Immune Thrombocytopenia: Study In Mice May Identify New Treatments

Immune thrombocytopenia (ITP), is an autoimmune disease where the immune system creates antibodies to attack and destroy the body’s platelets, the blood cells responsible for controlling bleeding.

Halting ITP is essential because if platelet counts in a body fall too low, a simple cut could continue to bleed for hours. More severe injuries can be fatal, and the body’s inability to control bleeding can lead to stroke.

Effectiveness of ITP’s treatment, and it’s severity, vary from case to case. Now, a new study, may explain why there is so much variance in symptoms and response to treatment.

Each platelet’s surface is covered with thousands of different proteins, with each type of antibody targeting a specific protein on the platelet. The first antibody to find a platelet latches on and leads the platelet to an organ where it will be destroyed.

It has previously been believed that all ITP antibodies lead platelets to the spleen for destruction, said Dr. Heyu Ni, a scientist in the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital:

“Every existing treatment for ITP has been dedicated to stopping antibodies from destroying platelets in the spleen, but we’ve discovered that some antibodies actually destroy platelets in the liver.”

In the study, mice were treated with two different types of antibodies most common to ITP. Each of these two antibodies targets a different protein on the surface of platelets, either GPIb or GPIIbIIIa.

The researchers found that antibodies targeting GPIb lead to platelets to be destroyed in the liver, whereas those targeting GPIIbIIIa caused platelet destruction in the spleen.

“By detecting the specific antibodies present in someone with ITP, we may be able to detect where and how the immune system will attack,” said Dr. Heyu Ni, who is also a scientist with Canadian Blood Services and a professor at the University of Toronto. “And because we now know the liver’s immune response destroys platelets covered with GPIb, we may be able to design new therapies to stop this type of platelet destruction.”

There are drugs, such as Tamiflu, Dr. Ni said, which may be able to inhibit the liver’s immune response to the platelets.

Building on an early abstract of this study, some ITP patients around the world have been given Tamiflu to treat the disease. These people were in life-threatening condition and extremely drug-resistant to existing treatments targeting the spleen.

Although these instances of experimental treatment have been successful, Dr. Ni said more research is needed to verify the safety and efficacy of this approach.

Heyu Ni, et al
Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia
Nature Communications 6, Article number: 7737 doi:10.1038/ncomms8737