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Biomedical subjects

G Agnelli

Publications and source records attributed to G Agnelli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Management of oral anticoagulant therapy in Italy.

The clinical outcome of oral anticoagulant therapy (OAT) depends on how successful physicians and patients are in achieving and maintaining levels of anticoagulation capable of preventing thromboembolic events without increasing the risk of hemorrhagic complications. Concerning the patient, education and compliance are the major problems. Concerning the physicians, the management of patients receiving OAT is a complex task that requires frequent laboratory testing, dosage regulation, prompt diagnosis, and treatment of thromboembolic and hemorrhagic events. Anticoagulation clinics, which provide patient education, close monitoring of prothrombin times and continuous clinical surveillance, have been claimed to help in improving the overall quality of OAT. In 1989, following the experience of other countries, a national Federation of Centers for the Surveillance of Anticoagulant (FCSA) therapies was founded in Italy. In the last 10 years the main objectives of FCSA have been: (1) favoring the development of new centers in areas of the country lacking proper services; (2) standardazing the management of OAT by recommending organizational and technical procedures; (3) stimulating participation in laboratory quality-control programs; (4) implementing continuous education programs for medical and paramedical personnel and for the patients themselves; (5) making health administrators aware of the social impact of OAT and of the need for the formal recognition of the centers; and (6) planning and organizing multicenter studies. Some of these goals have been successfully achieved, but problems remain to be solved to guarantee an optimal control of OAT in the entire national territory.

Administration, Oral↗
PubMed1999

Pre-operative plasma levels of soluble fibrin polymers correlate with the development of deep vein thrombosis after elective neurosurgery.

The role of blood tests in identifying patients at high risk for post-operative venous thromboembolism is undefined. The aim of this study was to evaluate the correlation between pre-operative plasma levels of soluble fibrin polymers (SFP), as determined by a recently developed enzyme-linked immunosorbent assay (ELISA) assay (TpP), and the incidence of deep vein thrombosis (DVT) after elective neurosurgery. Blood samples for SFP assay were withdrawn on the day before surgery from 157 consecutive patients undergoing elective neurosurgery for brain or spinal tumour. Patients were randomized to subcutaneous enoxaparin (40 mg once daily) or placebo given for at least 7 days. All patients wore compression stockings. DVT was assessed by bilateral venography, performed on day 8 +/- 1. Thirty-four patients (21.7%) were found to have a DVT, proximal in 11 (7%) and isolated distal in 23. Patients with and without DVT had a plasma pre-operative SFP levels of 6.2 +/- 4.6 and 1.9 +/- 1.5 mg/ml respectively (mean +/- SD) (P < 0.001). SFP levels in patients with proximal and isolated distal DVT were 7.6 +/- 5.1 and 5.5 +/- 4.4 microg/ml, respectively (P = 0.22). SFP cut-off levels categorized patients into three classes of DVT incidence. The incidence of DVT was 7.4% (6 of 81) for SFP levels < 2 microg/ml, 20.4% (11 of 54) for levels between 2 and 4.5 microg/ml, and 77.3% (17 of 22) for levels > 4.5 microg/ml (P= 0.001, Cochran-Mantel-Haenszel test). We conclude that pre-operative SFP levels correlate with post-operative DVT in elective neurosurgery patients. Further studies are required to define whether pre-operative SFP measurement could be useful in patient management.

Adult↗
PubMed1999

Dermatan sulphate for the prevention of postoperative venous thromboembolism in patients with cancer. DOS (Dermatan sulphate in Oncologic Surgery) Study Group.

BACKGROUND: Patients undergoing surgery for cancer are at high risk for venous thromboembolism (VTE). Agents that selectively inhibit thrombin, such as dermatan sulphate, have potential for a favourable benefit-risk ratio in the prevention of this complication. METHODS: Patients scheduled for elective abdominal, thoracic, gynecologic or urologic surgery for cancer resection, were randomised to dermatan sulphate (600 mg intramuscularly on the second day before surgery, then 300 mg once daily), or calcium heparin (5,000 IU subcutaneously t.i.d., starting 2 hours before operation). Both treatments were continued until postoperative day 7 or until adequate mobilisation was achieved. Bilateral venography was scheduled at the end of treatment. Venograms were centrally assessed in blind conditions. The study outcomes were VTE (venographically proven deep vein thrombosis IDVT] or symptomatic, objectively confirmed pulmonary embolism) and bleeding complications. RESULTS: At 27 centres, 842 patients were randomised and underwent surgery (418 dermatan sulphate, 424 heparin). Efficacy was assessed in 521 patients with adequate venography and/or confirmed pulmonary embolism. DVT was observed in a total of 96 patients; symptomatic non-fatal pulmonary embolism developed in 2 patients (one per group), who also had DVT at venography. Postoperative VTE occurred in 40 of 267 patients on dermatan sulphate, 15.0%, versus 56 of 254 patients on heparin. 22.0% (p = 0.033). Relative risk reduction was 32.7% (95% confidence interval, 3.1 to 53.2%). The rate of bleeding complications in all operated patients was 6.9% with dermatan sulphate and 7.5% with heparin (confidence interval for the absolute risk difference, -4.1 to 2.9%). The inhospital mortality rate was 1.2% and 1.4%, respectively. CONCLUSIONS: In oncologic surgery, dermatan sulphate prevents VTE more effectively than heparin without increasing bleeding complications.

Aged↗
PubMed1999

Withdrawal of warfarin after deep vein thrombosis: effects of a low fixed dose on rebound thrombin generation.

The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis (DVT) is still not defined. Rebound thrombin generation, which occurs after the withdrawal of warfarin, has been said to be associated with early recurrence of DVT. The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation. Forty-one consecutive patients were randomly assigned to abrupt withdrawal of warfarin (group A), or to an additional month of warfarin, at the fixed dose of 1.25 mg/day (group B). Plasma samples were withdrawn for the assay of prothrombin fragment F1+2 (F1+2), protein C, factor VII and International Normalized Ratio (INR), before any anticoagulant treatment (I), during initial heparin (II) and full dose warfarin (III), at the end of full dose warfarin (IV) and then 1 (V), 4 (VI), 5 (VII) and 9 (VIII) weeks after randomization. The mean duration of full-dose warfarin treatment, the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups. A decrease in F1+2 was observed during heparin and warfarin treatment (II, 1.7 nmol/ml; III, 1.0 nmol/ml; IV, 0.7 nmol/ml; versus I, 3.5 nmol/ml; P<0.01). After the withdrawal of warfarin, an increase in F1+2 was observed in both groups, but without significant statistical differences (group A: V, 1.2 nmol/ml; VI, 1.5 nmol/ml; VII, 1.6 nmol/ml; VIII, 1.1 nmol/ml; group B: V, 1.3 nmol/ml; IV, 1.5 nmol/ml; VII, 1.4 nmol/ml; VIII, 1.4 nmol/ml). No significant difference between the two groups was observed in the recovery of protein C and factor VII. Four patients experienced a recurrence of DVT, three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin. Rebound thrombin generation is not reduced by a low, fixed dose of warfarin.

Adolescent↗
PubMed1999

Building effective prophylaxis of deep vein thrombosis in the outpatient setting.

Perioperative prophylaxis of venous thromboembolism (VTE) usually coincides with the duration of hospital stay, typically lasting between 5 and 14 days. However, mounting evidence indicates that the risk of postoperative VTE persists for at least five weeks after orthopaedic surgery and six weeks following general surgery, suggesting that prolonged prophylaxis may reduce the burden of thromboembolic complications. As interest in extending prophylaxis grows, however, economic pressures and patient preferences are contributing to ever shorter hospital stays, giving rise to an exploration of administering prolonged prophylaxis to ambulatory patients at home. Effective outpatient prophylaxis for VTE must be safe, simple to use and convenient for patients to maximize compliance. Low-molecular-weight heparins (LMWHs) are at least as safe and effective as standard low-dose unfractionated heparin (UFH) in preventing thromboembolic events, and can be administered subcutaneously at a fixed daily dose without monitoring. Clinical studies in patients with total hip replacement have demonstrated that LMWHs, administered at home once daily for up to four weeks following hospital discharge, are safe and well-tolerated and significantly reduce the incidence of post-discharge deep vein thrombosis. Due to the high costs of treating thromboembolic complications and post-thrombotic syndrome, appropriately targeted prolonged thromboprophylaxis may be cost-effective.

Ambulatory Care↗
PubMed1999

Local versus central assessment of venographies in a multicenter trial on the prevention of deep vein thrombosis in neurosurgery.

Venography is the diagnostic method of choice for end-point measurement in multicenter trials on the prevention of postoperative deep vein thrombosis (DVT). The aim of the study was to determine the inter-observer agreement between the local and central assessment of venographies in a multicenter trial comparing enoxaparin and placebo in the prevention of DVT after elective neurosurgery. The study was run in seven centers experienced in venography trials on DVT prevention. The central and local adjudication panels were both blind with respect to the assigned treatment. The central panel was unaware of the local adjudication. Venographies were adjudicated as positive, negative or inadequate for adjudication and positive venographies as proximal or distal DVT. Inter-observer agreement was assessed according to the Cohen's inter-observer variability index (K index). All 266 venographies (8 monolateral) were considered adequate for adjudication by both the central and local panels. A disagreement was found in 25 cases; K index = 0.75. Fourteen venographies adjudicated as negative centrally were considered positive locally (3 were proximal DVT). Eleven venographies adjudicated as positive centrally (1 was a proximal DVT) were considered negative locally. Enoxaparin was found to be more effective than placebo according to both the central and local adjudication: 16.9% versus 32.6% (Relative risk, RR = 0.52; CI 95% 0.33-0.82) according to central adjudication; 18.5% versus 33.3% (RR = 0.56; CI 95% 0.36-0.87) according to local adjudication. We conclude that a good inter-observer agreement in the assessment of venography was observed between the central and local adjudication in a study on DVT prevention run in a restricted experienced study framework. The cost and work overloading of central assessment of venographies in this study framework seems not to be justified.

Anticoagulants↗
PubMed1998

Utility of an integrated clinical, echocardiographic, and venous ultrasonographic approach for triage of patients with suspected pulmonary embolism.

The potential role of ultrasound techniques in diagnosing acute pulmonary embolism (PE) has been investigated in severe cases with hemodynamic compromise, but is still unclear for the whole clinical spectrum of patients with suspected PE. The aim of this study was to assess the utility of an integrated bedside evaluation for PE based on the combination of a clinical score, 2-dimensional echocardiography, and color venous duplex scanning. A group of 117 consecutive patients with suspected PE was assessed using a clinical likelihood score, echocardiography, and venous duplex scanning in order to obtain a preliminary diagnosis of PE, which was subsequently compared with the final diagnosis obtained by lung perfusion scintigraphy and angiography. A preliminary diagnosis of PE was made in 70 patients; a final diagnosis of PE was made in 63 patients, of which 56 had and 7 did not have a preliminary diagnosis of PE. The preliminary diagnosis therefore showed 89% sensitivity and 74% specificity, with a total accuracy of 82%. In patients with massive PE, sensitivity and negative predictive values of the preliminary diagnosis were 97% and 98%, respectively. Echocardiography was poorly sensitive (51%) but highly specific (87%) for PE. Thus, the integration of clinical likelihood, echocardiography, and venous duplex scanning provides a practical approach to patients with suspected PE, allows the rapid implementation of appropriate management strategies, and may reduce or postpone the need for further instrumental evaluation of more limited access.

Adult↗
PubMed1998

D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. The Multicentre Italian D-dimer Ultrasound Study Investigators Group.

OBJECTIVE: To investigate the efficacy of using a rapid plasma D-dimer test as an adjunct to compression ultrasound for diagnosing clinically suspected deep vein thrombosis. DESIGN: D-dimer concentrations were determined in all patients with a normal ultrasonogram at presentation. Repeat ultrasonography was performed 1 week later only in patients with abnormal D-dimer test results. MAIN OUTCOME AND MEASURES: Patients with normal ultrasonograms were not treated with anticoagulants and were followed for 3 months for thromboembolic complications. SETTING: University research and affiliated centres. SUBJECTS: 946 patients with clinically suspected deep vein thrombosis. RESULTS: Ultrasonograms were abnormal at presentation in 260 (27.5%) patients. Of the remaining 686 patients tested for D-dimer, 88 (12.8%) had abnormal concentrations. During follow up venous thromboembolic complications occurred in one of the 598 patients who were not treated with anticoagulants and who had an initial normal ultrasonogram and D-dimer concentration, whereas thromboembolic complications occurred in two of the 83 untreated patients who had abnormal D-dimer concentrations but a normal repeat ultrasonogram. The cumulative incidence of venous thromboembolic complications during follow up was 0.4% (95% confidence interval 0% to 0.9%). The rapid plasma D-dimer test used as an adjunct to compression ultrasonography resulted in a reduction in the mean number of repeat ultrasound examinations and additional hospital visits from 0.7 to 0.1 per patient. CONCLUSIONS: Testing for D-dimer as an adjunct to a normal baseline ultrasound examination decreased the number of subsequent ultrasound examinations considerably without any increased risk of venous thromboembolic complications in patients not receiving anticoagulants. The use of ultrasound and testing for D-dimer enabled treatment decisions to be made at the time of presentation in most patients.

Biomarkers↗
PubMed1998

Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery.

BACKGROUND: Compression stockings are recommended for prophylaxis against venous thromboembolism in patients undergoing neurosurgery, but anticoagulant agents have not gained wide acceptance because of concern about intracranial bleeding. METHODS: In a multicenter, randomized, double-blind trial, we assessed the efficacy and safety of enoxaparin in conjunction with the use of compression stockings in the prevention of venous thromboembolism in patients undergoing elective neurosurgery. Enoxaparin (40 mg once daily) or placebo was given subcutaneously for not less than seven days beginning within 24 hours after the completion of surgery. The primary end point was symptomatic, objectively confirmed venous thromboembolism or deep-vein thrombosis assessed by bilateral venography, which was performed in all patients on day 8+/-1. Bleeding side effects were carefully assessed. RESULTS: Among the 307 patients assigned to treatment groups, 129 of the 154 patients receiving placebo (84 percent) and 130 of the 153 patients receiving enoxaparin (85 percent) had venographic studies adequate for analysis. An additional patient in the placebo group died before venography of autopsy-confirmed pulmonary embolism. In this analysis, 42 patients given placebo (32 percent) and 22 patients given enoxaparin (17 percent) had deep-vein thrombosis (relative risk in the enoxaparin group, 0.52; 95 percent confidence interval, 0.33 to 0.82; P=0.004). The rates of proximal deep-vein thrombosis were 13 percent in patients receiving placebo and 5 percent in patients receiving enoxaparin (relative risk in the enoxaparin group, 0.41; 95 percent confidence interval, 0.17 to 0.95; P=0.04). Two patients in the placebo group died of autopsy-confirmed pulmonary embolism on days 9 and 16. Major bleeding occurred in four patients receiving placebo (intracranial bleeding in all four) and four patients (intracranial bleeding in three) receiving enoxaparin (3 percent of each group). CONCLUSIONS: Enoxaparin combined with compression stockings is more effective than compression stockings alone for the prevention of venous thromboembolism after elective neurosurgery and does not cause excessive bleeding.

Adult↗
PubMed1998

Anticoagulant agents in the management of pulmonary embolism.

The anticoagulant agents most commonly used in the prevention and treatment of pulmonary embolism (PE) are unfractionated heparin, oral anticoagulants, and low molecular weight heparins (LMWHs). Unfractionated heparin at low fixed dose is the prophylactic regimen of choice for PE in patients undergoing general surgery or with serious medical diseases (low to moderate risk patients). In high risk patients perioperative prophylaxis with LMWHs or oral anticoagulants should be adopted. Therapy of pulmonary embolism should start with an intravenous bolus dose of 5000 U heparin followed by an infusion of 1250 U/h. Then the dose should be adjusted to maintain the aPTTX2-2.5 pre-treatment value. Heparin is continued for 7-10 days and is followed by oral anticoagulants for at least 3 months. Unfractionated heparin has some pharmacological limitations, mainly due to the aspecific binding to plasma proteins that limits its anticoagulant effect and causes the heparin resistance observed in some patients with PE and the inter-subject variability of the anticoagulant effect. Other antithrombotic agents such as LMWHs and selective thrombin inhibitors (hirudin and its analogues) do not aspecifically bind to plasma proteins. They have recently been used with promising results in the prevention and treatment of PE. Their definitive value in this clinical setting will be defined by the ongoing clinical trials.

Anticoagulants↗
PubMed1998

Postdischarge prophylaxis for venous thromboembolism among high-risk surgery patients.

The role of pharmacological prophylaxis against venous thromboembolism in high-risk surgical patients is straightforward during hospitalization but controversial after hospital discharge. Clinical trials based upon venography-detected deep vein thrombosis (DVT), yield high DVT rates which may not be clinically relevant, since most cases are asymptomatic. On the other hand, clinical surveys based upon clinically overt venous thromboembolism yield low DVT rates that underestimate the problem. If postdischarge prophylaxis is used, oral anticoagulants may be more cost-effective than low-molecular-weight heparins. However, optimal strategies for venous thromboembolism prophylaxis after hospital discharge will not be definitively provided until large studies are performed with sufficient power to detect clinically relevant endpoints such as symptomatic DVT or pulmonary embolism.

Anticoagulants↗