- A cell-based model of coagulation and the role of factor VIIaMaureane Hoffman
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27705, USA
Blood Rev 17:S1-5. 2003..We believe that even in the presence of the FIXa/FVIIIa complex, rFVIIa may be able to enhance both FXa and FIXa levels on the surface of activated platelets, thus increasing the production of thrombin...
- Remodeling the blood coagulation cascadeMaureane Hoffman
Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27705, USA
J Thromb Thrombolysis 16:17-20. 2003..This cell-based model suggests that the "intrinsic" and "extrinsic" pathways are in fact not redundant systems, but operate in parallel on different cell surfaces...
- Coagulation 2006: a modern view of hemostasisMaureane Hoffman
Pathology and Laboratory Medicine Service 113, Durham Veterans Affairs Medical Center, 508 Fulton Street, Durham, NC 27705, USA
Hematol Oncol Clin North Am 21:1-11. 2007..Generation of the right amount of thrombin during the coagulation process not only may be essential for effective hemostasis but also may set the stage for effective wound healing...
- Perivascular tissue factor is down-regulated following cutaneous wounding: implications for bleeding in hemophiliaAnna G McDonald
Duke University, Durham, NC, USA
Blood 111:2046-8. 2008..Thus, perivascular TF expression is down-regulated during wound healing. This may prevent thrombosis of neovessels during angiogenesis but renders hemophiliacs vulnerable to hemorrhage during healing...
- Platelet binding and activity of recombinant factor VIIaMaureane Hoffman
Pathology and Laboratory Medicine Service, Durham VA Medical Center, 508 Fulton St, Durham, NC 27705, USA
Thromb Res 125:S16-8. 2010..Thus, there are still unanswered questions in fully understanding the mechanism of hemostatic action of recombinant FVIIa...
- Alterations of fibrinogen structure in human diseaseM Hoffman
Pathology and Laboratory Medicine Service 113, Durham Veterans Affairs, Medical Center, 508 Fulton St, Durham, NC 27705, USA
Cardiovasc Hematol Agents Med Chem 6:206-11. 2008..However, direct evidence is still lacking that these modifications contribute to the increased atherothrombotic risk associated with hyperhomocysteinemia and diabetes...
- Platelet binding and activity of a factor VIIa variant with enhanced tissue factor independent activityM Hoffman
Duke University, Pathology and Laboratory Medicine Service, Durham Veterans Affairs Medical Centers, Durham, NC 27705, USA
J Thromb Haemost 9:759-66. 2011..NN1731 has a conformation similar to TF-bound FVIIa, even in the absence of TF. This results in much greater intrinsic proteolytic activity, but similar activity in the presence of TF...
- Pro-thrombotic and pro-oxidant effects of diet-induced hyperhomocysteinemiaDerrick L Sauls
Pathology and Lab Medicine Service, Durham Veterans Affairs Medical Center, Durham, Nutrition Program, Department Food Science, NC State University, Raleigh, NC, USA
Thromb Res 120:117-26. 2007..Our findings suggest that an acquired dysfibrinogenemia could play a role in the increased risk of atherothrombotic disease in mildly hyperhomocysteinemic human subjects...
- Cutaneous wound healing is impaired in hemophilia BMaureane Hoffman
Laboratory Service 113, Durham Veterans Affairs Medical Center, 508 Fulton St, Durham, NC 27705, USA
Blood 108:3053-60. 2006..Our findings have significant implications for treatment of patients with hemophilia, and also highlight the importance of rapidly establishing hemostasis following trauma or surgery...
- Modification of fibrinogen by homocysteine thiolactone increases resistance to fibrinolysis: a potential mechanism of the thrombotic tendency in hyperhomocysteinemiaDerrick L Sauls
Research Service, Durham Veteran s Affairs Medical Center, 508 Fulton Street, Durham, North Carolina 27705, USA
Biochemistry 45:2480-7. 2006..We hypothesize that the modification of lysine by Hcys thiolactone might occur in vivo, lead to abnormal resistance of clots to lysis, and thereby contribute to the prothrombotic state associated with homocysteinemia...
- Low intensity laser therapy speeds wound healing in hemophilia by enhancing platelet procoagulant activityMaureane Hoffman
Department of Pathology, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina 27705, USA
Wound Repair Regen 20:770-7. 2012..These data suggest that trials of LILT as an adjunct to the usual hemostatic therapies in hemophilia are warranted...
- 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 patientsZhi Hong Meng
Department of Pathology, Duke University Medical Center, Durham, NC 27705, USA
J Trauma 55:886-91. 2003..High-dose FVIIa has also been used off-label to manage hemorrhage in trauma and surgical patients, many of whom also develop hypothermia and acidosis...
- Superactivated platelets: thrombus regulators, thrombin generators, and potential clinical targetsMarshall Mazepa
Department of Pathology, University of North Carolina Hospitals, Chapel Hill, NC 27599, USA
Arterioscler Thromb Vasc Biol 33:1747-52. 2013..Superactivated platelets' role in diseases of thrombosis and hemostasis, as either potentiating or mitigating factors, is not currently known, but may be an important pharmacological target. ..
- The multiple roles of tissue factor in wound healingMaureane Hoffman
Pathology and Laboratory Medicine Service, Durham VA Medical Center, Durham, NC 27705, USA
Front Biosci (Schol Ed) 4:713-21. 2012..The literature in this are remains somewhat sparse, but suggests that modulation of TF expression plays a role in modulating the host response to injury...
- Activated protein C cleaves factor Va more efficiently on endothelium than on platelet surfacesJulie A Oliver
Duke University and the Durham VA Medical Hospital, Durham, NC, USA
Blood 100:539-46. 2002..From the studies reported here, we conclude that in vivo, despite the important role of the protein C system in regulating thrombosis, activated protein C does not serve as a primary regulator of platelet-dependent thrombin generation...
- Homocysteinylated fibrinogen forms disulfide-linked complexes with albuminDerrick L Sauls
Research Service, Durham Veterans Affairs Medical Center, Durham, NC 27705, United States
Thromb Res 127:576-81. 2011....
- Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombinShahid M Nimjee
Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA
RNA 15:2105-11. 2009..This combination of exosite 1 and exosite 2 inhibitors may provide a particularly effective antithrombotic approach...
- Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literatureKelly L West
Department of Pathology, Duke University, Durham, North Carolina, USA
J Neurosurg 114:9-18. 2011..Based on their review of the literature, the authors suggest that in a hemodynamically stable patient population there is a range of mildly prolonged INR values for which FFP transfusion is not beneficial, and is potentially harmful...
- Some things I thought I knew about tissue factor that turn out to be wrongMaureane Hoffman
Department of Pathology, Duke University Medical Center, Durham Veterans Affairs Medical Center, Durham, NC, USA
Thromb Res 122:S73-7. 2008..The observed down-regulation of TF expression may serve to prevent thrombosis of developing neovessels and contribute to the well-recognized tendency of granulation tissue to bleed readily and profusely...
- A rationally designed heparin, M118, has anticoagulant activity similar to unfractionated heparin and different from Lovenox in a cell-based model of thrombin generationZoya Volovyk
Duke University Medical Center, Durham, NC 27710, USA
J Thromb Thrombolysis 28:132-9. 2009..Our data suggest that the ability to inhibit platelet surface IIa generation correlates with the therapeutic level of heparins and confirms similarities between the anticoagulant properties of M118 and UFH...
- Hypothesis: hyperhomocysteinemia is an indicator of oxidant stressMaureane Hoffman
Pathology and Laboratory Medicine Service, Durham VA Medical Center, Durham, NC 27705, USA
Med Hypotheses 77:1088-93. 2011....
- The cellular basis of traumatic bleedingMaureane Hoffman
Department of Pathology, Duke University Medical Center, Durham, NC, USA
Mil Med 169:5-7, 4. 2004..These articles discuss the causes of posttraumatic microvascular bleeding and the potential treatment options for controlling catastrophic hemorrhage in combat areas...
- Localization of heparin cofactor II in injured human skin: a potential role in wound healingMaureane Hoffman
Duke University School of Medicine and Pathology and Laboratory Medicine Service, Durham Veterans Affairs Medical Center, Durham, NC 27705, USA
Exp Mol Pathol 75:109-18. 2003..These findings support the notion that HCII could function as an extravascular thrombin inhibitor and might play a role in the regulation of wound healing...
- What does it take to make the perfect clot?Dougald M Monroe
Durham Veterans Affairs Medical Center, Department of Pathology, Duke University Medical Center, Durham, NC, USA
Arterioscler Thromb Vasc Biol 26:41-8. 2006..Our understanding of how specific cellular features control the processes of hemostasis and thrombosis is developing rapidly. This review discusses some aspects of the cellular control of coagulation...
- Hemostatic properties of the FVIIa analog NN1731Maureane Hoffman
Duke University and Durham Veterans Affairs Medical Centers, Pathology and Laboratory Medicine Svc, Durham, North Carolina 27705, USA
Thromb Res 129:S49-50. 2012..This molecule exhibits greater potency than FVIIa in biochemical assays, in vitro and animal models, and in early phase clinical trials...
- The clotting system - a major player in wound healingDougald M Monroe
Division of Hematology Oncology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7035, USA
Haemophilia 18:11-6. 2012..The goal of such treatment would be to avoid a feedback cycle in which bleeding tends to lead to further bleeding. Once initiated, this cycle may be difficult to control...
- Differences in the metabolic response to exogenous homocysteine in juvenile and adult rabbitsDerrick L Sauls
Department of Pathology, Duke University Medical Center, City, NC, USA
J Nutr Biochem 15:96-102. 2004..The difference in metabolism of homocysteine may protect the juvenile rabbits from the damaging effects of homocysteine. Future studies are planned to elucidate the mechanism of this adaptive response...
- Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability: implications for the mechanism of thrombosis in hyperhomocysteinemiaD L Sauls
Pathology and Laboratory Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina 27705, USA
J Thromb Haemost 1:300-6. 2003..The formation of clots that are abnormally resistant to fibrinolysis could directly contribute to the increased risk of thrombosis in hyperhomocysteinemia...
- The action of high-dose factor VIIa (FVIIa) in a cell-based model of hemostasisMaureane Hoffman
Dis Mon 49:14-21. 2003..Our data suggest that in a cellular system high-dose FVIIa acts primarily by enhancing the rate of thrombin generation on platelet surfaces and not by overcoming inhibition by zymogen FVII of TF-dependent activation of FX...
- New insights into the coagulation system and implications for new therapeutic options with recombinant factor VIIaAlex Veldman
J W Goethe University Hospital, Dept Pediatrics, Frankfurt, Germany
Curr Med Chem 10:797-811. 2003....
- High dose factor VIIa improves clot structure and stability in a model of haemophilia BAlisa S Wolberg
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599 7525, USA
Br J Haematol 131:645-55. 2005....
- Platelet-dependent action of high-dose factor VIIaMaureane Hoffman
Blood 100:364-5; author reply 365. 2002
- Manipulation of prothrombin concentration improves response to high-dose factor VIIa in a cell-based model of haemophiliaGeoffrey A Allen
Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Br J Haematol 134:314-9. 2006..Furthermore, these results suggest that increasing plasma prothrombin concentration prior to rFVIIa administration may offer advantages over the use of rFVIIa alone in the treatment of haemophilic bleeding...
- Coagulation factor interaction with plateletsDougald M Monroe
Center for Thrombosis and Hemostasis, University of North Carolina, Chapel Hill, NC, USA
Thromb Haemost 88:179. 2002
- Platelet heterogeneity: variation in coagulation complexes on platelet subpopulationsChristine L Kempton
University of North Carolina, Chapel Hill, NC 27599 7035, USA
Arterioscler Thromb Vasc Biol 25:861-6. 2005....
- Platelets and thrombin generationDougald M Monroe
Center for Thrombosis and Hemostasis, University of North Carolina, Chapel Hill 27599 7035, USA
Arterioscler Thromb Vasc Biol 22:1381-9. 2002..Individual differences in platelet thrombin generation might be accounted for by differences in platelet-binding proteins...
- Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current managementStephen H Caldwell
University of Virginia, Digestive Health Center of Excellence, GI Hepatology Division, Charlottesville, VA 22908 0705, USA
Hepatology 44:1039-46. 2006....
- Elevated prothrombin results in clots with an altered fiber structure: a possible mechanism of the increased thrombotic riskAlisa S Wolberg
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, USA
Blood 101:3008-13. 2003..We hypothesize that this alteration in fibrin clot structure is an important determinant of the risk of thrombosis...
- Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhageGeoffrey A Allen
Center for Thrombosis and Hemostasis and Pediatric Hematology Oncology, University of North Carolina School of Medicine, Chapel Hill 27599 7220, USA
Can J Anaesth 49:S7-14. 2002..We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings...
- A cell-based model of thrombin generationHarold R Roberts
School of Medicine, Division of Hematology Oncology, Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, North Carolina 27599 7035, USA
Semin Thromb Hemost 32:32-8. 2006..We have also shown that activated protein C does not inactivate Va on the platelet surface but rather on endothelial cell surfaces...
- Fathers of modern coagulationDougald M Monroe
UNC Medical School Hematology Oncology, 932 Mary Ellen Jones, CB 7035 Chapel Hill, North Carolina 27599 7035, USA
Thromb Haemost 98:3-5. 2007
- A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet functionAlisa S Wolberg
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
J Trauma 56:1221-8. 2004..Hypothermia-associated bleeding has been hypothesized to result from dysregulation of enzymatic function, reduced platelet activity, and/or altered fibrinolysis...
- Laboratory monitoring of high-dose factor VIIa therapyMaureane Hoffman
Ann Intern Med 139:791. 2003
- Safety profile of recombinant factor VIIaHarold R Roberts
Division of Hematology, Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, USA
Semin Hematol 41:101-8. 2004..Finally, those situations in which rFVIIa therapy may not be safe, such as disseminated intravascular coagulation (DIC) and sepsis, will also be discussed...