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PubMed1979

Cimetidine: interaction with oral anticoagulants in man.

In 6 patients anticoagulated with warfarin, nicoumalone, or phenindione the addition of cimetidine prolonged the prothrombin-time (PT) by a mean of 12.6 s (range 5--23 s). In 7 volunteers taking daily subtherapeutic doses of warfarin the addition of cimetidine increased the PT from 19.4 to 22.9 s and the plasma-warfarin concentration from 0.96 to 1.76 microgram/ml. Cimetidine reduced the single-dose clearance of warfarin and antipyrine. The basis of the interaction between cimetidine and oral anticoagulants is probably inhibition of drug metabolism. Care should be exercised in concomitant therapy.

Acenocoumarol↗
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↗
PubMed2002

[Half-stay and morbidity in a cohort of patients treated with urologic surgery iin the treatment with acenocumarol (Sintrom)].

OBJECTIVE: Our objective was to evaluate the effect about half stay at hospital, in patients treated with Sintrom, which required different urological surgery. PATIENTS AND METHOD: We evaluated 55 patients in treatment with Sintrom which required different urological surgery. We analysed a cohort control group with similar characteristic without anticoagulation therapy. The patients was at hospital 3 days before surgery to realize the change Sintrom/Heparina. We used the haematology service's protocol at the Hospital del Mar. We analysed in each patient the half stay at hospital and the morbidity referred to bleeding complications. The decrease of haemoglobin higher than 2 g/dl was considered significant. RESULTS: About half stay, all patients required more days of hospitalization. The additional morbidity was obvious in the transurethral resection of the prostate and in great not endoscopical surgery. In the rest of surgery the complications referred to bleeding have repercussion about stay at hospital. CONCLUSIONS: We found a significant increased half stay at hospital and the morbidity referred to bleeding complications and its consequence (transfusion, second surgery,...).

Acenocoumarol↗
PubMed1983

Analysis of acenocoumarin and its amino and acetamido metabolites in body fluids by high-performance liquid chromatography.

Acenocoumarin and its acetamido metabolite, after extraction at pH 4.4, were analysed by isocratic reversed-phase high-performance liquid chromatography using aqueous acetonitrile (pH 4.90) as eluent. Warfarin was used as internal standard. The amino metabolite, after back-extraction into 0.5 N HCl, was derivatized by diazotization and heat treatment. The resulting product was analysed by the same reversed-phase system. The sensitivity of the method for acenocoumarin and its amino metabolite was in the range of 20 ng/ml. To achieve this sensitivity for the analysis of the acetamido compound, the acetonitrile content of the eluent had to be lowered. The assay was applied to the analysis of plasma samples of patients under acenocoumarin therapy. The disposition of the amino compound in rats was investigated.

Acenocoumarol↗
PubMed1999

[Antithrombin deficiency and thrombosis in a young child].

BACKGROUND: Thromboses represent a rare event in children and may be due to a deficiency of antithrombin. CASE REPORT: A 10-year-old boy developed thrombosis due to a congenital quantitative deficiency in antithrombin, confirmed by molecular biology. His father was diagnosed with the same deficiency. The child was first treated with heparin and is now on antivitamin K. He is well 26 months after diagnosis. CONCLUSION: When a young patient presents with a thrombotic event, a congenital deficiency in one of the inhibitors of coagulation, one of which is antithrombin, should be looked for and the condition treated as soon as possible.

Acenocoumarol↗
PubMed1980

Impending asphyxia induced by anticoagulant therapy.

A case is presented of spontaneous haemorrhage into the floor of the mouth occurring in a patient receiving anticoagulants. Spread of interstitial haematoma to the submucosal tissues of the pharynx and larynx caused respiratory embarrassment necessitating a tracheostomy. The genesis and management of such a problem are discussed, and it can be appreciated that close co-operation between the otolaryngologist, haematologist and anaesthetist is essential.

Acenocoumarol↗
PubMed1981

Photoaffinity inhibition of rat liver NAD(P)H dehydrogenase by 3-(alpha-acetonyl-p-azidobenzyl)-4-hydroxycoumarin.

NAD(P)H dehydrogenase was purified in four steps from a homogenate of rat liver. The final step was affinity chromatography on Sepharose coupled to 3,3'-(m-hydroxybenzylidene)bis(4-hydroxycoumarin). The purified enzyme was inhibited competitively with respect to NADH by 3-(alpha-acetonyl-p-nitrobenzyl)-4-hydroxycoumarin (acenocoumarin) (Ki = 1.7 microM). The acenocoumarin was converted into an azide which was used to photoaffinity inhibit the enzyme. Following photolysis in the presence of the azide, the enzyme was inactivated in proportion to the concentration of azide present during irradiation. A maximum of 35-40% inhibition could be achieved by a single irradiation at 254 nm for 1.5 min. This inhibition was noncompetitive with respect to NADH. The inactivation was shown to be specific as acenocoumarin afforded complete protection against inactivation, irradiation was required to achieve inactivation, and the enzyme was unaffected by irradiation alone.

Acenocoumarol↗
PubMed1989

Drug binding to alpha 1-acid glycoprotein studied by circular dichroism.

The interactions of acidic and basic drugs with alpha 1-acid glycoprotein (alpha 1-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to alpha 1-AGP. The CD data suggested the presence of a single binding site on the alpha 1-AGP molecule. The induced ellipticities of the acidic drug-alpha 1-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to alpha 1-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with alpha 1-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs.

Acenocoumarol↗
PubMed2003

[Oral anticoagulation with vitamin K antagonists].

Coumarins are broadly employed in clinical practice and should therefore belong to the group of 'well known' drugs. The present review will deal with some concepts of anticoagulant therapy: the role of vitamin K in the synthesis of functional coagulation factors, some clinically relevant pharmacokinetic aspects of coumarins, the management of oral anticoagulant therapy with special emphasis on the laboratory monitoring, and the most frequent complication, bleeding.

Acenocoumarol↗
PubMed1993

Management of the anticoagulated patient for ophthalmic surgery.

The outcome of 50 surgical procedures in 41 patients who were anticoagulated at the time of surgery were reviewed to determine whether anticoagulation was associated with an increase in ophthalmic morbidity. Twenty-seven patients were receiving warfarin and 14 patients nicoumalone. The International Normalised Ratio (INR) was determined immediately prior to surgery and ranged from 1.1 to 4.9. Thirty-nine operations were performed under local anaesthetic and 11 under general anaesthetic. Thirty-three patients had extracapsular cataract extractions with posterior chamber lens implantation. No major haemorrhagic complications were associated with the local anaesthetic or the surgical procedure. Patients on anticoagulation therapy are at risk of life-threatening complications if their anticoagulation is stopped or reduced. This study demonstrates that most ophthalmic surgical procedures can be safely performed whilst the patient is therapeutically anticoagulated.

Acenocoumarol↗