Coumadin Warnings

The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue or organ and, less frequently, necrosis and/or gangrene of skin and other tissues. The risk of hemorrhage is related to the level of intensity and the duration of anticoagulant therapy. Hemorrhage and necrosis have, in some cases, been reported to result in death or permanent disability. Necrosis appears to be associated with local thrombosis and usually appears within a few days of the start of anticoagulant therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast or penis has been reported. Careful diagnosis is required to determine whether necrosis is caused by an underlying disease. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis and heparin therapy may be considered for anticoagulation. Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective. The following information on predisposing conditions. These and other risks associated with anticoagulant therapy must be weighed against the risk of thrombosis or embolization in untreated cases.
It cannot be emphasized too strongly that treatment of each patient is a highly individualized matter. Dosage should be controlled by periodic determinations of prothrombin time (PT) or other suitable coagulation tests. Determinations of whole blood clotting and bleeding times are not effective measures for control of therapy. Heparin prolongs the 1-stage PT. When heparin and Coumadin are administered concomitantly, refer to conversion from heparin therapy for recommendations.
Caution should be observed when Coumadin is administered in any situation or in the presence of any predisposing condition where added risk of hemorrhage or necrosis is present.
Anticoagulation therapy with Coumadin may enhance the release of atheromatous plaque emboli, thereby increasing the risk of complications from systemic cholesterol microembolization, including the "purple toes syndrome." Discontinuation of Coumadin therapy is recommended when such phenomena are observed.
Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms including purple toes syndrome, livedo reticularis, rash, gangrene, abrupt and intense pain in the leg, foot or toes, foot ulcers, myalgia, penile gangrene, abdominal pain, flank or back pain, hematuria, renal insufficiency, hypertension, cerebral ischemia, spinal cord infarction, pancreatitis, symptoms stimulating polyarteritis, or any other sequelae of vascular compromise due to embolic occlusion. The most commonly involved visceral organs are the kidneys followed by the pancreas, spleen and liver. Some cases have progressed to necrosis or death.
Purple toes syndrome is a complication of oral anticoagulation characterized by a dark, purplish or mottled color of the toes, usually occurring between 3-10 weeks, or later, after the initiation of therapy with warfarin or related compounds. Major features of this syndrome include purple color of plantar surfaces and sides of the toes that blanches on moderate pressure and fades with elevation of the legs; pain and tenderness of the toes; waxing and waning of the color over time. While the purple toes syndrome is reported to be reversible, some cases progress to gangrene or necrosis which may require debridement of the affected area or may lead to amputation.
The decision to administer anticoagulants in the following conditions must be based upon clinical judgment in which the risks of anticoagulant therapy are weighed against the benefits.
Use in lactation: Coumadin appears in the milk of nursing mothers in an inactive form. Infants nursed by Coumadin-treated mothers had no change in prothrombin times (PTs). Effects in premature infants have not been evaluated.
Severe to moderate hepatic or renal insufficiency.
Infectious diseases or disturbances of gastrointestinal flora (sprue, antibiotic therapy).
Trauma which may result in internal bleeding.
Surgery or trauma resulting in large exposed raw surfaces.
Indwelling catheters.
Severe to moderate hypertension.
Known or Suspected Deficiency in Protein C: This hereditary or acquired condition, which should be suspected if there is a history of recurrent episodes of thromboembolic disorders in the patient or in the family, has been associated with an increased risk of developing necrosis following warfarin administration. Tissue necrosis may occur in the absence of protein C deficiency. It has been reported that concurrent anticoagulation therapy with heparin for 5-7 days during initiation of therapy with Coumadin may minimize the incidence of this reaction. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis and heparin therapy may be considered for anticoagulation.
Miscellaneous: Polycythemia vera, vasculitis, severe diabetes, severe allergic and anaphylactic disorders.
Patients with congestive heart failure may become more sensitive to Coumadin, thereby requiring more frequent laboratory monitoring and reduced doses of Coumadin.
Concurrent use of anticoagulants with streptokinase or urokinase is not recommended and may be hazardous. (Please note recommendations accompanying these preparations.)