Historical Background and Epidemiology of Acute Venous Thromboembolic Disease

The incidence of deep venous thrombosis (DVT) ranges from 5 to 9 per 10,000 person-years in the general population, and the incidence of venous thromboembolism (DVT and pulmonary embolism [PE] combined) (VTE) is about 14 per 10,000 person-years.^1,2 This equates to more than 275,000 new cases of VTE per year in the United States.³ The number of identifiable risk factors that predispose to the development of VTE has steadily grown. This information has allowed physicians to provide more effective thromboembolism prophylaxis that is evidence-based and stratified according to the number of risk factors present. In patients with established DVT and PE, there has been a relatively recent emphasis evaluating the rate of recurrence and the clinical factors that predispose to recurrent VTE. In turn, the type and duration of long-term anticoagulation also continue to be stratified, based on the number of risk factors for recurrence.

Physicians from a variety of medical and surgical specialties participate in the care of these patients, and vascular surgeons often are called on to assist in their care and should therefore be familiar with the risk factors for VTE and the optimal medical therapy for these patients. This chapter describes risk factors for a first episode of VTE and the options for initial anticoagulation. An increasing number of risk factors and associated conditions that increase the predilection for recurrent VTE continue to be identified. The optimal duration and type of longer-term antithrombotic therapy are also covered, and the role of adjunctive vena cava filters is discussed briefly. VTE prophylaxis, modalities for the diagnosis of VTE, and thrombolytic therapy for VTE are beyond the scope of this chapter and are not discussed in detail.

Etiology and Natural History of Acute Venous Thromboembolism

APC, Activated protein C; HRT, hormone replacement therapy; OCP, oral contraceptives; VTE, venous thromboembolism.

When multiple inherited and acquired risk factors are present in the same patient, a synergistic effect may occur. Clinically manifest thrombosis most often occurs with the convergence of multiple genetic and acquired risk factors.⁴ Hospitalized patients have an average of 1.5 risk factors per patient, with 26% having three or more risk factors.⁵ Multiple risk factors often act synergistically to increase risk dramatically above the sum of individual risk factors. For example, patients who are heterozygous for factor V Leiden are at only moderately increased risk for VTE (4- to 8-fold). However, when combined with the additional risk of oral contraceptive use, the risk for VTE increases to approximately 35-fold, the same order of magnitude as for someone who is homozygous for factor V Leiden. The concomitant presence of obesity, advancing age, and factor V Leiden increases the thrombosis risk associated with hormone replacement therapy alone. In symptomatic outpatients, the odds ratio for an objectively documented DVT increases from 1.26 for one risk factor to 3.88 for three or more risk factors.⁶

Other factors associated with venous thrombosis include traditional cardiovascular risk factors (obesity, hypertension, diabetes), and there is a racial predilection among whites and African Americans compared with Asians and Native Americans. Certain gene variants (single nucleotide polymorphisms) are associated with a mild increased risk for DVT, and their presence may interact with other risk factors to increase the overall risk for venous thrombosis. However, testing for these polymorphisms is not common in clinical practice.

Natural History

Overt venous injury appears to be neither a necessary nor sufficient condition for thrombosis, although the role of biologic injury to the endothelium is increasingly apparent. Under conditions favoring thrombosis, the normally antithrombogenic endothelium may become prothrombotic, producing tissue factor, von Willebrand factor, and fibronectin. Stasis alone is probably also an inadequate stimulus in the absence of low levels of activated coagulation factors.⁷

The rate of VTE recurrence in patients with untreated isolated calf DVT is approximately 20% to 30%. In contrast, the rate of recurrence in patients with untreated proximal DVT is more difficult to determine, since the majority of patients with proximal DVT receive therapeutic anti-coagulation. Limited older data suggest that about 50% of patients with inadequately treated proximal DVT will develop symptomatic PE.

Therapeutic anticoagulation effectively stabilizes venous thrombus, prevents propagation, and promotes dissolution by endogenous plasmin and its mediators. However, there is a low rate of VTE recurrence, even with adequate dosages of heparin, low-molecular-weight heparin, pentasaccharides, and/or vitamin K antagonists. Most VTE recurrence takes place in the first few weeks after anticoagulant therapy is initiated, and it is dependent upon the location of the original DVT. Extension of isolated calf DVT is effectively attenuated by anticoagulation. However, even adequately treated proximal DVTs have a low rate of recurrence.

Diagnosis and Imaging

The patient presentation varies widely, depending on the extent of the venous thrombosis and the presence of concurrent medical and surgical problems. In some, the DVT will be discovered during routine screening of patients who are at high risk for VTE.

Imaging

The venous duplex scan is the most commonly performed test for the detection of infrainguinal DVT, both above and below the knee, with sensitivity and specificity of greater than 95% in symptomatic patients. In a venous duplex examination performed with the patient supine, spontaneous flow, variation of flow with respiration, and response of flow to the Valsalva maneuver, all are assessed. Continued improvements in ultrasound technology also have improved the ability to visualize color flow within the tibial veins. However, the primary method of detecting DVT with ultrasound is demonstration of the lack of compressibility of the vein with probe pressure on B-mode imaging. Normally, in transverse section, the vein walls should coapt with pressure (Figs. 12-1 and 12-2). Lack of coaptation indicates thrombus.

Fig 12–1 Common femoral vein without and with compression. Complete vein wall coaptation indicates absence of deep vein thrombosis.

Fig 12–2 Normal saphenofemoral junction.

Venography

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