Chapter 111. Venous Thrombosis (Part 5) Withholding further diagnostic testing and anticoagulant treatment in those patients with an unlikely clinical probability and a normal D-dimer level, which constitutes 30–50% of all referred patients, is safe. The remaining patients need to undergo (repeated) compression ultrasonography. An alternative approach is to perform a whole-leg imaging test on the day of referral. The advantage of this approach is that it eliminates the need for a repeat test (and may even obviate the probability assessment and D-dimer testing). The major disadvantage is the detection and likely treatment of a substantial number of isolated calf DVTs that may otherwise have lysed spontaneously. Pulmonary Embolism The signs and symptoms of PE, such as dyspnea, pleuritic chest pain, cough, and hemoptysis, are nonspecific and, as for DVT, insufficiently accurate to confirm or refute the diagnosis of PE. The classic gold standard is pulmonary angiography, which is an invasive method requiring expertise. Hence, very similar to the developments in the diagnosis of DVT, two (complementary) strategies have evolved. The first is the combination of the assessment of clinical probability and the measurement of the D-dimer blood level; the second is the introduction of spiral CT of the chest. The clinical probability can be categorized accurately using the rule developed for suspected PE (Table 111-2). In those with an unlikely probability, a D-dimer test should be performed and, if normal, the disease can be safely ruled out and no anticoagulant therapy is indicated. Depending on the referral pattern of patients, this combination rules out PE in 30–60% of all referred patients. Those with either a likely clinical probability at presentation or an abnormal D-dimer (and unlikely probability) need to undergo an imaging test. At present the most attractive method is the multi-slice spiral CT of the chest. This technique accurately detects pulmonary embolism and, if normal, has been shown to also safely rule out the presence of emboli. Another advantage is the possibility of detecting an alternative disease in the thorax in those in whom PE is excluded, which may provide an explanation for the presenting symptoms. Alternative diagnostic methods in the workup of suspected PE are perfusion- ventilation scintigraphy, ultrasonography of the legs, and pulmonary angiography. Although a normal perfusion scan adequately rules out PE and a high probability perfusion-ventilation scan adequately rules in PE, the major disadvantages are the high proportion of nondiagnostic test results (~50%) and therefore the need for additional (costly) testing, usually with pulmonary angiography. The role of compression ultrasonography of the legs before angiography or spiral CT is limited, as only a small fraction of patients have abnormal results and it further complicates the workup. Deep Vein Thrombosis and Pulmonary Embolism: Treatment The objectives of anticoagulant treatment for DVT and PE are to minimize local extension of the disease in the acute phase and to reduce the risk of recurrence of the disease in the months to years after the initial episode. In addition, in DVT, treatment lowers the risk of the development of the postthrombotic syndrome (swelling, stasis dermatitis, ulceration, venous claudication); in PE, treatment reduces the risk of pulmonary hypertension. A spectrum of treatment options is available. At one end an expectant approach is indicated with no treatment in the setting of minimal disease without a tendency to extend or recur (as is the case, for example, with small calf thrombi). At the other end is the DVT or PE that is massive, either with serious compromise of lung perfusion or with impending gangrene of the leg. In these circumstances, aggressive treatment with either thrombolysis or even surgical intervention may be required. However, the vast majority of patients with DVT or PE require treatment in the middle part of the spectrum, which consists of the use of anticoagulants, usually low-molecular-weight heparin (LMWH) and a vitamin K antagonist (VKA) such as warfarin. Although the treatments of DVT and PE have much in common, they will be discussed separately. Deep Vein Thrombosis The standard treatment for DVT consists of an initial course of LMWH, given once or twice daily via SC injection at a dose of 100 U/kg, followed by a VKA. Unfractionated heparin given IV is an alternative for LMWH but is less and less used these days. LMWH does not require laboratory monitoring and is given in a fixed dose, usually adapted for body weight (categories). An alternative for the initial LMWH therapy is the short-acting synthetic pentasaccharide fondaparinux, which can be given as a once-a-day SC injection of 2.5 mg, without laboratory monitoring. Therapy with LMWH or fondaparinux should be started as soon as the diagnosis is confirmed or during the diagnostic workup if the clinical suspicion is high. VKA (warfarin) can be safely started at the same day and the dose is titrated according to the international normalized ratio (INR) with a target of 2.5 (range 2–3). LMWH therapy should be continued for at least 5 days and can be discontinued if the INR is >2 on two consecutive measurements at least 24 h apart. The recommendations for the duration of VKA treatment for a first episode of DVT are summarized in Table 111-3. For a first DVT secondary to a transient (reversible) risk factor, such as following surgery, after immobilization, or associated with oral contraceptive use, a treatment duration of 3 months with a VKA is recommended. For patients with a first episode of idiopathic DVT, the recommendation is to treat for 6–12 months. At present, evidence is insufficient to treat patients with a first episode of DVT and a documented thrombophilic abnormality differently from those with idiopathic thrombosis. Hence, the recommendation is also 6–12 months of VKA. A duration of 12 months is recommended for patients with a first episode of DVT with documented antiphospholipid antibodies or two or more thrombophilic abnormalities. The decision to continue VKA treatment after 6–12 months requires the balancing of the risks of recurrence and bleeding and should take the patient's preference into account. No strong recommendations exist about the treatment duration for a second episode of DVT, but minimally 12 months are usually given and often treatment is continued longer. Again, this decision requires the balancing of risk and benefit. . Chapter 111. Venous Thrombosis (Part 5) Withholding further diagnostic testing and anticoagulant treatment in those. clinical probability can be categorized accurately using the rule developed for suspected PE (Table 111- 2). In those with an unlikely probability, a D-dimer test should be performed and, if normal,. small fraction of patients have abnormal results and it further complicates the workup. Deep Vein Thrombosis and Pulmonary Embolism: Treatment The objectives of anticoagulant treatment for DVT