin at therapeutic doses, followed by moderate range oral anticoagulants. In the initial treatment, low-molecular weight heparins at single subcutaneous daily dosing can substitute for standard heparin. Indication to thrombolytic therapy should be restricted to selected cases; thrombectomy has limited application. Caval filters may be useful in strictly selected indications, especially in presence of contraindications or resistance to anticoagulant treatments.

Anticoagulants↗
PubMed1994

Activation of blood coagulation after abrupt or stepwise withdrawal of oral anticoagulants--a prospective study.

The occurrence of a "rebound hypercoagulable state" in patients after dicontinuation of oral anticoagulants is still a matter of debate and no definite recommendation can be made on the best procedure for anticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (pts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, group B: 2/3 of initial dose the 1st week, 1/3 the 2nd weeks and nothing from the 3rd week on). Blood was sampled at baseline, once a week for the first three weeks and after 2 months. At the 1st week group A had significantly higher F1+2 and TAT values (p < 0.001); at the 2nd week F1+2 levels remained higher (p < 0.05) though INR values were not different from those of group B. After baseline, higher than normal F1+2 levels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) in group B (p < 0.01); at the 2nd week, 10/17 (59%) patients in group A vs 1/15 (7%) in group B still had higher than normal F1+2 levels (p < 0.01). The values of areas under curve (AUC) and maximum concentrations of all variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thrombotic events (one DVT recurrence and one thrombophlebitis in a varicose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AUC values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prolonged very low calorie diet in highly obese subjects reduces plasma viscosity and red cell aggregation but not fibrinogen.

Epidemiological studies have shown that obesity, as well as haemorheological changes are risk factors for cardiovascular disease. The aim of this study performed in grossly obese subjects was to investigate: (a) the effects on haemorheological parameters of a 3 month period of very low calorie diet (VLCD, 514 and 470 Kcal/day in women and men respectively), and (b) the relationship between haemorheological test results at baseline and the different types of body fat distribution. Fifty-two obese healthy subjects (31 women), with BMI > 30, were examined at baseline; 34 of these (19 women), compliant with the diet, were also examined after 3 months VLCD. At baseline, the results of haemorheological variables were not significantly different for patients in the highest waist-to-hip ratio (WHR) tertile vs those in the other two tertiles. After VLCD, body weight and BMI decreased markedly. The values of Ht, plasma viscosity (PV), erythrocyte aggregation index (EAI) values (P < 0.001) and white blood cell (WBC) counts (P < 0.01) significantly dropped. Globulin levels decreased, while albumin levels increased leading to significantly (P < 0.001) higher A/G ratios. No significant changes in fibrinogen (Fgn) levels were recorded after diet. In conclusion, the present study demonstrates that prolonged VLCD associated with slimming in grossly obese subjects is effective in improving related haemorheological disorders, mainly of plasmatic type, except Fgn. Second, we found that, at least in these grossly obese subjects, there is no clear evidence of a relationship between the degree of haemorheological changes and WHR values.

Adult↗
PubMed1993

Interaction between vitamin B6 deficiency and low EFA dietary intake on kidney phospholipids and PGE2 in the rat.

Vitamin B6 is involved in the metabolism of long chain polyunsaturated fatty acids and phospholipids. We have studied the interaction between pyridoxine deficiency and low amounts of dietary essential fatty acids (EFA) in the rat. The fatty acid composition of kidney phospholipids of pyridoxine deficient animals shows a decrease of 20:3 n9 and an increase of 20:4 n6 in comparison with control and pair fed animals. This variation of fatty acid composition could be due to the simultaneous effect of vitamin B6 deficiency, which reduces the oxidation of linolenate, and of a low intake of EFAs which stimulates delta-6-desaturase. The dietary treatment also influences kidney Prostaglandin E2 (PGE2) levels which are higher in vitamin B6 deficient animals. This effect could be correlated with a higher response to sympathetic stimulation caused by the simultaneous presence of vitamin B6 deficiency and low EFA availability. Also the higher level of arachidonate could be involved in promoting PGE2 synthesis.

Animals↗
PubMed1993

Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation.

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially alpha 1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex "lytic" state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.

Adolescent↗