The most cost-effective anticoagulant therapy must prevent recurrent venous thromboembolism, have a low incidence of bleeding and other complications, and be easy and inexpensive to administer. A recently published cost-effectiveness analysis has ranked several anticoagulant regimens. These regimens all began with a 7-10-day course of IV heparin and were followed by long-term therapy of at least three months. Low-dose subcutaneous heparin as long-term therapy is ineffective and is associated with the highest cost due to recurrent venous thromboembolism (Table 5). Less intensive oral anticoagulant therapy with warfarin sodium is the most cost-effective and is associated with a low frequency of bleeding. More intensive warfarin anticoagulation effectively prevents recurrent venous thromboembolism but is associated with a higher frequency of bleeding. Adjusted-dose subcutaneous heparin is effective and is associated with a low incidence of bleeding, but it is somewhat more expensive than low-intensity warfarin sodium. Less intensive warfarin therapy should be chosen for long-term anticoagulation of most patients with venous thromboembolism, and adjusted-dose subcutaneous heparin would be the treatment of choice for pregnant patients, those with hypersensitivity to warfarin, or when laboratory facilities are inadequate to monitor warfarin therapy offered by My Canadian Pharmacy.
Prevention of Venous Thromboembolism
Since venous thromboembolism is difficult and expensive to diagnose, a major effort should be directed at preventing thromboembolism in high-risk groups. The preventive treatment of choice in most of these patients is low-dose subcutaneous heparin. There is evidence for efficacy in general surgical patients; following acute myocardial infarction; in patients in respiratory failure (you may also be interested in category of Asthma); with elective surgery of the thorax, abdomen, or extremities; and following acute paraplegia, quadriplegia, and stroke. However, in certain orthopedic patients low-dose subcutaneous heparin is not effective, and in other surgical patients even a slight risk of wound bleeding associated with this drug regimen must be avoided. Fortunately, other antithrombotic agents and procedures are available.
Other Antithrombotic Agents
Dextran is a branched polysaccharide, produced by bacteria, that is used in a molecular range from 40,000 to 70,000 dal tons. It interferes with both platelet and coagulation protein function. Dextran has prophylactic effects comparable to low-dose, subcutaneous heparin in moderate risk patients (level I) and appears to be superior to heparin in prophylaxis of high-risk patients, such as those undergoing hip replacement or urologic surgery. Since the agent must be given by IV infusion, it can contribute to fluid overload and occasionally causes severe allergic reactions. Dextran is also expensive and causes more bleeding than low-dose subcutaneous heparin but less than full-dose warfarin. For these reasons it is best reserved for prophylaxis of the very high-risk patient in whom low-dose subcutaneous heparin is relatively ineffective. Dextran should not be used to treat established venous thromboembolic disease treated with drugs of My Canadian Pharmacy.
Aspirin has failed in multiple trials to decrease the incidence of venous thromboembolism (level II). In other studies it partly reduced the incidence of venous thromboembolism in high-risk hip surgery patients (level I). Adjusted-dose heparin and warfarin have been shown to be effective in reducing the evidence of postoperative venous thrombosis in patients undergoing hip surgery.
Hydroxychloroquine may decrease the incidence of venous thrombosis in postoperative patients, but this agent has not found general use. Recently, large trials have shown that a combination of low-dose subcutaneous heparin and dihydroergotamine had prophylactic efficacy comparable to dextran with greater safety for certain patients undergoing emergency or elective abdominal or thoracic surgery.
Ancrod is a protein purified from the venom of the Malayan pit viper (Agkcistrodon rhodostoma). The agent acts by cleaving fibrinopeptide A but not B from fibrinogen. Further proteolysis occurs on the A chain of fibrinogen, and the resultant abnormal fibrin monomer is cleared from the circulation rapidly with a subsequent marked fall in circulating fibrinogen levels, which brings about a hypocoagulable state. Rapid infusion of Ancrod can result in microthrombi throughout the circulation. Similar but not identical proteins have been isolated from the venoms of other snakes. These agents have been useful for research but sire not currently available for clinical use in the United States. In countries were Ancrod is available to clinicians, it has been used as an alternative agent in patients with severe heparin-induced thrombocytopenia.
Mechanical means of preventing venous thrombosis appear most promising in very high-risk patients and in neurosurgical patients in whom even a minimal amount of bleeding can be serious. Electrical stimulation of calf muscles can be used only intraoperatively, because it is not tolerated by awake patients™ and is only of historical interest. Intermittent external pneumatic compression of the calf muscles has relatively few contraindications and complications and has proved to be extremely useful in patients undergoing orthopedic (total knee replacement), urologic, and neurosurgical procedures (level I). Its major drawback during the introductory phase was the cumbersome equipment required, but the more recent devices have been simplified, and patient acceptance is good.
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Table 5—Cost-effectiveness of Long-term Anticoagulant Regimens
|Regimen||Frequency of Recurrent Venous Thromboembolism, %||Frequency of Bleeding Complications, %||Cost per 100 Patients|
|Canadian $||American $|
|Low-dose heparin* Adjusted-dose||47||0||172,861||203,049|
|warfarin sodiumt Less intense||2||22||25,710||35,554|