About

Professor Maureane Hoffman is a Professor of Pathology and Assistant Professor of Integrative Immunobiology at Duke University. Her laboratory focuses on studying the mechanisms of hemostasis, contributing significantly to the field by developing a cell-based model of coagulation that offers a more physiologically relevant alternative to the traditional cascade model. This innovative approach has enhanced the understanding of how drugs can modulate hemostasis to prevent thrombosis, aiming to design improved therapeutic strategies. Additionally, her research explores the influence of coagulation products on inflammatory and immune responses, angiogenesis, and tissue repair, highlighting the complex interplay between coagulation and other biological processes.

Research topics

• Medicine
• Internal medicine
• Immunology
• Intensive care medicine
• Surgery
• Biochemistry
• Biology
• Cell biology
• Anesthesia
• Chemistry

Selected publications

• Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet‐like particles

  UNC Libraries · 2026-04-08

  articleOpen access

  Platelets crucially facilitate wound healing but can become depleted in traumatic injury or chronic wounds. Previously, our group developed injectable platelet-like particles (PLPs) comprised of highly deformable, ultralow crosslinked pNIPAm microgels (ULCs) coupled to fibrin binding antibodies to treat post-trauma bleeding. PLP fibrin-binding facilitates homing to sites of injury, promotes clot formation, and, due to high particle deformability, induces clot retraction. Clot retraction augments healing by increasing clot stability, enhancing clot stiffness, and promoting cell migration into the wound bed. Because post-traumatic healing is often complicated by infection, the objective of these studies was to develop antimicrobial nanosilver microgel composite PLPs to augment hemostasis, fight infection, and promote healing post-trauma. A key goal was to maintain particle deformability following silver incorporation to preserve PLP-mediated clot retraction. Clot retraction, antimicrobial activity, hemostasis after trauma, and healing after injury were evaluated via confocal microscopy, colony-forming unit assays, a murine liver trauma model, and a murine full-thickness injury model in the absence or presence of infection, respectively. We found that nanosilver incorporation does not affect base PLP performance while bestowing significant antimicrobial activity and enhancing infected wound healing outcomes. Therefore, Ag-PLPs have great promise for treating hemorrhage and improving healing following trauma.

  PublisherDOI

• Postoperative venous thromboembolism following cesarean delivery: prevalence, pathophysiology, diagnosis, treatment, and prevention

  American Journal of Obstetrics and Gynecology · 2026-01-01 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• The kinetics and interplay of thrombin inhibition by 4 plasma proteinase inhibitors

  Blood Vessels Thrombosis & Hemostasis · 2025-07-05

  articleOpen accessSenior author

  Key Points • Multiple inhibitors including antithrombin (AT), heparin cofactor, α-2-macroglobulin, and α-1-antitrypsin contribute to thrombin inhibition. • As AT is lowered, the roles of these inhibitors become more significant and can completely inhibit thrombin even in the absence of AT. A novel therapeutic approach for restoring hemostasis in hemophilia is to reduce antithrombin (AT) to rebalance reduced thrombin generation. In plasma, multiple inhibitors including antithrombin (AT), heparin cofactor II (HCII), alpha-2-macroglobulin (A2M), and alpha-1-proteinase inhibitor (A1PI) play a role in thrombin inhibition. The goal was to study the kinetics of thrombin inhibition and the roles of various inhibitors across a broad range of AT levels. Thrombin inhibition was measured at varied concentrations of AT with and without A2M, HCII, and A1PI. Reducing AT to zero from plasma levels in the presence HCII, A2M, and A1PI, results in slower thrombin inhibition with the time required to inhibit half the thrombin increasing approximately four fold. Computational models of thrombin inhibition and thrombin generation in hemophilia were constructed and used to analyze thrombin inhibition and the relative contribution of each inhibitor. In a model of thrombin generation, decreased thrombin inhibition resulted in increased peak thrombin and increased area under the thrombin curve. Even at high concentrations of thrombin, all of the thrombin was inhibited with the relative contribution of other inhibitors increasing as AT was decreased. These studies show that in a system without heparin-like glycosaminoglycans, AT is the dominant inhibitor of thrombin, followed by A2M, HCII, and finally A1PI. As AT levels decrease, thrombin inhibition is slower resulting in higher levels of thrombin in a computational model of thrombin generation. Ultimately the other inhibitors compensate for AT to maintain a level of thrombin regulation.

  PublisherDOI

• True anticoagulation safety cannot be achieved without better anticoagulants

  BMJ Open Quality · 2025-10-01

  editorialOpen accessSenior author

  We read with great interest the recent publication by Lui et al in the May 2025 issue, entitled ‘Improving the Safety of Heparin Usage by Standardization Practice’.

  PublisherOA PDFDOI

• Effects on maternal and pregnancy outcomes of first-trimester malaria infection among nulliparous women from Kenya, Zambia, and the Democratic Republic of the Congo

  UNC Libraries · 2025-01-07

  articleOpen access

  Background Few studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes. Methods In a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democratic Republic of the Congo, we tested for first-trimester Plasmodium falciparum infection using quantitative polymerase chain reaction. We estimated site-specific effects on pregnancy outcomes using parametric g-computation. Results Compared to uninfected women, we observed the adjusted site-specific prevalence differences (PDs) among women with first-trimester malaria of the following pregnancy outcomes: preterm birth among Congolese (aPD = 0.06 [99% CI: -0.04, 0.16]), Kenyan (0.03 [-0.04, 0.09]), and Zambian (0.00 [-0.10, 0.20]) women; low birth weight among Congolese (0.07 [-0.03, 0.16]), Kenyan (0.01 [-0.04, 0.06]) and Zambian (-0.04 [-0.13, 0.16]) women; spontaneous abortion among Congolese (0.00 [-0.05, 0.04]), Kenyan (0.00 [-0.04, 0.04]), and Zambian (0.02 [-0.07, 0.24]) women, and anemia later in pregnancy among Congolese (0.04 [-0.09, 0.16]), Kenyan (0.05 [-0.06, 0.17]), and Zambian (0.07 [-0.12, 0.36]) women. The pooled PD for anemia later in pregnancy (26–30 weeks) was 0.08 [99% CI: 0.00, 0.16]. Conclusions First-trimester malaria was associated with increased prevalence of anemia later in pregnancy. We identified areas for further investigation including effects of first-trimester malaria on preterm birth and low birth weight.

  PublisherDOI

• Recombinant factor VIIa: new insights into the mechanism of action through product innovation

  Research and Practice in Thrombosis and Haemostasis · 2024-12-31 · 2 citations

  reviewOpen access

  <h2>Abstract</h2> Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. <i>In vitro</i> and <i>in vivo</i> studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X (FX); (2) directly activating FX on the surface of activated platelets; and (3) downregulating protein C anticoagulant activity through binding to the endothelial protein C receptor (EPCR). Studies of rFVIIa and rFVIIa variants in murine models demonstrate that platelet-dependent activity is sufficient for hemostatic efficacy. Dosing levels required in clinical practice are most consistent with a platelet-dependent mechanism of action. However, <i>in vivo</i> models also suggest that pathways involving EPCR binding contribute to rFVIIa hemostatic activity. Eptacog beta displays increased platelet- and EPCR-dependent endothelial cell binding compared to eptacog alfa. Thus, the relative contribution of these mechanisms to the overall hemostatic efficacy of eptacog alfa and eptacog beta may differ. Further research is required to assess the clinical relevance of these differences. A better understanding of the mechanisms by which rFVIIa promotes hemostasis in patients will provide insights when evaluating clinical outcomes of safety and efficacy for innovative bypassing therapies.

  PublisherOA PDFDOI

• Modelling the effects of 4-factor prothrombin complex concentrate for the management of factor Xa-associated bleeding

  PLoS ONE · 2024-09-27

  articleOpen accessSenior author

  The management of factor Xa (FXa) inhibitor-associated bleeding remains a clinical challenge. Massive bleeding is often associated with complex coagulopathy and, thus, the sole reversal of FXa inhibitors might not be sufficient to restore hemostasis, requiring instead a multimodal approach. Four-factor prothrombin complex concentrate (4F-PCC) is widely recognized as a viable treatment option for FXa inhibitor-associated bleeding. Here, we applied computational models to explore the effect 4F-PCC has on the coagulation cascade and restoration of thrombin generation in a system that simulates a patient that has received a FXa inhibitor. The coagulation model is largely based on a previously developed model with modifications incorporated from various other published sources. The model was calibrated and validated using data from a phase 3 clinical trial of vitamin K antagonist reversal with 4F-PCC. Using the parameters and initial conditions determined during the calibration and validation process, the prothrombin time (PT) test simulations predicted a PT of 11.4 seconds. The model successfully simulated the effects of rivaroxaban and apixaban on total thrombin concentration and showed that 4F-PCC increased thrombin generation in the presence of rivaroxaban or apixaban.

  PublisherDOI

• Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma

  Science Translational Medicine · 2024-04-10 · 38 citations

  articleOpen access

  Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly ( N -isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.

  PublisherOA PDFDOI

• Predictors of Plasmodium falciparum Infection in the First Trimester among Nulliparous Women from Kenya, Zambia, and the Democratic Republic of the Congo

  UNC Libraries · 2024-02-07 · 3 citations

  articleOpen access

  Background: Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-Trimester malaria. Methods: We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-Trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics. Results: First-Trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%-8.8%] in the Zambian site, 37.8% (95% CI, 34.2%-41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%-67.2%) in the DRC site. First-Trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified. Conclusions: First-Trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-Trimester malaria in high-prevalence settings.

  PublisherDOI

• Rebalancing Hemostasis in Hemophilia: Interplay between Antithrombin and Ancillary Thrombin Inhibitors

  Blood · 2024-11-05

  articleSenior author

  Introduction: Antithrombin (AT) is the dominant thrombin inhibitor under normal conditions. Hemophilia is a defect in thrombin generation (TG). One novel therapeutic approach for rebalancing hemostasis in hemophilia is to reduce the levels of AT to compensate for the reduced level of TG. Kinetic studies suggest that other inhibitors, including heparin cofactor II (HCII), alpha-1-protease inhibitor (a1PI), and alpha-2-macroglobulin (a2M) might assume greater importance when AT is low. We hypothesize that HCII, a1PI, and a2M contribute to the hemostatic balance in hemophilia when AT levels are reduced. Methods: We studied the effects of AT, HCII, a1PI, and a2M on TG in models of hemophilia. TG assays used lipid or 200,000 platelets/µL as the procoagulant surface and tissue factor as the initiator. Plasma assays used AT deficient plasma with a polyclonal anti-factor VIII antibody to model hemophilia A with inhibitors (HA plasma). Synthetic plasma contained normal plasma concentrations of factors II, V, VII, IX, X, XI, protein S and TFPI. AT concentration was varied in the presence or absence of plasma levels of HCII, a1PI, and a2M. ELISA assays were developed that recognized thrombin in complex with the Serpin inhibitors a1PI and HCII. Thrombin complexes with a2M could not be assessed by ELISA, since a2M does not uniformly form a covalent complex with thrombin. a2M inhibits thrombin by trapping it within the a2M protein, and blocking access of macromolecular substrates to its active site. Thrombin-a2M complexes were distinguished from free thrombin by measuring residual thrombin activity after addition of heparin and AT to inhibit all free thrombin. Prothrombin conversion to thrombin on platelets in a synthetic hemophilia A plasma was measured by gel electrophoresis and Western blotting with an anti-prothrombin antibody. Results: TG assays based on a fluorogenic thrombin substrate measure the concentration of free (uninhibited) thrombin as a function of time. In hemophilia, at 100% AT, TG is reduced relative to a non-hemophilic state. As AT levels are decreased, TG is increased. However, TG assays cannot be used to study very low levels of AT, because all of the fluorescent substrate is consumed. To assess the role of a1PI and HCII at very low AT levels, covalent complexes with thrombin were measured by ELISA in HA plasma. Decreasing AT increased the amount of thrombin complexed with a1PI or HCII. However, those complexes still only accounted for a small fraction of total thrombin inhibition, suggesting that a2M might play a dominant role in thrombin inhibition. a2M inhibits thrombin by forming a “caged” complex that blocks macromolecular substrates from being cleaved by the entrapped thrombin. Levels of these complexes were assessed by measuring cleavage of a small molecular weight substrate. As AT was decreased from 100% to 15%, a2M became a more dominant inhibitor of thrombin, with a2M-IIa complexes increasing from &amp;lt;20% to &amp;gt;50% of the thrombin generated. Thrombin is formed by activation of prothrombin. At 100% AT, prothrombin activation was minimal suggesting that AT not only inhibits formed thrombin but also reduces thrombin formation. Decreasing AT gave increasing levels of prothrombin conversion. At reduced levels of AT, addition of a2M reduced prothrombin conversion. Conclusions: In normal plasma, AT is the dominant regulator of hemostasis. AT inhibits thrombin and, surprisingly, regulates conversion of prothrombin to thrombin. In hemophilia, normal levels of AT results in thrombin activity too low to provide hemostasis. Reducing AT in a cell-based model of hemophilia rebalances hemostasis so that more prothrombin is converted to thrombin, and the thrombin is inhibited more slowly. Auxiliary thrombin inhibitors A2M, HCII, and A1PI maintain effective thrombin inhibition with A2M becoming a dominant thrombin inhibitor. One limitation of these in vitro studies is that they do not reflect any contribution of heparin like molecules from vessel walls or other sources. In particular, HCII activity is accelerated by heparin-like molecules, and so may have a greater role in vivo than in our studies. Even with this limitation, our data suggest that secondary thrombin inhibitors may serve as ‘back-up’ to prevent deleterious consequences of lowering AT levels, and may be relevant for therapies that lower AT to rebalance hemostasis by increasing TG in people with hemophilia A or B, with or without inhibitors.

  PublisherDOI

Frequent coauthors

• Dougald M. Monroe

  University of North Carolina at Chapel Hill

  262 shared

• Harold R. Roberts

  Washington University in St. Louis

  131 shared

• Alisa S. Wolberg

  University of North Carolina at Chapel Hill

  95 shared

• Derrick L. Sauls

  Saint Augustine's University

  34 shared

• Ulla Hedner

  32 shared

• Geoffrey Allen

  Fulcrum Therapeutics (United States)

  27 shared

• Frank Church

  25 shared

• Angela Lenkowski

  Novo Nordisk (Denmark)

  25 shared

Education

• Residency Training AP/CP, Pathology

  Duke University Health System

  1985

• MD, PhD, Pharmacology/Toxicology

  University of Iowa

  1982