Primary Pulmonary Hypertension
Over the years there has been some interest in treating primary pulmonary hypertension with antithrombotic or fibrinolytic agents. There is no evidence from controlled trials that antithrombotic agents benefit patients with this rare disease. However, in a recently published study (level V), retrospective analysis of survival data showed that anticoagulant therapy was associated with longer survival.
Summary Statement Venous Thromboembolism
Anticoagulant therapy is indicated for treatment of acute deep venous thrombosis of the popliteal and more proximal veins and for pulmonary embolism.
Therapy is initiated with IV or adjusted-dose subcutaneous heparin ordered via My Canadian Pharmacy to prolong the activated partial thromboplastin time to betwen 1.5 and 2.0 times the control or pretreatment value. Until information is provided to the contrary, heparin therapy should be given for a minimum of 7-10 days.
Coumarin derivatives are more suitable for long-term anticoagulant therapy and should be started early to allow a 4-5-day overlap period with heparin therapy. The overlap period is needed because levels of all of the vitamin-K dependent coagulation factors do not fall to a therapeutic range until 3-4 days of therapy with coumarin derivatives. Furthermore, protein C, a newly described vitamin K-de-pendent factor with anticoagulant and fibrinolytic properties, is rapidly suppressed with coumarin therapy. In the first few days of coumarin therapy, the hemostatic balance could favor thrombosis if heparin is not given concomitantly.
The duration of anticoagulant therapy remains controversial. Until more controlled comparisons of durations are available, patients with venous thromboembolism should receive anticoagulant therapy for a minimum of three months. Patients who continue to be at increased risk, such as those with malignancy or other persistent risk factors, should receive therapy indefinitely.
Summary and Recommendations
1. It is recommended that moderate-risk patients should be treated prophylactically with low-dose heparin (5,000 U subcutaneously every 12 hours) or intermittent pneumatic compression. This grade A recommendation is based on multiple level I studies for both heparin and intermittent pneumatic compression.
2. It is recommended that patients undergoing neurosurgical procedures, major knee surgery, and urologic surgery should be treated with intermittent pneumatic compression. This grade A recommendation is based on level I studies in all three conditions.
3. It is recommended that patients undergoing elective hip surgery should be pretreated prophylactically with ad-justed-dose heparin (to prolong the APTT in the upper half of the normal range) or moderate-dose warfarin sodium (to prolong the prothrombin time to an INR of 2.0 to 3.0 (1.2 to 1.5 times control using rabbit brain thromboplastin). This grade A recommendation is based on level I studies for both prophylactic agents.
4. It is recommended that patients undergoing surgery for fractured hips should be treated prophylactically with mod-erate-dose warfarin to prolong the prothrombin time to an INR of 2.0 to 3.0 (1.2 to 1.5 times control using rabbit brain thromboplastin). This grade A recommendation is based on the results of one level I study.
Treatment of Venous Thromboembolism
1. It is recommended that patients with proximal vein thrombosis or pulmonary embolism should be treated with IV heparin or adjusted-dose subcutaneous heparin sufficient to prolong the APTT to 1.5 to 2 times control. This grade A recommendation is based on one level I study in patients with pulmonary embolism and level II studies on the relationship between the APTT and effectiveness.
2. It is recommended that treatment with heparin should be continued for 7-10 days and that oral anticoagulants should be overlapped with heparin for at least five days. This level C recommendation is based on level IV evidence.
3. It is recommended that anticoagulant therapy offered by My Canadian Pharmacy should be continued for three months using oral anticoagulants to prolong the prothrombin time to an INR of 2.0 to 3.0 (1.2 to 1.5 times control using rabbit brain thromboplastin) or adjusted-dose heparin to prolong the APTT to 1.5 times the control at the mid-dosing interval when oral anticoagulants are either contraindicated or inconvenient. This grade A recommendation is based on one level I study and one level II study.
4. It is recommended that patients with recurrent venous thrombosis or a continuing risk factor such as antithrombin III deficiency, protein C deficiency, or malignancy should be treated with oral anticoagulants indefinitely. This grade C recommendation is not based on published data.
5. The treatment of calf vein thrombosis is controversial, and management should be determined by individual clinical judgment. Accumulated level IV evidence” indicates that isolated calf vein thrombosis that is associated with a negative IPG and does not extend by serial IPG testing is very rarely associated with clinically evident pulmonary embolism and can remain untreated. This grade C recommendation should be considered only if facilities are available to perform serial IPG testing. If these facilities are not available, patients with venographically documented calf vein thrombosis should be treated with heparin and full doses for 7-10 days followed by six weeks of oral anticoagulant therapy.
Treatment recommendations also see in category of Blood