Chapter 111. Venous Thrombosis (Part 3) Thrombophilia Testing Testing for prothrombotic abnormalities outside the setting of abundant familial thrombophilia serves no purpose. A positive test does not help in the diagnosis of thrombosis, nor does it predict the risk of recurrent thrombosis, nor, therefore, does it affect long-term preventive strategies. Hereditary Thrombophilia Individuals from families with a hereditary tendency for venous thrombosis generally have a more severe thrombotic tendency than individuals not from such families. Even when the genetic defect is the same in the two groups, those with hereditary thrombophilia from affected families have their first thrombosis at a young age (20–35 years), few fail to develop thrombosis in their lifetime, and many have recurrent disease. Early studies on thrombotic risk associated with prothrombotic defects were based on such families and overestimated risks for all patients with thrombophilic defects. Generally, individuals from such families need not be treated differently than others, except (1) oral contraceptives containing estrogens should be discouraged in all, and (2) postpartum anticoagulant prophylaxis should be considered in those with prothrombotic defects. Long-term treatment can be considered after a first episode of thrombosis, but only in high-risk families, particularly those with antithrombin deficiency. Thrombosis at Rare Sites One in 25 venous thromboses occurs in the arm, while other, even more rare locations are the brain (cerebral vein thrombosis), the digestive system (mesenteric vein thrombosis), and the liver (portal vein thrombosis, and hepatic vein thrombosis, also known as Budd-Chiari syndrome). Thrombosis of the arm is almost invariably associated with central venous catheters. Deteriorating liver function and portal hypertension may point to thrombosis in the hepatic or portal veins, neurologic defects to cerebral vein thrombosis, and severe abdominal complaints to mesenteric vein thrombosis. In rare cases, DVT may be associated with embolic stroke, when a patent foramen ovale is present (paradoxical stroke). Although local abnormalities often play a role, a procoagulant state due to cancer or hereditary abnormalities increases the incidence of thrombosis in rare locations. In all these cases diagnosis is based on imaging, and treatment should consist of anticoagulation similar to that of more common forms of thrombosis, as well as treatment of local causes and consequences. Superficial Thrombophlebitis A painful red string is a clear sign of superficial thrombophlebitis. This is the only type of venous thrombosis that can reliably be diagnosed without imaging techniques. Although research is limited, the causes of superficial thrombophlebitis appear similar to those of other forms of venous thrombosis, and extension to the deep vein occurs. Treatment options are a matter of debate and vary from anticoagulants to an expectant approach. Global Data Venous thrombosis occurs in all ethnic groups, with possibly a somewhat higher incidence in Africans than in whites and Asians. Whereas acquired risk factors are largely identical in these large ethnic groups, the two most common genetic risk factors (factor V Leiden and prothrombin 20210A) are found only in whites. These are unique gain-of-function mutations with a very low mutation rate (i.e., they occurred only once). Loss-of-function mutations leading to deficiencies of antithrombin, protein C, and protein S do not differ much by ethnic group. Due to founder effects, prevalences of factor V Leiden and prothrombin 20210A may vary widely in ethnic subpopulations, i.e., in various European populations the prevalence of factor V Leiden varies between 1% (Italy) and 15% (southern Sweden). Acquired risk factors may vary by local circumstances, e.g., hyperhomocysteinemia due to differences in diet, reproductive factors due to number of pregnancies, and use of oral contraceptives. The literature on Africans and Asians is sparse. Diagnosis The true prevalence of thrombosis in patients presenting with either clinically suspected DVT of the leg or PE is ~15–25%. Therefore, the diagnostic workup for both these diseases has two objectives: (1) to exclude the disease quickly and safely in as many patients as possible, preferably with noninvasive and easy-to-use and cost-effective methods; and (2) to confirm the presence of thrombosis in the remaining patients with an accurate imaging technique. The purpose of the first step is to withhold both unnecessary further diagnostic testing and anticoagulant treatment. Although the diagnostic workup of DVT and PE have much in common, they will be discussed separately. . Chapter 111. Venous Thrombosis (Part 3) Thrombophilia Testing Testing for prothrombotic abnormalities outside. (cerebral vein thrombosis) , the digestive system (mesenteric vein thrombosis) , and the liver (portal vein thrombosis, and hepatic vein thrombosis, also known as Budd-Chiari syndrome). Thrombosis. forms of venous thrombosis, and extension to the deep vein occurs. Treatment options are a matter of debate and vary from anticoagulants to an expectant approach. Global Data Venous thrombosis