Content Reviewers:Rishi Desai, MD, MPH
Thrombophlebitis can be broken down into “thrombo” or thrombus which refers to a blood clot, “phleb” which refers to a vein, and “itis” which refers to inflammation. So thrombophlebitis is a blood clot that gets lodged in a vein and causes inflammation.
Normally, the process starts with damage to the endothelium, or inner lining of the blood vessel walls, after which there’s an immediate vasoconstriction or narrowing of the blood vessel which limits the amount of blood flow. After that, some platelets adhere to the damaged vessel wall, and become activated by collagen and tissue factor, which are proteins that are normally kept separated from the blood by an intact endothelium. These platelets then recruit additional platelets to form a platelet plug. The formation of the platelet plug is called primary hemostasis.
After that, the coagulation cascade is activated. First off in the blood there’s a set of clotting factors, most of which are proteins synthesized by the liver, and usually these are inactive and just floating around in the blood. The coagulation cascade starts when one of these proteins gets proteolytically cleaved. This active protein then proteolytically cleaves and activates the next clotting factor, and so on. The final step is activation of the protein fibrinogen to fibrin, which deposits and polymerizes to form a mesh around the platelets. So these steps leading up to fibrin reinforcement of the platelet plug make up the process called secondary hemostasis and results in a hard clot at the site of the injury.
This cascade has a huge degree of amplification and takes only a few minutes from injury to clot formation. So the activation of the cascade is carefully controlled by anticoagulation proteins that target and inactivate key clotting factors. For example, antithrombin inactivates Factors IXa, Xa, XIa, XIIa, VIIa and thrombin while protein C inactivates Factors Va and VIIIa.
As the clot grows in size, it limits the amount of blood able to pass by, and pressure in the vein increases. Usually the clot might start naturally breaking down, for example, enzymes like plasmin break down fibrin into fragments called D-dimers.
There are three main factors that lead to thrombosis, which are referred to as Virchow’s triad. The first factor is slowed blood flow, also called stasis, in the veins. Typically, blood continuously flows smoothly through the blood vessel, but if the blood flow becomes turbulent, the linear flow is disrupted and slow or static pockets of blood are formed. Stasis can also happen during long periods of inactivity of the skeletal muscle pump like bed rest or long flights and car rides, or even during pregnancy when a growing baby compresses nearby veins.
The second factor is a state of hypercoagulation, where altered amounts of clotting factors increase primary or secondary hemostasis. This can happen for genetic or acquired reasons like surgery or taking certain medications like birth control pills. During surgery, physical damage to the vessels activates the clotting cascade. And birth control pills tip the balance towards clotting because they increase the levels of clotting factors and decrease the levels of some anti-coagulation factors like protein C and antithrombin.
A third factor is damage to the endothelial cell lining of a blood vessel which exposes tissue factor and collagen. Damage can be caused by infections, chronic inflammation or toxins like those found in tobacco cigarettes.