Scholars@Duke
Maureane Hoffman

Maureane Hoffman

Professor of Pathology
Pathology
Duke Box 3712, Durham, NC 27710
F3184 VA Med Ctr, 508 Fulton St, Durham, NC 27705

Featured Works

The Tissue Factor Pathway and Wound Healing.

Journal article Semin Thromb Hemost · March 2018 Featured Publication The role of tissue factor (TF) as the major initiator of hemostatic blood coagulation is well recognized. The ability to form an adequate hemostatic clot is essential to the normal healing of an injury by staunching bleeding, stabilizing the injured tissue ... Full text Link to item Cite

An activated factor VII variant with enhanced tissue factor-independent activity speeds wound healing in a mouse hemophilia B model.

Journal article J Thromb Haemost · June 2016 Featured Publication UNLABELLED: Essentials Disorders of hemostasis can lead to delayed and defective wound healing. In hemophilia B (HB) mice, 7 days of Factor (F)IX or VIIa are needed to normalize wound healing. One dose of a highly active FVIIa variant (DVQ) restored normal ... Full text Open Access Link to item Cite

The multiple roles of tissue factor in wound healing.

Journal article Front Biosci (Schol Ed) · January 1, 2012 Featured Publication The procoagulant role of tissue factor (TF) is well recognized. The ability to form a hemostatic clot is essential to normal healing of an injury. However, TF also has additional activities as a regulator of cellular processes. Both by production of coagul ... Full text Link to item Cite

Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress.

Journal article Med Hypotheses · December 2011 Featured Publication Elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and thrombosis, as well as a variety of other pathologies such as birth defects, Alzheimer's disease and other dementias, osteoporosis, diabetes and renal disease. ... Full text Link to item Cite

Platelet binding and activity of a factor VIIa variant with enhanced tissue factor independent activity.

Journal article J Thromb Haemost · April 2011 Featured Publication BACKGROUND AND OBJECTIVES: Platelet binding and activity play important roles in the efficacy of factor VIIa (FVIIa) as a bypassing agent for hemophilia treatment. An analog of FVIIa with increased tissue factor (TF)-independent activity, NN1731, has been ... Full text Link to item Cite

Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature.

Journal article J Neurosurg · January 2011 Featured Publication Prophylactic fresh-frozen plasma (FFP) transfusion is often undertaken in hemodynamically stable patients with a minimally elevated international normalized ratio (INR) prior to invasive procedures, despite little evidence in support of this practice. The ... Full text Link to item Cite

Wound healing in haemophilia--breaking the vicious cycle.

Journal article Haemophilia · May 2010 Featured Publication Our group has been studying how haemostasis interacts with repair processes and also how to optimize treatment of bleeding disorders in a mouse model of haemophilia B. We have found that cutaneous wounds heal more slowly in haemophilic mice than in wild-ty ... Full text Link to item Cite

Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin.

Journal article RNA · December 2009 Featured Publication Thrombin is a multifunctional protease that plays a key role in hemostasis, thrombosis, and inflammation. Most thrombin inhibitors currently used as antithrombotic agents target thrombin's active site and inhibit all of its myriad of activities. Exosites 1 ... Full text Link to item Cite

A rationally designed heparin, M118, has anticoagulant activity similar to unfractionated heparin and different from Lovenox in a cell-based model of thrombin generation.

Journal article J Thromb Thrombolysis · August 2009 Featured Publication Unfractionated heparin (UFH) enhances antithrombin (AT) inhibition of thrombin (IIa) and factor Xa (FXa). Low molecular weight heparins (LMWH) primarily enhance AT inhibition of FXa. M118 is a LMWH produced from UFH and retains its ability to promote both ... Full text Link to item Cite

The coagulation cascade in cirrhosis.

Journal article Clin Liver Dis · February 2009 Featured Publication The coagulation "cascade" model accurately represents the mechanisms of the prothrombin time and activated partial thromboplastin time tests. However, these tests and the "cascade" model do not accurately reflect the risk of hemorrhage or thrombosis in viv ... Full text Link to item Cite

Alterations of fibrinogen structure in human disease.

Journal article Cardiovasc Hematol Agents Med Chem · July 2008 Featured Publication Products of normal and pathologic metabolism can react with proteins to cause covalent modification. When such modifications affect fibrinogen they can potentially alter fibrinogen function. Those that have been best studied are oxidation, nitration, homoc ... Full text Link to item Cite

Perivascular tissue factor is down-regulated following cutaneous wounding: implications for bleeding in hemophilia.

Journal article Blood · February 15, 2008 Featured Publication Healing of skin wounds is delayed in hemophilia B (HB) mice. HB mice do not bleed excessively at wounding, yet rebleed hours to days later. Tissue factor (TF) expression is up-regulated by inflammatory cytokines and has been linked to angiogenesis. We hypo ... Full text Link to item Cite

Restoring hemostatic thrombin generation at the time of cutaneous wounding does not normalize healing in hemophilia B.

Journal article J Thromb Haemost · August 2007 Featured Publication BACKGROUND: We recently reported that wound healing is abnormal in hemophilia B (HB) mice [1]. The wounds show abnormal histology: s.c. hematoma formation; delayed re-epithelialization; delayed macrophage influx; and an increase in wound site angiogenesis. ... Full text Link to item Cite

Tissue factor around dermal vessels has bound factor VII in the absence of injury.

Journal article J Thromb Haemost · July 2007 Featured Publication BACKGROUND: 'Idling' or ongoing low-level activity of the tissue factor (TF) pathway is a postulated mechanism by which the coagulation process can become active without a lag period at sites of injury. OBJECTIVE: To determine whether TF around cutaneous v ... Full text Link to item Cite

Coagulation 2006: a modern view of hemostasis.

Journal article Hematol Oncol Clin North Am · February 2007 Featured Publication The authors propose that hemostasis occurs in a stepwise process, regulated by cellular components in vivo. The effectiveness of hemostasis in vivo depends not only on the procoagulant reactions but also on the fibrinolytic process. Causes of coagulopathic ... Full text Link to item Cite

Cutaneous wound healing is impaired in hemophilia B.

Journal article Blood · November 1, 2006 Featured Publication We used a mouse model to test the hypothesis that the time course and histology of wound healing is altered in hemophilia B. Punch biopsies (3 mm) were placed in the skin of normal mice and mice with hemophilia. The size of the wounds was measured daily un ... Full text Link to item Cite

Circulating tissue factor accumulates in thrombi, but not in hemostatic plugs.

Journal article J Thromb Haemost · September 2006 Featured Publication Full text Link to item Cite

A cell-based model of thrombin generation.

Journal article Semin Thromb Hemost · April 2006 Featured Publication We have developed a cell-based model of thrombin generation using activated monocytes as a source of tissue factor (TF) and platelets serving as a surface for thrombin generation. Monocytes are activated by lipopolysaccharide and express cell-bound TF. To ... Full text Link to item Cite

Modification of fibrinogen by homocysteine thiolactone increases resistance to fibrinolysis: a potential mechanism of the thrombotic tendency in hyperhomocysteinemia.

Journal article Biochemistry · February 28, 2006 Featured Publication We have previously shown functional differences in fibrinogen from hyperhomocysteinemic rabbits compared to that in control rabbits. This acquired dysfibrinogenemia is characterized by fibrin clots that are composed of abnormally thin, tightly packed fiber ... Full text Link to item Cite

What does it take to make the perfect clot?

Journal article Arterioscler Thromb Vasc Biol · January 2006 Featured Publication The coagulation process has been conceptualized as being primarily dependent on adequate levels of the coagulation proteins. This concept was based on the clear relationship between the bleeding tendency and factor levels in hemophilia. The field is now ev ... Full text Link to item Cite

High dose factor VIIa improves clot structure and stability in a model of haemophilia B.

Journal article Br J Haematol · December 2005 Featured Publication Factor IX (FIX) deficiency results in haemophilia B and high dose recombinant activated factor VII (rFVIIa) can decrease bleeding. Previously, we showed that FIX deficiency results in a reduced rate and peak of thrombin generation. We have now used plasma ... Full text Link to item Cite

A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function.

Journal article J Trauma · June 2004 Featured Publication BACKGROUND: Hypothermia is associated with an increased risk of bleeding and is a significant contributing factor to the morbidity and mortality of trauma and complicated surgical procedures. A core temperature of 33 degrees C is associated with a signific ... Full text Link to item Cite

Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system.

Journal article J Thromb Haemost · March 2004 Featured Publication Using a cell-based model system of coagulation, we performed a systematic examination of the effect of varying individual procoagulant proteins (over the range of 0-200% of pooled plasma levels) on the characteristics of thrombin generation. The results re ... Full text Link to item Cite

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.

Journal article J Trauma · November 2003 Featured Publication BACKGROUND: Recombinant coagulation factor VIIa (FVIIa) is approved for treating hemophiliacs with inhibitors. High-dose FVIIa has also been used off-label to manage hemorrhage in trauma and surgical patients, many of whom also develop hypothermia and acid ... Full text Link to item Cite

Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability: implications for the mechanism of thrombosis in hyperhomocysteinemia.

Journal article J Thromb Haemost · February 2003 Featured Publication Elevated plasma homocysteine is associated with an increased risk of atherosclerosis and thrombosis. However, the mechanisms by which homocysteine might cause these events are not understood. We hypothesized that hyperhomocysteinemia might lead to modifica ... Full text Link to item Cite

Activated protein C cleaves factor Va more efficiently on endothelium than on platelet surfaces.

Journal article Blood · July 15, 2002 Featured Publication The protein C/protein S system is known to regulate thrombin generation in vivo by cleaving factors Va and VIIIa. We have examined the activity of activated protein C in several tissue factor-initiated models of coagulation. We used 4 models: monocytes as ... Full text Link to item Cite

Generation of species cross-reactive aptamers using "toggle" SELEX.

Journal article Mol Ther · December 2001 Featured Publication Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected b ... Full text Link to item Cite

A cell-based model of hemostasis.

Journal article Thromb Haemost · June 2001 Featured Publication Based on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that ... Link to item Cite

The factor VII-platelet interplay: Effectiveness of recombinant factor VIIa in the treatment of bleeding in severe thrombocytopathia

Journal article Seminars in Thrombosis and Hemostasis · November 25, 2000 Featured Publication Recently, high-dose factor VIIa has been used to correct bleeding in patients with various thrombocytopathias including Glanzmann's thrombasthenia, Bernard-Soulier syndrome, and uremia. High-dose factor VIIa is postulated to act on platelets in the absence ... Cite

Thrombin activates factor XI on activated platelets in the absence of factor XII.

Journal article Arterioscler Thromb Vasc Biol · January 1999 Featured Publication Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides. However, a physiological cofactor for thrombin activation of factor XI has not been identified. We examined this question in a cell-based, tissue factor-initiated model syste ... Full text Link to item Cite

Activated factor VII activates factors IX and X on the surface of activated platelets: thoughts on the mechanism of action of high-dose activated factor VII.

Journal article Blood Coagul Fibrinolysis · March 1998 Featured Publication High levels of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) have been found to be effective in providing haemostasis in haemophiliacs and in normal individuals with acquired inhibitors to factor VIII (FVIII) or FIX ... Link to item Cite

Platelet activity of high-dose factor VIIa is independent of tissue factor.

Journal article Br J Haematol · December 1997 Featured Publication High-dose recombinant factor VIIa has been successfully used as therapy for haemophiliacs with inhibitors. The mechanism by which high-dose factor VIIa supports haemostasis is the subject of some controversy. Postulating a mechanism in which activity is de ... Full text Link to item Cite

From antiphospholipid syndrome to antibody-mediated thrombosis.

Journal article Lancet · November 22, 1997 Featured Publication Full text Link to item Cite

Transmission of a procoagulant signal from tissue factor-bearing cell to platelets.

Journal article Blood Coagul Fibrinolysis · June 1996 Featured Publication The goal of the current study was to examine the mechanism by which factor VIIa/tissue factor (TF) activity leads to platelet activation as the first step in initiation of coagulation. Adherent, endotoxin-treated monocytes were used as a cellular source of ... Full text Link to item Cite

Platelet procoagulant complex assembly in a tissue factor-initiated system.

Journal article Br J Haematol · October 1994 Featured Publication The aim of this study was to examine the assembly of the factor IXa/VIIIa (Xase) and factor Xa/Va (IIase) complexes on the platelet surface in a system designed to mimic tissue factor-initiated coagulation. The experimental system contained tissue factor-b ... Full text Link to item Cite

Antibody-coated erythrocytes induce secretion of tumor necrosis factor by human monocytes: a mechanism for the production of fever by incompatible transfusions.

Journal article Vox Sang · 1991 Featured Publication The transfusion of incompatible red blood cells (RBC) rapidly results in the development of fever by an unknown mechanism. In this study, the human monocyte secretion of the endogenous pyrogens tumor necrosis factor (TNF) and interleukin-1 (IL-1) was measu ... Full text Link to item Cite

The macrophage-mediated regulation of hepatocyte synthesis of antithrombin III and alpha 1-proteinase inhibitor.

Journal article Thromb Res · March 1, 1986 Featured Publication Antithrombin III (ATIII) is an anticoagulant protein which binds and inactivates thrombin and other serine proteinases. Little is known about regulation of its synthesis. We confirm that ATIII is synthesized by isolated rat hepatocytes, and that its synthe ... Full text Link to item Cite