Thrombophilia

Clinical Aspects | Genetic Causes | Acquired Causes

Genetic Causes of Venous Thrombosis

Specific genetic defects should be suspected when a thrombotic event has any of the following characteristics^12,14,15:

• Spontaneous with no predisposing condition, such as prolonged immobilization or surgery
• Patient suffers from more than one thrombotic event
• Patient has a positive family history of thrombosis
• Patient is less than 50 years old
• Thrombosis occurs at an unusual site (eg, mesenteric or cerebral brain)

Three general categories of test methodology are useful in the assessment of congenital thrombotic conditions:

1. Genetic tests for specific mutations
2. Clotting-based measurements for specific factor activity levels
3. Immunoassays to measure the concentration of specific antigens

Genetic conditions associated with thrombophilia are listed below in order of their relative frequency of occurrence.^12,14,16

Table 1.-Genetic Conditions Associated With Thrombosis.

*While factor VIII elevation is associated with a number of acquired conditions, some individuals appear to have congenitally elevated factor VIII levels that are associated with increased risk of thrombosis.¹²

• 500058 Thrombotic Risk Profile, Congenital

Genetic testing is useful for the diagnosis or confirmation of MTHFR, factor V Leiden, and the prothrombin 20210 mutations. Regardless of clinical status, genetic testing can be definitive because the patient's DNA remains constant. Antigen and activity levels must be measured to diagnose the other congenital thrombotic conditions. It is important to understand, however, that the results of activity and antigen level tests can be affected by the clinical state of the patient. In many clinical circumstances, such as those listed below, tests for activity or antigen levels may produce misleading results if the clinical state of the patient is not considered.^14,16

Table 2.-Clinical Conditions that Affect Tests for Congenital Thrombotic Risk.

References