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CHAPTER 133 traditional standard anticoagulant therapy. Rivaroxaban and apixaban can be

VENOUS THROMBOSIS used as a single drug approach. Dabigatran and edoxaban are preceded by at
least 5 days of heparin or low-molecular-weight heparin treatment. The direct
oral anticoagulants are preferred over the vitamin K antagonists in most new
patients commencing anticoagulant therapy. In cancer patients with venous
Gary E. Raskob, Russell D. Hull, and Harry R. Buller thromboembolism, treatment with low-molecular-weight heparin for at least
6 months is the recommended approach. Thrombolytic therapy is indicated for
patients with pulmonary embolism who present with hypotension or shock,
SUMMARY and in selected patients who have impaired right ventricular function who are
at high risk of hemodynamic collapse. Insertion of a vena cava filter is indicated
Venous thromboembolism, consisting of deep vein thrombosis and/or pul- for patients who have an absolute contraindication to anticoagulant therapy
monary embolism, is a common disorder with an estimated 900,000 patients or who have recurrent venous thromboembolism despite adequate antico-
each year in the United States and more than 1 million each year in the Euro- agulant treatment. Anticoagulant treatment should be continued for at least
pean Union. Approximately one-third of these cases are fatal pulmonary 3 months in all patients, and 3 months is a sufficient duration for patients with
emboli, and the remaining two-thirds are nonfatal episodes of symptomatic first episode of venous thromboembolism secondary to a reversible risk factor.
deep vein thrombosis or pulmonary embolism. The majority of fatal events Indefinite anticoagulant therapy should be considered for patients with unpro-
occur as sudden death, underscoring the importance of prevention as the crit- voked (idiopathic) venous thromboembolism, and those with recurrent venous
ical strategy for reducing death from pulmonary embolism. Of the nonfatal thromboembolism.
cases, approximately 60 percent present clinically as deep vein thrombosis
and 40 percent present as pulmonary embolism. Most clinically important
pulmonary emboli arise from proximal deep vein thrombosis of the leg (pop- DEFINITION AND EPIDEMIOLOGY
liteal, femoral, or iliac vein thrombosis). Upper-extremity deep vein throm-
bosis also may lead to clinically important pulmonary embolism. The clinical Venous thrombosis commonly develops in the deep veins of the leg or
features of deep vein thrombosis and pulmonary embolism are nonspecific. the arm or in the superficial veins of these extremities. Venous throm-
Objective diagnostic testing is required to confirm or exclude the presence bosis of superficial veins is a relatively benign disorder unless exten-
of venous thromboembolism. A validated assay for plasma D-dimer, if avail- sion into the deep venous system occurs. Confusingly, one of the major
deep veins in the leg is called the superficial femoral vein. Thrombosis
able, provides a simple, rapid, and cost-effective first-line exclusion test in involving the deep veins of the leg is divided into two prognostic catego-
patients with low, unlikely, or intermediate clinical probability. Compression ries: (1) calf vein thrombosis, in which thrombi remain confined to the
ultrasonography is highly sensitive and specific for clinically important deep deep calf veins, and (2) proximal vein thrombosis, in which thrombosis
vein thrombosis and is the primary imaging test for symptomatic patients. involves the popliteal, femoral, or iliac veins. 1
Compression ultrasonography of the proximal veins performed at presenta- Pulmonary emboli originate from thrombi in the deep veins of the
tion, and if normal, repeated once 5 to 7 days later, can safely exclude clini- leg in 90 percent or more of patients. Other less common sources of
cally important deep vein thrombosis. In centers with the expertise, a single pulmonary embolism (PE) include the deep pelvic veins, renal veins,
comprehensive evaluation of the proximal and calf veins with duplex ultra- inferior vena cava, right side of the heart, and axillary veins. Most
sonography is sufficient. In patients with suspected pulmonary embolism, clinically important pulmonary emboli arise from proximal deep vein
computed tomographic angiography, with or without additional testing using thrombosis (DVT) of the leg. Upper-extremity DVT also may lead to
2
computed tomographic venography or compression ultrasonography of the important PE. DVT and/or PE are referred to collectively as venous
thromboembolism (VTE).
legs, provides a definitive basis to give or withhold antithrombotic therapy in VTE is a common disorder. The estimated annual incidence of
3
90 percent of patients. Anticoagulant therapy is the preferred treatment for clinically evident VTE ranges between 0.75 and 2.7 per 1000 population
most patients with acute venous thromboembolism. Initial treatment with based on studies done in North America, Western Europe, Australia,
heparin or low-molecular-weight heparin, followed by long-term treatment and Argentina. The literature indicates a strong and consistent associ-
3
with an oral vitamin K antagonist such as warfarin, is highly effective for pre- ation of increasing incidence of VTE with increasing age. The annual
venting recurrent venous thromboembolism, and has been the traditional incidence increased to between 2 and 7 per 1000 population among
standard care. More recently, the direct oral anticoagulants including the those 70 years of age, and to between 3 and 12 per 1000 population
3
thrombin inhibitor dabigatran, and the factor Xa inhibitors rivaroxaban, apix- among those 80 years of age or older. Although the incidence is lower
3
aban, and edoxaban, have been established to be as effective and safer than in individuals of Chinese and Korean ethnicity, their disease burden is
not low because of population aging. The high incidence of VTE in the
elderly likely reflects the high prevalence of comorbid acquired risk fac-
tors in these patients, especially malignancy, heart failure, and surgery
or hospitalization for medical illness, which account for the majority of
Acronyms and Abbreviations: aPTT, activated partial thromboplastin time; CDT, the population-attributable risk of VTE in older individuals.
catheter-directed thrombolysis; CT, computed tomography; CTA, computed tomo- VTE causes a major burden of disease across low-, middle-, and
graphic angiography; CTV, computed tomographic venography; DOAC, direct-acting high-income countries. VTE associated with hospitalization was the
oral anticoagulant; DVT, deep vein thrombosis; ELISA, enzyme-linked immunosor- leading cause of premature death and years lived with disability in low-
bent assay; INR, international normalized ratio; LMW, low molecular weight; PE, and middle-income countries, and second in high-income countries,
pulmonary embolism; PIOPED, Prospective Investigation of Pulmonary Embolism and responsible for more premature death and disability than nosoco-
Diagnosis; VTE, venous thromboembolism. mial pneumonia, catheter-related bloodstream infections, and adverse
drug events. 3

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