Hoffman, M, and Monroe, DM. "Coagulation 2006: a modern view of hemostasis." Hematol Oncol Clin North Am 21, no. 1 (February 2007): 1-11. (Review)
Maureane Richardson Hoffman, MD, PhD
The blood coagulation system is a delicately balanced homeostatic mechanism. Inappropriate clotting is a major cause of morbidity and mortality, resulting in strokes, heart attacks, thrombophlebitis and pulmonary embolism. My research is directed toward understanding basic mechanisms in hemostasis, and the connections between inflammation/immunity and coagulation responses to injury. We are also committed to translating our basic finding into clinical practice.
We have developed a cell-based model of tissue factor-initiated coagulation. This model is a powerful tool for understanding and studying basic mechanisms in hemostasis. It has taught us that the cellular LOCATION of activation of the clotting factors is critically important in determining their ability to initiate and support formation of a hemostatic clot. Using this model system we have been able to explain why factors VIII and IX (the factors that are deficient in hemophilia A and B) are essential for hemostasis in vivo, and also how high dose FVIIa can bypass the need for FVIII or FIX and restore hemostasis in hemophiliacs. We have also modeled the hemostatic defects in dilutional coagulopathy, liver disease and anticoagulant treatment. These models are helping us understand why the common clinical coagulation tests do not predict the risk of bleeding well in these conditions.
We have also examined the role of the coagulation process in wound healing. Clinicians have long felt that wound healing is delayed in hemophiliacs. We have now ascertained that hemophilia B mice do indeed have delayed wound healing. They have poor influx of phagocytic cells into the wound area and delayed clearance of debris and iron from hemorrhage. Surprisingly, the mice with defective hemostasis have greater angiogenesis during the healing process. This is a result of the inflammatory effects of iron in the tissues. The excess angiogenesis may be one reason why hemophiliacs often have recurrent bleeding into their joints - the healing process produces a large number of fragile vessels.
Anticoagulation also impairs wound healing. Patients are often anti coagulated after surgery to prevent deep vein thrombosis and pulmonary embolism. However, the impact of this therapy on tissue repair is not well understood. Our aim is to define the extent and time frame of hemostatic function that is needed for optimal healing, thereby setting the stage for scientifically based strategies for anticoagulation.
Education and Training
- Assistant Professor, Pathology, Duke University, 1991 - 1995
- Assistant Professor Of Pathology, Pathology, University of North Carolina at Chapel Hill, 1987 - 1991
- Resident, Pathology, Duke University, 1982 - 1985
- Ph.D., University of Iowa, 1982
- M.D., University of Iowa, 1982
Hoffman, M, Harger, A, Lenkowski, A, Hedner, U, Roberts, HR, and Monroe, DM. "Cutaneous wound healing is impaired in hemophilia B." Blood 108, no. 9 (November 1, 2006): 3053-3060.
Hoffman, M, Whinna, HC, and Monroe, DM. "Circulating tissue factor accumulates in thrombi, but not in hemostatic plugs." J Thromb Haemost 4, no. 9 (September 2006): 2092-2093. (Letter)
Roberts, HR, Hoffman, M, and Monroe, DM. "A cell-based model of thrombin generation." Semin Thromb Hemost 32 Suppl 1 (April 2006): 32-38. (Review)
Sauls, DL, Lockhart, E, Warren, ME, Lenkowski, A, Wilhelm, SE, and Hoffman, M. "Modification of fibrinogen by homocysteine thiolactone increases resistance to fibrinolysis: a potential mechanism of the thrombotic tendency in hyperhomocysteinemia." Biochemistry 45, no. 8 (February 28, 2006): 2480-2487.
Monroe, DM, and Hoffman, M. "What does it take to make the perfect clot?." Arterioscler Thromb Vasc Biol 26, no. 1 (January 2006): 41-48. (Review)
Wolberg, AS, Allen, GA, Monroe, DM, Hedner, U, Roberts, HR, and Hoffman, M. "High dose factor VIIa improves clot structure and stability in a model of haemophilia B." Br J Haematol 131, no. 5 (December 2005): 645-655.
Wolberg, AS, Meng, ZH, Monroe, DM, and Hoffman, M. "A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function." J Trauma 56, no. 6 (June 2004): 1221-1228.
Allen, GA, Wolberg, AS, Oliver, JA, Hoffman, M, Roberts, HR, and Monroe, DM. "Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system." J Thromb Haemost 2, no. 3 (March 2004): 402-413.
Meng, ZH, Wolberg, AS, Monroe, DM, and Hoffman, M. "The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients." J Trauma 55, no. 5 (November 2003): 886-891.
Sauls, DL, Wolberg, AS, and Hoffman, M. "Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability: implications for the mechanism of thrombosis in hyperhomocysteinemia." J Thromb Haemost 1, no. 2 (February 2003): 300-306.
Oliver, JA, Monroe, DM, Church, FC, Roberts, HR, and Hoffman, M. "Activated protein C cleaves factor Va more efficiently on endothelium than on platelet surfaces." Blood 100, no. 2 (July 15, 2002): 539-546.
White, R, Rusconi, C, Scardino, E, Wolberg, A, Lawson, J, Hoffman, M, and Sullenger, B. "Generation of species cross-reactive aptamers using "toggle" SELEX." Mol Ther 4, no. 6 (December 2001): 567-573.
Hoffman, M, and Monroe, DM. "A cell-based model of hemostasis." Thromb Haemost 85, no. 6 (June 2001): 958-965. (Review)
Monroe, DM, Hoffman, M, Allen, GA, and Roberts, HR. "The factor VII-platelet interplay: Effectiveness of recombinant factor VIIa in the treatment of bleeding in severe thrombocytopathia." Seminars in Thrombosis and Hemostasis 26, no. 4 (November 25, 2000): 373-377. (Review)