Hoffman, M, Chang, J-Y, Ezban, M, and Monroe, DM. "An activated factor VII variant with enhanced tissue factor-independent activity speeds wound healing in a mouse hemophilia B model." Journal of thrombosis and haemostasis : JTH 14, no. 6 (June 2016): 1249-1254.
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, and Monroe, DM. "The multiple roles of tissue factor in wound healing. (Published online)" Front Biosci (Schol Ed) 4 (January 1, 2012): 713-721. (Review)
Hoffman, M. "Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress." Med Hypotheses 77, no. 6 (December 2011): 1088-1093.
Hoffman, M, Volovyk, Z, Persson, E, Gabriel, DA, Ezban, M, and Monroe, DM. "Platelet binding and activity of a factor VIIa variant with enhanced tissue factor independent activity." J Thromb Haemost 9, no. 4 (April 2011): 759-766.
West, KL, Adamson, C, and Hoffman, M. "Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature." J Neurosurg 114, no. 1 (January 2011): 9-18. (Review)
Hoffman, M, and Monroe, DM. "Wound healing in haemophilia--breaking the vicious cycle." Haemophilia 16 Suppl 3 (May 2010): 13-18. (Review)
Nimjee, SM, Oney, S, Volovyk, Z, Bompiani, KM, Long, SB, Hoffman, M, and Sullenger, BA. "Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin." RNA 15, no. 12 (December 2009): 2105-2111.
Volovyk, Z, Monroe, DM, Qi, Y, Becker, R, and Hoffman, M. "A rationally designed heparin, M118, has anticoagulant activity similar to unfractionated heparin and different from Lovenox in a cell-based model of thrombin generation." J Thromb Thrombolysis 28, no. 2 (August 2009): 132-139.
Hoffman, M, and Monroe, DM. "Tissue factor in brain is not saturated with factor VIIa: implications for factor VIIa dosing in intracerebral hemorrhage." Stroke 40, no. 8 (August 2009): 2882-2884.
Monroe, DM, and Hoffman, M. "The coagulation cascade in cirrhosis." Clin Liver Dis 13, no. 1 (February 2009): 1-9.
Hoffman, M. "Alterations of fibrinogen structure in human disease." Cardiovasc Hematol Agents Med Chem 6, no. 3 (July 2008): 206-211. (Review)
McDonald, AG, Yang, K, Roberts, HR, Monroe, DM, and Hoffman, M. "Perivascular tissue factor is down-regulated following cutaneous wounding: implications for bleeding in hemophilia." Blood 111, no. 4 (February 15, 2008): 2046-2048.
McDonald, A, Hoffman, M, Hedner, U, Roberts, HR, and Monroe, DM. "Restoring hemostatic thrombin generation at the time of cutaneous wounding does not normalize healing in hemophilia B." J Thromb Haemost 5, no. 8 (August 2007): 1577-1583.
Hoffman, M, Colina, CM, McDonald, AG, Arepally, GM, Pedersen, L, and Monroe, DM. "Tissue factor around dermal vessels has bound factor VII in the absence of injury." J Thromb Haemost 5, no. 7 (July 2007): 1403-1408.
Sauls, DL, Banini, AE, Boyd, LC, and Hoffman, M. "Elevated prothrombin level and shortened clotting times in subjects with type 2 diabetes." J Thromb Haemost 5, no. 3 (March 2007): 638-639. (Letter)