Scholars@Duke
Gowthami Morey Arepally

Gowthami Morey Arepally

Professor of Medicine
Medicine, Hematology
arepa001@mc.duke.edu
Duke Box 3486, Durham, NC 27710
Rm 356A Sands Bldg, Research Drive, Durham, NC 27710

Selected Publications

Red cell exchange modulates neutrophil degranulation responses in sickle cell disease.

Journal Article Transfusion · September 2024 BACKGROUND: Neutrophils in sickle cell disease (SCD) are activated, contributing to disease. Red cell exchange (RCE), with the goal of lowering hemoglobin S (HbS), is an important part of therapy for many SCD patients. Whether RCE impacts neutrophil reacti ... Full text Link to item Cite

Platelet and red cell responses to three North American pit vipers.

Journal Article Toxicon · August 28, 2024 We investigated the hemotoxic effects of three North American pit vipers in healthy human donor blood. Using experiments focusing on platelet and red blood cell activity, we found differential effects of these venoms on these cellular components. Platelet ... Full text Link to item Cite

Coagulation and platelet biology at the intersection of health and disease: illustrated capsules of the 11th Symposium on Hemostasis at the University of North Carolina.

Conference Res Pract Thromb Haemost · March 2024 The University of North Carolina Symposia on Hemostasis began in 2002, with The First Symposium on Hemostasis with a Special Focus on FVIIa and Tissue Factor. They have occurred biannually since and have maintained the primary goal of establishing a forum ... Full text Link to item Cite

Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs.

Journal Article J Immunol · February 15, 2024 The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition ... Full text Link to item Cite

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

Journal Article Blood · January 25, 2024 Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity ... Full text Link to item Cite

Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic?

Journal Article Blood Adv · August 8, 2023 Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia associated with a highly prothrombotic state due to the development of pathogenic antibodies that recognize human platelet factor 4 (hPF4) complexed with various polyanions. Althou ... Full text Link to item Cite

Clot Imaging Using Photostable Nanodiamond.

Journal Article Nanomaterials (Basel) · March 7, 2023 While thrombosis is the leading cause of morbidity and mortality in the United States, an understanding of its triggers, progression, and response to anticoagulant therapy is lacking. Intravital fluorescence microscopy has advanced the study of thrombus fo ... Full text Link to item Cite

Modulation of ultralarge immune complexes in heparin-induced thrombocytopenia.

Journal Article J Thromb Haemost · March 2023 BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious thrombotic disorder caused by ultralarge immune complexes (ULICs) containing platelet factor 4 (PF4) and heparin that form the HIT antigen, together with a subset of anti-PF4 antibodies. ULICs ... Full text Link to item Cite

Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.

Journal Article J Leukoc Biol · December 2022 Differences in the ability of neutrophils to perform relevant effector functions has been identified in a variety of disease states. Although neutrophil functional heterogeneity is increasingly recognized during disease, few studies have examined neutrophi ... Full text Link to item Cite

Minimal role for the alternative pathway in complement activation by HIT immune complexes.

Journal Article J Thromb Haemost · November 2022 BACKGROUND: Anti-platelet factor 4 (PF4)/heparin immune complexes that cause heparin-induced thrombocytopenia (HIT) activate complement via the classical pathway. Previous studies have shown that the alternative pathway of complement substantially amplifie ... Full text Link to item Cite

The Predictive Value of the 4Ts and HEP Score at Recommended Cutoffs in Patients With Mechanical Circulatory Support Devices.

Journal Article J Cardiothorac Vasc Anesth · July 2022 OBJECTIVES: Despite the increasing utilization of mechanical circulatory support (MCS) devices, the 4Ts and heparin-induced thrombocytopenia (HIT) Expert Probability (HEP) scores have not been validated in patients with suspected HIT requiring MCS. DESIGN: ... Full text Link to item Cite

Aptamer-based factor IXa inhibition preserves hemostasis and prevents thrombosis in a piglet model of ECMO.

Journal Article Mol Ther Nucleic Acids · March 8, 2022 Extracorporeal membrane oxygenation (ECMO) requires anticoagulation to prevent clotting when the patient's blood contacts the circuit. Unfractionated heparin (UFH) usually prevents clotting but can cause life-threatening bleeding. An anticoagulant that sel ... Full text Link to item Cite

Complement mediates binding and procoagulant effects of ultralarge HIT immune complexes.

Journal Article Blood · November 25, 2021 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by ultra-large immune complexes (ULICs) containing immunoglobulin G (IgG) antibodies to a multivalent antigen composed of platelet factor 4 and heparin. The limitations of current ... Full text Link to item Cite

COVID-19 and VITT: same or different?

Journal Article Blood · October 7, 2021 Full text Link to item Cite

C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.

Journal Article Nat Commun · September 15, 2021 Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement componen ... Full text Link to item Cite

Vaccine-induced immune thrombotic thrombocytopenia: what we know and do not know.

Journal Article Blood · July 29, 2021 The development of vaccines to fight COVID-19 has been a remarkable medical achievement. However, this global immunization effort has been complicated by a rare vaccine-related outcome characterized by thrombocytopenia and thrombosis in association with pl ... Full text Link to item Cite

Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): What We Know and Don't Know.

Journal Article Blood · June 1, 2021 Development of vaccines to fight COVID19 has been a remarkable medical achievement. However, this global immunization effort has been complicated by a rare vaccine-related outcome characterized by thrombocytopenia and thrombosis in association with platele ... Full text Link to item Cite

Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults

Journal Article Kidney International Reports · June 1, 2021 Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often ... Full text Cite

Heparin-Induced Thrombocytopenia: A Focus on Thrombosis.

Journal Article Arterioscler Thromb Vasc Biol · January 2021 Heparin-induced thrombocytopenia is an immune-mediated disorder caused by antibodies that recognize complexes of platelet factor 4 and heparin. Thrombosis is a central and unpredictable feature of this syndrome. Despite optimal management, disease morbidit ... Full text Link to item Cite

Pathogenesis of heparin-induced thrombocytopenia.

Journal Article Transl Res · November 2020 There are currently no effective substitutes for high intensity therapy with unfractionated heparin (UFH) for cardiovascular procedures based on its rapid onset of action, ease of monitoring and reversibility. The continued use of UFH in these and other se ... Full text Link to item Cite

Recognition of PF4-VWF complexes by heparin-induced thrombocytopenia antibodies contributes to thrombus propagation.

Journal Article Blood · April 9, 2020 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by complexes between platelet factor 4 (PF4) and heparin or other polyanions, but the risk of thrombosis extends beyond exposure to heparin implicating other PF4 partners. We recen ... Full text Link to item Cite

Fc-modified HIT-like monoclonal antibody as a novel treatment for sepsis.

Journal Article Blood · March 5, 2020 Sepsis is characterized by multiorgan system dysfunction that occurs because of infection. It is associated with high morbidity and mortality and is in need of improved therapeutic interventions. Neutrophils play a crucial role in sepsis, releasing neutrop ... Full text Link to item Cite

The Developing Balance of Thrombosis and Hemorrhage in Pediatric Surgery: Clinical Implications of Age-Related Changes in Hemostasis.

Journal Article Clin Appl Thromb Hemost · 2020 Bleeding and thrombosis in critically ill infants and children is a vexing clinical problem. Despite the relatively low incidence of bleeding and thrombosis in the overall pediatric population relative to adults, these critically ill children face unique c ... Full text Link to item Cite

Understanding How Fc-Modification Transforms a Pathogenic Heparin-Induced Thrombocytopenia (HIT)-like Monoclonal Antibody into a Novel Treatment for Sepsis.

Journal Article Blood · November 13, 2019 DISCLOSURES: Arepally: Biokit: Patents & Royalties; Apotex Pharmaceuticals: Consultancy; Veralox Therapeutics: Membership on an entity's Board of Directors or advisory committees. ... Full text Link to item Cite

The risk of major bleeding in patients with suspected heparin-induced thrombocytopenia.

Journal Article J Thromb Haemost · November 2019 BACKGROUND: The presence of a hypercoagulable disorder such as heparin-induced thrombocytopenia (HIT) may protect against anticoagulant-associated bleeding. OBJECTIVES: To determine the incidence of major bleeding in patients with suspected HIT. METHODS: W ... Full text Link to item Cite

Heterogeneity in neutrophil responses to immune complexes.

Journal Article Blood Adv · October 8, 2019 Immune complexes (ICs) can trigger inflammation and thrombosis, in part, by activating neutrophils. Much attention has focused on the serologic characteristics of ICs and Fc receptors associated with cellular activation, but few studies have examined host ... Full text Link to item Cite

Bad weed: synthetic cannabinoid-associated coagulopathy.

Journal Article Blood · February 28, 2019 Recent multistate outbreaks of coagulopathy caused by brodifacoum-tainted synthetic cannabinoids or "fake weed" highlight the public health impact of long-acting anticoagulant rodenticides (LAARs). Patients presenting with this syndrome have had recent exp ... Full text Link to item Cite

Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway.

Journal Article Blood · December 6, 2018 The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B c ... Full text Link to item Cite

Prospective comparison of the HEP score and 4Ts score for the diagnosis of heparin-induced thrombocytopenia.

Journal Article Blood Adv · November 27, 2018 The HIT Expert Probability (HEP) score compared favorably with the 4Ts score in a retrospective study. We assessed the diagnostic accuracy of the HEP score compared with the 4Ts score in a prospective cohort of 310 patients with suspected heparin-induced t ... Full text Link to item Cite

American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia.

Journal Article Blood Adv · November 27, 2018 BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin. Patients are at markedly increased risk of thromboembolism. OBJECTIVE: These e ... Full text Link to item Cite

Neutrophil accumulation and NET release contribute to thrombosis in HIT.

Journal Article JCI Insight · September 20, 2018 Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenic disorder associated with a severe prothrombotic state. We investigated whether neutrophils and neutrophil extracellular traps (NETs) contribute to the development of thrombosis i ... Full text Link to item Cite

Dynamic intercellular redistribution of HIT antigen modulates heparin-induced thrombocytopenia.

Journal Article Blood · August 16, 2018 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies to platelet factor 4 (PF4)/heparin complexes. PF4 released from platelets binds to surface glycosaminoglycans on hematopoietic and vascular cells that are heterogeno ... Full text Link to item Cite

Indications for and outcomes of therapeutic plasma exchange after cardiac transplantation: A single center retrospective study.

Journal Article J Clin Apher · August 2018 INTRODUCTION: Limited data are available describing indications for and outcomes of therapeutic plasma exchange (TPE) in cardiac transplantation. METHODS: In a retrospective study of patients who underwent cardiac transplantation at Duke University Medical ... Full text Open Access Link to item Cite

Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

Journal Article Nat Biotechnol · August 2018 Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the ... Full text Link to item Cite

PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

Journal Article Thromb Res · November 2017 INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies ... Full text Link to item Cite

Novel therapeutic approaches for thrombotic thrombocytopenic purpura.

Journal Article Curr Opin Hematol · November 2017 PURPOSE OF REVIEW: Acquired thrombotic thrombocytopenic purpura is an immune-mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13). Standard treatment with t ... Full text Link to item Cite

Human Leukocyte Antigen Sensitization in Solid Organ Transplantation: A Primer on Terminology, Testing, and Clinical Significance for the Apheresis Practitioner.

Journal Article Ther Apher Dial · October 2017 The human leukocyte antigen (HLA) system is an important immunologic barrier that must be considered for successful solid organ transplantation. Formation of donor-specific HLA antibodies in solid organ transplantation is an important cause of allograft in ... Full text Open Access Link to item Cite

Heparin-induced thrombocytopenia.

Journal Article Blood · May 25, 2017 Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes ... Full text Link to item Cite

Etiology and complications of thrombocytopenia in hospitalized medical patients.

Journal Article J Thromb Thrombolysis · May 2017 To determine incidence, risk factors, hematologic complications, and prognostic significance of thrombocytopenia in the general medicine population, we performed a single-institutional, retrospective study of all adult patients admitted to a general medica ... Full text Link to item Cite

Serologic characterization of anti-protamine/heparin and anti-PF4/heparin antibodies.

Journal Article Blood Adv · April 25, 2017 Anti-protamine (PRT)/heparin antibodies are a newly described class of heparin-dependent antibodies occurring in patients exposed to PRT and heparin during cardiac surgery. To understand the biologic significance of anti-PRT/heparin antibodies, we develope ... Full text Link to item Cite

Endothelial antigen assembly leads to thrombotic complications in heparin-induced thrombocytopenia.

Journal Article J Clin Invest · March 1, 2017 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies against complexes between human platelet factor 4 (hPF4) and heparin. A better understanding of the events that initiate the prothrombotic state may improve approach ... Full text Link to item Cite

Thrombocytopenia in hospitalized patients with severe clostridium difficile infection.

Journal Article J Thromb Thrombolysis · January 2017 Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has ... Full text Link to item Cite

The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery.

Journal Article J Thromb Haemost · January 2017 UNLABELLED: Essentials We evaluated antibody status, thromboembolism and survival after cardiac surgery. Positive antibody tests are common - over 50% are seropositive at 30 days. Seropositivity did not increase thromboembolism or impair survival after car ... Full text Link to item Cite

Heparin-induced thrombocytopenia: research and clinical updates.

Journal Article Hematology Am Soc Hematol Educ Program · December 2, 2016 Heparin-induced thrombocytopenia (HIT) remains an important diagnosis to consider in hospitalized patients developing thrombocytopenia. HIT is an immune-mediated prothrombotic disorder caused by antibodies to platelet factor 4 (PF4) and heparin. Recent bas ... Full text Link to item Cite

Mechanism of Complement Activation By PF4/ Heparin Complexes

Conference Blood · December 2, 2016 AbstractThe mechanisms underlying the PF4/heparin immune response are poorly understood. In recent studies, we showed that PF4/heparin complexes, but not PF4 alone or heparin alone, activate complement (C') ... Full text Cite

Novel ELISA-Based Assay for Detection of Complement Activation By PF4/Heparin Complexes

Conference Blood · December 2, 2016 AbstractThe immune response to platelet factor 4 (PF4)/heparin complexes is a frequent iatrogenic complication of heparin therapy associated with development of heparin-induced thrombocytopenia (HIT). Our re ... Full text Cite

RNA Aptamer Against FXa Synergizes with FXa Catalytic Site Inhibitors to Effectively and Reversibly Anticoagulate Blood in an Ex Vivo Oxygenator Circuit

Conference Blood · December 2, 2016 AbstractDespite notable disadvantages, unfractionated heparin (UFH) remains the standard anticoagulant for clinical procedures requiring potent and reversible anticoagulation such as cardiopulmonary bypass ( ... Full text Cite

Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia.

Journal Article Blood Adv · November 29, 2016 Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder initiated by antibodies to complexes between platelet factor 4 (PF4) and heparin. The risk of recurrent thromboembolism persists after heparin is cleared and platelet activation leading to rel ... Full text Link to item Cite

Should we avoid heparin to eliminate HIT?

Journal Article Blood Adv · November 29, 2016 Full text Link to item Cite

Immune pathogenesis of heparin-induced thrombocytopenia.

Journal Article Thromb Haemost · October 28, 2016 The immune response to heparin is one of the most common drug-induced allergies, and yet, atypical for a drug hypersensitivity reaction. Whereas most drug-induced allergies are rare, idiosyncratic and life-long, the allergic response to heparin is common, ... Full text Link to item Cite

The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21).

Journal Article Blood · October 6, 2016 Heparin-induced thrombocytopenia is a prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)/heparin complexes. The mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of patients exposed to heparin i ... Full text Link to item Cite

THROMBOCYTOPENIA IN HOSPITALIZED NON-ICU PATIENTS

Journal Article AMERICAN JOURNAL OF HEMATOLOGY · September 1, 2016 Link to item Cite

The Thrombotic Microangiopathy Registry of North America

Conference Blood · December 3, 2015 AbstractThe thrombotic microangiopathies (TMAs) are rare, life-threatening thrombotic disorders of diverse etiologies. Systematic studies of TMA have been difficult to perform due to their rare occurrence, d ... Full text Cite

Characterization of Human and Murine Anti-Protamine/Heparin Antibodies

Conference Blood · December 3, 2015 AbstractProtamine/heparin (PRT/H) antibodies (Abs) are a newly described class of heparin-dependent antibodies found in ~25% of patients exposed to protamine and heparin during cardiopulmonary bypass surgery ... Full text Cite

Atomic description of the immune complex involved in heparin-induced thrombocytopenia.

Journal Article Nat Commun · September 22, 2015 Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) ... Full text Link to item Cite

Heparin enhances uptake of platelet factor 4/heparin complexes by monocytes and macrophages.

Journal Article J Thromb Haemost · August 2015 BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an iatrogenic complication of heparin therapy caused by antibodies to a self-antigen, platelet factor (4) and heparin. The reasons why antibodies form to PF4/heparin, but not to PF4 bound to other cellu ... Full text Link to item Cite

Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin?

Journal Article Annu Rev Med · 2015 The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment ... Full text Link to item Cite

Predicting the Temporal Course of Laboratory Abnormality Resolution in Patients with Thrombotic Microangiopathy

Conference Blood · December 6, 2014 AbstractBackground:Screening for deficiency of ADAMTS- 13, a von Willebrand factor-cleaving protease, is commonly performed when there exists a clinical suspicion for thrombo ... Full text Cite

Biologic Activities of Protamine/Heparin Antibodies

Conference Blood · December 6, 2014 AbstractProtamine/heparin (PRT/H) antibodies (Ab) are a newly described class of heparin-dependent Abs found in ~25% of patients exposed to protamine and heparin during cardiopulmonary bypass surgery (CPB). ... Full text Cite

Antibody desensitization therapy in highly sensitized lung transplant candidates.

Journal Article Am J Transplant · April 2014 As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value ... Full text Link to item Cite

Autoantibodies in Heparin-Induced Thrombocytopenia

Chapter · January 1, 2014 Heparin-induced thrombocytopenia (HIT) is a common and clinically important autoimmune disease in which antibodies to complexes of platelet factor 4 (PF4) and heparin cause platelet activation, thrombocytopenia, and predisposition to thrombosis. HIT provid ... Full text Cite

Distinct specificity and single-molecule kinetics characterize the interaction of pathogenic and non-pathogenic antibodies against platelet factor 4-heparin complexes with platelet factor 4.

Journal Article J Biol Chem · November 15, 2013 Heparin-induced thrombocytopenia (HIT) is a thrombotic complication of heparin therapy mediated by antibodies to complexes between platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans. However, only a fraction of patients with anti-PF4-hepari ... Full text Link to item Cite

Diagnosis and management of heparin-induced thrombocytopenia.

Journal Article Hematol Oncol Clin North Am · June 2013 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by antibodies to platelet factor 4/heparin (PF4/H) complexes. It presents with declining platelet counts 5 to 14 days after heparin administration and results in a predisposition to ... Full text Link to item Cite

Novel diagnostic assays for heparin-induced thrombocytopenia.

Journal Article Blood · May 2, 2013 Laboratory testing for heparin-induced thrombocytopenia (HIT) has important shortcomings. Immunoassays fail to discriminate platelet-activating from nonpathogenic antibodies. Specific functional assays are impracticable due to the need for platelets and ra ... Full text Link to item Cite

Critical role for mouse marginal zone B cells in PF4/heparin antibody production.

Journal Article Blood · April 25, 2013 Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that can cause fatal arterial or venous thrombosis/thromboembolism. Immune complexes consisting of platelet factor 4 (PF4), heparin, and PF4/heparin-reactive antibodies are central to th ... Full text Link to item Cite

High incidence of antibodies to protamine and protamine/heparin complexes in patients undergoing cardiopulmonary bypass.

Journal Article Blood · April 11, 2013 Protamine is routinely used to reverse heparin anticoagulation during cardiopulmonary bypass (CPB). Heparin interacts with protamine to form ultralarge complexes that are immunogenic in mice. We hypothesized that patients exposed to protamine and heparin d ... Full text Link to item Cite

Heparin-induced thrombocytopenia.

Journal Article Hematology Am Soc Hematol Educ Program · 2013 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. HIT is frequently considered in the differential diagnosis of thrombocytopenia occurring in patients on ... Full text Link to item Cite

Autoantibodies in Heparin-Induced Thrombocytopenia

Journal Article · January 1, 2013 Heparin-induced thrombocytopenia (HIT) is a common and clinically important autoimmune disease in which antibodies to complexes of platelet factor 4 (PF4) and heparin cause platelet activation, thrombocytopenia, and predisposition to thrombosis. HIT provid ... Full text Cite

High Incidence of Antibodies to Protamine and Protamine/Heparin Complexes in Patients Undergoing Cardiopulmonary Bypass

Conference Blood · November 16, 2012 AbstractAbstract 3344INTRO:Protamine (PRT) is routinely used to reverse heparin (H) anticoagulation d ... Full text Cite

Novel Techniques for Measurement of Variable Sized PF4/H Complexes.

Conference Blood · November 16, 2012 AbstractAbstract 2204Electrostatic interactions between Platelet factor 4 (PF4), a cationic protein, and heparin, an anionic carbohydrate result in the formation of ultra-lar ... Full text Cite

PF4/H Complexes Induce Germinal Centers in Vivo

Conference Blood · November 16, 2012 AbstractAbstract 269Mice injected with ultra-large complexes (ULCs) of platelet factor-4 (PF4) and heparin (PF4/H) exhibit a strong immune response which mimics that seen in ... Full text Cite

Dynamic antibody-binding properties in the pathogenesis of HIT.

Journal Article Blood · August 2, 2012 Rapid laboratory assessment of heparin-induced thrombocytopenia (HIT) is important for disease recognition and management. The utility of contemporary immunoassays to detect antiplatelet factor 4 (PF4)/heparin antibodies is hindered by detection of antibod ... Full text Link to item Cite

PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI.

Journal Article Blood · May 31, 2012 Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 ... Full text Link to item Cite

Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH).

Journal Article Thromb Haemost · April 2012 Recent studies have shown that ultra-large complexes (ULCs) of platelet factor 4 (PF4) and heparin (H) play an essential role in the pathogenesis of heparin-induced thrombocytopenia (HIT), an immune-mediated disorder caused by PF4/H antibodies. Because ant ... Full text Link to item Cite

Anticoagulation techniques in apheresis: from heparin to citrate and beyond.

Journal Article J Clin Apher · 2012 Anticoagulation is essential for maintaining the fluidity of extravascular blood on the apheresis circuit. Although both citrate and heparin are used as an anticoagulant during apheresis, citrate is preferred for the majority of exchange procedures because ... Full text Link to item Cite

American Society for Apheresis white paper: considerations for medical staff apheresis medicine physician credentialing and privileging.

Journal Article J Clin Apher · 2012 INTRODUCTION: Physician supervision of apheresis contributes to safe and high-quality patient care. Literature is limited regarding the requirements for hospital privileges of physicians providing apheresis services. This report provides recommendations fr ... Full text Link to item Cite

Lenalidomide-Associated ITP.

Journal Article Case Rep Hematol · 2011 Lenalidomide is a potent immunomodulatory agent being used increasingly for treatment of hematologic malignancies including multiple myeloma and myelodysplasia. The common toxicities of lenalidomide, including dose-limiting myelosuppression, are well descr ... Full text Link to item Cite

Heparin modifies the immunogenicity of positively charged proteins.

Journal Article Blood · December 23, 2010 The immune response in heparin-induced thrombocytopenia is initiated by and directed to large multimolecular complexes of platelet factor 4 (PF4) and heparin (H). We have previously shown that PF4:H multimolecular complexes assemble through electrostatic i ... Full text Link to item Cite

The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion.

Journal Article J Thromb Haemost · December 2010 BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. Over-diagnosis and over-treatment are common. OBJECTIVES: To develop a pre-test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding c ... Full text Link to item Cite

Platelet factor 4/heparin antibodies in blood bank donors.

Journal Article Am J Clin Pathol · November 2010 Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximat ... Full text Link to item Cite

Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients.

Journal Article Ann Thorac Surg · October 2010 BACKGROUND: Bleeding is a major cause of morbidity in recipients of continuous-flow left ventricular assist devices (CF-LVAD). A better understanding of the impact of CF-LVAD support on the hemostatic profile is necessary to establish better strategies for ... Full text Link to item Cite

Validation of the high-dose heparin confirmatory step for the diagnosis of heparin-induced thrombocytopenia.

Journal Article Blood · September 9, 2010 The diagnosis of heparin-induced thrombocytopenia (HIT) requires detection of antibodies to the heparin/platelet factor 4 (PF4) complexes via enzyme-linked immunosorbent assay. Addition of excess heparin to the sample decreases the optical density by 50% o ... Full text Link to item Cite

Aprotinin improves functional outcome but not cerebral infarct size in an experimental model of stroke during cardiopulmonary bypass.

Journal Article Anesth Analg · July 2010 BACKGROUND: Aprotinin, a nonspecific serine protease inhibitor, has been used to decrease bleeding and reduce the systemic inflammatory response after cardiopulmonary bypass (CPB). Studies have variably linked aprotinin administration with both improved as ... Full text Open Access Link to item Cite

The use of antithrombotic therapies in the prevention and treatment of arterial and venous thrombosis: a survey of current knowledge and practice supporting the need for clinical education.

Journal Article Crit Pathw Cardiol · March 2010 Arterial and venous thrombosis are serious health threats. Patients with atrial fibrillation (AF), acute coronary syndromes (ACS), and venous thromboembolism (VTE) can reduce their risk of thrombosis through proper anticoagulation. Multiple evidence-based ... Full text Link to item Cite

Comparative analysis of von Willebrand factor profiles in pulsatile and continuous left ventricular assist device recipients.

Journal Article ASAIO J · 2010 A higher rate of nonsurgical bleeding has been observed in nonpulsatile left ventricular assist device (LVAD) recipients. von Willebrand factor (vWF) profiles were compared for nonpulsatile and pulsatile LVAD recipients to explore mechanisms that may contr ... Full text Link to item Cite

Plasmapheresis and heparin reexposure as a management strategy for cardiac surgical patients with heparin-induced thrombocytopenia.

Journal Article Anesth Analg · January 1, 2010 BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicates the management of patients presenting for cardiac surgery, because high-dose heparin anticoagulation for cardiopulmonary bypass is contraindicated in these patients. Alternative anticoagulants ... Full text Link to item Cite

Heparin-induced thrombocytopenia.

Journal Article Annu Rev Med · 2010 Heparin-induced thrombocytopenia (HIT) is an immune-mediated hypercoagulable disorder caused by antibodies to platelet factor 4 (PF4) and heparin. HIT develops in temporal association with heparin therapy and manifests either as an unexplained thrombocytop ... 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

Risk factors for inhibitor formation in haemophilia: a prevalent case-control study.

Journal Article Haemophilia · September 2009 Inhibitor formation is a major complication of haemophilia treatment. In a prevalent case-control study, we evaluated blood product exposure, genotype and HLA type on haemophilia A inhibitor formation. Product exposure was extracted from medical records. G ... Full text Link to item Cite

Platelet and monocyte antigenic complexes in the pathogenesis of heparin-induced thrombocytopenia (HIT).

Journal Article J Thromb Haemost · July 2009 Heparin-induced thrombocytopenia (HIT) is an iatrogenic disorder that occurs in a small subset of patients receiving heparin. Twenty-five per cent (or higher) of affected patients develop limb or life-threatening thrombosis. The effectiveness of therapy is ... Full text Link to item Cite

SEROPREVALENCE OF PF4/HEPARIN ANTIBODIES AMONG BLOOD BANK DONORS

Journal Article PEDIATRIC BLOOD & CANCER · June 1, 2009 Link to item Cite

Nothing typical about HIT.

Journal Article Blood · May 14, 2009 Full text Link to item Cite

Optimization of a murine immunization model for study of PF4/heparin antibodies.

Journal Article J Thromb Haemost · May 2009 SUMMARY BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life-threatening thrombotic illness caused by drug-dependent antibodies recognizing complexes of platelet factor 4 (PF4) and heparin. Little is known about the immune pathogenesis of HIT, in p ... Full text Link to item Cite

Transplantation-mediated alloimmune thrombocytopenia: Guidelines for utilization of thrombocytopenic donors.

Journal Article Liver Transpl · December 2008 Transplantation-mediated alloimmune thrombocytopenia (TMAT) is donor-derived thrombocytopenia following solid-organ transplantation. To date, no clear consensus on the appropriateness of organ utilization from cadaver donors with a history of idiopathic th ... Full text Link to item Cite

Use of the levonorgestrel-releasing intrauterine system in women with hemostatic disorders.

Journal Article Fertil Steril · September 2008 OBJECTIVE: To evaluate the use of the levonorgestrel-releasing intrauterine system (LNG-IUS) in women with known hemostatic disorders and abnormal uterine bleeding. DESIGN: Retrospective case series. SETTING: Tertiary medical center. PATIENT(S): Women with ... Full text Link to item Cite

Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results.

Journal Article J Thromb Thrombolysis · August 2008 Featured Publication PURPOSE: We determined the seroprevalence of platelet factor 4 (PF4)/heparin antibodies in healthy subjects. METHODS: A literature search identified studies in which healthy subjects were evaluated using commercial immunoassays for PF4/heparin antibody (Ig ... Full text Link to item Cite

Response to Boctor and Smith

Journal Article American Journal of Hematology · March 1, 2008 Full text Cite

Determinants of PF4/heparin immunogenicity.

Journal Article Blood · December 15, 2007 Featured Publication Heparin-induced thrombocytopenia (HIT) is an antibody-mediated disorder that occurs with variable frequency in patients exposed to heparin. HIT antibodies preferentially recognize large macromolecular complexes formed between PF4 and heparin over a narrow ... Full text Link to item Cite

Autoantibodies in heparin-induced thrombocytopenia

Journal Article · December 1, 2007 Heparin-induced thrombocytopenia and thrombosis (HITT) is a common and clinically important autoimmune disease in which antibodies to complexes between heparin and platelet factor 4 (PF4) cause platelet activation, thrombocytopenia and thrombosis. HITT pro ... Full text Cite

Influence of sample collection and storage on the detection of platelet factor 4-heparin antibodies.

Journal Article Am J Clin Pathol · July 2007 Heparin-induced thrombocytopenia is a life threatening thrombotic disorder caused by antibodies to platelet factor 4 (PF4) and heparin. Commercial immunoassays are frequently used for the detection of PF4-heparin antibodies, and several studies have report ... Full text Link to item Cite

Thrombotic thrombocytopenic purpura induced by trimethoprim-sulfamethoxazole in a Jehovah's Witness.

Journal Article Am J Hematol · July 2007 We report a case of Thrombotic Thrombocytopenic Purpura occurring as an allergic response to trimethoprim-sulfamethoxazole therapy (Bactrim, Septra) in a Jehovah's Witness patient. The patient presented with fulminant microangiopathic hemolytic anemia and ... 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 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

Effect of combined anticoagulation using heparin and bivalirudin on the hemostatic and inflammatory responses to cardiopulmonary bypass in the rat.

Journal Article Anesthesiology · February 2007 BACKGROUND: Despite high-dose heparin anticoagulation, cardiopulmonary bypass (CPB) is still associated with marked hemostatic activation. The purpose of this study was to determine whether a reduced dose of bivalirudin, added as an adjunct to heparin, wou ... Full text Link to item Cite

Heparin-induced thrombocytopenia: an autoimmune disorder regulated through dynamic autoantigen assembly/disassembly.

Journal Article J Clin Apher · February 2007 Featured Publication Heparin-induced thrombocytopenia (HIT) is the most common drug-induced, antibody-mediated cause of thrombocytopenia and thrombosis. HIT is caused by IgG antibodies that bind to epitopes on platelet factor 4 (PF4) released from activated platelets that deve ... Full text Link to item Cite

Antidote-controlled platelet inhibition targeting von Willebrand factor with aptamers.

Journal Article Oligonucleotides · 2007 Thrombus formation is initiated by platelets and leads to cardiovascular, cerebrovascular, and peripheral vascular disease, the leading causes of morbidity and mortality in the Western world. A number of antiplatelet drugs have improved clinical outcomes f ... Full text Link to item Cite

The authors reply [21]

Journal Article New England Journal of Medicine · December 14, 2006 Full text Cite

Lepirudin: Walking the dosing line

Journal Article Blood · September 1, 2006 Full text Cite

Clinical practice. Heparin-induced thrombocytopenia.

Journal Article N Engl J Med · August 24, 2006 Full text Link to item Cite

Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications.

Journal Article Blood · March 15, 2006 Heparin-induced thrombocytopenia (HIT) antibodies recognize complexes between heparin and platelet factor 4 (PF4). Heparin and PF4 bind HIT antibodies only over a narrow molar ratio. We explored the involvement of platelet surface-bound PF4 as an antigen i ... Full text Link to item Cite

The immune paradox of fondaparinux

Journal Article Blood · December 1, 2005 In this issue of Blood, Warkentin and colleagues demonstrate that fondaparinux elicits an immune response to PF4/heparin. Antibodies induced by the drug do not recognize complexes of PF4/fondaparinux but, paradoxically, bind complexes of PF4/heparin and PF ... Full text Cite

PF4/heparin complexes are T cell-dependent antigens.

Journal Article Blood · August 1, 2005 Featured Publication Heparin-induced thrombocytopenia (HIT) is a life-threatening, thrombotic disorder associated with development of anti-platelet factor 4 (anti-PF4)/heparin autoantibodies. Little is known about the antigenic and cellular requirements that initiate the immun ... Full text Link to item Cite

Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia.

Journal Article Blood · January 1, 2005 Heparin-induced thrombocytopenia and thrombosis (HITT) is a severe complication of heparin therapy caused by antibodies to complexes between unfractionated heparin (UFH) and platelet factor 4 (PF4) that form over a narrow molar range of reactants and initi ... Full text Link to item Cite

Pathogenesis of heparin-induced thrombocytopenia and thrombosis.

Journal Article Autoimmun Rev · May 2002 Heparin-induced thrombocytopenia and thrombosis (HIT/T) is a common immune-mediated disorder often manifested by life-threatening thrombosis. There is increasing evidence to indicate that HIT/T is caused by antibodies to complexes between platelet factor 4 ... Full text Link to item Cite

Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody.

Journal Article Blood · February 15, 2002 Heparin-induced thrombocytopenia/thrombosis (HIT/T) is a common complication of heparin therapy that is caused by antibodies to platelet factor 4 (PF4) complexed with heparin. The immune response is polyclonal and polyspecific, ie, more than one neoepitope ... Full text Link to item Cite

Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA.

Journal Article Blood · October 15, 2001 Heparin-induced thrombocytopenia/thrombosis (HIT/HITT) is a severe, life-threatening complication that occurs in 1% to 3% of patients exposed to heparin. Interactions between heparin, human platelet factor 4 (hPF4), antibodies to the hPF4/heparin complex, ... Full text Link to item Cite

Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8.

Journal Article Blood · August 15, 2001 Thrombosis is a life-threatening complication that occurs in a subset of patients with heparin-induced thrombocytopenia (HITT). The pathogenic mechanisms underlying the variable occurrence of thrombosis in HITT is poorly understood. It was hypothesized tha ... Full text Link to item Cite

Heparin-induced thrombocytopenia: bovine versus porcine heparin in cardiopulmonary bypass surgery.

Journal Article Ann Thorac Surg · June 2001 BACKGROUND: Studies have demonstrated a high incidence of antibodies to heparin/platelet factor 4 complexes, the antigen in heparin-induced thrombocytopenia, in patients after cardiopulmonary bypass surgery. In many hospitals, beef lung heparin has been us ... Full text Link to item Cite

Binding and activation of monocytes by pf4/heparin specific antibodies

Journal Article Blood · December 1, 2000 Since only a subset of patients with platelet activating auto-antibodies develop thrombosis in Heparin-Induced Thrombocytopenia and Thrombosis (HITT), it is presumed that other factors, in addition to platelet activation, contribute to thrombogenesis. To t ... Cite

Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model demonstrates the requirement for human platelet factor 4 and platelet activation through fcyriia

Journal Article Blood · December 1, 2000 Heparin-induced thrombocytopenia/thrombosis (HIT/HITT) is a severe, lifethreatening complication in 3-5% of patients exposed to heparin. The factors responsible for development of the disease are heparin, platelet factor 4 (PF4), antibodies to the heparin/ ... Cite

Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies.

Journal Article Blood · March 1, 2000 Antibodies to PF4/heparin can be demonstrated in almost all patients with heparin-induced thrombocytopenia/thrombosis (HIT/HITT) and in some persons exposed to heparin who do not have clinical manifestations. The role of anti-PF4/heparin antibodies in the ... Link to item Cite

A mouse model for heparin-induced thrombocytopenia

Journal Article Seminars in Hematology · January 28, 1999 Heparin-induced thrombocytopenia (HIT) occurs in 1% to 3% of patients receiving heparin and results from the development of antibodies that recognize heparin-platelet factor 4 (H-PF4) complexes that form on the surface of activated platelets and on the vas ... Cite

A mouse model for heparin-induced thrombocytopenia.

Journal Article Semin Hematol · January 1999 Heparin-induced thrombocytopenia (HIT) occurs in 1% to 3% of patients receiving heparin and results from the development of antibodies that recognize heparin-platelet factor 4 (H-PF4) complexes that form on the surface of activated platelets and on the vas ... Link to item Cite

Defining an antigenic epitope on platelet factor 4 associated with heparin-induced thrombocytopenia.

Journal Article Blood · November 1, 1998 Heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy. Antibodies to platelet factor 4 (PF4)/heparin complexes have been implicated in the pathogenesis of this disorder, but the antigenic epitope(s) on the protein ... Link to item Cite

Heparin-induced thrombocytopenia and thrombosis.

Journal Article Clin Rev Allergy Immunol · 1998 Full text Link to item Cite

Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin.

Journal Article Clin Exp Immunol · May 1997 Heparin-induced thrombocytopenia/thrombosis (HIT) is a severe thrombotic disorder that occurs in approximately 1% of patients treated with heparin. Affected patients commonly develop antibodies that recognize PF4/heparin complexes that may form on the surf ... Full text Link to item Cite

Prevalence of heparin-associated antibodies without thrombosis in patients undergoing cardiopulmonary bypass surgery.

Journal Article Circulation · March 4, 1997 BACKGROUND: Patients with cardiovascular disease almost invariably receive heparin before cardiopulmonary bypass surgery, which places them at risk of developing heparin-associated antibodies with a risk of thromboembolic complications. This study was desi ... Full text Link to item Cite

Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-heparin/platelet factor 4 antibodies and clinical course in patients with heparin-induced thrombocytopenia and thrombosis.

Journal Article Blood · January 15, 1997 The explanation why only a subset of patients with heparin-induced thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains uncertain. It has been proposed that platelet activation induced by cross-linking of Fc gamma RIIA by anti-hepar ... Link to item Cite

FcγRIIA H/R131 polymorphism, subclass-specific IgG anti- heparin/platelet factor 4 antibodies and clinical course in patients with heparin-induced thrombocytopenia and thrombosis

Journal Article Blood · January 15, 1997 The explanation why only a subset of patients with heparin-induced thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains uncertain. It has been proposed that platelet activation induced by cross- linking of FcγRIIA by anti-heparin/pl ... Full text Cite

Rapid detection of the Fc gamma RIIA-H/R 131 ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED).

Journal Article J Immunol Methods · November 29, 1996 A polymorphism of the gene for Fc gamma RIIA, arginine (R) or histidine (H) at position 131, alters the ability of the receptor to bind certain IgG subclasses. Identification of the Fc gamma RIIA-H/R 131 genotype has assumed increasing importance in disord ... Full text Link to item Cite

Late onset of isolated central nervous system metastasis of liposarcoma--a case report.

Journal Article Am J Clin Oncol · August 1996 Metastatic soft-tissue sarcoma of the central nervous system (CNS) is exceedingly rare. We report a case of a 56-year-old male treated for a right lower extremity liposarcoma at the age of 30 years, whose first recurrence was an intracerebral metastasis oc ... Full text Link to item Cite

Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia.

Journal Article Am J Clin Pathol · December 1995 The diagnosis of heparin-induced thrombocytopenia (HIT) may be affirmed by demonstrating heparin-dependent anti-platelet antibodies using the 14C-serotonin release assay (SRA). In this study, results of the SRA was compared with the recently described plat ... Full text Link to item Cite

Kaposi's sarcoma mimicking cellulitis.

Journal Article Postgrad Med · December 1993 Although Kaposi's sarcoma is not the most common cause of death in AIDS patients, it is often one of the initial opportunistic illnesses associated with human immunodeficiency virus infection. Extensive plaque formation and edema in the lower extremities m ... Full text Link to item Cite