Clinical Information

Thrombophilia is defined as an acquired or familial disorder associated with thrombosis. The clinical presentation of an underlying thrombophilia predominantly includes venous thromboembolism (deep vein thrombosis, pulmonary embolism, superficial vein thrombosis). Other manifestations that have been linked to thrombophilia include recurrent miscarriage and complications of pregnancy (eg, severe preeclampsia, abruptio placentae, intrauterine growth restriction, stillbirth). Thrombophilia does not predict arterial thrombosis. Demographic or environmental exposures that compound the risk of venous thromboembolism among persons with a thrombophilia include increasing age, male gender, obesity, surgery, trauma, hospitalization for medical illness, malignant neoplasm, prolonged immobility during travel (eg, prolonged airplane travel), oral contraceptive use, estrogen therapy (both oral and transdermal), tamoxifen and raloxifene therapy, and infertility drugs. Central venous catheters and transvenous pacemaker wires increase the risk for upper extremity deep vein thrombosis; this risk is unrelated to thrombophilia.

Inherited thrombophilias include:

-Deficiency due to reduced plasma protein level or dysfunctional protein of:

-Antithrombin

-Protein C

-Protein S

-Dysfibrinogenemias (rare)

-Activated protein C resistance due to the factor V Leiden variant (F5 c.1601G>A; p.Arg534Gln, historically known as R506Q)

-Prothrombin F2 c.*97G>A variant (historically known as G20210A)

Acquired thrombophilias include a lupus-like anticoagulant (antiphospholipid antibodies) and disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF). DIC/ICF may cause thrombotic as well as hemorrhagic events. Positive tests for DIC/ICF can also occur as consequences of thrombosis.

Acquired deficiencies of fibrinogen, protein C, protein S, and antithrombin may be found in conjunction with liver disease (they are produced by the liver) or DIC/ICF and are of uncertain significance with respect to thrombosis risk.

Acquired deficiencies of protein C and protein S are also found in patients with liver disease who are being treated with oral anticoagulants (eg, warfarin, Coumadin), since both proteins are dependent upon the action of vitamin K for normal function.

Acquired protein S deficiency also occurs in thrombotic thrombocytopenic purpura, pregnancy or estrogen therapy, nephrotic syndrome, and sickle cell anemia. In acute illness, the levels of acute-phase reactants rise (including C4b binding protein, which binds and inactivates protein S in the plasma), and the portion of bound protein S also rises, leaving a lower proportion of free protein S. The significance of acquired protein S deficiency with respect to thrombosis risk is unknown.