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Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.

Patients with mild traumatic brain injury (TBI) who use anticoagulants prior to injury have an increased risk of intracranial complications. Sometimes these complications are delayed, even if the initial CT scan of the head is normal.An 84-year-old woman who was using acenocoumarol presented elsewhere with mild TBI. She had no focal neurological deficit. The initial CT scan revealed no abnormalities and the patient was discharged home. That evening she had diffuse headache. The next day she was found with a reduced level of consciousness and was brought to our hospital. Her INR was 9.0 and a new CT scan showed an acute, left-sided subdural haematoma with a large mass effect.Serious delayed intracranial complications in patients with mild TBI who use anticoagulants are rare. In these patients INR measurement and a CT scan of the head are always indicated. Admission for observation may be considered. On discharge it is necessary to give clear instructions about warning symptoms.

Implanon is a widely used contraceptive. It is a progestagen-containing implant which is inserted subcutaneously on the inside of the upper arm. This procedure is relatively simple.A 26-year-old woman had her contraceptive implant replaced in the outpatient clinic. Because of a mechanical heart valve, she used phenprocoumon, which she did not discontinue prior to the procedure. Three days after the Implanon replacement, the patient presented with persistent blood loss from the insertion site and a large hematoma around the new implant. The placement of a new pressure bandage was not sufficient. The concentration of Hb fell from 8.1 to 5.0 mmol/l with an INR of 3.5; therefore, the patient received a blood transfusion. The use of phenprocoumon was temporarily discontinued and the INR was corrected with prothrombin complex. Good hemostasis was ultimately achieved.Although the replacement of a subcutaneous hormone implant is a relatively simple procedure, a severe complication such as hemorrhaging may occur, particularly when there are risk factors.

Een 69-jarige man werd geopereerd aan een subduraal hematoom, ontstaan tijdens acenocoumarolgebruik. Direct na de operatie kreeg de patiënt sondevoeding; de toediening van acenocoumarol werd later herstart. De benodigde dosering acenocoumarol voor een goede instelling van de INR was tijdens toediening van de sondevoeding 2 maal zo hoog als daarvóór. Dit was niet toe te schrijven aan interacties met geneesmiddelen. Na de overgang van sondevoeding naar orale voeding was de oude dosis acenocoumarol weer voldoende. De hogere benodigde dosering was waarschijnlijk veroorzaakt door een verhoogde binding aan eiwitten in de sondevoeding. Patiënt werd opgenomen in het verpleeghuis. De combinatie acenocoumarol en sondevoeding komt vaak voor bij revaliderende patiënten. Het is belangrijk de INR te controleren bij het starten, het afbouwen en het beëindigen van sondevoeding.

A drug interaction between capecitabine and coumarin may result in an increased INR and bleeding complications.We describe an 80-year-old woman who presented with rectal bleeding and an increased INR due to the concomitant use of acenocoumarol and capecitabine for atrial fibrillation and metastatic cecal cancer, respectively.In patients with a compelling indication for treatment with capecitabine and anticoagulant therapy, conversion to low-molecular weight heparin should be considered.

Recent meta-analysis has demonstrated that self-management in oral anticoagulant therapy results in fewer thromboembolic complications and a decrease in mortality in comparison to conventional treatment, while the number of bleeding complications remains unchanged. We discuss the importance of these findings for the situation in the Netherlands with its specialized anticoagulation clinics and the possible consequences for the introduction of new anticoagulants like dabigatran and rivaroxaban.

Cerebral infarction is the most serious complication of atrial fibrillation. Coumarin derivatives (vitamin K antagonists) counteract systemic thromboembolism and reduce the risk of stroke by more than 60%, but carry a risk of serious bleeding. Antiplatelet therapy and subcutaneous low-molecular-weight heparin are as yet not sufficiently effective and are associated with a bleeding risk similar to vitamin K antagonists. Vitamin K antagonists require intensive INR monitoring to ensure efficacy and safety. In the past decade, oral agents have been developed that directly inhibit the activity of thrombin (factor IIa) and of activated factor X (Xa), which is the first compound in the final common pathway of the coagulation cascade. These do require INR monitoring and have rapid onset and offset of action. The first results with thrombin blockers, such as dabigatran, look promising in efficacy and safety and Xa inhibitors are currently under investigation in atrial fibrillation in 3 large clinical trials. Long-term safety of the new agents in patients with atrial fibrillation has not yet been determined.

VIII, 165 p. ill.

In users of vitamin K-antagonists (VKA), antibiotics can lead to excessive anticoagulation. --It is unclear what the optimal policy is for prevention of an excessive anticoagulant effect during use of antibiotics. --This article describes the increased sensitivity to VKA during use of antibiotics, and also provides a practical recommendation for the correct method for use of antibiotics in combination with VKA treatment. --During use of antibiotics for more than one day, the prothrombin time-'international normalized ratio' (PTT-INR) must be checked both after 3 and after 7 days, and the dose of VKA must be adapted if necessary. --Use of co-trimoxazole for more than one day should, if possible, be avoided.

What treatment is appropriate for a patient who has to undergo an invasive dental procedure if that patient is using medication that influences the blood coagulation system? Should the medication be stopped before the invasive procedure, with the risk of complications involving re-thrombosis? Or should the procedure be carried out without adjusting the medication? What is the risk of bleeding complications? Recent studies appear to indicate that temporarily stopping medication is in many cases unnecessary and can even harm the patient. In recent decades dentists have received a great number of diverse recommendations. In this article recent research in this field is summarized and evaluated. The authors advocate the development of evidence-based clinical guidelines.

A 73-year-old woman with endocarditis was treated with flucloxacillin and rifampicin. She already used the anticoagulant acenocoumarol because of a recent heart valve replacement. After starting rifampicin therapy the sensitivity for the acenocoumarol was reduced. The international normalised ratio (INR) did not exceed 2.0, while values of 2.5-3.5 were required. Increase of the daily dose of acenocoumarol with a factor 6 compared to the dose which resulted in a therapeutic INR before hospitalisation, proved insufficient to obtain a therapeutic INR during long-term rifampicin therapy. 21 days after rifampicin discontinuation the INR finally responded to high coumarin dosages. The breakdown of coumarins in the liver is increased by rifampicin due to induction of several isoenzymes of the cytochrome P450-system. This case illustrates that sensitivity to coumarins can be decreased profoundly even after discontinuation of rifampicin therapy. INR should be monitored closely not only at the start and discontinuation of rifampicin therapy, but also during the weeks after discontinuation of rifampicin treatment.

A 69-year-old man was operated on for a subdural haematoma which had developed during the use of acenocoumarol. Directly after the operation the patient was started on enteral feeding. The acenocoumarol was restarted at a later stage. The dose of acenocoumarol needed for an appropriate level of blood-dilution was twice as high during the period of enteral feeding than it had been preoperatively. After the transition from enteral feeding to oral feeding it was possible to lower the dose of acenocoumarol. The need for a higher dose was probably due to enhanced binding of the proteins in the enteral feeding. The patient was admitted to a nursing home. The combination of acenocoumarol and enteral feeding occurs frequently in patients being rehabilitated. It is important to monitor the blood-dilution when starting and stopping enteral feeding.

Een 69-jarige man werd geopereerd aan een subduraal hematoom, ontstaan tijdens acenocoumarolgebruik. Direct na de operatie kreeg de patiënt sondevoeding; de toediening van acenocoumarol werd later herstart. De benodigde dosering acenocoumarol voor een goede instelling van de INR was tijdens toediening van de sondevoeding 2 maal zo hoog als daarvóór. Dit was niet toe te schrijven aan interacties met geneesmiddelen. Na de overgang van sondevoeding naar orale voeding was de oude dosis acenocoumarol weer voldoende. De hogere benodigde dosering was waarschijnlijk veroorzaakt door een verhoogde binding aan eiwitten in de sondevoeding. Patiënt werd opgenomen in het verpleeghuis. De combinatie acenocoumarol en sondevoeding komt vaak voor bij revaliderende patiënten. Het is belangrijk de INR te controleren bij het starten, het afbouwen en het beëindigen van sondevoeding.

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.Descriptive.Data were drawn from the medical annual reports of 62 of the 63 Thrombosis Services in the Netherlands over the period 1998-2002. In 2002 the Thrombosis Services treated 325,072 patients and performed 4,469,730 INR laboratory tests. The half-yearly figures produced by the Thrombosis Services were calculated as an average percentage per year per thrombosis service and then recalculated as a percentage per year.Seventy-three per cent of the patients were treated for an arterial and 27% for a venous indication. Depending on the required intensity of anticoagulation a mean of 74-78% of the long-term treated patients fell within the therapeutic range and a mean of 6-10% below. The mean number of major bleedings per 100 treatment years was 1.0. A mean of 79% of the patients was treated with acenocoumarol and 21% with phenprocoumon. When acenocoumarol was used, a mean of 72-77% fell within the therapeutic range and in the case of phenprocoumon 79-82%. In the last few years the number of patients had increased due to a growing number of patients treated for atrial fibrillation. The percentages of INR within the therapeutic range were unchanged or showed a slight increase.The quality of the anticoagulation therapy with coumarin derivatives was good or acceptable.

Anticoagulant therapy with vitamin K antagonists is effective in the prevention and treatment of thrombotic disease. The variable effect of these agents and the relatively small therapeutic width necessitate frequent checks on the intensity of the anticoagulation therapy as well as frequent dose-adjustments. Recently, small and reliable portable machines have become available which enable patients themselves, by means of a drop of blood obtained from a finger prick, to measure the intensity of the anticoagulation therapy and if necessary to adjust the treatment dose. In studies within the Netherlands where (selected) patients determined the 'international normalised ratio' (INR) themselves and if necessary adjusted the dose of the anticoagulant medication, the INR was mostly within the therapeutic target area. Furthermore, the independence, the possibility for travelling and the time saved were experienced as positive aspects. Under certain conditions, allowing patients themselves to check the INR and if needs be to adjust the dose of the anticoagulation treatment, may be an acceptable alternative for anticoagulation therapy check-ups performed by the thrombosis service.

Atrial fibrillation is a chronic disorder, which significantly increases the risk of stroke. The risk of stroke largely depends on cardiac failure, age, sex, the presence of hypertension and a history of previousthromboembolism. In low risk patients with atrial fibrillation stroke can effectively be prevented with acetylsalicylic acid (100-200 mg/day). With increasing stroke risk coumarin derivatives are more effective than acetylsalicylic acid and its use has an acceptable bleeding risk. The target international normalized ratio (INR) should be between 2.0 and 3.0.