Image by Andre E.X. Brown
A new approach for treating thrombotic thrombocytopenic purpura (TTP) has proven effective in mice, according to a paper published in Blood.
Researchers showed they could “hide” functional recombinant human ADAMTS13 (rADAMTS13) inside mouse platelets to prevent antibodies from impairing ADAMTS13 activity.
These rADAMTS13-expressing platelets were able to inhibit thrombosis and prevent the development of hereditary and acquired TTP in mice.
If a similar technique were to prove effective in humans, it could reduce the amount of plasma transfusions TTP patients require, the researchers said.
They also believe such a method could be used in emergency situations to treat strokes, heart attacks, malignant malaria, and pre-eclampsia, as all of these conditions are associated with relative deficiency of plasma ADAMTS13 activity.
This research began when X. Long Zheng, MD, PhD, of the University of Alabama at Birmingham, had the idea that he could treat TTP by hiding ADAMTS13 inside platelets where autoantibodies can’t see it.
He reasoned that, if he could fill platelets with ADAMTS13, the platelets would then carry the enzyme right to the place it was most needed to dissolve thrombi.
So he and his colleagues developed transgenic mice that expressed rADAMTS13 in their platelets.
The platelets had normal agglutination and aggregation. And they released rADAMTS13 upon stimulation with thrombin and collagen, although they released less when stimulated with 2MesADP.
Mice with rADAMTS13-expressing platelets were significantly protected in a vascular injury model of thrombus formation.
In mice that lacked plasma ADAMTS13 activity due to ADAMTS13 gene deletion and those that had antibody-mediated inhibition of plasma ADAMTS13 activity, rADAMTS13-expressing platelets protected the animals against TTP induced by bacterial toxin or recombinant von Willebrand factor.
These results, the researchers said, “suggest that platelets may be ideal carriers for antithrombic ADAMTS13, allowing its release at high concentrations at the site of thrombus formation without being inactivated by the potential circulating anti-ADAMTS13 inhibitors.”
To employ this treatment method in humans, Dr Zheng said researchers could investigate how to load ADAMTS13 inside donated platelets. They could then test these platelets to learn how many ADAMTS13-loaded platelets need to be transfused to produce antithrombotic and anti-TTP effects in patients with TTP.
