What is antithrombin
and how does it work?

Antithrombin is a natural protein in your blood plasma that helps keep clotting in check. When injured, your body activates a step-by-step process called hemostasis, which creates a clot to stop bleeding.

Antithrombin acts as an anticoagulant, meaning it helps prevent the blood from clotting. Normal hemostasis depends on a careful balance between proteins that help blood to clot (procoagulants) and those that prevent it from clotting too much (anticoagulants).

Antithrombin binds to certain procoagulant proteins that help your blood to form clots during an injury; this binding causes them to be removed from the blood. Maintaining this balance is essential to avoid overactivation of the blood-clotting system, which can lead to serious health problems.

Antithrombin activity is measured in the bloodstream. In adults, normal levels range from 80 to 120 IU/dL. Activity levels below 70 IU/dL are considered low and may indicate antithrombin deficiency.

Low levels of antithrombin in the blood can occur for different reasons. Some people are born with a condition called congenital antithrombin deficiency, while others may develop low levels later in life due to health issues, such as liver disease—this is known as acquired antithrombin deficiency. The acquired form of antithrombin deficiency is much more common than its hereditary form.

Antithrombin deficiency can also occur in people with hemophilia. When this happens, it can reduce how often and how severely they bleed, leading to a milder bleeding condition and longer periods without bleeding problems. This occurs because, when antithrombin levels are low, the body produces more thrombin, helping to restore hemostasis and increasing the chance of blood clotting.

There are two main tests for antithrombin: a functional test, which measures how well it works, and an antigen test, which measures how much antithrombin is in the blood. Doctors often start with the functional test because it’s quick, easy to automate, and readily available in many hospital laboratories.

For many years, the standard treatment for hemophilia has been to restore hemostasis and prevent bleeding by replacing missing clotting factors such as Factor VIII and Factor IX. Clotting factor replacements are produced from donated blood or made in a laboratory and given intravenously (through your vein).

However, a common complication of clotting factor replacement is the development of inhibitors (or neutralizing antibodies). These inhibitors are proteins that normally protect your body from harmful foreign substances, but in this case, they block the clotting factor replacement from working properly. This occurs in about 30% of patients with hemophilia A and about 10% of patients with hemophilia B. Inhibitors usually develop early in treatment, especially in young children. When this happens, clotting factor replacements become ineffective.

Therefore, antithrombin-lowering treatments have been developed to help rebalance blood clotting in hemophilia by reducing natural anticoagulants, allowing clotting factors to work more effectively. Antithrombin-lowering treatments do not get neutralized by anti-factor inhibitors and can increase thrombin generation in patients with both hemophilia A and B, whether they have inhibitors or not.