Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a approximately 5-fold greater in-hospital mortality. There is approximately 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, approximately 10% per patient-year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.

Cancer and its treatments are well-recognized risk factors for venous thromboembolism (VTE). Evidence suggests that the absolute risk depends on the tumor type, the stage or extent of the cancer, and treatment with antineoplastic agents. Furthermore, age, surgery, immobilization, and other comorbid features will also influence the overall likelihood of thrombotic complications, as they do in patients without cancer. The role of hereditary thrombophilia in patients with cancer and thrombosis is still unclear, and screening for this condition in cancer patients is not indicated. The most common malignancies associated with thrombosis are those of the breast, colon, and lung, reflecting the prevalence of these malignancies in the general population. When adjusted for disease prevalence, the cancers most strongly associated with thrombotic complications are those of the pancreas, ovary, and brain. Idiopathic thrombosis can be the first manifestation of an occult malignancy. However, intensive screening for cancer in patients with VTE often does not improve survival and is not generally warranted. Independently of the timing of cancer diagnosis (before or after the VTE), the life expectancy of cancer patients with VTE is relatively short, because of both deaths from recurrent VTE and the cancer itself. Patients with cancer and acute VTE who take anticoagulants for an extended period are at increased risk of recurrent VTE and bleeding. A recent randomized trial, the Randomized Comparison of Low Molecular Weight Heparin versus Oral Anticoagulant Therapy for Long-Term Anticoagulation in Cancer Patients with Venous Thromboembolism (CLOT) study, showed that low molecular weight heparin may be a better treatment option for this group of patients. The antineoplastic effects of anticoagulants are being actively investigated with promising preliminary results.

Until the 1990s, venous thromboembolism (VTE) was viewed primarily as a complication of hospitalization for major surgery (or associated with the late stage of terminal illness). However, recent trials in patients hospitalized with a wide variety of acute medical illnesses have demonstrated a risk of VTE in medical patients comparable with that seen after major general surgery. In addition, epidemiologic studies have shown that between one quarter and one half of all clinically recognized symptomatic VTEs occur in individuals who are neither hospitalized nor recovering from a major illness. This expanding understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who could benefit from prophylaxis. Factors sufficient by themselves to prompt physicians to consider VTE prophylaxis include major surgery, multiple trauma, hip fracture, or lower extremity paralysis because of spinal cord injury. Additional risk factors, such as previous VTE, increasing age, cardiac or respiratory failure, prolonged immobility, presence of central venous lines, estrogens, and a wide variety of inherited and acquired hematological conditions contribute to an increased risk for VTE. These predisposing factors are seldom sufficient by themselves to justify the use of prophylaxis. Nevertheless, individual risk factors, or combinations thereof, can have important implications for the type and duration of appropriate prophylaxis and should be carefully reviewed to assess the overall risk of VTE in each patient.

Venous thromboembolism (VTE) occurs for the first time in approximately 100 persons per 100,000 each year in the United States, and rises exponentially from <5 cases per 100,000 persons <15 years old to approximately 500 cases (0.5%) per 100,000 persons at age 80 years. Approximately one third of patients with symptomatic VTE manifest pulmonary embolism (PE), whereas two thirds manifest deep vein thrombosis (DVT) alone. Despite anticoagulant therapy, VTE recurs frequently in the first few months after the initial event, with a recurrence rate of approximately 7% at 6 months. Death occurs in approximately 6% of DVT cases and 12% of PE cases within 1 month of diagnosis. The time of year may affect the occurrence of VTE, with a higher incidence in the winter than in the summer. One major risk factor for VTE is ethnicity, with a significantly higher incidence among Caucasians and African Americans than among Hispanic persons and Asian-Pacific Islanders. Overall, approximately 25% to 50% of patient with first-time VTE have an idiopathic condition, without a readily identifiable risk factor. Early mortality after VTE is strongly associated with presentation as PE, advanced age, cancer, and underlying cardiovascular disease.