Thrombophilia: Clinical

In the 1800’s, the German physician Rudolph Virchow identified a triad of risk factors for thrombosis; endothelial injury, stasis, and hypercoagulability.

The last category, hypercoagulability or thrombophilia, occurs when the normal physiological balance between clot formation and clot lysis is tipped towards clot formation.

Before going into the individual thrombophilia disorders, let’s go through the normal coagulation system. The coagulation pathway is divided into an extrinsic and intrinsic pathways, which join into a common pathway that ultimately forms a clot made of strong fibrin mesh.

Let's start with the extrinsic pathway. It starts when trauma damages a blood vessel, and exposes the cells under the endothelial layer, which have tissue factor in their membrane.

Activated factor VII binds to tissue factor, forming a complex that then binds to and activates factor X.

The intrinsic pathway starts when a circulating factor XII, activates factor XI, which then activates factor IX.

Finally, factor IX forms a complex with factor VIII, and this complex binds to and activates factor X.

In the common pathway, activated factor X activates factor V, which converts prothrombin to thrombin, or factor II.

Thrombin then converts fibrinogen into fibrin, which cross-links to form a fibrin clot.

In order to regulate coagulation, the liver makes protein S, which activates protein C.

Protein C inactivates factors V and VIII.

Finally, a protein called antithrombin III inhibits factor X and factor II.

The prothrombin time, or PT assesses the extrinsic and common coagulation pathways, while the partial thromboplastin time, or PTT assess the intrinsic and common coagulation pathways.

Alright, so you can imagine that increasing or decreasing certain factors in the coagulation pathway can lead to thrombophilia.

Disorders that cause thrombophilia can be genetically inherited, like factor V Leiden, prothrombin gene mutation, and protein C and S deficiency, or acquired like antiphospholipid syndrome - which is an autoimmune condition.

The most common presentation of thrombophilia is in the form of a venous thromboembolism, which includes deep vein thrombosis of the upper and lower limbs, as well as pulmonary embolism.