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PubMedDate not supplied

Determination of nanogram levels of the anticoagulant acenocoumarin in serum by high-performance liquid chromatography.

A simple, rapid, and sensitive method for the determination fo the short-acting coumarin anticoagulant acenocoumarin in human serum is described. This drug is estracted from the acidified biological matrix together with the internal standard 5-methoxypsoralen. Separation and quantitation are performed on a high-performance liquid chromatograph with a reversed-phase column and an ultraviolet detector operating at 308 nm. Accuracy and precision are good. The lowest limit of detection is 15 microgram/L, which means that acenocoumarin concentrations can be measured in serum from the subtherapeutic to the toxic range. This method can also be used for rapid measurement of warfarin serum concentrations.

Acenocoumarol↗
PubMed2006

Management of cardiovascular risk in patients receiving calcineurin inhibitors--a case report.

Cardiovascular disease is the main cause of death after renal transplantation. There are few trials evaluating the efficacy of prevention strategies in renal transplant patients on major adverse cardiac events (MACE) and cardiovascular mortality. However, there is general agreement that active prevention strategies can significantly decrease cardiovascular mortality after renal transplantation. Here, we present the case of a 52-year-old male patient who received a first kidney transplant in 1993. He showed a small fixed perfusion defect on thallium scintigraphy before transplant. He was admitted at 13 months due to an antero-lateral myocardial infarction that was complicated with ventricular fibrillation. Despite anti-coagulation with acenocumarol, treatment with statins and angiotensin II receptor blocking agents and an excellent preservation of renal function, the patient presented with a second episode of myocardial infarction at 9 years post-transplant. This case report is discussed in order to highlight the way in which attitudes have been modified in the past decade in order to systematically pursue an early diagnosis of pre-existing coronary artery disease, aggressively treat MACE and actively decrease cardiovascular risk in transplant patients, using all available efficacious treatments as well as individualizing immunosuppression to prolong not only graft but also patient survival.

Acenocoumarol↗
PubMed1994

Effect of various antithrombotic regimens (aspirin, aspirin plus dipyridamole, anticoagulants) on the functional status of patients and grafts one year after coronary artery bypass grafting.

From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery.

Acenocoumarol↗
PubMed1986

Two-dimensional echocardiographic assessment of anticoagulant therapy in left ventricular thrombosis early after acute myocardial infarction.

This study was designed to assess, by two-dimensional echocardiography, the effects of anticoagulant therapy on left ventricular thrombosis detected after acute myocardial infarction. Thirty-eight patients with left ventricular thrombi detected by two-dimensional echocardiology within 5 weeks (mean 4) of the onset of infarction were randomly assigned to the following groups: group A consisted of 19 patients who received oral anticoagulants (acenocoumarin 1-6 mg daily regulated to keep prothrombin time within the range of 25 to 35%) and group B which consisted of 19 non-treated control patients. Seventeen patients from both groups were restudied 15 days, 3 months and one year later to evaluate the changes in size of thrombi. Echocardiographic examinations were read blindly; a significant decrease in ventricular thrombus size was taken as a greater than or equal to 5 mm reduction of thickness in the apical views. In Group A, 9 patients showed a complete resolution of thrombus at the 15 day study; at one year, thrombus had resolved in 15 and persisted unchanged in size in 2 patients. The mean dimension of thrombi in patients of group A was 18 +/- 6.6 mm at the screening examination and decreased to 6.6 mm, 3.8 mm and 2.2 mm, respectively, at 15 days, 3 months and one year follow-up studies. Among 17 patients of group B at the 15 day study, two had resolution of thrombus and 15 were unchanged; at the one year examination thrombus was resolved in 4, decreased in size in 4 and persisted unchanged in 9 patients. Analysis of variance of the dimensional changes of thrombi in the two groups of patients confirmed a significant efficacy of anticoagulant therapy (P less than 0.001). On the basis of our results we conclude that full-dose anticoagulant therapy, started early (within 5 weeks) after acute myocardial infarction, is effective in the resolution of left ventricular thrombosis.

Acenocoumarol↗
PubMed2001

Reversal of excessive oral anticoagulation with a low oral dose of vitamin K1 compared with acenocoumarine discontinuation. A prospective, randomized, open study.

We performed a prospective, randomized, open study in 109 outpatients under chronic anticoagulation with acenocoumarine, presenting with International Normalized Ratios (INRs) > or = 6.0 and no or minor bleeding. All the patients withheld one dose of acenocoumarine; in addition, a treated group also received 1 mg oral vitamin K1. We aimed at a post-intervention INR < 6.0, with a target zone of 2.0-4.0. The INRs were lowered from a mean of 8.1 +/- 1.7 to 4.9 +/- 2.5 in the controls (P = 0.0000) and from 8.4 +/- 2.4 to 3.3 +/- 3 in the treated patients (P = 0.0000). There were no differences in the percentage of patients with post-intervention INRs < 6.0 or within the therapeutic zone. One-third of the treated patients and only 2% of the controls reached INRs < 2.0 (P = 0.0003). Oral vitamin K1 offered no advantage to the simple discontinuation of one dose of acenocoumarine. A substantial number of treated patients were consequently exposed to under-anticoagulation.

Acenocoumarol↗
PubMed2003

Wheezing in patients with acute pulmonary embolism with and without previous cardiopulmonary disease.

BACKGROUND: Wheezing is a little known but possible presentation feature of acute pulmonary embolism. PATIENTS AND METHODS: A retrospective review of the records of 154 consecutive patients with acute pulmonary embolism, who survived long enough for diagnostic evaluation. RESULTS: Fourteen patients with acute pulmonary embolism (9.1%) had wheezing at presentation. Wheezing was more frequent in patients with previous cardiopulmonary disease than in those without previous cardiopulmonary disease, although this did not reach statistical significance (13.5 versus 6.9%; P=0.17). Dyspnoea, cough and respiratory failure were more frequent with statistical significance in our patients with wheezing than in those without wheezing. The hospital mortality rate was similar in both groups. CONCLUSION: Wheezing in acute pulmonary embolism may be more frequent in patients with previous cardiopulmonary disease. However, wheezing also occurs in patients with acute pulmonary embolism without previous cardiopulmonary disease. Wheezing may be a sign of severity in acute pulmonary embolism.

Acenocoumarol↗
PubMed2003

Successful management of a large pulmonary cement embolus after percutaneous vertebroplasty: a case report.

Percutaneous vertebroplasty is increasingly used for the treatment of vertebral compression fractures. Local leakage of polymethylmethacrylate cement into the perivertebral space is a common complication, but important systemic effects have rarely been reported. The authors describe the case of a 52-year-old patient with central pulmonary embolism after percutaneous vertebroplasty of the eleventh thoracic vertebral body. The large cement embolus was removed from the right pulmonary artery with a hybrid technique combining an interventional catheter procedure with an open heart operation. The patient made an uneventful recovery. The authors review how appropriate arthroplasty techniques might minimize the risk of this dreadful complication.

Acenocoumarol↗
PubMed2003

Low rate of bleeding and thrombotic complications of oral anticoagulant therapy independent of age in the real-practice of an anticoagulation clinic.

Over past years, there has been a world-wide increase in oral anticoagulant treatment (OAT). This study was aimed at evaluating the efficacy and safety of OAT managing in a real-practice situation. Nine hundred and three consecutive unselected patients referred for the control of OAT to the Anticoagulation Clinic of the University of Florence were studied. The total follow-up period was 1679 patient-years. The rate of total, major and fatal bleeding events was 5.0, 1.1 and 0.06 per 100 patient-years, respectively. In patients with a target International Normalized Ratio (INR) > or = 3, a significantly higher rate of bleeding (P = 0.02) with respect to patients with a target INR < 3 was observed. The rate of all thrombotic events was 3.8 per 100 patient-years. The rate of major and fatal thrombotic events were 2.4 and 0.4 per 100 patient-years, respectively. At INR >/= 4.5 the rate of bleeding was significantly higher (P = 0.005) than at lower INR. At INR < 2 the rate of all thrombotic events was significantly higher (P = 0.00001) with respect to more elevated intensities of anticoagulation. A low incidence of complications may be obtained even in elderly outpatients on OAT followed at an anticoagulation clinic.

Acenocoumarol↗
PubMed1984

Effect of atenolol and metoprolol on the anticoagulant activity of acenocoumarin.

In patients receiving long-term acenocoumarin treatment, the effect on anticoagulant activity of atenolol (100 mg once-daily) and metoprolol (100 mg twice daily) was compared in a randomised within-patient open trial. No significant differences were demonstrated between mean prothrombin time and Thrombotest during treatment with atenolol, metoprolol or placebo. These data do not suggest the existence of an interaction between acenocoumarin and the moderately lipophilic beta-adrenoceptor blocker metoprolol, or the hydrophilic beta-adrenoceptor blocker atenolol. The results are discussed in the light of published data for the highly lipophilic beta-adrenoceptor blocker propranolol.

Acenocoumarol↗
PubMed1988

Stereospecific assay of nicoumalone: application to pharmacokinetic studies in man.

1. A stereospecific h.p.l.c. assay of nicoumalone in plasma has been developed. 2. The assay was applied to a study in which 20 mg racemic nicoumalone was given orally to three volunteers and blood samples taken for 168 h. 3. The mean pharmacokinetic parameters of the individual enantiomers were: clearance/bioavailability 1.28 1 h-1, R-enantiomer; 17.5 1 h-1, S-enantiomer: volume of distribution/bioavailability 12.5 1, R-enantiomer; 22.6 1, S-enantiomer: terminal half-life 6.8 h, R-enantiomer; 0.91 h, S-enantiomer. 4. The data are consistent with a substantial first-pass hepatic loss of S-nicoumalone.

Acenocoumarol↗
PubMed1989

Cimetidine-nicoumalone interaction in man: stereochemical considerations.

1. The cimetidine-nicoumalone interaction was studied in five subjects who received a single 10 mg oral dose of racemic nicoumalone alone and 3 days into an oral regimen of cimetidine of 200 mg three times daily and 400 mg at night. 2. The concentrations of R(+)- and S(-)-nicoumalone in plasma were measured using a stereospecific h.p.l.c assay; augmentation of prothrombin time was used as a measure of response. 3. Cimetidine increased the rate (but not extent) of absorption of both R(+)- and S(-)-nicoumalone, and reduced the clearance of R(+)-nicoumalone but not that of the S(-)-enantiomer. 4. Cimetidine increased the anticoagulant response produced by nicoumalone in some but not all subjects, despite a consistent effect on the pharmacokinetics of the oral anti-coagulant. 5. Cimetidine appears to produce its effect by stereoselectively inhibiting the elimination of R(+)-nicoumalone.

Acenocoumarol↗
PubMed1990

Lack of effect of ponsinomycin on the pharmacokinetics of nicoumalone enantiomers.

Pharmacokinetic interaction between ponsinomycin-nicoumalone was studied in six subjects who received an 8 mg oral dose of racemic nicoumalone alone and 4 days into an oral regimen of ponsinomycin 800 mg twice daily. The concentrations of R(+) and S(-)-nicoumalone in plasma were measured using a stereospecific h.p.l.c. assay. The disposition characteristics of nicoumalone enantiomers in the control phase of this study were similar to those reported previously with the exception of the data for one subject whose oral clearance for S(-)-nicoumalone was seven times lower than those in the other subjects. A statistically significant effect of ponsinomycin on the kinetics of R(+) and S(-)-nicoumalone was not demonstrated.

Acenocoumarol↗
PubMed2004

Coumarin necrosis induced by renal insufficiency.

Cutaneous necrosis is an infrequent complication of coumarin therapy. Skin necrosis has usually been reported in patients with congenital protein C deficiency or, less commonly, protein S deficiency. However, this complication may also occur with acquired and transient protein C and/or S deficiency. In coumarin therapy there is a relatively hypercoagulable state at the start of treatment, and most lesions appear between the third and sixth days. We describe a 75-year-old man receiving coumarin therapy (acenocumarol) for 7 years who was given a nonsteroidal anti-inflammatory agent (diclofenac) for a pain in his knee. Two days later, his renal function deteriorated and skin necrosis became evident. Biopsy showed histological changes consistent with coumarin-induced necrosis. Protein C and S levels were normal. We concluded that in our patient acute renal insufficiency aggravated by diclofenac treatment probably associated with an inadvertent withdrawal could have been the precipitating factor for transient protein C deficiency.

Acenocoumarol↗
PubMed1980

Evaluation of a new chromogenic assay for factor VII and its application in patients on oral anticoagulant treatment.

A new chromogenic method has been developed and rigorously standardized for the estimation of factor VII in defibrinated diluted plasma. This method employs a mixture of CaCl2-rabbit brain thromboplastin as activator, diluted factor VII deficient plasma as source of factor X and the chromogenic substrate S2222 for the measurement of factor Xa. The chromogenic method was insensitive to cold- and kaolin-induced activation of factor VII, this in contrast to the one-stage clotting assay. Results obtained with the chromogenic method revealed good correlation with the clotting method in 33 normal subjects, in 42 patients on oral anticoagulant therapy and in five patients with severe congenital factor VII deficiency. A good correlation was also obtained with 'Thrombotest'. Comparative estimation of factor VII and of factor VII cross-reacting material in supernatants of BaCl2 adsorbed plasma of coumarin treated patients revealed that the chromogenic method does not measure decarboxy factor VII. Detailed investigations revealed a half life for decarboxy factor VII of 2.1 +/- 0.6 h.

Acenocoumarol↗
PubMed1981

An evaluation of chromogenic substrates in the control of oral anticoagulant therapy.

A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and four modified amidolytic assays in the assessment of laboratory control of oral anticoagulant administration in short-term and long-term patients. The results were also correlated with the APTT and specific assays for factors VII and X based on established coagulation techniques. The chromogenic substrate assays did not give as close agreement with the BCT as the clotting assays for factors VII and X. A combination of the amidolytic factor II and X results did not improve the correlation. Agreement with the BCT was better in long-term patients with the substrates but there was no obvious advantage between the factor II and X amidolytic methods in this group. The development of a specific amidolytic assay for factor VII should be considered based on the evidence of this study although its reliability for oral anticoagulant control would need to be validated by clinical trial. In the interim, it may be anticipated that thromboplastins showing less sensitivity than BCT to factor VII would give a better correlation with the amidolytic assays.

Acenocoumarol↗