Content Reviewers:Rishi Desai, MD, MPH
With thrombophlebitis, thrombo-, or thrombus, refers to a blood clot, phleb- refers to a vein, and -itis 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 the inner lining of a blood vessel’s walls. After this, there’s an immediate vasoconstriction, or narrowing of the blood vessel, which limits 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 plug. The formation of the platelet plug is called primary hemostasis.
Next, the coagulation cascade is activated. In the blood, there’s a set of clotting factors, most of which are proteins synthesized by the liver; usually, these are inactive and just floating around in the blood. The coagulation cascade starts when one of these proteins is proteolytically cleaved. This active protein then proteolytically cleaves and activates the next clotting factor, and so on. The final step in the coagulation cascade is the activation of the protein fibrinogen to fibrin, which then deposits and polymerizes to form a mesh around the platelets. All of these steps leading up to fibrin reinforcement of the platelet plug make up the process called secondary hemostasis, and they result in a hard clot at the site of the injury.
This cascade has a huge degree of amplification and takes only a few minutes to progress from injury to clot formation. 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 through the vein, 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, and these are referred to as Virchow’s triad. The first factor is slowed blood flow, 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. Stasis can even happen during pregnancy, when a growing baby compresses nearby veins.
The second factor is a state of hypercoagulation, where altered amounts of clotting factors increase either primary or secondary hemostasis. This can happen for genetic reasons or acquired ones, like surgery or taking certain medications, including birth control pills. During surgery, physical damage to vessels activates the clotting cascade. Birth control pills can tip the balance towards clotting because they increase levels of clotting factors and decrease the levels of some anti-coagulation factors, like protein C and antithrombin.
The third factor in Virchow’s triad is damage to the endothelial cell lining of a blood vessel that exposes tissue factor and collagen. Damage can be caused by infections, chronic inflammation, or toxins, like those found in tobacco cigarettes.