Thrombophilic Factor Deficiencies and Pulmonary Embolism

Primary Thrombophilic Factor Deficiencies

Protein C deficiency impairs the natural anticoagulant system, increasing the risk of thrombosis, as it normally inactivates procoagulant factors Va and VIIIa, according to the European Society of Cardiology 1, 2
Protein S deficiency increases thrombosis risk as it functions as a cofactor for activated Protein C in the inactivation of factors Va and VIIIa, as stated by the European Society of Cardiology 1, 3

Antithrombin normally functions as a serine protease inhibitor (SERPIN) that irreversibly inhibits thrombin, and its deficiency leads to unchecked thrombin generation and increased fibrin formation, as explained by the American College of Medical Genetics 4
The natural anticoagulant system (antithrombin, protein C, protein S) normally prevents pathologic thrombus formation, and deficiencies in these natural anticoagulants disrupt this balance, allowing thrombi to form more readily, according to the European Society of Cardiology 1, 3

Antithrombin deficiency should be considered in patients with unexplained thrombotic episodes below age 40, recurrent DVT or PE, and a positive family history, as recommended by the European Society of Cardiology 1, 2
Factor XII deficiency is associated with thrombosis risk despite being a contact activation factor, as reported by the European Society of Cardiology 1, 3

Not all patients with inherited thrombophilias develop thrombosis, and these deficiencies often need to interact with acquired risk factors before thrombosis occurs, as stated by the European Respiratory Society 1, 5
Testing for thrombophilia should be considered in patients with unexplained thrombotic episodes, especially those occurring at a young age, in unusual sites, or with recurrence, as recommended by the European Respiratory Society 5, 6