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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.

Background: A drug interaction between capecitabine and coumarin may result in an increased INR and bleeding complications., Case Description: 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., Conclusion: In patients with a compelling indication for treatment with capecitabine and anticoagulant therapy, conversion to low-molecular weight heparin should be considered.

A 63-year-old woman was referred to the dermatology outpatient department with extremely painful ulcers on the right lower leg. Medical history listed hypertension, diabetes mellitus and chronic obstructive pulmonary disease. Intensive analgesia was insufficient. Blood analysis, microbial cultures and venous ultrasound did not reveal a cause. At histopathologic examination of an ulcer, arteriolosclerosis was revealed. The patient was treated for Martorell arteriolosclerotic ulcer with nifedipine, acenocoumarol and split-thickness skin grafts followed by vacuum-assisted closure therapy. Two weeks postoperative, analgesia was discontinued and all ulcers were healed. Nifedipine and acenocoumarol were continued in the outpatient setting to prevent relapses. Patients with long-standing hypertension are particularly prone to cutaneous arteriolosclerosis. Thrombosis of the cutaneous arterioles results in painful ischemic ulcers. This disease probably frequently goes unrecognised.

A 34-year-old patient underwent a knee exarticulation amputation and developed symptoms of pain, redness and swelling of the stump in combination with a feeling of tightness in the chest. These symptoms were first attributed to muscle pain and exertion but further examination revealed deep venous thrombosis (DVT) of the stump and a pulmonary embolism for which he was treated with nadroparine and acenocoumarol. Shortly after treatment he could resume the use of the prosthesis. A DVT in the amputation stump is not frequently encountered, but is a serious complication that can, together with a pulmonary embolism, be life threatening. The literature mentions an incidence ranging from 0-12%. Physical examination is often not conclusive and further examination of the patient with duplex scanning is necessary, with a ventilation-perfusion scan if a pulmonary embolism is suspected. Patients with a lower extremity amputation have a higher risk of developing a DVT because of immobility and increased venous pooling in the residual limb. Symptoms of a red, swollen, warm and painful stump should trigger the physician to suspect a DVT.

A 78-year-old man was treated with coumarin derivatives following myocardial infarction. The international normalised ratio was not increased by using standard loading doses and dose adjustments for acenocoumarol and phenprocoumon. The desired level of anticoagulation was achieved with a high dosage of phenprocoumon (18-21 mg daily). This dose was associated with a phenprocoumon serum concentration that was ten times higher than the normal therapeutic concentration. The serum concentration of vitamin K1 was low. After exclusion of alternative causes, we concluded that the exceptionally high dose of phenprocoumon needed was due to partial resistance to coumarin derivatives. Partial resistance is related to a polymorphism of the gene coding for the enzyme vitamin K epoxide reductase. The patient was successfully treated with chronic high-dose phenprocoumon. Resistance to coumarin derivatives caused by a congenital polymorphism in the vitamin K reductase gene is a rare phenomenon. Resistance is seldom absolute. The desired anticoagulation effect can be achieved with doses that are 10-20 times higher than standard doses. Phenprocoumon is advantageous in this situation because it requires fewer tablets than acenocoumarol. Determination of serum concentrations of acenocoumarol and phenprocoumon can be used to exclude other causes of treatment resistance.

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.

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. 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., Results: 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., Conclusion: The quality of the anticoagulation therapy with coumarin derivatives was good or acceptable.

A 34-year-old woman was admitted on the 10th day post partum complaining of loss of strength in the left arm and headache. The next day she started having seizures. Although the clinical picture suggested sinus thrombosis, initially a CT scan showed no abnormalities. The diagnosis of sinus sagittalis superior thrombosis was finally made by means of arteriography. The patient was treated successfully with anticoagulants and recovered without sequelae.