[Resistance to coumarin derivatives due to mutated vitamin-K enzyme].

In 2006 a case report was published in this journal describing partial acenocoumarol- and phenprocoumon resistance in a 78-year-old man. A mutation in the VKORC1 gene was suggested to be the cause of the observed resistance. We examined the patient and found a new and hitherto unknown mutation in the VKORC1 gene which may well explain the observed resistance.

Variability of INR in patients on stable long-term treatment with phenprocoumon and acenocoumarol and implications for analytical quality requirements.

Within each patient treated with vitamin K antagonist (VKA), variation of the international normalised ratio (INR) occurs over the treatment period. The purpose of the present study was to assess INR variation in selected patients on long-term treatment in whom the dose of VKA was not changed. This type of variation is considered as "biological variation" which is caused by many factors but not VKA dose changes or other medication.

Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin.

Treatment with coumarin derivatives is highly individualised due to high intra- and inter-individual variation in dose response and risks of severe bleeding or thromboembolic complications. Treatment focuses on reaching and maintaining a stable target international normalised ratio (INR). However, unexpected INRs that are not explained by noncompliance or vitamin K intake may occur.

Improvement in the regulation of the vitamin K antagonist acenocoumarol after a standard initial dose regimen: prospective validation of a prescription model.

Background: In a retrospective study we have developed a model which determines the dose of acenocoumarol based on the age of the patient and on the first INR obtained after a standard initial loading dose. The group of patients of this study was used as the control group of the present study.

Aim: The aim of this study was to prospectively validate the model and to assess whether the use of this model improves the quality of the treatment in the 0-2 months study period.

Invasive procedures in the outpatient setting: managing the short-acting acenocoumarol and the long-acting phenprocoumon.

Treatment with vitamin K antagonists (VKAs) has to be interrupted when invasive procedures are planned. We compared various methods of interruption in patients on acenocoumarol or phenprocoumon in a prospective study. In patients on acenocoumarol (n = 141), 99 stopped three days before the intervention and 42 stopped two days before.

The influence on INRs and coagulation factors of the time span between blood sample collection and intake of phenprocoumon or acenocoumarol: consequences for the assessment of the dose.

Managing treatment with vitamin K antagonists, the prothrombin time (PT), expressed as international normalized ratio (INR), may not represent the INR during the entire 24 hour (h) period, and this variation may be different between long-acting phenprocoumon and short-acting acenocoumarol. For both drugs we investigated the variation in 24 h of the PT/INR, the consequencesfor the assessment of the doses and which vitamin K-dependent factor causes the daily variation. Patients on self-management took their medication at 6 p.

Coumarin anticoagulants and co-trimoxazole: avoid the combination rather than manage the interaction.

Objective: The objective of our study was to examine the management of the interaction between acenocoumarol or phenprocoumon and several antibiotics by anticoagulation clinics and to compare the consequences of this interaction on users of co-trimoxazole with those for users of other antibiotics.

Methods: A follow-up study was conducted at four anticoagulation clinics in The Netherlands. Data on measurements of the International Normalised Ratio (INR), application of a preventive dose reduction (PDR) of the coumarin anticoagulant, fever and time within or outside the therapeutic INR range were collected.

Discrepancies between medication records of anticoagulation clinics and pharmacy records.

Purpose: To determine whether there were discrepancies between with coumarin anticoagulants interacting medications recorded in medical files of anticoagulation clinics (AC-records) and computerized records of community pharmacies (pharmacy records).

Methods: A descriptive study was conducted at two Dutch anticoagulation clinics (AC's). Records of with coumarin anticoagulants interacting drugs at the AC's were compared with the pharmacy records.

VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation.

Objective: Our objective was to assess the effects of VKORC1 and CYP2C9 genotypes on severe overanticoagulation and time to achieve stability and their contributions to dose requirement during the initial phase of acenocoumarol treatment.

Methods: A prospective follow-up study was conducted at 2 anticoagulation clinics in The Netherlands. We assessed the CYP2C9 genotype (CYP2C9*2 and CYP2C9*3 polymorphisms) and the VKORC1 C1173T genotype of the subjects and collected data on international normalized ratio, dose, comedication, and comorbidity.

Preanalytical variables and off-site blood collection: influences on the results of the prothrombin time/international normalized ratio test and implications for monitoring of oral anticoagulant therapy.

Background: The quality of oral anticoagulant therapy management with coumarin derivatives requires reliable results for the prothrombin time/International Normalized Ratio (PT/INR). We assessed the effect on PT/INR of preanalytical variables, including ones related to off-site blood collection and transportation to a laboratory.

Methods: Four laboratories with different combinations of blood collection systems, thromboplastin reagents, and coagulation meters participated.

[Extent and quality of anti-coagulation treatment with coumarin derivatives by the Dutch Thrombosis Services].

Objective: To obtain an impression of the extent and quality of the anti-coagulation treatment with coumarin derivatives carried out by the Thrombosis Services in the Netherlands.

Design: Descriptive.

Method: Data were drawn from the medical annual reports of 62 of the 63 Thrombosis Services in the Netherlands over the period 1998-2002.

Acenocoumarol stabilization is delayed in CYP2C93 carriers.

Objective: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial 3 to 6 months of acenocoumarol treatment.

Methods: A prospective follow-up study was performed at 2 anticoagulation clinics in the Netherlands. Included subjects started with a standard dose regimen as follows: 6 mg on the first day, 4 mg on the second day, and 2 mg on the third day.

Age and first INR after initiation of oral anticoagulant therapy with acenocoumarol predict the maintenance dosage.

Background: This retrospective study was performed to develop a model to predict the maintenance dosage of the vitamin K antagonist acenocoumarol, based upon the first INR after a standard initial dosage regimen.

Material And Methods: Outpatients with atrial fibrillation ( n = 284) and initial regimens of 6-4 or 6-4-2 mg acenocoumarol on day 1, 2 and 3, respectively, were included. The maintenance dosage of the period 3-6 months after the installment was related to the first INR after those standard initial dosage regimens, because in that period the INR was 76% of the time within the therapeutic range and therefore considered suitable to perform the analysis.