教育演講3:抗凝劑的最新發展
New Development in anti-coagulant therapy

程 序 表

E3-1
Venous Thromboembolism and Anticoagulant Therapy
Ming-Ching Shen, MD
Changhua Christian Hospital

  Vascular thrombosis is one of the 10 leading causes of death in Taiwan. Both genetic and environmental factors are equally important in the pathogenesis of venous thromboembolism (VET). The annual incidence of objectively confirmed episodes of VTE is 2-3 per 1000 inhabitants in Caucasians, this rate may be lower in our country. The factor V gene mutation (Arg506Gln) named factor V Leiden was found to be most prevalent in venous thrombophilia in Caucasians (20-60%) Case-control studies of patients with venous thrombophilia indicate that protein C deficiency, protein S deficiency and probably AT III deficiency are the major and most important risk factors in venous thrombophilic patients in Taiwan (~50%); screening for natural anticoagulant deficiencies in Tawianese thrombophilic patients is therefore highly recommended. Factor V Leiden mutation or prothrombin 20210 G/A mutation is extremely rare or even absent in Taiwan.
A majority of patients with symptomatic deep vein thrombosis (DVT) also have pulmonary embolism (PE) (symptomatic or asymptomatic), and a majority of those with symptomatic PE also have DVT (symptomatic or asymptomatic). There is much overlap in their pathogenesis, occurrence, prognosis and treatment. These two diseases are indeed a single clinical entity.
In untreated or inadequately treated patients with venous thromboembolism (VTE) mainly including DVT and PE, fatal pulmonary embolism and recurrent venous thrombosis may occur. Anticoagulant therapy is the cornerstone of initial treatment of VTE. The requirement for an initial course of heparin in addition to VKA (Vitamin K antagonist) as compared to starting treatment with VKA therapy alone, was established in a randomized control study that reported a threefold-higher rate of recurrent VTE in patients who received VKA only. In relationship to the duration of initial heparin therapy, the clinical trials reported that intravenous unfractionated heparin (IVUFH) administered for 5 to 7 days is as effective as UFH administered for 10 to 14 days. Therefore the currently recommended approach is to start both heparin and VKA at the time of diagnosis of acute VTE, and to discontinue heparin after 5 days provided the INR is ≧2.0 for at least 24h. The low intensity VKA treatment (target INR, 1.5 to 1.9) was found in clinical studies to be less effective than conventional-intensity therapy (target INR, 2.0 to 3.0) and did not provide a safety advantage. Low molecular weight heparin (LMWH) is at least as effective and safe as IVUFH, LMWH has advantage that it is much easier to administer which makes outpatient treatment feasible and that it has a lower potential for heparin-induced thrombocytopenia, but the disadvantage is that its use should be cautious in patients with renal failure. Long-term treatments has two goals: (1) to complete treatment of acute episode of VTE (first 3 months), and (2) to prevent new episodes of VTE that are not directly related to the acute event (after the first 3 months). The optimal duration of long-term therapy is mostly determined by the risk factor of recurrent VTE after stopping VKA therapy, i.e., a reversible or provoked risk factor vs unproked event (primary factors), DVT confined to the distal vein vs DVT involving the proximal veins, whether the DVT was a first episode of VTE or a second or subsequent episode of VTE (all are secondary factors). The presence of hereditary thrombophilia has not been used as a major factor to guide duration of anticoagulation for VTE because evidence suggests that these factors are not major determinants of the risk of recurrence once the primary and secondary factors have been considered. Because the balance of risks and benefits with catheter-directed thrombolysis (CDT) and systemic fibrinolysis is uncertain, and particularly because of concerns about major bleeding, anticoagulant alone is an acceptable alternate to CDT or systemic fibrinolysis in all patients with acute DVT who do not have impending venous gangrene; similarly, systemic fibrinolysis is only indicated in patients with acute PE associated with hypotension and catheter-assisted thrombus removal (CATR) or surgical embolectomy in patients who have contraindication to or failed thrombolysis or CATR; although such treatments that actively remove thrombus in patients with acute VTE have the potential to achieve lysis of thrombus more rapidly and to reduce the risk of developing post thrombotic symptoms.