Photo of Haemophilia B blood treatment with Rare FIX Inhibitor

Disease Awareness

The Role of Rare FIX Inhibitors in Haemophilia B

June 25th, 2018 - 0 Comments

John was diagnosed with severe haemophilia B when he was just a year old. He then began primary prophylaxis with plasma-derived FIX concentrate (pdFIXC). Tests for inhibitors were repeatedly negative, and John lived a normal life until he was 10.

Bruising and an increase in FIX consumption were detected when he was 11. The inhibitor remained negative. John developed spontaneous haematoma on his right leg. He did not respond to high doses of recombinant factor IX concentrates (rFIXC). Recovery was poor.

An inhibitor against FIX was detected this time. John was diagnosed with haemophilia B with an inhibitor and began immune tolerance induction with rFIXC. Recombinant activated factor VII (rFVIIa) was used to treat bleedings and for prophylaxis. In the course of the following year, the inhibitor showed negative. You may have questions about inhibitors if you’re not involved in the healthcare sector, so let’s explore the topic in some detail.

What Are Inhibitors?

A person with haemophilia develops inhibitors: a severe medical condition that occurs when the immune system responds against clotting factor concentrates. The immune system, as we all know, is responsible for defending the body against foreign entities. Sometimes, however, a person’s immune system may respond to protein factor concentrates as if they were potentially harmful foreign entities.

This medical situation arises because the body has never encountered protein factor concentrates before. What happens next is that this allows the formation of inhibitors (antibodies) in the blood that fight against the proteins factors, preventing the factor concentrates from fixing the bleeding issue in haemophilia patients.

A person with inhibitors experiences more bleeding and pain because treatment with factor concentrates does not work. It is possible to get rid of inhibitors using a technique called immune tolerance induction, as mentioned above. However, this type of treatment requires specialized medical capability, and setup is expensive. It also takes a long time to implement.

Seeking Better Treatments

The risk of developing an inhibitor is highest in the previously untreated population, especially during the first six years of life. The rate of inhibitor formation in haemophilia B is around 1.5%-3% with either Recombinant FIX concentrate (rFIXC) or Plasma-derived FIX concentrate (pdFIXC) that is lower than that observed in haemophilia A.

The difference is due to that the defects in FIX are usually caused by missense mutations, i.e. alterations that permit protein expression at an amount large enough to confer immune tolerance. Patients with large F9 gene deletions carry the highest risk of inhibitor formation among haemophilia B patients.

FIX Inhibitor development in the healthcare sector still represents the major clinical challenge in the management of patients with haemophilia B. Inhibitor eradication is the only way to significantly make an impact on the morbidity related to such complication. Immune tolerance induction treatment is highly used but not fully effective in this area, since several predictors of success and failure interact in the same patient. Thus, future studies have to be designed to obtain a better treatment approach among different patient groups.

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