As hemophilia treatments expand beyond traditional factor replacement, new therapies can sound promising and confusing at the same time. For example, you may have heard about anti-TFPI therapies in conversations about bleeding disorders care and wondered what they are and how they work.
Here, we explain what TFPI is and how anti-TFPI therapies can help people with hemophilia A or B — with or without inhibitors — to better control bleeding.
Blood Clotting as a Balance System
Blood clotting is a delicately balanced system, with the body activating various proteins, also called factors, to achieve the right amount of clotting.
These proteins work to form clots that stop the bleeding, while other kinds of proteins, including tissue factor pathway inhibitor (TFPI), slow the clotting cascade to avoid too much clotting.
People with hemophilia already have low factor levels, but TFPI continues to work normally. For them, TFPI’s role of slowing clotting may make bleeding even harder to control.
How TFPI Inhibitors Work in Hemophilia
If TFPI proteins are the brakes in the clotting cascade, then anti-TFPI agents ease up on those brakes by reducing TFPI’s activity.
Anti-TFPI is called a rebalancing agent because it helps to restore the balance between bleeding and clotting.
During the clotting process, anti-TFPI binds to TFPI to prevent it from attaching to factor VIIa and factor X, allowing the clotting cascade to continue and clots to form.
How This Approach Differs from Other Hemophilia Treatments
People with hemophilia have a variety of treatment options, so it’s important to understand where anti-TFPI therapies fit in.
Factor therapies replace missing factor in the body to boost the ability to clot. Nonfactor therapies such as aminocaproic acid, bispecific antibody therapy, and desmopressin work to affect the clotting process in various ways. Gene therapy introduces new genes to the body that have instructions on how to make factor.
Anti-TFPI works differently from these other therapies. For example, because it doesn’t directly interact with protein factors — including factor VIII and factor IX — anti-TFPI can be used to manage hemophilia A and B. Anti-TFPI treatments may also be an option for people with FVIII or FIX inhibitors.
Anti-TFPI is delivered by subcutaneous injection (under the skin) to provide a steady state of activity. This medication is for preventing bleeds, so you might still need factor replacement therapy or other medications to treat bleeds.
To find the right treatment option for you, it’s best to consult the comprehensive care team at your hemophilia treatment center.
For details about specific anti-TFPI medications, check out NBDF’s MASAC Document 293: Recommendation on the Use and Management of Anti-Tissue Factor Pathway Inhibitors in Hemophilia.