Temperature-dependent drug may prevent blood clots during therapeutic hypothermia

April 9, 2010, American Heart Association

To prevent blood clots during therapeutic hypothermia, scientists have developed what may be the first drug activated by cool temperatures and turned off by warm ones, according to research presented at the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2010.

"We used biotechnology to create a modern intelligent drug," said Karlheinz Peter, M.D., Ph.D., leading author of the study and associate director of Baker IDI Heart & Diabetes Institute in Melbourne, Australia. "This drug is tailored for preventing clots during and for minimizing bleeding problems especially after rewarming."

Doctors use therapeutic hypothermia when the heart temporarily stops beating either spontaneously (cardiac arrest) or during cardiovascular surgery. In this procedure, doctors lower a patient's internal body temperature to prevent organ injury, including brain damage, by reducing metabolic rate and oxygen requirements.

The new drug works only at cooler temperatures by inhibiting the activity of platelets, which are cells that bind together to stop bleeding. In mouse and human blood samples, researchers demonstrated that the experimental drug bound to platelets and prevented them from clumping together at cool temperatures (22º C or 71.6º F). When the researchers raised the temperature to normal (37º C or 98.6º F), the anti-platelet action stopped.

"Our idea was to develop a reagent that is highly active at the moment it is really needed ─ when patients are at low temperature ─ and that loses its function when it is no longer needed ─ when patients are rewarmed," Peter said.

Peter and his collaborators at Baker and Emory University in Atlanta, Ga., used recombinant DNA technology to fuse a temperature-dependent protein with a protein that inhibits platelet activity. The first part of this new protein is similar to the protein elastin, which gives skin and other organs their flexibility and is known to change shape in response to temperature changes. The second, antibody portion of this combined protein inhibits platelet activity by blocking the receptors that normally enable these cells to clot together to heal an injury.

For centuries, physicians have recognized therapeutic hypothermia's benefits, but its use in cardiac patients is relatively recent. In the 1950s, doctors began using the treatment for cardiac surgery, such as valve and bypass surgery. Also, hypothermia is often used in surgical repair of structural cardiac defects in infants and children. However, cardiac hypothermic surgery is associated with a substantial risk of clotting.

To prevent this serious complication, anti-clotting medication is a standard part of therapeutic hypothermia. The drawback is that the effects of current anti-clotting medicines continue even after body temperature is raised to a normal level, which sometimes leads to excessive post-surgical bleeding, researchers said. In contrast, the new combined protein not only inhibited blood clot formation during cooling but also prevented bleeding problems after rewarming.

After extensive clinical studies, the American Heart Association in October 2002 recommended that therapeutic hypothermia also be used to treat selected patients who have suffered cardiac arrest. Using cooling blankets, ice packs or other methods, doctors lower a patient's internal body temperature for 12 to 24 hours. This highly effective therapy can increase survival rate and decrease long-term disability, but it can sometimes cause .

To assure that the novel temperature-dependent drug also protects patients subjected to this type of therapeutic hypothermia used for the protection of the brain in patients after cardiocirculatory arrest, further studies are needed to determine the extent of platelet inhibition at temperatures such as 32º C to 34ºC (89.6 º F to 93.2 º F), Peter said.

Related Stories

Recommended for you

Anemia discovery offers new targets to treat fatigue in millions

January 22, 2018
A new discovery from the University of Virginia School of Medicine has revealed an unknown clockwork mechanism within the body that controls the creation of oxygen-carrying red blood cells. The finding sheds light on iron-restricted ...

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.