Versiti Blood Research Institute Articles
Understanding the Connection Between the Blood Coagulation and Immune Systems
Blood coagulation affects a variety of diseases, including how the immune system responds to viruses, bacteria and injury.
Throughout his career at Versiti Blood Research Institute (BRI), Senior Investigator Hartmut Weiler, PhD, has studied how the blood coagulation system and natural anticoagulant mechanisms affect the body’s stress responses to challenges like pregnancy, injury and infections. Among the scientific community, it is now a well-recognized fact that activation of the blood coagulation system makes an important contribution to the body’s defenses in a variety of conditions and diseases, in large part by regulating the functions of immune cells and of endothelial cells lining the inner surface of our blood vessels.
“Many different mechanisms in the human body need to go right in order for it to effectively manage illness and injury,” Dr. Weiler said. “We believe that many of the insights we have gained are applicable to a fairly large number of pathological states, which will help generate new drugs to treat various diseases. In this way, we provide the scientific knowledge that enables better decision making, treatment and approach.”
Blood coagulation and viral infections
Activation of blood coagulation and endothelial inflammation are hallmarks of respiratory infections with RNA viruses that contribute significantly to the morbidity and mortality of patients with severe disease, such as COVID-19. Dr. Weiler’s group investigates how activated blood coagulation factors alter the function of infected endothelial cells. They found that the coagulation factor thrombin greatly amplifies the prothrombotic and proinflammatory function of endothelial cells, and they identified part of the molecular mechanism that is responsible for this effect. In their current work, Dr. Weiler’s group is testing drug candidates to suppress this self-amplifying vicious circle of thrombo-inflammation and trying to understand why this response of endothelial cells to viral infection can vary drastically between individual patients.
Blood coagulation and bacterial sepsis
Dr. Weiler is also researching how the blood coagulation system, as part of the immune system, affects patients who develop sepsis, or blood poisoning. His interest in sepsis began more than 10 years ago, when he found that a common genetic predisposition for thrombosis, the so-called factor V Leiden gene variant, appeared to protect patients against the life-threatening consequences of bacterial infection. Based on this initial observation, Dr. Weiler’s group was able to explain why a highly promising, first-ever drug for the treatment of patients suffering from severe sepsis eventually failed to show consistent efficacy in large clinical trials.
“We felt that this drug, recombinant human activated protein C, was used in an incorrect manner,” he said. He and his collaborators discovered a way to use a slightly altered version of the same drug that only activated protective mechanisms but lacked harmful side effects. This drug candidate is currently being evaluated for use in stroke patients and may eventually be available for treatment of severe sepsis. Current efforts are focused on revealing the precise nature of the protective effects of this drug as a basis for the development of novel, further-improved drug candidates.
Blood coagulation and radiation injury
Several years ago, Dr. Weiler’s group began collaborating with researchers from three different institutions to show that the key effector molecule of the natural protein C anticoagulant pathways, activated protein C, can protect mice against the injury caused by exposure to high doses of radiation. Current work examines how activated protein C protects blood-forming stem cells in the bone marrow, how radiation alters the function of blood vessel endothelial cells, and how natural anticoagulant mechanisms alter this response.
Innovation, freedom and Versiti Blood Research Institute
The BRI hosts world-class experts in the fields of von Willebrand disease, natural anticoagulant mechanisms, platelet biology as well as immunology. It was this unique constellation of expertise bridging hematology and immunology that brought Dr. Weiler to Versiti. “The BRI has a strong background in all these areas, so it’s easy to find highly competent collaborators amongst your colleagues,” he said. “There’s a concentration of knowledge.”
This breadth of expertise enables investigators to follow where their research takes them and explore new areas. “It’s an environment that has the focus and the expertise,” Dr. Weiler said. “It allows someone who knows very little about a specific topic to collaborate with experts in the field and grow the collective knowledge to benefit the larger scientific community and the patients we’re working to help.”
Dr. Weiler credits the Versiti Blood Research Institute Foundation for enabling this. “The Foundation is an innovation machine,” he said. “It gives us the freedom to take calculated risks in the pursuit of discovery. If you want innovation, you need to give researchers the freedom to see where their work takes them.”
About the expert: Hartmut Weiler, PhD, is a senior investigator at Versiti Blood Research Institute and associate professor in the Department of Physiology at the Medical College of Wisconsin.