الفهرس 
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Abstract
Venous thromboembolic (VTE) disease is a term commonly used to describe an evolving, multifactorial disease spectrum ranging from deep venous thrombosis (DVT) to pulmonary embolism (PE) (Michael et al., 2009).
Epidemiology
Venous thrombosis has an overall annual incidence of < 1 in 1000. It is rare in the pediatric population, with rates of deep vein thrombosis of about 1 in 100,000 (Hoppe et al., 2002) and increases in frequency in older patients. While significant advances have been made in understanding congenital thrombophilias, there may still be many more heritable forms of thrombophilia as yet undiscovered. Thus, it is not possible to determine the true prevalence of congenital thrombophilia.
Risk Factors
Venous stasis can occur under any circumstance where there is prolonged immobility or immobilization, or if there is obstruction of flow of a blood vessel, either externally or internally. Besides immobility or prolonged bed rest (eg, in a hospital/nursing home), there are multiple other risk factors for the development of a venous thrombus, including increasing age, surgery within the last 3 months (especially lower extremity surgery and orthopedic procedures) (Kroegel and Reissig., 2003), prolonged travel of >4 hours within the last 2 months (Trujillo et al., 2008), trauma, cancer (particularly adenocarcinoma and metastatic cancers), paresis of the lower extremity, oral contraceptive use, and hormone replacement therapy. Cancer has received much interest in the current published data. It has been shown that malignancy is an important risk factor for VTE, with an odds ratio of 6.5. By contrast, 10%-20% of patients who develop a spontaneous, idiopathic DVT will ultimately be diagnosed with a malignancy, and this group of patients has a 1-year survival rate of only 12% (Behranwala and Williamson., 2009). In addition, there has been recent research to suggest that patients with vasculitis, particularly antineutrophil cytoplasmic antibody-associated vasculitis, have increased risk of thrombotic events (Tomasson et al., 2009).There are also genetic risk factors, termed thrombophilias, including factor V Leiden mutation, and protein C or S deficiency, which lead to a hypercoaguable state (Kroegel and Reissig., 2003). The risk for a VTE event is further increased when both acquired and genetic risk factors are present.
Factor V Leiden and risk of thrombosis
Activated protein C (APC) resistance is the most common abnormality of the coagulation system in patients with hereditary venous thromboembolism (VTE). It has been found in 18% of patients with a first thrombosis, in about 40% of thrombophilic families, and has a prevalence of 3% to 5% in the general population, with important geographical differences (Gouin et al., 2002).APC resistance phenotype is associated in a majority of patients with heterozygosity or homozygosity for a single-point mutation in the factor V gene, which substitutes G with A at nucleotide 1691. This mutation replaces Arg with Gln at position 506 in the factor V molecule (factor V Leiden, FVL), thus modifying one of the three APC cleavage sites. The slower degradation of the mutated activated factor V by APC leads to a higher rate of thrombin generation and a hypercoagulable state.
A mutation in the 3′-untranslated region of prothrombin gene at position 20210 (G/A) has been shown to be associated with an increased risk for venous thrombosis. This mutation was found in a high prevalence