Warfarin Disease Interactions

In general, the use of oral anticoagulants is contraindicated in patients with active bleeding or a hemorrhagic diathesis or other significant risks for bleeding, including hemostatic and/or coagulation defects associated with hemophilia, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, severe hepatic impairment, and myeloproliferative disorders such as leukemia or polycythemia vera. Additionally, oral anticoagulants are usually contraindicated in the presence of any active ulceration of the gastrointestinal, respiratory, or genitourinary tracts; cerebrovascular hemorrhage; aneurysms (cerebral, dissecting aortic); pericarditis and pericardial effusions; bacterial endocarditis; and eclampsia, preeclampsia, or threatened abortion. These patients may be at increased risk for uncontrollable hemorrhage or bleeding complications during therapy with oral anticoagulants. Other potential contraindications include diverticulitis, vasculitis, malnutrition, and vitamin C or vitamin K deficiency. The decision to administer anticoagulants must be based upon clinical judgment in which the risks are weighed against the benefits in each patient.

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Therapy with oral anticoagulants should be administered cautiously in patients with severe diabetes because they may be at increased risk for hemorrhage. The INR should be monitored closely, and patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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In general, the use of oral anticoagulants is contraindicated in patients with malignant or severe, uncontrolled hypertension. These patients may be at increased risk for cerebral hemorrhage. Therapy with oral anticoagulants should be administered cautiously in patients with moderate hypertension.

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Oral anticoagulants (coumarin and indandione derivatives) are primarily metabolized by the liver. Patients with hepatic impairment may have a heightened response to these agents due to decreased clearance of the drugs as well as defective hemostasis associated with impaired synthesis of clotting factors by the liver. Therapy with oral anticoagulants should be administered cautiously in patients with severe or moderate liver disease. The INR should be monitored closely, and patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools

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Tissue necrosis is a rare complication that develops during the initiation of oral anticoagulant therapy due to thrombotic occlusion of venules in the dermis and subcutaneous tissues. Hereditary, familial, or clinical deficiencies of protein C or its cofactor, protein S, may be associated with a hypercoagulable state and an increased risk of the complication. Therapy with oral anticoagulants should be administered cautiously in patients with known or suspected deficiency in protein C-mediated anticoagulant response. Concomitant administration with heparin for the first 5 to 7 days of oral anticoagulant therapy may minimize the risk. If tissue necrosis develops, oral anticoagulant therapy should be discontinued promptly and vitamin K or frozen plasma administered at once. Heparin should then be considered for anticoagulation.

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Patients with edema, hereditary coumarin resistance, hyperlipidemia, hypothyroidism, or nephrotic syndrome may exhibit lower than expected hypoprothrombinemic response to oral anticoagulants. Thus, more frequent laboratory (PT/INR) monitoring and dosage adjustment of anticoagulant may be required based on changes in the patient's condition.

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Patients with a collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma), congestive heart failure (especially decompensated disease), severe or prolonged diarrhea, fever, hyperthyroidism, malabsorption, or steatorrhea may exhibit greater than expected hypoprothrombinemic response to oral anticoagulants. Thus, more frequent laboratory (PT/INR) monitoring and dosage adjustment of anticoagulant may be required based on changes in the patient's condition. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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There is no evidence that hypoprothrombinemic response to oral anticoagulants (coumarin and indandione derivatives) is altered in renal impairment due to decreased plasma protein binding, thus dosage adjustments are generally not necessary. However, patients with renal impairment may demonstrate platelet defects and may be at increased risk for bleeding. Therapy with oral anticoagulants should be administered cautiously in patients with severe or moderate renal dysfunction. The INR should be monitored closely, and patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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