Researchers find link between blood clotting, immune response

Rice University researchers have found an unexpected link between a protein that triggers the formation of blood clots and other proteins that are essential for the body's immune system. The find could lead to new treatments for thousands of patients who suffer from inflammatory diseases and disorders that cause abnormal blood clotting.

The research is available online in the journal PLOS ONE.

"This link opens the door for studying severe, debilitating inflammatory disorders where the disease mechanism is still poorly understood, including lupus, rheumatoid arthritis, regional ileitis and ulcerative colitis, as well as age-related macular degeneration," said study co-author Dr. Joel Moake, a hematologist and senior research scientist in bioengineering at Rice. "There's clinical evidence that clotting and inflammation are somehow linked in many patients, even in the absence of an infection. This linkage could help explain some of the clinical cases that have long baffled physicians."

The link is biochemical. Nancy Turner, a research technician in Moake's lab, established the link after conducting hundreds of experiments on more than a dozen proteins, including key molecules involved with both clotting and the body's innate immune response.

"In addition to the clinical evidence, there's also a logical basis for this connection," Moake said. "Clotting is a type of wound response, and wounds are magnets for infection, so there could be a selective advantage in triggering both responses at the same time."

But the link could also have a downside. For example, if a person has a genetic mutation or acquired disorder that causes their blood to clot more often or more extensively than normal, the overactive clotting could lead to the kind of inflammation that would typically be caused by an infection. Furthermore, initiation of the clotting process may initiate clinical relapses in patients susceptible to various types of severe inflammatory disease.

In fact, the symptoms in the above scenarios are not uncommon. For example, in prior research, Moake's lab conducted pioneering research on two disorders: thrombotic thrombocytopenic purpura (TTP), which causes clots to form in small blood vessels throughout the body; and hemolytic uremic syndrome (HUS), which causes abnormal blood clots in the kidneys. Both HUS and TTP come in two varieties -- one that is triggered by infection or inappropriate antibody formation, and another that is hereditary. Moake said the newfound link between clot formation and the immune response could help improve the diagnosis and treatment for TTP, HUS and other puzzling blood disorders with similar symptoms.

The experiments Turner used to establish the link between clotting and the body's immune response involved a key clotting protein called von Willebrand factor (VWF) and about a dozen other proteins that are components of the "complement system." The complement system, a part of the body's innate immune system, is one of biology's most ancient forms of defense against invading pathogens.