Image from Andre E.X. Brown
Platelets (blue) in a thrombus
Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.
Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.
The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).
“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.
“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”
Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.
The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.
In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm-1 and 11.5 ± 1.6 kdyne cm-1, respectively.
In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm-1 and 4.1 ± 0.4 kdyne cm-1, respectively.
The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.
The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.
However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.
The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.
In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.
Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.
With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.
If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.
“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”