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Biomedical subjects

E Cofrancesco

Publications and source records attributed to E Cofrancesco.

At least 19 recordsLinked to original sources
PubMed2000

Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t-plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT study). Fluvastatin Alone and in Combination Treatment.

AIM OF THE STUDY: We studied the effects of fluvastatin and bezafibrate in monotherapy and in combination on plasma fibrinogen, t-plasminogen activator inhibitor (PAI-1) and C reactive protein (CRP) in patients with coronary artery disease (CAD) and mixed hyperlipidaemia. DESIGN: In this randomised, double blind, multicentre trial 333 patients with stable angina pectoris or previous myocardial infarction or coronary revascularisation and mixed hyperlipidaemia (LDL-cholesterol 135-250 mg/dl and triglycerides (TG) 180-400 mg/dl) were randomised to fluvastatin 40 mg, bezafibrate 400 mg, fluvastatin 20 mg + bezafibrate 400 mg or fluvastatin 40 mg + bezafibrate 400 mg treatments for 24 weeks. RESULTS: Plasma fibrinogen significantly decreased after treatment with the combinations fluvastatin+bezafibrate (-14 and -16%) and with bezafibrate monotherapy (-9%). No significant reduction was observed after fluvastatin monotherapy (-4%). No significant changes were observed in PAI-1 and CRP plasma levels. Combination therapy significantly decreased both LDL-C and TG, and significantly increased HDL-C. CONCLUSIONS: The combined effects on fibrinogen and plasma lipids achieved by fluvastatin and bezafibrate combination treatment might be more useful than the simple reduction of cholesterol in preventing ischaemic cardiovascular disease.

Adult↗
PubMed1999

Preoperative plasma levels of prothrombin fragment 1 + 2 correlate with the risk of venous thrombosis after elective hip replacement.

Better preoperative identification of those patients at high risk of developing a deep vein thrombosis (DVT) after hip surgery could reduce the incidence of this postoperative complication, which still occurs despite prophylaxis. One hundred fifty-nine patients undergoing elective total hip replacement and given anticoagulant prophylaxis, were investigated, looking for the presence of a hypercoagulable state, that represents one element of Virchow's triad predisposing to DVT. Plasma levels of three markers of coagulation activation, namely prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer were measured using ELISA procedures and were correlated with the results of the postoperative phlebography. A high correlation (p < 0.001) between the preoperative plasma levels of F1 + 2 and the risk of postoperative venous thromboembolism was detected. The performance of TAT and D-dimer levels in predicting DVT was lower. These findings support the hypothesis that preoperative measurement of coagulation activation markers might be useful in predicting DVT following a total hip replacement.

Adult↗
PubMed1998

Clinical utility of prothrombin fragment 1+2, thrombin antithrombin III complexes and D-dimer measurements in the diagnosis of deep vein thrombosis following total hip replacement.

BACKGROUND: Measurements of prothrombin fragment 1+2 (F1+2), thrombin antithrombin III complexes (TAT) and D-dimer plasma levels have been proposed as non-invasive screening tests to exclude postoperative deep venous thrombosis (DVT). We investigated the diagnostic efficacy of these coagulation activation markers to rule out postoperative DVT in patients undergoing hip surgery under antithrombotic prophylaxis. METHODS: In this substudy of a randomized double-blind thrombosis prophylaxis trial comparing three doses of desirudin (10, 15 or 20 mg b.i.d.) with unfractionated heparin (5000 IU t.i.d.) we used ELISA procedures to measure F1+2, TAT and D-dimer in 159 patients undergoing total hip replacement at baseline (day 0) and on postoperative days 1, 3 and 6. Bilateral venography was performed in all cases 8-11 days after surgery. RESULTS: For the F1+2 assay sensitivity ranged from 73 to 83% in the three postoperative days investigated, and negative predictive value (NPV) from 68 to 74%. For TAT and D-dimer sensitivity ranged from 71 to 73% and from 71 to 83% and NPV from 61 to 65% and from 61 to 74% respectively. INTERPRETATION: In terms of sensitivity and NPV F1+2 and D-dimer are equivalent and are superior to TAT. However, their accuracy is too low to rule out the presence of DVT after hip surgery under antithrombotic prophylaxis.

Anticoagulants↗
PubMed1997

Coagulation activation markers in the prediction of venous thrombosis after elective hip surgery.

BACKGROUND: Despite prophylaxis, deep vein thrombosis (DVT) after hip surgery continues to occur frequently. Thus it would be helpful if before surgery patients at higher risk of DVT could be identified and more adequate prophylaxis given. As part of an international study on the prevention of DVT after total hip replacement, we investigated whether preoperative levels of three coagulation activation markers, prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer, correlate with results of postoperative venography. METHODS: 159 patients undergoing total hip replacement were randomized to receive 10, 15 or 20 mg desirudin bid or 5000 IU unfractionated heparin tid immediately before surgery and then for 11 days, until bilateral venography was performed. Preoperative F1 + 2, TAT and D-dimer plasma levels were measured using ELISA procedures. As no difference among anticoagulant treatments or in the interaction between treatments and DVT was detected for any of the three variables, results are reported as pooled data. FINDINGS: The frequency of DVT was 18.8% in the low (0.75-1.33 nM) vs 65.7% in the high third of distribution (1.77-3.47 nM) of F1 + 2 (p < .001), 27.3% in the low (2.00-2.50 micrograms/l) vs 57% in the high third (5.10-61.00 micrograms/l) of TAT (p = .042), and 29.4% in the low (39-59 micrograms/l) vs 57.1% in the high third (129-651 micrograms/l) of D-dimer (p = .051). INTERPRETATION: Preoperative F1 + 2, TAT and D-dimer levels are associated with the risk of development of DVT after total hip replacement.

Adult↗
PubMed1996

Relation between hemostatic variables and increase of common carotid intima-media thickness in patients with peripheral arterial disease.

BACKGROUND AND PURPOSE: Increases in common carotid intima-media thickness (CC-IMT), as measured by B-mode ultrasonography, have been widely used in both population studies and clinical trials in the search for risk factors for early atherosclerosis progression and have been found to correlate with age and with high concentrations of low-density lipoprotein cholesterol, leukocytes, and hemoglobin. We have now investigated the relation between several baseline hemostatic and conventional risk factors and CC-IMT changes over 16 months in 64 patients with peripheral arterial disease randomly selected from the prospective PLAT study series. METHODS: Samples from 24 patients (37.5%) who showed increases in CC-IMT during the follow-up period were compared with those from 40 (62.5%) in whom CC-IMT remained unchanged. RESULTS: Baseline conventional risk factors and coagulation variables were similar in the two groups except for higher plasma concentrations of von Willebrand factor (vWF) (178.3 +/- 53.6% versus 141.2 +/- 53.7%, P=.01) and factor VII (FVII) (133.9 +/- 36.4% versus 107.0 +/- 27.3%, P=.001) in the patients with increased CC-IMT. CC-IMT increase correlated positively with plasma levels of FVII (r=.31, P<.01) and vWF (r=.31, P<.01). Multiple stepwise regression analysis identified FVII as the only independent variable associated with an increase in CC-IMT (beta=.83, P=.01). CONCLUSIONS: High plasma concentration of FVII and vWF may be associated with the progression of early carotid atherosclerosis in patients with peripheral arterial disease.

Age Factors↗
PubMed1996

Markers of hemostatic system activation during thromboprophylaxis with recombinant hirudin in total hip replacement.

Coagulation activation markers were studied in 148 patients undergoing total hip replacement under recombinant-hirudin (Desirudin, Revasc) prophylaxis with the aim of investigating the efficacy and safety of this anticoagulant compared with heparin in terms of biological effects on coagulation variables and bleeding. Hirudin (10, 15 or 20 mg s.c. b.i.d.) or unfractionated heparin (5000 IU s.c. t.i.d.) was administered immediately before surgery and continued for 8-12 days. Activated partial thromboplastin time (aPTT), prothrombin activation fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer were measured at baseline and on postoperative days 1,3 and 6, immediately before the morning injection. In comparison with baseline values, heparin had little effect on aPTT whereas the three hirudin doses prolonged aPTT significantly with no differences among the three doses. Moreover, there were no group differences in perioperative or cumulative blood loss or transfusion requirements. F1 + 2 fragment, TAT and D-dimer plasma levels were higher than at baseline during the entire postoperative period, with different trends (F1 + 2 increasing, TAT decreasing, D-dimer increasing, decreasing and then increasing again), but without significant differences among the four treatment groups. Our findings suggest that specific inhibition of thrombin seems a safe and efficacious mode of blocking thrombin activity after hip surgery although it does not prevent thrombin generation.

Adult↗
PubMed1995

Association of lipoprotein(a) with atherothrombotic events and fibrinolytic variables. A case-control study.

Elevated plasma levels of lipoprotein(a) [Lp(a)] have been associated with an increased risk of cardiovascular disease. The aim of the present study was to investigate whether Lp(a) plasma levels were associated with subsequent ischemic events and with fibrinolytic variables in patients with established atherosclerotic disease enrolled in the prospective PLAT study. Lp(a) levels and fibrinolytic variables in 37 atherosclerotic patients who subsequently developed an atherothrombotic event during the first year of follow-up (cases) were compared with those in paired controls, matched for age, sex, diagnosis at enrollment and lipid pattern, who remained free from vascular events during the same time frame. Median and mean Lp(a) levels were similar in cases (6.05 mg/dl; 13.8 +/- 19.4 mg/dl) and controls (6.05 mg/dl; 17.1 +/- 21.6 mg/dl). In the whole group plasma Lp(a) levels correlated significantly with the increase of t-PA antigen (r = 0.368; p = 0.002) and fibrinolytic activity (r = 0.410; p = 0.001) induced by venous stasis but not with baseline fibrinolytic variables. These findings indicate that in patients with established atherosclerotic disease Lp(a) may interfere in vivo with the fibrinolytic process but is not predictive of subsequent ischemic events.

Adult↗
PubMed1994

Dermatan sulphate for the treatment of disseminated intravascular coagulation (DIC) in acute leukemia: a randomised, heparin-controlled pilot study.

Efficacy and safety of i.v. dermatan sulphate (DS) and heparin (H) in controlling laboratory alterations due to DIC were compared in 10 patients with acute leukaemia, in a prospective, randomised pilot study. The time courses of the coagulation and fibrinolysis markers for DIC were similar in the two treatment groups except for activated partial thromboplastin time and thrombin time, which were prolonged in the H but not in the DS group. Blood product support tended to be greater in the H than in the DS group. DS appears to be as effective as H in controlling thrombin production during leukaemic cytolysis and may represent a safer alternative to H in the management of DIC in acute leukaemia.

Acute Disease↗
PubMed1994

Association of increased fibrin turnover and defective fibrinolytic capacity with leg atherosclerosis. The PLAT Group.

Patients with peripheral arterial disease have a high risk of death from cardiovascular events. As defective fibrinolysis associated with leg atherosclerosis has been suggested as a predisposing factor, we sought a relation among decreased fibrinolysis, the presence of leg atherosclerosis and the incidence of thrombotic events in a case-control study nested in the PLAT. Fifty-eight patients with coronary and/or cerebral atherothrombotic disease, free of leg atherosclerosis at Doppler examination, were compared with 50 atherosclerotic patients with leg involvement. High D-dimer (153.0 vs 81.3 ng/ml, p < 0.001) and tPA antigen before venous stasis (14.4 vs 11.8 ng/ml, p < 0.03), and low tPA antigen (6.7 vs 15.6 ng/ml, p < 0.01) and fibrinolytic activity released after venous stasis (fibrinolytic capacity: 113.2 vs 281.4 mm2, p < 0.001) were found in patients with leg atherosclerosis. D-dimer and fibrinolytic capacity, in addition to age, were selected by stepwise discriminant analysis as characterizing patients with leg atherosclerosis. Moreover, higher D-dimer and tPA inhibitor characterized patients with leg atherosclerosis who subsequently experienced thrombotic events. These findings constitute evidence of high fibrin turnover and impaired fibrinolytic potential in patients with leg atherosclerosis. Thus impaired fibrinolysis may contribute to the prothrombotic state in these patients.

Aged↗
PubMed1993

Evidence of clonal progression in a case of Richter syndrome.

BACKGROUND: The debate continues as to whether Richter syndrome should be defined as non-Hodgkin lymphoma (NHL) because of a more malignant clone of neoplastic cells superimposed on preexisting chronic lymphocytic leukemia (CLL) or as the chance occurrence of two unrelated tumors. The cellular characteristics of the neoplastic clone involved in the CLL phase and the subsequent NHL were investigated in a patient in whom Richter syndrome developed. METHODS: Cell analysis was performed with immunofluorescence, histologic analysis, DNA extraction, and Southern blot analysis. RESULTS: The separated CLL and NHL B-cells from blood and bone marrow, as well as the neoplastic cells in autopsy specimens of the organs affected by NHL, particularly the brain, were found to express the same light chain of surface immunoglobulin (SIg). The change MD-->M in the SIg heavy-chain expression and the appearance of cytoplasmic IgMk suggested isotype switching simulating that observed on the final phases of primary B-cell differentiation. This hypothesis was confirmed by Southern blot analysis of DNA from blood cells in the CLL phase and in Richter transformation, which showed that the two cell populations had identical Ig gene rearrangement. CONCLUSIONS: The NHL in the patient in this study represented a malignant progression of CLL, not a second lymphoid malignancy.

Antigens, Surface↗
PubMed1993

Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. The PLAT Group.

A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (delta = difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of delta t-PA antigen (P = .047), higher D-dimer (P = .024), and higher t-PA inhibitor (P = .001) levels. delta Fibrinolytic activity was correlated inversely with t-PA inhibitor (P < .01) and triglycerides (P < .05). D-Dimer was also correlated with systolic blood pressure (P < .01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease.

Aged↗
PubMed1993

Idarubicin in the therapy of acute myeloid leukemia: final analysis in 57 previously untreated patients.

Fifty-seven previously untreated adult acute myeloid leukemia patients received idarubicin (IDA) in sequential combination with cytarabine as induction therapy; post-remission treatment included two courses of IDA and cytarabine alternating with two courses of VP-16 and cytarabine. As late intensification, patients received either high-dose cytarabine or, in 10 cases, autologous bone marrow transplantation. Complete remission (CR) was achieved in 48 patients (84.2%), 41 after one induction course and seven after two courses. Median length of disease-free survival (DFS) was 26 months. Univariate analysis did not identify any of the investigated variables as having prognostic significance in predicting DFS. On the other hand, patients achieving CR after one induction course had a better DFS than those requiring two courses. Furthermore, the analysis of DFS slightly favors autologous bone marrow transplantation. In conclusion, the antileukemic activity of the present IDA protocol is testified by the high CR rate and by the possibility of minimizing the role of prognostic factors. The better outcome of patients achieving CR after one induction course further supports the opinion that the intensity of the induction treatment, offered by an agent as potent as IDA, might significantly influence DFS.

Acute Disease↗
PubMed1992

Immunoglobulin classes and subclasses of platelet antibodies in a case of post-transfusion purpura.

A multiparous white woman developed severe thrombocytopenia following transfusion of red blood cells. Six ineffective platelet transfusions (a total of 42 random donor concentrates) were given from day 0 to day +6, high-dose steroids from day +1, progressively tapered until day +30, and a total of 150 g of intravenous immunoglobulins from day +2 to day +6. As platelet count had not increased significantly by day +8, four plasma exchange procedures, each consisting of 2,000 ml of plasma exchanged with 5% albumin solution, were performed on days +8, +10, +14 and +18. Platelet count was 5, 50, 100 and 234 x 10(9)/l on days +8, +14, +26 and +32 (discharge), respectively. The patient's acute phase serum contained increased levels of platelet alloantibodies with anti-HPA-1a (PlA1, Zwa) specificity and a titer of 3,200. IgG1, IgG2 and IgG3 subclasses of platelet-reactive antibodies in the patient's serum were elevated, whereas IgG4, IgM and IgA were within the reference values. Levels of IgG1, IgG2 and IgG3 of antiplatelet antibodies showed a marked and parallel reduction during treatment, but were still above the reference values at the end of treatment and 1 year later, when the patient platelet count was normal. Although a failure of intravenous immunoglobulins cannot be proven in this case, plasma exchange seems to have contributed more than intravenous immunoglobulins to clinical remission.

Aged↗