Warfarin thrombosis

The two most widely used coumarins are warfarin (US, Canada, and UK) and phenprocoumon (continental Europe). The long half-life (60 h) of prothrombin means that coumarin cannot achieve therapeutic anticoagulation for at least 5 days following initiation. Thus, for patients with acute thrombosis, oral anticoagulants are usually started only when the patient is receiving a rapidly active agent, usually UFH or LMWH. 

Heparin and warfarin are widely used in the treatment of thrombotic and thromboembolic conditions, such as deep vein thrombosis and pulmonary embolus. Heparin is administered first, because of its prompt onset of action, whereas warfarin takes several days to reach full effect. Their effects are closely monitored by use of appropriate tests of coagulation (see below) because of the risk of producing hemorrhage. 

Convert to oral warfarin pharmacotherapy once the platelet count has returned to baseline values (preferably >100-150 x 109/L). Continue for at least 30 d in patients without evidence of thrombosis (optimal duration is not known but one author recommends at least 2-3 mo of warfarin Blood, 2003). Continue for at least 6 mo in patients with evidence... 

First episode of VTE secondary to a transient (reversible) risk factor Warfarin 3 Recommendation applies to both proximal and calf vein thrombosis... 

In the case of thrombosis-related SVCS, anticoagulation is controversial because there is a lack of survival benefit. However, thrombolytics (e.g., alteplase) and anti coagulation with heparin and warfarin may be beneficial in patients with thrombosis owing to indwelling catheters if it is used within 7 days of onset of symptoms, although catheter removal maybe required. 

Anticoagulant drugs include heparin and warfarin (Coumadin ) —agents used to prevent deep vein thrombosis. They are also used to prevent formation of emboli due to atrial fibrillation, valvular heart disease, and other cardiac disorders. Heparin, which is not absorbed by the gastrointestinal tract, is available only by injection its effect is immediate. 

Warfarin is a K-vitamin antagonist used to decrease blood clothing and reduce risk of thrombosis. Warfarin has a narrow therapeutic interval. Food with a high K-vitamin content such as green leaf vegetables, strawberries, liver etcetera counteract the Warfarin effects. 

Medical history venous thrombosis Medication record warfarin 7.5 mg daily... 

Animals fed spoiled sweet clover were prone to fatal haemorrhages. The canse was traced to the presence of dicoumarol. This compound interferes with the effects of vitamin K in blood coagulation, the blood loses its ability to clot, and minor injnries can lead to severe internal bleeding. Synthetic dicoumarol has been nsed as an oral blood anticoagnlant in the treatment of thrombosis, where the risk of blood clots becomes life threatening. It has since been snperseded by warfarin, a synthetic development based on the natnral prodnct. 

Heparin-induced thrombocytopenia Warfarin should be used with caution in patients with heparin-induced thrombocytopenia and deep venous thrombosis. 

A 75 year old man was examined on a routine visit 1 month after discharge from hospital for a myocardial infarction. No communication had been received from the hospital on the patients stay and management. The patient seemed well but had a few purpuric 1 cm round lesions on his hands. The doctor assessed these as senile purpura. He then noticed that there were several more on both legs. He felt that these were both more extensive than with senile purpura and in an unusual site. He questioned the patient about injury, which the patient denied. On ringing the hospital it was learned that the patient had had a deep venous thrombosis and was treated with warfarin. They apologised for not informing the doctor earlier ... 

Harper P, Monahan K, Baker B. Warfarin induction at 5 mg daily is safe with a low risk of anticoagulant overdose results of an audit of patients with deep vein thrombosis commencing warfarin. Intern Med J 2005 35 717-20. 

A 23-year old pregnant woman who has been administered IV heparin for treatment of deep vein thrombosis has developed heparin-induced thrombocytopenia. Altering therapy by removing heparin and adding warfarin is not a viable option, because warfarin can cross the placenta and exert an anticoagulant effect in the fetus. Suggest a treatment approach. 

Answer Treatment of thrombosis can be initiated during pregnancy with infusion of argatroban, a direct inhibitor of thrombin. This drug does not cross the placenta and has not been reported to produce effects in the fetus. Argatroban is discontinued at the time of delivery, and thrombosis is then managed postpartum for 2 months with warfarin. 

Vitamin K antagonists, such as dicoumarol (8.61, a natural product) and warfarin (8.62), are used as anticoagulants in human therapy (thrombosis, atherosclerosis) and as rat poisons that lead to internal bleeding and death in rodents. Heparin, a polysaccharide consisting of 2-0-sulfonated glucuronic acid and 2-N,6-0-disulfonated glucosamine, is also a widely used anticoagulant, but its effect is connected not with Vitamin K but with enzyme inhibition. 

Ginseng product (42) Male/58 Coronary heart disease, diabetes Warfarin Several (but no details mentioned) Decreased INR to 1.4, thrombosis Not known... 

Rosado MF. Thrombosis of a prosthetic aortic valve disclosing a hazardous interaction between warfarin and a commercial ginseng product. Cardiology 2003 99 111. 

Decreased INR associated with the use of P. ginseng was reported in a 47-year-old patient who had been stabilized on warfarin (25). Another case of inadequate anticoagulation with ginseng product resulting in thrombosis on a mechanical aortic valve prosthesis was reported in a 58-year-old patient (26). Additional details of these two case reports are discussed in Chapter 5. 

Morbidity and mortality in HIT are related to thrombotic events. Venous thrombosis occurs most commonly, but occlusion of peripheral or central arteries is not infrequent. If an indwelling catheter is present, the risk of thrombosis is increased in that extremity. Skin necrosis has been described, particularly in individuals treated with warfarin in the absence of a direct thrombin inhibitor, presumably due to acute depletion of the vitamin -dependent anticoagulant protein C occurring in the presence of high levels of procoagulant proteins and an active hypercoagulable state. 

Argatroban is a small molecule thrombin inhibitor that is FDA-approved for use in patients with HIT with or without thrombosis and coronary angioplasty in patients with HIT. It, too, has a short half-life, is given by continuous intravenous infusion, and is monitored by aPTT. Its clearance is not affected by renal disease but is dependent on liver function dose reduction is required in patients with liver disease. Patients on argatroban will demonstrate elevated INRs, rendering the transition to warfarin difficult (ie, the INR will reflect contributions from both warfarin and argatroban). (INR is discussed in detail in the discussion of warfarin administration.) A nomogram is supplied by the manufacturer to assist in this transition. 

Primary prevention of venous thrombosis reduces the incidence of and mortality rate from pulmonary emboli. Heparin and warfarin may be used to prevent venous thrombosis. Subcutaneous administration of low-dose unfractionated heparin, low-molecular-weight heparin, or fondaparinux provides effective prophylaxis. Warfarin is also effective but requires laboratory monitoring of the prothrombin time. 

Treatment for established venous thrombosis is initiated with unfractionated or low-molecular-weight heparin for the first 5-7 days, with an overlap with warfarin. Once therapeutic effects of warfarin have been established, therapy with warfarin is continued for a minimum of 3-6 months. Patients with recurrent disease or identifiable, nonreversible risk factors may be treated indefinitely. Small thrombi confined to the calf veins may be managed without anticoagulants if there is documentation over time that the thrombus is not extending. 

Warfarin (Fig. 10-22c) is a synthetic compound that inhibits the formation of active prothrombin. It is particularly poisonous to rats, causing death by internal bleeding. Ironically, this potent rodenticide is also an invaluable anticoagulant drug for treating humans at risk for excessive blood clotting, such as surgical patients and those with coronary thrombosis. ... 

The bis(hydroxycoumarin) derivative dicoumarol (45), which was first identified as the causative agent of sweet clover disease in cattle, is used as an anticoagulant in the treatment of thrombosis. Similar compounds with other linking groups have been used, and warfarin (46), which was first introduced as a rodenticide, is also of value. The hydroxycoumarins interfere with the function of vitamin K in the synthesis of prothrombin and other blood... 

Organic anticoagulants are used in vivo in the treatment of numerons conditions where blood coagulation can be dangerous, as in cerebral thrombosis and coronary heart disease, among others which will be described later. The main anticoagulants used are heparin and coumarin compounds, such as warfarin. 

In present times, because of early mobilization and shorter stays in hospital, venous thrombosis in the legs and resulting pulmonary embolism has declined to a large degree. In persons with acute myocardial infarction, prophylactic low-dose heparin has reduced the incidence of venous thrombosis in the legs. It is considered as a reasonable alternative to warfarin in selected patients. Preventive anlicoagulalion may be indicated in some cases to prevent strokes due to left ventricular mitral thrombi embolizing in tire brain. 

Editor s Note Tile following references have been selected to provide the interested reader wiLli more detail on the pharmacologic complexities of anticoagulants Tile article by Edwin W. Salzman, M.D. is a short, but excellent summary of the status of antithrombotic drugs as of early 1992. The article on heparin by Jack Hirsh, MD. and the article on warfarin by the same author proride important fundamental background information on the pharmacokinetics and pharmacodynamics of the most widely used anticoagulant drugs, Brandjes. D.P.M., et al. Acenocoumarol and Heparin Compared with Acenocoumarol. Alone in the Initial Treatment of Proximal-Vein Thrombosis," N. Eng. J. Med., 1485 (November 19, 1992). 

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