Thrombophlebitis

Definitions & Key takeaways

Thrombophlebitis is a blood clot that gets lodged in a vein and causes inflammation. All factors that lead to abnormal clot formation are grouped into three factors, known as Virchow's triad. They include venous stasis; a state of hypercoagulation; and damage to the endothelial cell lining. Venous stasis is said when blood doesn't flow appropriately in the veins, which can occur in situations of prolonged periods of inactivity. Endothelial injury can occur when there is an injury or trauma to a blood vessel; and finally, hypercoagulable states can be seen in certain conditions like cancer, pregnancy, and certain medications such as hormonal birth control or chemotherapy.

Thrombophlebitis can cause pain, swelling, and redness in the affected area, and may be accompanied by a fever. In some cases, a clot can break loose from the vein and travel to the lungs, causing a pulmonary embolism, which can be life-threatening. The treatment of thrombophlebitis involves thrombolytics to help break down the clot, or a thrombectomy, which is an intervention that aims to surgically remove the clot. Long-term treatment to prevent future thrombi from forming can include anticoagulant medications like warfarin or heparin.

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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 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 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, 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.
During stasis, platelets and other clotting factors contact the endothelium, and prolonged interaction leads to clotting factor adhesion, and, ultimately, activation of the clotting cascade.
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 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 that exposes tissue factor and collagen. Damage can be caused by infections, chronic inflammation or toxins like those found in tobacco cigarettes.
Thrombophlebitis most often occurs in superficial and deep leg veins - leading to superficial thrombophlebitis and deep venous thrombosis, called a DVT.
That being said, it can also develop in other areas of the body, like at the site of an IV insertion - especially if an IV has been sitting in the vein for days to weeks.
Other conditions that can increase the risk of thrombophlebitis are Trousseau syndrome, which is where some people with pancreatic cancer get thrombophlebitis in various veins, as well as Mondor disease, where thrombophlebitis occurs in the breast or front chest wall.
Sometimes, thrombophlebitis can get infected or it can happen the other way with an infection in the skin or soft tissue causing the thrombophlebitis.
A classic cause is a Staphylococcus aureus - and when the blood clot is infected, it’s called septic thrombophlebitis. As you might guess, having an infected blood clot can be quite dangerous because it can lead to sepsis and can quickly allow that infection to get carried in the blood to other parts of the circulatory system.
Thrombophlebitis is most common in a limb - usually the lower leg, and it can make the area around the clot inflamed - and this causes pain, swelling, redness, and warmth.
Superficial thrombophlebitis can cause the affected vein to get hard like an electrical cord. If there is a septic thrombophlebitis it can also cause systemic symptoms like fevers.
If the septic thrombophlebitis is severe enough it can lead to shock where there’s a drop in blood pressure and organs can fail from not getting enough blood.
The diagnosis of a thrombophlebitis can be made by ultrasound. Alternatively, if the ultrasound is inconclusive a more invasive venography procedure can be performed.
This is when a dye is injected into the veins and an X-ray is taken to identify blockages. Also, a D-dimer blood test can be helpful, because fibrin break-down product levels are usually higher in presence of a clot.
Generally speaking the body makes and breaks blood clots all the time, and some small clots resolve on their own over time, but large clots that cause symptoms typically need an intervention.
Thrombolytic enzymes can be given to help break down the clot or a thrombectomy can be done to surgically remove the clot.
Long-term treatment to prevent future thrombi from forming can include anticoagulant medications like warfarin or heparin, which inhibit the clotting cascade and prevent clot formation.
Prevention of a deep vein thrombosis is also important - compression stockings and frequent calf exercises during long periods of sitting still can help move blood through the veins to prevent stasis.
All right, as a quick recap, thrombophlebitis is the inflammation of a vein around a blood clot that can be infected, in which case it’s called septic thrombophlebitis.
The three main causes: stasis, hypercoagulation of clotting factors, and damage of the endothelial lining are often referred to as Virchow’s Triad.
It most often develops in the legs and can be categorized as either superficial thrombophlebitis or deep venous thrombosis, though it can also occur in other areas of the body, especially at the site of an IV insertion.