Warfarin
Monitoring
A prerequisite for therapy with Warfarin is the patient's strict adherence to the recommended dose of the drug.
The target INR value for oral anticoagulant therapy to prevent thromboembolic complications in patients with prosthetic heart valves is 2.5-3.0; for other indications - 2.0-3.0.
Patients suffering from alcoholism or dementia may be unable to adhere to the prescribed regimen of Warfarin.
Factors influencing the effect of warfarin
In conditions such as fever, hyperthyroidism, decompensated heart failure, alcoholism with concomitant liver damage, the effect of Warfarin may be enhanced. Increased effects of warfarin, requiring dose reduction, may also occur with weight loss, acute comorbidities, and smoking cessation.
The effect of warfarin may be reduced in hypothyroidism. A decrease in the effect of warfarin, requiring an increase in the dose of the drug, is possible with weight gain, as well as with diarrhea and vomiting.
Patients with a mutation of the gene encoding the CYP2C9 isoenzyme
Patients with a mutation in the gene encoding the CYP2C9 isoenzyme have a longer T1/2 of warfarin. These patients require lower doses of Warfarin, since the risk of bleeding increases when using normal therapeutic doses. If it is necessary to achieve a rapid antithrombotic effect, it is recommended to begin therapy with the administration of heparin; then, for 5-7 days, combination therapy with heparin and warfarin should be carried out until the target INR value is maintained for 2 days (see section "Dosage and Administration").
In the case of rare individual resistance to warfarin (extremely rare), 5-20 loading doses of Warfarin are required to achieve a therapeutic effect.
If the use of Warfarin in such patients is ineffective, other possible reasons should be identified, for example, concomitant use of other drugs (see section “Interaction with other drugs”), inadequate diet, laboratory errors.
Calciphylaxis
Calciphylaxis is a rare syndrome characterized by calcification of blood vessels with skin necrosis and is associated with high mortality. This complication is mainly observed in patients with end-stage renal disease on dialysis, or in patients with known risk factors such as protein C or S deficiency, hyperphosphatemia, hypercalcemia, or hypoalbuminemia. Rare cases of calciphylaxis have been described when taking warfarin in patients who do not have kidney disease. If calciphylaxis develops, appropriate treatment should be initiated and discontinuation of warfarin therapy should be considered.
Thrombophilia
Patients with protein C deficiency are at increased risk of developing skin necrosis when starting warfarin. In patients with protein C deficiency, treatment with warfarin should be initiated without a loading dose, even if heparin is used concomitantly. With protein S deficiency there is also a risk of skin necrosis, so it is advisable for such patients to start warfarin therapy with low doses.
Ischemic stroke
Anticoagulant therapy after ischemic stroke increases the risk of secondary hemorrhage in the necrotic area of the brain. In patients with atrial fibrillation, long-term use of warfarin is beneficial. However, the risk of early recurrence of embolism is low, so temporary cessation of therapy after an ischemic stroke is advisable. Warfarin treatment should be restarted 2 to 14 days after an ischemic stroke, depending on the size of the infarction and blood pressure. In patients with major embolic stroke or uncontrolled hypertension, warfarin should be discontinued for 14 days.
Surgical interventions
Surgeries not associated with the risk of severe bleeding can be performed with an INR < 2.5. If there is a risk of serious bleeding, warfarin should be discontinued 3 days before surgery. If it is necessary to continue anticoagulant therapy (for example, with a high risk of life-threatening thromboembolic complications), the INR should be reduced to <2.5 and heparin therapy should be started (see section "Dosage and Administration").
If surgery is necessary and warfarin cannot be stopped 3 days before surgery, the anticoagulant effect of warfarin should be stopped with low-dose vitamin K supplements.
The timing of resumption of warfarin therapy depends on the risk of postoperative bleeding. In most cases, warfarin can be restarted as soon as the patient can take the tablets by mouth.
Dental procedures
You should not stop taking warfarin before routine dental procedures (for example, before a tooth extraction).
Renal dysfunction
In chronic renal failure or nephrotic syndrome, the concentration of the free fraction of warfarin in the blood plasma increases, which, depending on concomitant diseases, can lead to either an increase or decrease in the effect. In cases of moderate renal failure, the effect of warfarin is enhanced. Caution is recommended when using warfarin in patients with impaired renal function. In all of the above conditions, careful monitoring of INR values should be carried out.
Thyroid diseases
The rate of warfarin metabolism depends on the functional state of the thyroid gland. Therefore, patients with hyper- or hypothyroidism require careful monitoring when initiating warfarin therapy.
Elderly patients
Treatment of elderly patients should be carried out with caution, because the synthesis of blood coagulation factors and hepatic metabolism in such patients is reduced, as a result of which the effect of warfarin may be enhanced.
Blood INR - what is the norm?
How do doctors determine blood's ability to clot?
To do this, a blood test is performed - prothrombin time. Previously, doctors received the result of this analysis in the form of prothrombin index (PTI). Currently, all over the world, the laboratory produces the result of a prothrombin time study in the form of INR - international normalized ratio. All healthy people not receiving warfarin have an INR within one (0.9-1.1). As blood clotting time increases, the INR value increases. For example, to prevent thrombosis in chronic atrial fibrillation, it is necessary to lengthen the coagulation time by 2-3 times. In this case, the INR should be within the therapeutic range of 2.0-3.0. When implanting artificial heart valves, the interval shifts towards greater “thinning” of the blood - from 2.5 to 3.5. Your doctor will tell you what INR goals you need to adhere to.
Use (effect) of warfarin, dose, overdose
The body needs vitamin K to ensure blood clotting.
A person gets vitamin K from food, mainly from vegetables. Vitamin K can also be produced in the human intestine by special intestinal bacteria. From the intestines, vitamin K is absorbed into the blood and goes to the liver, the “laboratory” of the body. In the liver, with the participation of vitamin K, blood clotting factors necessary for the formation of a blood clot (thrombus) are synthesized. These are prothrombin (factor II), factors VII, IX and X. They are called “vitamin K-dependent factors”.
The action of warfarin is to reduce the formation of vitamin K-dependent factors. As long as warfarin is regularly injected into your body, your blood's clotting time is prolonged and this prevents blood clots from forming. There is also a risk of bleeding if the dose of the drug is excessive.
The effect of warfarin on blood clotting varies from person to person.
Therefore, each patient receives his own, individually selected dose. To achieve the desired effect, a minimum of 4-5 days is required, often dose selection lasts up to 2-3 weeks. Prescription of the drug and further monitoring are carried out using the determination of INR. The daily dose of warfarin is taken orally once a day, in the evening (at 18.00-19.00 hours); if necessary, the tablet or part of it can be chewed and washed down with water.
What should you tell your doctor about if you start taking warfarin or are already being treated with it?
About all problems associated with bleeding or its risk (stomach or duodenal ulcers, colon; hemorrhoidal bleeding; heavy menstruation), liver and kidney diseases, high blood pressure and diabetes. Very important if you are planning a pregnancy or are already pregnant. Warfarin has a teratogenic effect. This means that taking it can lead to various deformities in the fetus (if taken in the first trimester of pregnancy) or to intrauterine bleeding (in later stages). Therefore, women whose pregnancy occurred while taking warfarin are recommended to terminate it.
Can warfarin cause kidney damage?
Often, for heart problems, cardiologists prescribe warfarin to patients.
However, the instructions for this medicine say that it can cause kidney damage. What should I do? Anticoagulants are drugs whose effects on the body reduce blood clotting and prevent the formation of blood clots. To avoid or minimize the consequences of thrombotic complications, it is necessary to reduce coagulation, and it is in such cases that anticoagulants are used.
The coagulation system is multicomponent and depends on many components. However, the synthesis of a number of factors is associated with the influence of vitamin K (clotting factor). Warfarin interferes with the action of this vitamin, thereby preventing the formation of blood clots. The patient taking it is constantly balancing between an insufficient dose of the drug, when thrombotic complications may develop, and an excessive decrease in coagulation, when the risk of bleeding increases. Staying safely within an acceptable “corridor” requires careful and regular monitoring of clotting.
The INR (international normalized ratio) indicator, which comprehensively evaluates the body's self-regulation system, is currently chosen as a laboratory parameter controlled throughout the world. The level of clotting may fluctuate even with a constant dose of the drug. The body's susceptibility to the action of anticoagulants depends on many things - nutrition, physical activity, concomitant diseases, the functional state of the liver and kidneys, and the treatment received. Currently, there are anticoagulants that do not require constant monitoring of clotting. However, taking any drugs in this group can cause damage to internal organs, including the kidneys. Therefore, such serious drugs are prescribed according to strict indications, and the doctor will weigh the pros and cons many times.
Kidney damage usually occurs in patients with concomitant damage as a result of diabetes mellitus, heart failure, arterial hypertension or glomerulonephritis. Damage is also possible with an overdose of such drugs. In this case, microhemorrhages occur in the kidneys, ultimately leading to a decrease in their function.
According to statistics, this problem occurs much more often in the first two months after starting to take the drug, in fact, when selecting its stable dose. Therefore, during this period it is very important to monitor your health, take tests on the doctor’s recommendation and make the necessary adjustments if something goes wrong. To avoid adverse consequences, you must strictly follow the doctor’s instructions, follow the dosage and rules of administration. Patients taking anticoagulants should keep a diary, recording the dose of the drug, the INR level and the date of its determination. And, of course, it is important to periodically undergo examination by a nephrologist or urologist.
Yuri KUZMENKOV , doctor, Republican Scientific and Practical Center “Cardiology”.
The doctor's areas of interest are therapy, cardiology, endocrinology.
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