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Maureane Hoffman

Maureane Hoffman

Professor of Pathology
Pathology
maureane@duke.edu
Duke Box 3712, Durham, NC 27710
F3184 VA Med Ctr, 508 Fulton St, Durham, NC 27705

Selected Publications

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

Journal Article Research and Practice in Thrombosis and Haemostasis · January 1, 2025 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 Unio ... Full text Cite

Emicizumab promotes factor Xa generation on endothelial cells.

Journal Article J Thromb Haemost · June 2024 BACKGROUND: Until recently, the treatment of hemophilia A relied on factor (F)VIII replacement. However, up to one-third of patients with severe hemophilia A develop neutralizing alloantibodies that render replacement therapies ineffective. The development ... Full text Link to item Cite

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

Journal Article Science translational medicine · April 2024 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 limit ... Full text Cite

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

Journal Article PloS one · January 2024 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, requi ... Full text Cite

Clinical Relevance of Preclinical and Clinical Studies of Four-Factor Prothrombin Complex Concentrate for Treatment of Bleeding Related to Direct Oral Anticoagulants.

Journal Article Ann Emerg Med · September 2023 Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of venous thromboembolism and stroke. When emergency reversal of DOAC-related anticoagulation is required, specific DOAC reversal agents are recommended, including idaruciz ... Full text Link to item Cite

Analytical validation and quality control/quality assurance practices for improved rigor and reproducibility of biochemical assays in orthopaedic research.

Journal Article J Orthop Res · July 2023 Orthopaedic research, and biomedical research in general, has made enormous strides to develop treatments for conditions long thought to be inevitable or untreatable; however, there is growing concern about the quality of published research. Considerable e ... Full text Link to item Cite

Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury.

Journal Article Mol Ther Nucleic Acids · March 14, 2023 Acute lung injury (ALI) is a syndrome of acute inflammation, barrier disruption, and hypoxemic respiratory failure associated with high morbidity and mortality. Diverse conditions lead to ALI, including inhalation of toxic substances, aspiration of gastric ... Full text Open Access Link to item Cite

Thrombin generation and implications for hemophilia therapies: A narrative review.

Journal Article Res Pract Thromb Haemost · January 2023 Thrombin plays an essential role in achieving and maintaining effective hemostasis and stable clot formation. In people with hemophilia, deficiency of procoagulant factor (F)VIII or FIX results in insufficient thrombin generation, leading to reduced clot s ... Full text Link to item Cite

Author Correction: Trauma-induced coagulopathy.

Journal Article Nat Rev Dis Primers · April 22, 2022 Full text Link to item Cite

Efficacy and safety of next-generation tick transcriptome-derived direct thrombin inhibitors.

Journal Article Nat Commun · November 25, 2021 Despite their limitations, unfractionated heparin (UFH) and bivalirudin remain standard-of-care parenteral anticoagulants for percutaneous coronary intervention (PCI). We discovered novel direct thrombin inhibitors (DTIs) from tick salivary transcriptomes ... Full text Link to item Cite

Emizicumab Promotes Factor Xa Generation on Activated Endothelium in a Blood Cell-Independent Manner

Conference Blood · November 5, 2021 AbstractIntroductionHemophilia A (HA) is an inherited bleeding disorder caused by the deficiency of coagulation factor VIII (FVIII) resulting in severe hemorrhage if untreate ... Full text Cite

Thrombosis and novel hemophilia therapies: the fine line between clotting and bleeding.

Journal Article Blood Adv · September 28, 2021 The availability of novel nonfactor therapeutics is revolutionizing the management of hemophilia in individuals with inhibitory antibodies, as well as making prophylaxis more convenient even in the absence of inhibitors. Unfortunately, the use of these pro ... Full text Link to item Cite

Trauma-induced coagulopathy.

Journal Article Nat Rev Dis Primers · April 29, 2021 Uncontrolled haemorrhage is a major preventable cause of death in patients with traumatic injury. Trauma-induced coagulopathy (TIC) describes abnormal coagulation processes that are attributable to trauma. In the early hours of TIC development, hypocoagula ... Full text Link to item Cite

In Hemophilia Α Plasma Treated with Emicizumab, Factor IXa in Activated Prothrombin Complex Concentrates Is the Dominant Contributor to Enhanced Thrombin Generation

Conference Blood · November 5, 2020 Background. Recently a novel bifunctional antibody (emicizumab) that binds both factor IXa and factor X has been used to treat hemophilia A. Emicizumab has proven remarkably effective as a prophylactic treatment for hemophilia A; however there are ... Full text Cite

In Hemophilia Α Plasma Treated with Emicizumab, Factor IX Activation By Factor VIIa Drives Thrombin Generation

Conference Blood · November 5, 2020 Background.Recently a novel bifunctional antibody (emicizumab) that binds both factor IXa (FIXa) and factor X (FX) has been used to treat hemophilia A. Emicizumab has proven remarkably effective as a prophylactic treatment for hemophilia A; however ... Full text Cite

Cell-Mediated hemostasis

Chapter · October 12, 2020 The coagulation "cascade" with its intrinsic and extrinsic pathways is a widely accepted paradigm for coagulation. It accurately portrays the reactions in the common screening tests, the prothrombin time, and activated partial thromboplastin time. However, ... Full text Cite

Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects.

Journal Article J Colloid Interface Sci · October 1, 2020 Following injury, a fibrin-rich provisional matrix is formed to stem blood loss and provide a scaffold for infiltrating cells, which rebuild the damaged tissue. Defects in fibrin network formation contribute to impaired healing outcomes, as evidenced in he ... Full text Link to item Cite

Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet-like particles.

Journal Article J Biomed Mater Res B Appl Biomater · August 2020 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 (ULC ... Full text Link to item Cite

Fibrinogen-Coated Albumin Nanospheres Prevent Thrombocytopenia-Related Bleeding.

Journal Article Radiat Res · August 1, 2020 Thrombocytopenia (TCP) may cause severe and life-threatening bleeding. While this may be prevented by platelet transfusions, transfusions are associated with potential complications, do not always work (platelet refractory) and are not always available. Th ... Full text Link to item Cite

EPCR knockout: inflaming the discussion.

Journal Article Blood · June 18, 2020 In this issue of Blood, Magisetty et al provide some surprising results from their studies of the role of endothelial protein C receptor (EPCR) in hemophilic arthropathy. There is a rationale for studying EPCR in hemophilia. It is well recognized that EPCR ... Full text Link to item Cite

Red blood cell microvesicles activate the contact system, leading to factor IX activation via 2 independent pathways.

Journal Article Blood · March 2020 Storage lesion-induced, red cell-derived microvesicles (RBC-MVs) propagate coagulation by supporting the assembly of the prothrombinase complex. It has also been reported that RBC-MVs initiate coagulation via the intrinsic pathway. To elucidate the mechani ... Full text Cite

Aortic Ring Angiogenesis is Maintained Despite Minimal Expression of Tissue Factor

Conference ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY · 2020 Cite

Characterization of a Novel Human Factor VIIa Chimera with Increased Tissue Factor-Independent Activity for Emergency Hemostasis

Conference Blood · November 13, 2019 While prophylactic treatment with emicizumab has shown remarkable efficacy in patients with hemophilia A, the treatment options for traumatic, perioperative, and breakthrough bleeding in hemophilia A or B patients with inhibitors remain extremely l ... Full text Cite

The central role of thrombin in bleeding disorders.

Journal Article Blood Rev · November 2019 Maintaining normal hemostasis relies on a regulated system of procoagulant and anticoagulant pathways, and disruption of these processes leads to the loss of hemostatic control, with the potential for excessive bleeding or thrombosis. Evaluation of bleedin ... Full text Link to item Cite

Preclinical Development of a vWF Aptamer to Limit Thrombosis and Engender Arterial Recanalization of Occluded Vessels.

Journal Article Mol Ther · July 3, 2019 Endothelial surface and circulating glycoprotein von Willebrand factor (vWF) regulates platelet adhesion and is associated with thrombotic diseases, including ischemic stroke, myocardial infarction, and peripheral vascular disease. Thrombosis, as manifeste ... Full text Link to item Cite

A unique protein kinase C-dependent pathway for tissue factor downregulation in pericytes.

Journal Article J Thromb Haemost · April 2019 Essentials Many mediators increase tissue factor (TF) expression in a wide variety of cell types. The only known example of TF downregulation is by pericytes during wound healing angiogenesis. Downregulation of TF mRNA and protein in cultured pericytes is ... Full text Link to item Cite

The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review.

Journal Article Int J Emerg Med · December 3, 2018 BACKGROUND: Bleeding complications are a risk associated with all anticoagulants. Currently, the treatment options for the management of direct oral anticoagulant (DOAC)-associated bleeding are limited. Prothrombin complex concentrates (PCCs) have been pro ... Full text Link to item Cite

Biochemical Characteristics of Emicizumab Activity with Factors IXa, X, and VIIa

Conference Blood · November 29, 2018 AbstractIntroduction. Emicizumab (Hemlibra) is a bivalent antibody that binds to factor IXa and factor X; this binding can promote factor IXa activation of factor X. In patients on prophylaxis with emicizuma ... Full text Cite

Nitric Oxide Mediates Downregulation of Tissue Factor Expression in Primary Human Pericytes through a p38 MAPK Signaling Pathway

Conference Blood · November 29, 2018 AbstractTissue factor (TF) is a high-affinity receptor for FVII/FVIIa that serves as a key initiator of hemostasis and is thought to also play a functional role in angiogenesis. Elevated TF expression has be ... Full text Cite

The next best thing in factor VIIa.

Journal Article J Thromb Haemost · October 2018 Full text Link to item Cite

Biology of Coagulation and Coagulopathy in Neurologic Surgery.

Journal Article Neurosurg Clin N Am · October 2018 Hemostasis is a cell-based process that is regulated in a tissue-specific manner by the differential expression of procoagulant and anticoagulant factors on endothelial cells from different sites throughout the vasculature. The central nervous system, in p ... Full text Link to item Cite

Human platelets express endothelial protein C receptor, which can be utilized to enhance localization of factor VIIa activity.

Journal Article J Thromb Haemost · September 2018 UNLABELLED: Essentials Factor VIIa binds activated platelets to promote hemostasis in hemophilia patients with inhibitors. The interactions and sites responsible for platelet-FVIIa binding are not fully understood. Endothelial cell protein C receptor (EPCR ... Full text Link to item Cite

Abstract 288: Nitric Oxide Mediates Active Downregulation of Tissue Factor Expression in Human Pericytes

Conference Arteriosclerosis, Thrombosis, and Vascular Biology · May 2018 Tissue Factor (TF) is a transmembrane protein that not only expresses pro-coagulant enzymatic activity, but also mediates signal transduction by several second messenger pathways. It plays an obvious role in hemostasis and thrombosis, ... Full text Cite

Differentiating between cold agglutinins and rouleaux: a case series of seven patients.

Journal Article Perfusion · March 2018 We present a case series of seven patients with suspected cold agglutinin antibodies, discovered after initiation of bypass. Laboratory analysis of blood samples intraoperatively determined the cause of the aggregation to be rouleaux formation in three of ... Full text Link to item Cite

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

Impact of Non-Vitamin K Antagonist Oral Anticoagulants From a Basic Science Perspective.

Journal Article Arteriosclerosis, thrombosis, and vascular biology · October 2017 The biochemical properties of the non-vitamin K antagonist oral anticoagulants (NOACs) and their differences from the mechanism of action of vitamin K antagonists contribute to their properties as anticoagulants. These properties include as follows: (1) In ... Full text Cite

Inhibition of von Willebrand Factor Activity Does Not Delay Cutaneous Wound Healing

Conference ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY · May 1, 2017 Link to item Cite

Abnormal joint and bone wound healing in hemophilia mice is improved by extending factor IX activity after hemarthrosis.

Journal Article Blood · April 13, 2017 Wound healing requires interactions between coagulation, inflammation, angiogenesis, cellular migration, and proliferation. Healing in dermal wounds of hemophilia B mice is delayed when compared with hemostatically normal wild-type (WT) mice, with abnormal ... Full text Link to item Cite

Using antifibrinolytics in the peripartum period - concern for a hypercoagulable effect?

Journal Article J Neonatal Perinatal Med · 2017 INTRODUCTION: Although antifibrinolytic agents are used to prevent and treat hemorrhage, there are concerns about a potential increased risk for peripartum venous thromboembolism. We sought to determine the impact of tranexamic acid and ɛ-aminocaproic acid ... Full text Open Access Link to item Cite

Ciraparantag safely and completely reverses the anticoagulant effects of low molecular weight heparin.

Journal Article Thromb Res · October 2016 UNLABELLED: Major bleeding with low molecular weight heparin (LMWH) therapy occurs in up to 5% of patients and its anticoagulation is only partially reversed by protamine sulfate. We studied the ability of ciraparantag (PER977), a novel agent that reverses ... Full text Link to item Cite

No association between donor age and recipient outcomes: transfusion of plasma in patients undergoing coronary artery bypass grafting surgery.

Journal Article Transfusion · July 2016 BACKGROUND: Recent animal studies suggest that transfusion of plasma from young donors reverses age-related neurologic and cardiac changes in older recipients. Associations between age of blood product donors and corresponding outcomes in recipients have n ... 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

Coated platelets and severe haemophilia A bleeding phenotype: Is there a connection?

Journal Article Haemophilia · January 2016 INTRODUCTION: Coated platelets are a subpopulation of platelets that possess highly prothrombotic properties. Previous observational data suggest that bleeding phenotype in severe haemophilia A is associated with coated platelet levels. Haemophilia A patie ... Full text Link to item Cite

Cell-mediated hemostasis

Chapter · January 1, 2016 The coagulation “cascade” with its intrinsic and extrinsic pathways is a widely accepted paradigm for coagulation. It accurately portrays the reactions in the common screening tests, the prothrombin time and activated partial thromboplastin time. However, ... Full text Cite

Phorbol 12-myristate 13-acetate Downregulates Tissue Factor Gene Expression in Human Pericytes

Conference ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY · 2016 Cite

Downregulation of Tissue Factor in Pericytes By a Protein Kinase C-Dependent Mechanism

Conference Blood · December 3, 2015 AbstractTissue factor (TF) is a transmembrane protein in the type II cytokine receptor family that serves as a cofactor for factor VIIa activity, and is essential for normal initiation of hemostasis. Its exp ... Full text Cite

Coagulation in Liver Disease.

Journal Article Semin Thromb Hemost · July 2015 The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory test ... Full text Link to item Cite

Novel oral anticoagulants and reversal agents: Considerations for clinical development.

Other Am Heart J · June 2015 This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at ... Full text Link to item Cite

Testing an in vitro model of laminar flow for use in large-scale aptamer screening

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · June 1, 2015 Link to item Cite

Epidermal tissue factor in wound healing

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · June 1, 2015 Link to item Cite

The effects of a novel long-acting factor IX product (N9-GP) on wound healing

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · June 1, 2015 Link to item Cite

Fibrinogen-Coated Nanospheres Prevent Thrombocytopenia-Related Bleeding

Conference Biology of Blood and Marrow Transplantation · February 2015 Full text Cite

Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate.

Journal Article Anesthesiology · February 2015 BACKGROUND: The oral thrombin inhibitor dabigatran has the drawbacks that it does not have a validated antidote. Data from animal studies and plasma coagulation assays suggest that prothrombin complex concentrate (PCC) or recombinant factor VIIa (FVIIa) mi ... Full text Link to item Cite

Effect of antifibrinolytic drugs on in vitro clot formation among peripartum women

Conference AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY · January 1, 2015 Link to item Cite

161: Effect of antifibrinolytic drugs on in vitro clot formation among peripartum women

Journal Article American Journal of Obstetrics and Gynecology · January 2015 Full text Cite

Coated platelet levels in severe hemophilia do not correlate to bleeding phenotype

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · 2015 Cite

Reversing targeted oral anticoagulants.

Journal Article Hematology Am Soc Hematol Educ Program · December 5, 2014 Dabigatran, rivaroxaban, and apixaban are orally active anticoagulants that are approved in many countries. Dabigatran inhibits thrombin, whereas rivaroxaban and apixaban are factor Xa inhibitors. In clinical trials, these novel oral anticoagulants were at ... Full text Link to item Cite

A mouse bleeding model to study oral anticoagulants.

Journal Article Thromb Res · May 2014 New oral anticoagulants to reduce the incidence of thrombosis have recently become available. When compared to the existing therapy, warfarin, these novel agents have similar efficacy with a reduced risk of spontaneous bleeding. However, these novel agents ... Full text Link to item Cite

Hemostasis: old system, new players, new directions.

Journal Article Thromb Res · May 2014 Initiation of clotting cascade by tissue factor (TF): Factor VII (FVII) complex is essential for hemostasis however pathologic expression of TF leads to thrombosis. In contrast, the contact pathway factor XII, and to the smaller extent FXI are dispensable ... Full text Link to item Cite

Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?

Journal Article Thromb Haemost · February 2014 Newer oral anticoagulants offer several advantages over traditional agents (e.g. warfarin), but they are still associated with a bleeding risk and currently there is no validated reversal treatment for them. While there is little support for the use of fre ... Full text Link to item Cite

Theories of Blood Coagulation: Basic Concepts and Recent Updates

Chapter · January 1, 2014 Coagulation is the series of controlled reactions that leads to thrombin generation and fibrin formation. One model of hemostasis views the process as having three overlapping phases: initiation, amplification, and propagation. In initiation, factor VIIa/t ... Full text Cite

Reversal Of Dabigatran Anticoagulation By a 4-Factor Prothrombin Complex Concentrate: Correlation Between Effects On Parameters Of Thrombin Generation and Hemostatic Effect In Vivo

Conference Blood · November 15, 2013 AbstractDabigatran etexilate (Pradaxa®) is a prodrug that is metabolized to a small molecule direct thrombin inhibitor. It has the drawback that it is not readily reversible. Several studies have suggested t ... Full text Cite

Progressive improvement in wound healing with increased therapy in haemophilia B mice.

Journal Article Haemophilia · November 2013 Previous work has shown that normalized haemostasis only at the time of an injury is not sufficient to promote optimal wound healing in haemophilia B (HB) mice. However, the duration of treatment required for optimal healing has not been established. The g ... Full text Link to item Cite

Superactivated platelets: thrombus regulators, thrombin generators, and potential clinical targets.

Journal Article Arterioscler Thromb Vasc Biol · August 2013 Platelets contribute to hemostasis by forming the platelet plug and then contributing to coagulation by providing a catalytic surface where thrombin generation occurs efficiently. This catalytic activity, known as the platelet procoagulant response, is bei ... Full text Link to item Cite

Reversal of dabigatran effects by factor VIIa in a cell-based model of coagulation

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · July 1, 2013 Link to item Cite

Bleeding risk in warfarinized patients with a therapeutic international normalized ratio: the effect of low factor IX levels.

Journal Article J Thromb Haemost · June 2013 OBJECTIVE: Bleeding is the main complication of warfarin therapy, even patients with an international normalized ratio (INR) in the target range can suffer bleeding, suggesting that INR does not perfectly reflect the therapeutic effect of warfarin. We hypo ... Full text Link to item Cite

Partial Reversal of Dabigatran Effect by a Prothrombin Complex Concentrate in a Model of Thrombin Generation

Conference Blood · November 16, 2012 AbstractAbstract 3420Dabigatran etexilate (Pradaxa) is a prodrug that is metabolised to a small molecule direct thrombin inhibitor. It has some more desirable charactersitics ... Full text Cite

Mechanisms and monitoring of bypassing agent therapy.

Journal Article J Thromb Haemost · August 2012 Understanding the mechanism of action of normal hemostasis and how the bypassing agents recombinant activated factor VII (rFVIIa; NovoSeven) and plasma-derived activated prothrombin complex concentrate (Factor Eight Inhibitor Bypassing Agent [FEIBA]) contr ... Full text Link to item Cite

Wound healing in bleeding disorders

Conference HAEMOPHILIA · July 1, 2012 Link to item Cite

The clotting system - a major player in wound healing.

Journal Article Haemophilia · July 2012 Wound healing involves a complex series of interactions between coagulation, inflammation, angiogenesis, and cellular migration and proliferation. Our laboratory has developed an excisional dermal wound model in mice in order to study some of these process ... Full text Link to item Cite

Consequences of intra-articular bleeding in haemophilia: science to clinical practice and beyond.

Journal Article Haemophilia · July 2012 Blood in the joint causes a number of physiological and pathological events that eventually lead to haemophilic arthropathy. Animal models show that blood in the joint induces inflammation that continues long after blood has been cleared. TNF-alpha, IL-1 b ... Full text Link to item Cite

Hemostatic properties of the FVIIa analog NN1731.

Journal Article Thromb Res · May 2012 Recombinant activated coagulation factor VII (rFVIIa) has proven to be a useful prohemostatic agent in patients with hemophilia and antibody inhibitors. It has also been used off-label in other settings. A major mechanism of its hemostatic efficacy is its ... Full text 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

Low intensity laser therapy speeds wound healing in hemophilia by enhancing platelet procoagulant activity.

Journal Article Wound Repair Regen · 2012 Our group has previously shown that cutaneous wound healing is delayed and histologically abnormal in a mouse model of hemophilia. Hemostasis is not only required to stop bleeding at the time of wounding, but also produces bioactive substances that promote ... 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

An analogue of factor VIIa improves wound healing in hemophilia B mice

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · July 1, 2011 Link to item Cite

Homocysteinylated fibrinogen forms disulfide-linked complexes with albumin.

Journal Article Thromb Res · June 2011 We have shown that homocysteinemic rabbits have altered fibrinogen that forms fibrin clots with increased resistance to fibrinolysis. Homocysteine thiolactone is a metabolite of homocysteine (Hcys) that can react with amines and introduce a new sulfhydryl ... 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

International normalized ratio Response

Journal Article JOURNAL OF NEUROSURGERY · January 1, 2011 Open Access 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

International normalized ratio.

Journal Article J Neurosurg · January 2011 Full text Link to item Cite

Regulation of Hemostasis and Thrombosis

Journal Article · December 1, 2010 Full text Cite

Folate Deficiency Promotes a Prothrombotic State

Conference ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY · November 1, 2010 Link to item Cite

Heparins: Clinical use and laboratory monitoring

Journal Article Laboratory Medicine · October 1, 2010 Heparin has long been used as an antithrombotic to treat and prevent thromboembolic events, as well as for systemic anti-coagulation during cardiopulmonary bypass and dialysis. Heparin continues to have distinct advantages when intense anti-coagulation is ... Full text 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

Platelet binding and activity of recombinant factor VIIa.

Journal Article Thromb Res · April 2010 Recombinant FVIIa was developed for the purpose of treating hemophiliacs with antibody inhibitors. It was initially assumed to act by enhancing factor X activation by a tissue factor-dependent mechanism. However, the very high levels of FVIIa required for ... Full text Link to item Cite

Wound healing in hemophilia B mice and low tissue factor mice.

Journal Article Thromb Res · April 2010 Wound healing involves a number of physiologic mechanisms including coagulation, inflammation, formation of granulation tissue, and tissue remodeling. Coagulation with robust thrombin generation leading to fibrin formation is necessary for wound healing. I ... Full text Link to item Cite

Contributors

Chapter · 2010 Full text 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

Heparin cofactor II in atherosclerotic lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.

Journal Article Exp Mol Pathol · December 2009 Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes ... Full text Link to item Cite

Platelet functions beyond hemostasis.

Journal Article J Thromb Haemost · November 2009 Although their central role is in the prevention of bleeding, platelets probably contribute to diverse processes that extend beyond hemostasis and thrombosis. For example, platelets can recruit leukocytes and progenitor cells to sites of vascular injury an ... 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

Wound healing in hemophilia: progressive improvement with longer treatment

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · 2009 Cite

Prolongation of the aPTT may depend on inhibition of contact factors

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · 2009 Cite

Prothrombin levels are increased in type II diabetics

Conference JOURNAL OF THROMBOSIS AND HAEMOSTASIS · 2009 Cite

Dysregulation of hemostasis by cancer.

Journal Article Cancer Treat Res · 2009 Full text Link to item Cite

FVIIa: you've come a long way, baby!

Journal Article Blood · October 15, 2008 Full text Link to item Cite

Animal models of bleeding and tissue repair.

Journal Article Haemophilia · July 2008 While a number of animal models have been developed for human haemophilia, it has been difficult to develop reproducible measures of bleeding in these models. They have also not been extensively utilized to study the complications of haemophilia beyond blo ... 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

Circulating fibrinogen-albumin complexes in subjects with elevated plasma homocysteine levels

Conference ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY · June 1, 2008 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

Some things I thought I knew about tissue factor that turn out to be wrong.

Journal Article Thromb Res · 2008 Tissue factor (TF) plays an critical role in hemostasis and some types of thrombosis. However, it also has roles beyond its coagulant function. TF is a member of the cytokine receptor superfamily. Its expression is upregulated by inflammatory cytokines and ... Full text Link to item Cite

Hypercoagulation and thrombophilia in liver disease.

Journal Article J Thromb Haemost · January 2008 A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well-known bleeding diathesis of liver disease. These events may be clinically ... 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

Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease.

Journal Article Aliment Pharmacol Ther · July 15, 2007 BACKGROUND: Prothrombin time (PT)-derived international normalized ratio (INR) is used to assess bleeding risk and prognosis in cirrhosis, and to guide management of associated coagulation disturbances. Recent studies cast doubt on the validity of the assu ... 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

Fathers of modern coagulation.

Journal Article Thromb Haemost · July 2007 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

Pro-thrombotic and pro-oxidant effects of diet-induced hyperhomocysteinemia.

Journal Article Thromb Res · 2007 Elevated plasma homocysteine levels are associated with the risk of atherosclerosis and arterial and venous thrombosis. We have previously demonstrated that rabbits rendered hyperhomocysteinemic by parenteral administration of homocysteine develop a dysfib ... Full text Link to item Cite

Tissue Factor Is Absent from Sites of Cutaneous Wounds: Implications for Bleeding in Hemophilia.

Conference Blood · November 16, 2006 AbstractTissue factor (TF) plays an important role in hemostasis. Its expression is upregulated by a variety of proinflammatory cytokines and thus can link inflammation with thrombosis. We have been studying ... Full text 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

Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management.

Journal Article Hepatology · October 2006 Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a "common" pathway at the level of the ... 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

Manipulation of prothrombin concentration improves response to high-dose factor VIIa in a cell-based model of haemophilia.

Journal Article Br J Haematol · August 2006 Clinical reports suggest that treatment regimens employing both activated prothrombin complex concentrates (aPCCs) and recombinant activated factor VII (rFVIIa) may control the bleeding in patients with haemophilia who fail to respond to either agent alone ... 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

Why are young college women not using condoms? Their perceived risk, drug use, and developmental vulnerability may provide important clues to sexual risk.

Journal Article Arch Psychiatr Nurs · February 2006 BACKGROUND: Young multiethnic college women (YMCW) are at risk for STDs and HIV secondary to high-risk sexual behaviors that are related to developmental issues such as invincibility, low perceived risk, and substance use. METHOD: One hundred YMCW on a sou ... 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

Delayed wound healing in hemophilia B mice.

Conference BLOOD · November 16, 2005 Link to item Cite

Rethinking the coagulation cascade.

Journal Article Curr Hematol Rep · September 2005 The concept of coagulation as a "cascade" of proteolytic reactions was a conceptual breakthrough in understanding how the coagulation process acts as a biologic amplifier. The model that it evolved into, with "extrinsic" and "intrinsic" pathways meeting in ... Link to item Cite

Protein C inhibitor (plasminogen activator inhibitor-3) expression in the CWR22 prostate cancer xenograft.

Journal Article Exp Mol Pathol · August 2005 The serine protease inhibitor (serpin) protein C inhibitor (PCI) has been found in the prostate and possibly is a marker to distinguish normal prostate, benign prostatic hyperplasia, and prostate cancer. In this study, we assessed PCI expression in normal, ... Full text Link to item Cite

Excess factor VIII and hypercoagulability [3] (multiple letters)

Journal Article Journal of the American Board of Family Practice · July 1, 2005 Cite

Platelet heterogeneity: variation in coagulation complexes on platelet subpopulations.

Journal Article Arterioscler Thromb Vasc Biol · April 2005 OBJECTIVE: Previous work has shown that platelets stimulated with the combination of thrombin and convulxin, a glycoprotein VI agonist, develop 2 populations with different levels of alpha-granule factor V bound to the platelet surface. To evaluate whether ... Full text Link to item Cite

One more way that mice and men are different.

Journal Article J Thromb Haemost · March 2005 Full text Link to item Cite

Rethinking the Coagulation Cascade

Journal Article Japanese Journal of Thrombosis and Hemostasis · 2005 Full text Cite

Excess factor VIII and hypercoagulability.

Journal Article J Am Board Fam Pract · 2005 Full text Link to item Cite

The cellular basis of traumatic bleeding.

Journal Article Mil Med · December 2004 Bleeding is clearly a major cause of morbidity and death after trauma. When bleeding is attributable to transection of major vessels, surgical repair is appropriate. Posttraumatic microvascular bleeding attributable to coagulopathy secondary to metabolic d ... Full text Link to item Cite

COAT Platelet Formation Is P2Y12-Dependent.

Conference Blood · November 16, 2004 AbstractInhibition of the platelet ADP receptor, P2Y12, has been shown to reduce thrombin-stimulated exposure of platelet phosphatidylserine and tissue factor (TF)-dependent thrombin generation in human plat ... Full text 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

Differences in the metabolic response to exogenous homocysteine in juvenile and adult rabbits.

Journal Article J Nutr Biochem · February 2004 Homocysteine has recently received a lot of attention as an independent risk factor for atherosclerotic and thrombotic cardiovascular disease. Plasma homocysteine levels tend to rise with age, but are also greatly influenced by nutritional factors. Early r ... Full text Link to item Cite

Safety profile of recombinant factor VIIa.

Journal Article Semin Hematol · January 2004 Recombinant factor VIIa (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) has been used for many years in the successful management of bleeding episodes in patients with hemophilia and inhibitors. More recently, rFVIIa has also shown considerable su ... Full text Link to item Cite

The Potential Role of Factor VIIa in Transfusion Medicine

Journal Article Transfusion Alternatives in Transfusion Medicine · December 2003 SUMMARYTherapy with high doses of recombinant factor VIIa (rFVIIa) is effective in promoting hemostasis in hemophiliacs. There is also some evidence to support the idea that this agent can enhance hemostasis in patients wit ... Full text Cite

Laboratory monitoring of high-dose factor VIIa therapy.

Journal Article Ann Intern Med · November 4, 2003 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

Localization of heparin cofactor II in injured human skin: a potential role in wound healing.

Journal Article Exp Mol Pathol · October 2003 The physiologic function of the serpin heparin cofactor II (HCII) is not fully understood. We have hypothesized that HCII functions as an extravascular inhibitor of thrombin. Thrombin formed at a site of injury has been hypothesized to contribute to migrat ... Full text Link to item Cite

A cell-based model of coagulation and the role of factor VIIa.

Journal Article Blood Rev · September 2003 Our cell-based model of haemostasis replaces the traditional 'cascade' hypothesis, and proposes that coagulation takes place on different cell surfaces in three overlapping steps: initiation, amplification, and propagation. In highlighting the importance o ... Full text Link to item Cite

Protease-activated receptor-2 signaling triggers dendritic cell development.

Journal Article Am J Pathol · June 2003 Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, th ... Full text Link to item Cite

Hyperhomocysteinemia leads to elevated levels of plasminogen activator inhibitor-1

Conference ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY · May 1, 2003 Link to item Cite

New insights into the coagulation system and implications for new therapeutic options with recombinant factor VIIa.

Journal Article Curr Med Chem · May 2003 The classical model of the coagulation cascade is to be replaced by a new, cell based model of coagulation emphasizing the interaction of coagulation proteins with cell surfaces of platelets subendothelial cells and the endothelium. According to current kn ... Full text Link to item Cite

Elevated prothrombin results in clots with an altered fiber structure: a possible mechanism of the increased thrombotic risk.

Journal Article Blood · April 15, 2003 Individuals with elevated prothrombin levels are at increased risk of venous thrombosis. To understand the mechanism behind this observation, we studied the effect of prothrombin concentration on thrombin generation and fibrin clot structure. The pattern o ... 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

The action of high-dose factor VIIa (FVIIa) in a cell-based model of hemostasis.

Journal Article Dis Mon · January 2003 We have developed a cell-based model of hemostasis. This model suggests that the defect in hemophilia is specifically a failure of platelet-surface factor Xa (FXa) generation, leading to a failure of platelet surface thrombin generation. Activation of FX b ... Full text Link to item Cite

Remodeling the blood coagulation cascade.

Journal Article J Thromb Thrombolysis · 2003 The concept of a coagulation cascade describes the biochemical interactions of the coagulation factors, but has flaws as a model of the hemostatic process in vivo. For example, the model cannot explain why hemophiliacs bleed when they have an intact factor ... Full text Link to item Cite

Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhage.

Journal Article Can J Anaesth · December 2002 PURPOSE: Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa ... Link to item Cite

Haemostasis: from bench to bedside.

Journal Article Haemophilia · September 2002 Full text Link to item Cite

Platelets and thrombin generation.

Journal Article Arterioscler Thromb Vasc Biol · September 1, 2002 This review examines the evidence that platelets play a major role in localizing and controlling the burst of thrombin generation leading to fibrin clot formation. From the first functional description of platelets, it has been recognized that platelets su ... Full text Link to item Cite

Analyzing fibrin clot structure using a microplate reader.

Journal Article Blood Coagul Fibrinolysis · September 2002 Fibrin clot structure studies are often performed using optical methods. For example, the clot's fiber structure can be assessed by measuring light scattering as a function of wavelength. From these measurements, one can calculate the mass/length ratio (mu ... Full text Link to item Cite

Coagulation factor interaction with platelets.

Journal Article Thromb Haemost · August 2002 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

Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo.

Journal Article Blood · July 1, 2002 Residue K5 in factor IX gamma-carboxyglutamic acid (Gla) domain participates in binding endothelial cells/collagen IV. We injected recombinant factor IX containing mutations at residue 5 (K5A, K5R) into factor IX-deficient mice and compared their behavior ... 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

Exposure of mice to topical bovine thrombin induces systemic autoimmunity.

Journal Article Am J Pathol · November 2001 Bovine thrombin is used as an aid to hemostasis in medical and surgical procedures. At least 500,000 Americans are exposed to this therapeutic annually and reports suggest that exposure is associated with the development of autoreactive antibodies. To dete ... Full text Link to item Cite

The action of high-dose factor VIIa (FVIIa) in a cell-based model of hemostasis.

Journal Article Semin Hematol · October 2001 We have developed a cell-based model of hemostasis. This model suggests that the defect in hemophilia is specifically a failure of platelet-surface factor Xa (FXa) generation, leading to a failure of platelet surface thrombin generation. Activation of FX b ... Full text Link to item Cite

High-dose factor VIIa increases initial thrombin generation and mediates faster platelet activation in thrombocytopenia-like conditions in a cell-based model system.

Journal Article Br J Haematol · July 2001 Clinical experience has shown that high doses of recombinant factor VIIa (rFVIIa) may ensure haemostasis in thrombocytopenic patients. We have used a cell-based model system to mimic thrombocytopenia and analyse the effect of rFVIIa. Lowering the platelet ... 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

Hyperhomocysteenemia induces alterations in fffirinogen function and fibrin clot structure in a rabbit model

Journal Article Blood · December 1, 2000 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. Most studies have focused on the effects of homocysteine on endo ... Cite

In vivo behavior of factor ix and certain gla domain mutants evaluated in coagulation factor k-deficient mice

Journal Article Blood · December 1, 2000 To investigate the role of certain y-carboxyglutamic acid (gla) domain residues that mediate factor IX endothelium/collagen IV binding, we compared the clearance and distribution of molecules containing mutations at residue K5 (to A or R, K5A, K5R) to that ... 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

Inhibition of human and pig thrombin by a high-affinity nuclease-resistant RNA aptamer

Journal Article Journal of the American College of Surgeons · October 2000 Full text Cite

Pneumococcal vaccine administration associated with splenectomy: the need for improved education, documentation, and the use of a practical checklist.

Journal Article Am J Hematol · September 2000 An audit was performed of the documentation of pneumococcal vaccination in splenectomy patients in three major hospitals involving a geographical population base of 350,000 patients in British Columbia, Canada. Overall, 111 of the 164 hospitalized splenect ... Full text Link to item Cite

Coagulation factor XI is a contaminant in intravenous immunoglobulin preparations

Journal Article American Journal of Hematology · September 2000 Full text Cite

Coagulation factor XI is a contaminant in intravenous immunoglobulin preparations.

Journal Article Am J Hematol · September 2000 A small number of thromboembolic events, including deep venous thrombosis and myocardial infarction, have been reported in patients receiving IVIG. These events have primarily occurred in patients receiving high-dose IVIG and have been attributed to an inc ... Full text Link to item Cite

Deencryption of cellular tissue factor is independent of its cytoplasmic domain.

Journal Article Biochem Biophys Res Commun · June 7, 2000 Tissue factor (TF) is a transmembrane molecule that, when exposed to plasma, is the key initiator of coagulation. Cellular TF activity is normally "encrypted", but treating cells with calcium ionophore (i.e. , ionomycin or A23187) increases ("deencrypts") ... Full text Link to item Cite

The effect of factor X level on thrombin generation and the procoagulant effect of activated factor VII in a cell-based model of coagulation.

Journal Article Blood Coagul Fibrinolysis · April 2000 We used a cell-based, in-vitro model of normal hemostasis and hemophilia to address the question of whether factor (F) X concentration affects the hemostatic response to high-dose activated factor VII (FVIIa). Under conditions designed to mimic normal tiss ... Full text Link to item Cite

Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver.

Journal Article Gastroenterology · January 2000 BACKGROUND & AIMS: Sinusoidal endothelial cell (SEC) apoptosis is a central feature of reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation with possible deleterious effects. We tested the hypothesis that platele ... Full text Link to item Cite

Links between the immune and coagulation systems: how do "antiphospholipid antibodies" cause thrombosis?

Journal Article Immunol Res · 2000 Inflammation and immune activation have been associated with thrombosis in a number of settings. We have been interested in the question of how the presence of a type of autoantibody, so-called "antiphospholipid" antibody, leads to thrombosis. Several mech ... Full text Link to item Cite

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

Journal Article Semin Thromb Hemost · 2000 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 ... Full text Link to item Cite

Platelets from thrombocytopenic ponies acutely infected with equine infectious anemia virus are activated in vivo and hypofunctional.

Journal Article Virology · June 20, 1999 Thrombocytopenia is a consistent finding and one of the earliest hematological abnormalities in horses acutely infected with equine infectious anemia virus (EIAV), a lentivirus closely related to human immunodeficiency virus. Multifactorial mechanisms, inc ... Full text Link to item Cite

Tissue factor de-encryption: ionophore treatment induces changes in tissue factor activity by phosphatidylserine-dependent and -independent mechanisms.

Journal Article Blood Coagul Fibrinolysis · June 1999 Coagulation is initiated on tissue-factor-bearing cells when factor VIIa complexes with membrane-bound tissue factor and activates factors X and IX. Cellular tissue factor activity does not correlate with tissue factor antigen; treatment with calcium ionop ... Link to item 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

Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.

Journal Article J Clin Invest · December 1, 1998 Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that has potent biological effects. Its actions are mediated by G protein-coupled thromboxane-prostanoid (TP) receptors. TP receptors have been implicated in the pathogenesis of cardiovascula ... Full text Link to item Cite

Protein C inhibitor in the human endometrium

Journal Article FASEB Journal · December 1, 1998 Protein C Inhibitor (PCI), also known as Plasminogen Activator Inhibitor-3, is a serine protease inhibitor (serpin) that regulates a variety of proteases. PCI is mainly present in the coagulation cascade; however it is also known to inhibit proteases invol ... Cite

Active site-inactivated factors VIIa, Xa, and IXa inhibit individual steps in a cell-based model of tissue factor-initiated coagulation.

Journal Article Thromb Haemost · October 1998 Factors VIIa, Xa, and IXa play different roles in the initiation of tissue factor-dependent coagulation. The consequences of competing with the different enzymes were investigated, thereby examining the effects of inhibiting the initiation process at diffe ... Link to item Cite

Newer concepts of blood coagulation.

Journal Article Haemophilia · July 1998 In this report we describe an in vitro model of blood coagulation reactions that mimics as closely as possible the in vivo condition. Our model indicates that the tissue factor-factor VIIa complex initiates coagulation by activating small amounts of both f ... Full text Link to item Cite

Protein C inhibitor in the human endometrium

Conference FASEB JOURNAL · April 24, 1998 Link to item Cite

A possible mechanism of action of activated factor VII independent of tissue factor.

Journal Article Blood Coagul Fibrinolysis · March 1998 We have used a cell-based model system to examine some aspects of coagulation. Unactivated platelets and tissue factor (TF)-bearing cells were mixed with plasma levels of zymogen factors IX (FIX), FVIII, FX, FV, and prothrombin, as well as coagulation inhi ... 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

The effects of activated factor VII in a cell-based model for tissue factor-initiated coagulation.

Journal Article Blood Coagul Fibrinolysis · March 1998 The importance of activated factor VII (FVIIa) in coagulation initiated by tissue factor (TF) was illustrated by competition of active site-inhibited FVIIa (FFR-FVIIa; FVIIa treated with D-Phe-Phe-Arg-chloromethyl ketone) with FVIIa in various cell-based a ... Link to item Cite

Platelets induce endothelial cell apoptosis upon reperfusion following cold ischemia in rat liver

Journal Article European Journal of Gastroenterology and Hepatology · January 1, 1998 Full text Cite

A randomized trial of recombinant human interleukin-11 following autologous bone marrow transplantation with peripheral blood progenitor cell support in patients with breast cancer.

Journal Article Biol Blood Marrow Transplant · 1998 This study assessed the safety and efficacy of recombinant human interleukin (rhIL)-11 in decreasing platelet transfusion requirements in patients with breast cancer who were undergoing autologous bone marrow transplantation (ABMT) with peripheral blood pr ... Full text 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

Protein C inhibitor biochemistry and pathology

Journal Article FASEB Journal · December 1, 1997 Protein C inhibitor (PCI) is a heparin-binding serine protease inhibitor that regulates a variety of proteases, including some in tumor metastasis. We are characterizing both the structural (heparin binding site and pathobiological properties (in normal an ... Cite

From antiphospholipid syndrome to antibody-mediated thrombosis.

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

The effect of active site-inhibited factor VIIa on tissue factor-initiated coagulation using platelets before and after aspirin administration.

Journal Article Thromb Haemost · October 1997 Active site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIIa (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa ... Link to item Cite

Protein C inhibitor biochemistry and pathology

Conference FASEB JOURNAL · 1997 Cite

Evidence of protein C inhibitor in prostatic carcinoma

Journal Article FASEB Journal · December 1, 1996 Prostate tumor cell invasion and metastasis involves numerous concerted interactions between both cellular and stromal components, including proteinases and their interactions with proteinase inhibitors. Protein C Inhibitor (PCI), also called plasminogen a ... Cite

A functional tethered ligand thrombin receptor is present on human hematopoietic progenitor cells.

Journal Article Exp Hematol · July 1996 The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism ... 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

Variability in platelet procoagulant activity in healthy volunteers.

Journal Article Thromb Res · March 1, 1996 Blood platelets provide the major surface for thrombin generation. When platelets are activated they expose phosphatidylserine (PS) on their outer membranes, providing the surface on which two procoagulant enzyme complexes, the Xase and prothrombinase comp ... Full text Link to item Cite

Culturing unactivated monocytes.

Journal Article J Leukoc Biol · February 1996 Full text Link to item Cite

Cellular interactions in hemostasis.

Journal Article Haemostasis · 1996 Coagulation reactions normally occur on cell membranes in vivo. Using a cell-based in vitro model system, we have shown that where a factor is located, not simply how much is activated, is critically important in determining its role in hemostasis. Factor ... Full text Link to item Cite

Vascular localization of the heparin-binding serpins antithrombin, heparin cofactor II, and protein C inhibitor

Journal Article Clinical and Applied Thrombosis/Hemostasis · January 1, 1996 Heparin is one of the most widely used drugs in the world, acting as an anticoagulant by stimulating the reaction between heparin-binding serpins and the serine proteases of the coagulation cascade. To determine whether the heparin-binding serpins antithro ... Full text Cite

Factors IXa and Xa play distinct roles in tissue factor-dependent initiation of coagulation.

Journal Article Blood · September 1, 1995 Tissue factor is the major initiator of coagulation. Both factor IX and factor X are activated by the complex of factor VIIa and tissue factor (VIIa/TF). The goal of this study was to determine the specific roles of factors IXa and Xa in initiating coagula ... Link to item Cite

Monocyte chemoattractant activity of Ser195-->Ala active site mutant recombinant alpha-thrombin.

Journal Article Exp Cell Res · August 1995 alpha-Thrombin is chemotactic for human monocytes with optimal activity between 10-100 nM. The mechanism by which this response is mediated remains a point of controversy. The purpose of this study was to compare the chemotactic activity of proteolytically ... Full text Link to item Cite

The monocyte monolayer assay: a noninvasive technique for predicting the severity of in utero hemolysis.

Journal Article Am J Perinatol · May 1995 To test the noninvasive monocyte monolayer assay in predicting hemolytic severity in utero, we studied 18 patients from two institutions with significant erythrocyte alloantibodies. Serum samples were obtained from each patient. Each subject donated a seru ... Full text Link to item Cite

Inhibition of platelet-derived growth factor-BB-induced fibroblast proliferation by plasmin-activated alpha 2-macroglobulin is mediated via an alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein-dependent mechanism.

Journal Article J Biol Chem · March 17, 1995 alpha 2-Macroglobulin (alpha 2M) is a potentially important regulator of platelet-derived growth factor-BB (PDGF-BB)-stimulated cell growth due to our previous observation that PDGF-BB binds to alpha 2M noncovalently (Bonner, J. C., Goodell, A. L., Lasky, ... Full text Link to item Cite

Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms.

Journal Article Blood Cells Mol Dis · 1995 Thrombosis and disseminated intravascular coagulation (DIC) are common complications of infections. Abnormal activation of coagulation is due in part of expression of tissue factor on intravascular cells in response to cytokines, including interleukin-1 be ... 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

Reticulated platelet counts in patients undergoing autologous bone marrow transplantation: an aid in assessing marrow recovery.

Journal Article Am J Hematol · August 1994 Thiazole orange (TO) is a fluorescent dye that is commonly used for flow cytometric measurement of erythrocytic reticulocytes. This technique has also been validated for counting "reticulated" platelets, as a measure of bone marrow thrombopoietic activity. ... Full text Link to item Cite

Platelets contain releasable coagulation factor IX antigen: response.

Journal Article Blood Coagul Fibrinolysis · August 1994 Link to item Cite

Human monocytes support factor X activation by factor VIIa, independent of tissue factor: implications for the therapeutic mechanism of high-dose factor VIIa in hemophilia.

Journal Article Blood · January 1, 1994 High doses of recombinant factor VIIa are useful in managing bleeding in hemophiliacs with inhibitors. Whether this therapeutic effect of factor VIIa is dependent on tissue factor (TF) is a matter of debate. We examined the ability of freshly isolated huma ... Link to item Cite

Heparin cofactor II and thrombin Heparin-binding proteins linking hemostasis and inflammation.

Journal Article Trends Cardiovasc Med · 1994 α-Thrombin is a trypsinlike serine proteinase involved in blood coagulation and wound-healing processes, which interacts with many different macromolecular substances. Heparin cofactor II is a serpin (serine proteinase inhibitor) superfamily member that sp ... Full text Link to item Cite

Platelets contain releasable coagulation factor IX antigen.

Journal Article Blood Coagul Fibrinolysis · December 1993 Platelets take up plasma proteins into their alpha granules. Platelet activation releases the alpha granule contents. The goal of this study was to test the hypothesis that human platelets also contain some coagulation factor IX in their alpha granules. Pl ... Link to item Cite

Response of blood leukocytes to thrombin receptor peptides.

Journal Article J Leukoc Biol · August 1993 Thrombin has receptor-mediated effects on a variety of cell types. A recently cloned platelet thrombin receptor exerts its effects by a tethered-ligand mechanism. A similar receptor was shown in at least two nonplatelet cell types, fibroblasts and endothel ... Full text Link to item Cite

PLATELETS CONTAIN RELEASABLE COAGULATION FACTOR-IX

Conference THROMBOSIS AND HAEMOSTASIS · June 30, 1993 Link to item Cite

RESPONSE OF BLOOD LEUKOCYTES TO THROMBIN RECEPTOR PEPTIDES

Journal Article FASEB JOURNAL · April 20, 1993 Link to item Cite

Platelet activation in patients with thrombotic thrombocytopenic purpura.

Journal Article Am J Hematol · February 1993 Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology. It is characterized by platelet microthrombi in small vessels, which results in tissue dysfunction and a microangiopathic hemolytic anemia. Activation of coagulation is not a ... Full text Link to item Cite

A rapid method to isolate platelets from human blood by density gradient centrifugation.

Journal Article Am J Clin Pathol · November 1992 Platelets can be damaged easily or activated during isolation, making them unsuitable for functional studies. The most common technique for isolating platelets involves centrifugation. Although gentler methods have been devised to isolate platelets by dens ... Full text Link to item Cite

Coagulation factor IXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study.

Journal Article Thromb Haemost · July 6, 1992 Factor IX plays a central role in blood coagulation, since it can be activated by either XIa (intrinsic pathway) or tissue factor-VIIa (extrinsic pathway). Activated factor IX (IXa), in a surface-bound complex with factor VIIIa, then activates factor X. Pl ... Link to item Cite

Reversible binding of platelet-derived growth factor-AA, -AB, and -BB isoforms to a similar site on the "slow" and "fast" conformations of alpha 2-macroglobulin.

Journal Article J Biol Chem · June 25, 1992 The mechanism by which the platelet-derived growth factor (PDGF)-binding protein, alpha 2-macroglobulin (alpha 2M), modulates PDGF bioactivity is unknown, but could involve reversible PDGF-alpha 2M binding. Herein we report that greater than 70% of 125I-PD ... Link to item Cite

The effects of heparin cofactor II-derived chemotaxins on neutrophil actin conformation and cyclic AMP levels.

Journal Article Biochim Biophys Acta · October 16, 1991 The serine proteinase inhibitor heparin cofactor II (HC) can be cleaved by polymorphonuclear leukocyte (PMN) elastase (LE) to yield potent chemotactic activity for PMN and monocytes. In contrast to the bacterially-derived chemotaxin formyl-Met-Leu-Phe (fML ... Full text Link to item Cite

The effect of alpha 2 macroglobulin-proteinase complexes on macrophage Ia expression in vivo.

Journal Article Immunol Invest · February 1991 Alpha-2-Macroglobulin (alpha 2M) is a major plasma proteinase inhibitor. It can also regulate the function of cells of the immune system, including macrophage expression of Ia antigens in tissue culture systems. The present work was done to assess the effe ... Full text Link to item Cite

Leukocyte chemoattractant peptides from the serpin heparin cofactor II.

Journal Article J Biol Chem · January 15, 1991 Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits the coagulant proteinase alpha-thrombin. We have recently demonstrated that proteolysis of HC by catalytic amounts of polymorphonuclear leukocyte proteinases (elastase ... 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

PDGF-stimulated fibroblast proliferation is enhanced synergistically by receptor-recognized alpha 2-macroglobulin.

Journal Article J Cell Physiol · October 1990 alpha-Macroglobulins derived from plasma or secreted by macrophages are platelet-derived growth factor (PDGF) binding proteins that compete with cell-surface receptors on fibroblasts for PDGF binding. alpha 2-Macroglobulin (alpha 2M) derived from bovine pl ... Full text Link to item Cite

Characteristics of the chemotactic activity of heparin cofactor II proteolysis products.

Journal Article J Leukoc Biol · August 1990 The physiological function of the serpin (serine proteinase inhibitor) heparin cofactor II (HCII) is not well understood. A role for HCII as an inhibitor of thrombin in the presence of dermatan sulfate and heparin has been proposed. Neutrophils (PMN) are t ... Full text Link to item Cite

Variability in the fibrinogen and von Willebrand factor content of cryoprecipitate. Implications for reducing donor exposure.

Journal Article Am J Clin Pathol · May 1990 Advances in the preparation of commercial Factor VIII concentrates have decreased the clinical use of cryoprecipitate to replace Factor VIII coagulant activity. Cryoprecipitate is now frequently transfused as a source of fibrinogen or von Willebrand factor ... Full text Link to item Cite

Effect of interferon-gamma and human alpha 2-macroglobulin on peritoneal macrophage morphology and Ia antigen expression.

Journal Article Biochim Biophys Acta · February 19, 1990 While the primary role of the plasma protein alpha 2-macroglobulin (alpha 2M) appears to be related to its proteinase inhibitory activity, alpha 2M has been reported to regulate the immune response in vitro. Previous studies have demonstrated that, althoug ... Full text Link to item Cite

Production of chemotactic peptides by neutrophil degradation of heparin cofactor II.

Journal Article Thromb Res · January 1, 1990 This study investigated the reaction of heparin cofactor II (HCII) with stimulated polymorphonuclear leukocytes (PMN). We have expanded upon previous studies showing that HCII can be degraded by stimulated PMN (Sie, P., Dupouy, D., Dol, F., and Boneu, B., ... Full text Link to item Cite

Comparison of the effects of IL-1 alpha and TNF-alpha on phagocyte accumulation and murine antibacterial immunity.

Journal Article Cell Immunol · October 1, 1989 IL-1 and TNF both are reported to increase host antibacterial resistance. To directly compare their effects on tissue phagocyte accumulation and antibacterial activity, we infused recombinant human IL-1 alpha and TNF-alpha into C3H/HeJ mice. Although IL-1, ... Full text Link to item Cite

Alpha-macroglobulin secreted by alveolar macrophages serves as a binding protein for a macrophage-derived homologue of platelet-derived growth factor.

Journal Article Am J Respir Cell Mol Biol · September 1989 Evidence is presented to support our hypothesis that an alpha-macroglobulin (alpha M) produced by lung macrophages serves as a specific binding protein for platelet-derived growth factor (PDGF) from these same macrophages. Culture medium "conditioned" by a ... Full text Link to item Cite

Heparin cofactor II-proteinase reaction products exhibit neutrophil chemoattractant activity.

Journal Article Blood · May 1, 1989 The physiologic function of the plasma glycoprotein heparin cofactor II (HCII) is not well understood. An in vivo role for thrombin (IIa) inhibition by HCII in the presence of certain glycosaminoglycans (dermatan sulfate and heparin) can be proposed. Many ... Link to item Cite

Alpha 2 macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages.

Journal Article Agents Actions · December 1988 alpha 2-Macroglobulin is a proteinase inhibitor which is converted from its native form into an electrophoretically "fast" form by reaction with a proteinase or methylamine. All alpha 2M "fast" forms bind to a specific high-affinity receptor on macrophages ... Full text Link to item Cite

Conditions influencing the interaction of asialo von Willebrand factor with human platelets--the effects of external ionized calcium concentration and the role of arachidonate pathway.

Journal Article Thromb Haemost · October 31, 1988 We have studied the interaction of ASvWf with human platelets in PRP and in suspensions of washed platelets containing either physiological or low external ionized calcium concentration [Ca2+]o. In hirudin-PRP or in washed platelets in 1.5-2 mM CaCl2, ASvW ... Link to item Cite

Reduced trypsin-binding capacity of alpha 2-macroglobulin in the peritoneal fluid of women with endometriosis: possible relevance to alterations in macrophase function.

Journal Article Fertil Steril · July 1988 Alpha 2-macroglobulin (alpha 2M) is a plasma protein with proteinase inhibitor and immune modulatory capabilities. The amounts of alpha 2M in peritoneal fluid (PF) from women with endometriosis and women with noninflammatory gynecologic conditions were ana ... Full text Link to item Cite

Clearance and distribution of recombinant murine gamma-interferon in mice.

Journal Article Cancer Res · April 15, 1988 Recombinant murine gamma-interferon (rIFN-gamma) was radiolabeled by a novel procedure which does not require the use of preiodinated Bolton-Hunter reagent (specific activities of 0.5-3.0 microCi/micrograms). Gel filtration chromatography of the radiolabel ... Link to item Cite

Tumor necrosis factor-alpha induces increased hydrogen peroxide production and Fc receptor expression, but not increased Ia antigen expression by peritoneal macrophages.

Journal Article J Leukoc Biol · December 1987 It has recently been shown that tumor necrosis factor (TNF) induces increased Ia antigen expression on a malignant murine macrophage cell line, and that TNF is synergistic with gamma interferon (IFN) in inducing Ia expression. This finding raises the possi ... Full text Link to item Cite

The effect of fibrin polymerization inhibitors on quantitative measurements of plasma fibrinogen.

Journal Article Am J Clin Pathol · October 1987 A number of reports have highlighted discrepancies between the DuPont aca and fibrometer-based methods for quantitating plasma fibrinogen levels. Although many authors have suggested that the presence of fibrin(ogen) degradation products are in some way re ... Full text Link to item Cite

Modulation of mouse peritoneal macrophage Ia and human peritoneal macrophage HLA-DR expression by alpha 2-macroglobulin "fast" forms.

Journal Article J Immunol · September 15, 1987 alpha 2-Macroglobulin (alpha 2M) is converted from its native form into electrophoretically "fast" forms by reaction with proteinases or with methylamine. The "fast" forms both bind to specific receptors on macrophages (MP). We have previously shown that a ... Link to item Cite

MODULATION OF PERITONEAL MACROPHAGE (MP) MEMBRANE-ANTIGENS BY ALPHA2-MACROGLOBULIN TRYPSIN (A2M-T) COMPLEXES

Journal Article PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH · March 1, 1987 Link to item Cite

Fibrinogen content of low-volume cryoprecipitate.

Journal Article Transfusion · 1987 Single-donor cryoprecipitate is the most convenient and reliable source of fibrinogen. A change by the regional Red Cross Blood Service to the production of low-volume cryoprecipitate led the authors to reexamine the fibrinogen content of cryoprecipitate u ... 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

ELECTRON-PROBE MICROANALYSIS OF HALLERVORDEN-SPATZ DISEASE

Journal Article AMERICAN JOURNAL OF CLINICAL PATHOLOGY · March 1, 1986 Link to item Cite

Unusual presentations of inflammatory conditions in cerebrospinal fluid.

Journal Article Acta Cytol · 1985 Unusual inflammatory reactions in cerebrospinal fluid (CSF) in five patients were explicable by the type of intracranial injury or surgical intervention that they had received or by their basic disease process. Lumbar puncture fluid from a 64-year-old man ... Link to item Cite

SYNTHESIS OF ANTITHROMBIN-III BY CULTURED RAT HEPATOCYTES

Conference LABORATORY INVESTIGATION · January 1, 1984 Link to item Cite

Alpha 2-macroglobulin 'fast' forms inhibit superoxide production by activated macrophages.

Journal Article Biochim Biophys Acta · November 8, 1983 Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human alpha 2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both alpha 2-ma ... Full text Link to item Cite

α2-macroglobulin 'fast' forms inhibit superoxide production by activated macrophages

Journal Article BBA - General Subjects · 1983 Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human α2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both α2-macroglobuli ... Cite

Effect of cyclooxygenase inhibitors and protease inhibitors on phorbol-induced stimulation of oxygen consumption and superoxide production by rat pulmonary macrophages.

Journal Article Biochem Pharmacol · March 1, 1982 Oxygen consumption and superoxide anion production by pulmonary macrophages are both increased by phorbol myristate acetate (PMA) but the two processes have been separated using protease inhibitors and cyclooxygenase inhibitors. Pretreatment with the prote ... Full text Link to item Cite

NADPH-dependent oxygen reductase activity in pulmonary macrophages.

Journal Article Bull Eur Physiopathol Respir · 1981 Link to item Cite

Adaptation to hyperoxia in the neonatal rat: kinetic parameters of the oxygen-mediated induction of lung superoxide dismutases, catalase and glutathione peroxidase.

Journal Article Toxicology · 1980 The activities of the enzymes superoxide dismutase, catalase and glutathione peroxidase increase in the lungs of neonatal rats exposed to normobaric hyperoxia. The oxygen-mediated increase in activity of these enzymes, known from previous studies to be an ... Full text Link to item Cite

Changes in oxygen consumption and phagocytosis in rat pulmonary macrophages related to animal maturation

Journal Article Experimental Lung Research · January 1, 1980 Differences in selected metabolic and functional parameters of pulmonary macrophages have been found in cells obtained from rats between birth and 40 days of age. Oxygen consumption ranged from 0.6-0.8 nM/106 viable macrophages/min in the pulmonary macroph ... Full text Cite