Our laboratory has two distinct research focuses:
- Basic science studies of hemostasis and vascular biology with a focus on the physiological function of Tissue Factor Pathway Inhibitor (TFPI)
- Clinical and translational research studies of iron metabolism in blood donors
The blood vessel contains several anticoagulant proteins that prevent the formation of blood clots. The work in our laboratory is focused on one of these proteins called TFPI. TFPI inhibits proteases in the very early stages of blood coagulation. Humans without TFPI have not been identified and genetically altered mice that do not make TFPI die during embryonic development demonstrating that TFPI has critically important physiological functions. Our laboratory uses a wide variety of biochemical, cellular (tissue culture) and animal models to define and characterize the physiological functions of TFPI. These include studies of the biochemical mechanisms that allow TFPI to associate with the surface of blood vessels and platelets, characterization and functional assessment of different alternatively spliced forms of TFPI and the development of new mouse models to examine the function of TFPI in vivo. The results of these studies will shed new light on a wide range of human diseases that are associated or caused by intravascular blood clots. We have recently demonstrated in mouse models that TFPI produced by the endothelial cells lining blood vessels as well as by platelets is important for preventing blood clots from forming in the brain. We are optimistic that our continued investigation of the physiological mechanisms underlying how TFPI functions in brain tissue will lead to new understanding of the causes and risk factors for stroke as well as vascular dementia.
a. Blood donation removes a large amount of iron from the blood donor. This results in a large number of donors becoming iron deficient and developing iron deficiency anemia. However, some donors can donate blood repeatedly over many years and not develop iron deficiency anemia. We have performed studies of these donors to define their behavioral, biochemical and genetic characteristics that allow them to donate so frequently.
b. Our laboratory is leading a large epidemiological study performed in collaboration with other scientists in the National Heart Lung and Blood Institute’s Retroviral Epidemiology Donor Study II (REDSII) group. This study investigates low hematocrit deferral in over 700,000 blood donors from across the country in order to define demographic features of blood donors that increase or decrease their risk for having low hematocrit deferral. These studies are important because approximately 10% of people attempting to donate blood can not donate because they have low hematocrit. Identification of new strategies to decrease these deferrals could have a significant impact on the national blood supply.
c. As mentioned above, many people who attempt to donate blood are found to have anemia. There are many causes for anemia including nutritional deficiency, repeated blood donation, arthritis and diabetes. However, of particular concern in blood donors who represent a generally healthy segment of the population are “invisible” causes of anemia such as pre-malignant or malignant lesions within the gastrointestinal tract. In collaboration with scientists at the Medical College of Wisconsin and the National Anemia Action Council we have developed a new informational pamphlet based on the recommendations from two focus groups consisting of a total of 25 donors that had been deferred for low hematocrit. We are currently testing the ability of this pamphlet to influence the correct donors (i.e. those with high risk for a medically treatable cause for anemia) to seek medical care in a randomized study. We feel that the development of effective educational programs for blood donors with anemia represents a highly efficient and heretofore overlooked use of blood/plasma centers to significantly improve public health in the United States.
Susan Maroney, DVM, PhD
Research Scientist II
Paul Ellery, PhD
Jeremy Wood, PhD
Asst. Research Technologist
Asst. Research Coordinator
Asst. Research Coordinator
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