acenocoumarol and fluindione

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Numerous factors are well documented to affect the response to vitamin K antagonists (VKA), including dietary vitamin K, other drugs, age, pharmacogenetics, and disease states. Body weight is perhaps not as well known as a variable affecting VKA dose. Our aim was to review the literature regarding body weight and VKA dose requirements.. We reviewed the English-language literature via PubMed and Scopus using the search terms VKA, warfarin, acenocoumarol, phenprocoumon, fluindione, AND body weight.. Among 32 studies conducted since the widespread use of the international normalized ratio, 29 found a correlation with body weight or body surface area and VKA dose requirement. Warfarin was evaluated in 27 studies and acenocoumarol, phenprocoumon, or fluindione were assessed in 5 investigations.. Because of varying study methodologies, further study is warranted. Based on current evidence, clinicians should include body weight, along with other established variables when dosing VKA. Most important, obese and morbidly obese patients may require a 30% to 50% increase with the initial dosing of VKA.

Topics: Acenocoumarol; Anticoagulants; Body Weight; Comorbidity; Drug Dosage Calculations; Humans; Obesity; Obesity, Morbid; Phenindione; Phenprocoumon; Vitamin K; Warfarin

To evaluate the therapeutic impact of an education program on patients undergoing oral anticoagulation treatment, within the hospital of Annecy (France).. Groups of 10 patients were invited to participate to two meetings. The education was carried out by two nurses. Thanks to this prospective study, we compare the population before and after education in terms of treatment knowledge and stability.. Within 9 months 88 patients have been included, amongst which 55 have attended the two meetings. The average of correct answers to the knowledge evaluation questionnaire distributed before and after 6 months of education were, respectively, 6.63/12, 10.09/12 (P < 0.0001). Through INR controls within the 6 months preceding (424 controls) and the 6 months following the education (619 controls), we observe: an increase of the total INR average in therapeutic zone, from 45% to 61% (P < 0.0001); a decrease of the difference average per patient between the INR value observed and the one targeted: 0.54 before education, 0.40 after education (P = 0.0016); at last, the average phasing per patient under the therapeutic zone increases after education, from 49% to 65% (P < 0.001).. The education improves objectively the knowledge of patient undergoing AVK. If the size of patient sample is not large enough to prove any consequence on hemorrhagic or thrombotic complications, the education program still improves significantly the treatment stability.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Chi-Square Distribution; Data Interpretation, Statistical; Female; Heart Diseases; Humans; Male; Middle Aged; Patient Education as Topic; Patient Satisfaction; Phenindione; Surveys and Questionnaires; Thromboembolism; Time Factors; Vitamin K

Vitamin K antagonists (VKA) decrease the synthesis of the active forms of four coagulation factors (factors II, VII, IX, X) and three inhibitors (proteins C, S, Z). There are VKA having a short half life (Sintrom, Pindione) and VKA having a long half life (Apegmone, Previscan, Coumadine). The treatment is monitored by the INR which in the majority of the indications must range between two and three. The first INR is usually performed 36 to 72 h after starting the treatment. There are a number of drug interactions. The rate of major bleedings range from 1.1 to 4.9 for 100 patient-year according to the published studies. Since around 600,000 patients are treated by VKA in our country, the absolute number of serious bleeding is high (> or = 17,000 per year). Anticoagulant clinics are structures aimed to instruct the patient and to advise the general practitioner to monitor the treatment, using computer assisted methods. It has been reported that these structures reduce the incidence of bleeding and of thrombotic events by 3 to 4 times.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Drug Interactions; Family Practice; Food; Hemorrhage; Humans; Patient Education as Topic; Phenindione; Thrombosis; Time Factors; Vitamin K; Warfarin

Vitamin K epoxide reductase complex, subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) polymorphisms are taken into account when predicting a safe oral dose of coumarin anticoagulant therapy, but little is known about the effects of genetic predictors on the response to fluindione and acenocoumarol. The aims of this study were to characterize the relationship between fluindione and acenocoumarol concentrations and the international normalized ratio (INR) response, and to identify genetic predictors that are important for dose individualization.. Fluindione concentrations, S- and R-acenocoumarol concentrations, the INR and genotype data from healthy subjects were used to develop a population pharmacokinetic-pharmacodynamic model in Monolix software. Twenty-four White healthy subjects were enrolled in the pharmacogenetic study. The study was an open-label, randomized, two-period cross-over study. The subjects received two doses of an oral anticoagulant: 20 mg of fluindione (period A) or 4 mg of acenocoumarol (period B). The pharmacokinetics and pharmacodynamics were studied from day 2 to day 3.. A two-compartment model with a first-order input model was selected as the base model for the two drugs. The pharmacodynamic response was best described by an indirect action model with S-acenocoumarol concentrations and fluindione concentrations as the only exposure predictors of the INR response. Three covariates (CYP2C9 genotype, VKORC1 genotype and body weight) were identified as important predictors for the pharmacokinetic-pharmacodynamic model of S-acenocoumarol, and four covariates (CYP2C9 genotype, VKORC1 genotype, CYP1A2 phenotype and body weight) were identified as predictors for the pharmacokinetic-pharmacodynamic model of fluindione. Because some previous studies have shown a dose-response relationship between smoking exposure and the CYP1A2 phenotype, it was also noted that smokers have greater CYP1A2 activity.. During initiation of therapy, CYP2C9 and VKORC1 genetic polymorphisms are important predictors of fluindione and acenocoumarol pharmacokinetic-pharmacodynamic responses. Our result suggests that it is important to take the CYP1A2 phenotype into account to improve individualization of fluindione therapy, in addition to genetic factors.

Topics: Acenocoumarol; Adult; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Body Weight; Cross-Over Studies; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; International Normalized Ratio; Male; Mixed Function Oxygenases; Models, Biological; Phenindione; Polymorphism, Genetic; Smoking; Vitamin K Epoxide Reductases

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Tests; Factor X; Female; Humans; Male; Middle Aged; Phenindione; Prothrombin; Reference Values; Vitamin K; Warfarin

Isolated arthralgia, without hemorrhagic side effect, exists and is considered as a very rare adverse drug reaction according to vitamin K antagonists' (VKAs) summary of product characteristics. Up to now, there are no literature reports of isolated, nonhemorrhagic joint complications in patients receiving VKAs. Hence, the objective of this study was to describe cases of VKA-related nonhemorrhagic joint disorders (fluindione, warfarin, and acenocoumarol) reported in the French Pharmacovigilance Database (FPVD). Sixty-one reports (male : female ratio, 1.18; median [interquartile range (IQR)] age: 60 [49-72]) were found. Fluindione, warfarin, and acenocoumarol were respectively suspected in 42, 12, and 7 cases. Arthralgia was reported in 47 cases (77%), arthritis in nine cases (15%), capsulitis in three cases (5%), and bursitis in two cases (3%). Although the joint symptoms mainly concerned the lower limbs, all types of joints were affected. Arthralgia was associated with myalgia in 14 cases and with tendinitis in three cases. The median (IQR) time interval between VKA introduction and arthralgia onset was 26 (10-98) days (range: 1-6935). VKA was withdrawn in 44 cases, and a decrease in the intensity of joint symptoms was observed in 30 cases. In three cases, reintroduction of the same VKA led to the recurrence of symptoms. In view of the large prescription of this drug class worldwide, patients and clinicians (and especially primary care physicians and geriatricians) should be aware of this possible adverse drug reaction when confronted with joint disorders in patients of all ages taking VKAs.

Topics: Acenocoumarol; Aged; Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Joint Diseases; Male; Middle Aged; Pharmacovigilance; Phenindione; Vitamin K; Warfarin

Despite the increasing utilization of direct oral anticoagulant (DOAC) prescriptions, vitamin K antagonists (VKAs) remain the treatment of choice for treating and preventing thromboembolic events. The morbidity and mortality of VKAs are partly due to the difficulty of keeping the patient within the therapeutic range. For patients treated by VKA, time in therapeutic range (TTR) is a quality parameter of treatment, widely used in clinical trials but rarely by prescribers. It is well established that its use correlates with the risk of hemorrhage, thrombosis or mortality. We studied this parameter in a cohort of patients to evaluate the quality of their therapeutic follow-up and tried to identify risk factors for low TTR.. The study was made in collaboration with LaboSud Oc Biologie for a duration of 4 months. It included 3387 patients representing 2,4029 INR. We calculated the patients' TTR. The laboratory transmitted to us the sex and age of each patient and the VKA molecule used, the therapeutic range and the specialty of the prescriber. We then analyzed the odds ratio associated with these different factors.. The mean TTR was 68%, close to the TTR recommended by scientific societies. Patient's sex was the only statistically correlated factor, with a worse equilibrium in females taking VKAs (OR=1.22, 95% CI: 1.06-1.39, P=0.00552). Many factors usually correlated with poor equilibrium under VKA have not been studied due to lack of information.. Given the context of economic restriction and the TTR of our cohort close to the recommended 70%, there would be no benefit in terms of safety to prefer DOAC for the patients involved in this study. Regular monitoring of the individual patient's as well as the cohort's TTR should optimize the management of patients receiving VKAs.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenindione; Risk Factors; Sex Factors; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions.. We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013.. Of 17,410 participants, 6705 switched to a NOAC (switchers) and 10,705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67-82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8.1 months (IQR 3.9-14.0). After a median follow-up of 10.0 months (IQR 9.8-10.0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0.54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0.87; 95% CI 0.67-1.13, p=0.30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0.78, 95% CI 0.54-1.09, p=0.15), switchers from a vitamin K antagonist to rivaroxaban (HR 1.04, 95% CI 0.68-1.58, p=0.86), and non-switchers.. In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed.. None.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Phenindione; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin

Due to improved implementation of guidelines, new scoring approaches to improve risk categorisation, and introduction of novel oral anticoagulants, medical management of patients with atrial fibrillation (AF) is continuously improving. The PREFER in AF registry enrolled 7,243 consecutive patients with ECG-confirmed AF in seven European countries in 2012-2013 (mean age: 71.5 ± 10.7 years; 60.1% males; mean CHA2DS2-VASc score: 3.4). While patient characteristics were generally homogeneous across countries, anticoagulation management showed important differences: the proportion of patients taking vitamin K antagonists (VKAs) varied between 86.0% (in France) and 71.4% (in Italy). Warfarin was used predominantly in the UK and Italy (74.9% and 62.0%, respectively), phenprocoumon in Germany (74.1%), acenocoumarol in Spain (67.3%), and fluindione in France (61.8 %). The major sites for international normalised ratio (INR) measurements were biology laboratories in France, anticoagulation clinics in Italy, Spain, and the UK, and physicians' offices or self-measurement in Germany. Temporary VKA discontinuation and bridging with other anticoagulants was frequent (at least once in the previous 12 months for 22.9% of the patients, on average; ranging from 29.7% in Germany to 14.9% in the UK). Time in therapeutic range (TTR), defined as at least two of the last three available INR values between 2.0-3.0 prior to enrolment, ranged from 70.3% in Spain to 81.4% in Germany. TTR was constantly overestimated by physicians. While the type and half-lives of VKA as well as the mode of INR surveillance differed, overall quality of anticoagulation management by TTR was relatively homogenous in AF patients across countries.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Humans; Male; Middle Aged; Phenindione; Phenprocoumon; Practice Guidelines as Topic; Registries; Vitamin K; Warfarin; Withholding Treatment

To identify, in a case-control study, the risk factors associated with a thrombotic or bleeding event in patients treated with vitamin K antagonists.. We performed a single-centre observational study during a three-month period where we consecutively included patients admitted to the emergency department of a secondary-level hospital and treated with vitamin K antagonists, regardless the reason for admission. Patients admitted for a thrombotic or bleeding event were included as cases and the other patients served as controls. Main thrombotic or bleeding risk factors during vitamin K antagonist therapy were a priori identified in literature and tested in conditional logistic regression.. Two hundred and forty subjects were identified, 40 of which (17%) were admitted for a bleeding event, 19 (8%) for a thrombotic event and 181 (75%) for another reason. Over 85% of patients were treated with fluindione. No risk factor was significantly associated with bleeding or thrombotic event in patients treated with vitamin K antagonist. Patients presenting a thrombotic event were however more likely to have a chronic respiratory disease.. In this study, no risk factor significantly associated with a bleeding or thrombotic event in patients treated with vitamin K antagonist were identified. The occurrence of these events supposes other risk factors, including potential genetic polymorphisms that should be considered in future studies.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Drug Interactions; Emergency Service, Hospital; Female; Genetic Predisposition to Disease; Hemorrhage; Humans; International Normalized Ratio; Male; Phenindione; Respiration Disorders; Risk Factors; Secondary Care Centers; Thrombosis; Vitamin K; Warfarin

To establish the prevalence of anticoagulation (vitamin K antagonists) and antiplatelet agent therapy in patients undergoing vitreoretinal surgery and to compare the outcome of peribulbar anesthesia and vitreoretinal surgery between users and nonusers.. We conducted a retrospective case series study in one academic center. No changes in the treatment regimen were made before surgery. Patients were divided into 3 groups: G1, patients with no anticoagulant or antiplatelet therapy; G2, patients treated with anticoagulants; and G3, patients treated with aspirin, clopidogrel, or both.. Two hundred and six eyes (206 patients) were included. G1, 144 eyes (69.9%) without any anticoagulant or antiplatelet therapy (69.9%); G2, 12 eyes (5.8%) with anticoagulants; and G3, 44 eyes (21.4%) with antiplatelet agents. Six patients (6 eyes) (2.9%) received both anticoagulant and antiplatelet agents. The incidence of overall and mild postoperative hemorrhagic complications was similar between groups, P = 0.075 and P = 0.127, respectively. However, potential sight-threatening hemorrhagic complications were more frequent in patients receiving antiplatelet agents, P < 0.003.. Peribulbar anesthesia for vitreoretinal surgery can probably be performed safely in patients receiving anticoagulants. However, retinal surgeons should be aware that severe bleeding complications are more frequent in patients receiving antiplatelet therapy.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anesthesia, Local; Anticoagulants; Aspirin; Clopidogrel; Conscious Sedation; Electrocardiography; Eye Hemorrhage; Female; Humans; Male; Middle Aged; Orbit; Oximetry; Phenindione; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Retrospective Studies; Ticlopidine; Vitreoretinal Surgery; Warfarin; Young Adult

Vitamin K antagonists (VKAs) are widely used in thromboembolic diseases. We report five cases of necrotic leg ulcers having a particularly severe course and in which withdrawal of VKA treatment alone enabled healing.. Five patients presented with necrotic leg ulcers clinically evocative of necrotic angiodermatitis or vasculitis. Histological features were variable, including inconstantly inflammatory lesions (leukocytoclastic vasculitis) and microthrombosis. None of the patients had laboratory signs of autoimmune disease. Healing occurred in all patients only after withdrawal of VKA therapy (fluindione or acenocoumarol). Associated vascular diseases included superficial venous, distal arterial insufficiency and postphlebitic disease. In three cases, thrombotic factors were observed: hyperhomocysteinaemia or heterozygous Factor V Leiden mutation.. Although the causative role of VKAs is based solely on chronological criteria, this potential side effect deserves publication because of its practical therapeutic consequences. The physiopathological mechanisms accounting for the role of VKAs, including immunoallergic phenomena and, above all, microcirculatory thrombotic processes, are hypothetical and not universally accepted.

Topics: Acenocoumarol; Activated Protein C Resistance; Aged; Aged, 80 and over; Anticoagulants; Diabetic Angiopathies; Factor V; Female; Humans; Hyperhomocysteinemia; Leg Ulcer; Male; Necrosis; Phenindione; Polyarteritis Nodosa; Postoperative Complications; Purpura; Thrombophilia; Varicose Ulcer; Vasculitis, Leukocytoclastic, Cutaneous; Vitamin K

Expert oral anticoagulation management is the key to good outcomes and is performed variably in different health care systems throughout the world. We set out to assess the quality of anticoagulation management in five countries in patients receiving vitamin K antagonists (VKAs) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF), and to compare the anticoagulation management practices in these countries.. This was a retrospective, multi-centre cohort study in the United States, Canada, France, Italy, and Spain. About 1,511 patients were randomly recruited from representative practices (routine medical care (RMC) in the US, Canada, and France; anticoagulation clinics in Italy and Spain) and data pertaining to their oral anticoagulation care were abstracted from their medical records. The predominant anticoagulant in use was warfarin in the US, Canada, and Italy; acenocoumarol in Spain; and fluindione in France. Documentation of care was poor in the US, Canada, and France, countries where RMC was studied. Percent INRs or time-in-therapeutic range was greater in the two anticoagulation clinic samples compared with the RMC samples.. Oral anticoagulation care varies considerably from country to country. Findings suggest that anticoagulation clinic care (ACC) may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate. Condensed Abstract Oral anticoagulation management (routine medical care or anticoagulation clinic care) was retrospectively assessed in 5 countries using a uniform, structured assessment tool. Major management differences were detected, especially between anticoagulation clinic care and routine care. Documentation was often a problem in the latter setting. Less time in therapeutic INR range was noted in routine medical care. Findings suggest that anticoagulation clinic care may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Canada; Cohort Studies; Drug Monitoring; Female; France; Humans; International Normalized Ratio; Italy; Male; Middle Aged; Phenindione; Practice Patterns, Physicians'; Quality of Health Care; Retrospective Studies; Spain; Stroke; Treatment Outcome; United States; Warfarin

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Acenocoumarol; Adverse Drug Reaction Reporting Systems; Anticoagulants; Birth Weight; Female; Fetal Diseases; Gestational Age; Humans; Phenindione; Phenprocoumon; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Prospective Studies; Vitamin K; Warfarin

Between 1997 and 2001, 150 children (one month to 16 years of age) were treated with oral anticoagulants after cardiac surgery (Fontan's operations and congenital heart diseases without valvulopathy: 62%, valvular prosthesis: 20%, arrhythmia: 4.6%, thrombosis: 4%, other: 9.4%). They were first treated by either unfractionated heparin (49%) or nadroparin (51%), then by acenocoumarol (n1 = 114) or fluindione (n2 = 36) until steady state.. The retrospective analysis of data (age, body weight, international normalized ratio, loading and maintenance doses, time to achieve the steady state) led to the building of a dosage nomogram usable in pediatrics.. We demonstrated that the mean maintenance dose depended on age and weight. After three years, that dose (mg/kg) was getting close to adult values; it was higher before three years of age, especially before 12 months (p < 0.01), and very variable from a child to another. The recommended loading dose should be as close as possible to the effective maintenance dose: within that cohort, about 0.14 and 0.05 (acenocoumarol) or 1.1 and 0.40 mg kg-1 day-1 (fluindione), before 12 months and after three years respectively.

Topics: Acenocoumarol; Administration, Oral; Adolescent; Anticoagulants; Cardiovascular Surgical Procedures; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Phenindione; Postoperative Care; Postoperative Complications; Retrospective Studies

Oral anticoagulants and pulse high-dose intravenous methylprednisolone are often administered concomitantly, but no data on potential interactions are available.. To assess possible potentiation of oral anticoagulation by high-dose intravenous methylprednisolone.. Prospective cohort study.. University hospital in Paris, France.. 10 consecutive patients concomitantly receiving methylprednisolone and oral anticoagulants (fluindione and acenocoumarol) and 5 consecutive controls receiving methylprednisolone alone.. Serial determinations of the international normalized ratio (INR) and clotting factors during administration of pulse methylprednisolone. The total plasma fluindione concentration was determined in 3 patients.. The mean INR was 2.75 (range, 2.02 to 3.81) at baseline and increased to 8.04 (range, 5.32 to 20.0) after methylprednisolone administration. Plasma fluindione concentrations and the INR increased after methylprednisolone administration. Methylprednisolone alone did not increase prothrombin time.. The action of oral anticoagulants is potentiated by intravenous high-dose methylprednisolone. The INR should be monitored daily during concomitant administration of these medications.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Blood Coagulation Factors; Drug Synergism; Female; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Methylprednisolone; Middle Aged; Phenindione; Prospective Studies; Protein C; Protein S; Prothrombin Time; Vitamin K