Temperature-dependent anti-platelet drug is turned on by hypothermia and off by rewarming
MONDAY, April 12 (HealthDay News) -- During medically employed hypothermia, use of a temperature-dependent anti-platelet drug that is activated by hypothermia and deactivated by rewarming of patients may help prevent activation, aggregation, and sequestration of platelets as well as vascular thrombus formation, according to research presented at the Arteriosclerosis, Thrombosis and Vascular Biology 2010 Scientific Sessions, held from April 8 to 10 in San Francisco.
Karlheinz Peter, M.D., of the Baker IDI Heart & Diabetes Institute in Melbourne, Australia, and colleagues investigated whether the fusion of an elastin-mimetic protein (EMP; 80 repeats of Ala-Val-Gly-Ile-Pro) to an activation-specific GPIIb/IIIa-blocking single-chain antibody (scFv) could enable hypothermia-induced anti-platelet therapy.
The researchers found that recombinant DNA techniques allowed them to successfully generate and purify an EMP-scFv fusion protein. After analyzing its conformational transition and evaluating the temperature-dependant binding to activated platelets in humans and mice, they used flow cytometric analyses to determine that anti-GPIIb/IIIa scFv fused to EMP demonstrated a strong binding to activated platelets at 22 degrees Celsius with no binding at 37 degrees Celsius. They also found that the binding of fibrinogen to activated platelets was abolished in the presence of EMP-anti-GPIIb/IIIa scFv at 22 degrees Celsius but restored at 37 degrees Celsius, and that EMP-scFv prevented aggregation of activated platelets at 22 degrees Celsius but was restored at 37 degrees Celsius. EMP-scFv also prevented aggregation of activated platelets at 22 but not 37 degrees Celsius.
"This is the first description of a temperature-dependent anti-platelet drug that can be turned on by hypothermia and turned off by rewarming of patients," the authors conclude. "In cardiac/vascular surgery, such a drug could provide anti-thrombotic protection during the hypothermic surgical procedure and avoid bleeding problems after rewarming at the end of surgical procedures."
Two authors disclosed being inventors on relevant patents and having a modest ownership interest.
Abstract No. P400