Recombinant platelet factor 4 for heparin neutralization.


:Protamine sulfate has been used for many years to reverse the effects of unfractionated heparin, but it can cause hemodynamic changes and other serious side effects. Platelet factor 4 (PF4) is a naturally occurring protein synthesized in megakaryocytes and eventually stored in the alpha granules of platelets for later release. Although the complete physiologic role of PF4 is unknown, it is highly effective for the neutralization of heparin anticoagulation. Several preliminary animal studies and trials using blood obtained from cardiopulmonary bypass circuits suggested recombinant PF4 (rPF4) would be an effective alternative to protamine. In the first open-label, phase 1 human study, patients received rPF4 in doses of 0.5, 1.0, 2.5, or 5.0 mg/kg over 3 minutes to reverse heparin anticoagulation after diagnostic cardiac catheterization. There were no important hemodynamic changes and the rPF4 was highly effective in neutralizing heparin. Serial measurements of rPF4 levels showed a monophasic elimination pattern with a serum half-life of 25.5 +/- 13.5 minutes that was independent of dose administered. A randomized and blinded trial comparing rPF4 to protamine confirmed the safety and effectiveness of rPF4. Although rPF4 was initially being evaluated as a clinical alternative to protamine, it is not currently being developed for general clinical use.


Semin Thromb Hemost


Mixon TA,Dehmer GJ




Has Abstract


2004-06-01 00:00:00












  • Recombinant peptides in thrombolysis.

    abstract::Recombinant thrombolytic peptides are mainly represented by recombinant forms of tissue plasminogen activator (t-PA), a proteolytic enzyme that catalyzes the conversion of plasminogen into active plasmin, which then functions to dissolve clots. The three clinically relevant recombinant thrombolytic peptides are altepl...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Campbell J,Hilleman D

    更新日期:2010-07-01 00:00:00

  • Biochemical studies on sulfated lactobionic acid amides.

    abstract::A series of sulfated bis-lactobionic acid amides was prepared. The compounds comprise highly charged poly-anions of very low molecular weight. Usually, the compounds contain 16 sulfate groups per molecule and are homogeneous, monodisperse substances. The molecular weights range from 2388 to 2514. The compounds were ev...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Klauser RJ,Meinetsberger E,Raake W

    更新日期:1991-01-01 00:00:00

  • Comparison of recombinant human thrombin and plasma-derived human alpha-thrombin.

    abstract::Bleeding can be a serious complication of surgery, and topical thrombin is widely used as an adjunct to hemostasis in diverse surgical settings. The potent hemostatic properties of thrombin derive from its ability to activate platelets directly to aggregate and adhere to damaged vessels and to catalyze the formation s...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Bishop PD,Lewis KB,Schultz J,Walker KM

    更新日期:2006-04-01 00:00:00

  • New insights into the pathogenesis of JAK2 V617F-positive myeloproliferative disorders and consequences for the management of patients.

    abstract::The identification of the JAK2 V617F mutation in patients with myeloproliferative disorders (MPDs) represents a major breakthrough in our understanding of the pathogenesis of these diseases. One year after its discovery, an impressive number of publications appeared. These articles confirmed most of the initial result...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Villeval JL,James C,Pisani DF,Casadevall N,Vainchenker W

    更新日期:2006-06-01 00:00:00

  • Disseminated intravascular coagulation in trauma injuries.

    abstract::Physical injuries, especially road traffic injuries, are a leading cause of death and morbidity worldwide, ranking fifth among the leading causes of death in the United States. Immediate and early trauma deaths are mainly determined by primary brain injuries and/or hemorrhages, whereas late mortality is caused by seco...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Lippi G,Cervellin G

    更新日期:2010-06-01 00:00:00

  • The Complications of Vascular Access in Hemodialysis.

    abstract::Complications related to hemodialysis vascular access continue to have a major impact on morbidity and mortality. Vascular access dysfunction is the single most important factor that determines the quality of dialysis treatment. Vascular access stenosis is a common complication that develops in a great majority of pat...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Masud A,Costanzo EJ,Zuckerman R,Asif A

    更新日期:2018-02-01 00:00:00

  • Asymmetric dimethylarginine, derangements of the endothelial nitric oxide synthase pathway, and cardiovascular diseases.

    abstract::Analogues of L-arginine that are chemically modified at the terminal guanidino nitrogen group, such as Nomega-monomethy-L-arginine (L-NMMA), have been used for nitric oxide synthase inhibition. However, L-NMMA and other methylated L-arginine analogues are also endogenously formed. Among these, asymmetric dimethylargin...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Böger RH,Bode-Böger SM

    更新日期:2000-01-01 00:00:00

  • Diagnosis and management of von Willebrand disease in The Netherlands.

    abstract::In the Netherlands, specialized care for patients with a bleeding disorder, including hemophilia, von Willebrand disease (VWD), and allied disorders, is concentrated in 13 Hemophilia Treatment Centers. The Dutch Hemophilia Treaters Society, the Dutch Hemophilia Nurses' Society, and the Netherlands Hemophilia Patients ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: de Wee EM,Leebeek FW,Eikenboom JC

    更新日期:2011-07-01 00:00:00

  • Platelets as Modulators of Inflammation.

    abstract::Platelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify i...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Kim SJ,Davis RP,Jenne CN

    更新日期:2018-03-01 00:00:00

  • The UK National External Quality Assessment Scheme for heritable bleeding disorders.

    abstract::Molecular genetic analysis of families with hemophilia and other heritable bleeding disorders is a frequently requested laboratory investigation. In the United Kingdom, laboratories undertaking genetic testing must participate in a recognized external quality assessment scheme for formal accreditation. The UK National...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Perry DJ,Cumming T,Goodeve A,Hill M,Jennings I,Kitchen S,Walker I

    更新日期:2014-03-01 00:00:00

  • Rational diagnosis of pulmonary embolism (RADIA PE) in symptomatic outpatients with suspected PE: an improved strategy to exclude or diagnose venous thromboembolism by the sequential use of a clinical model, rapid ELISA D-dimer test, perfusion lung scan,

    abstract::A prospective management decision analysis for the exclusion and diagnosis of pulmonary embolism (PE) based on pre-test clinical probability (PCP) estimation for PE, a rapid ELISA D-dimer test, perfusion lungscan (P-scan), CUS, spiral CT, and pulmonary angiography is proposed. The modified PCP model for PE of Wells et...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Michiels JJ

    更新日期:1998-01-01 00:00:00

  • The spectrum of coagulation abnormalities in thyroid disorders.

    abstract::The hemostatic balance is a complex system where the delicate equilibrium is regulated by several factors including hormones. A variety of endocrine disorders have been reported to be associated with coagulation abnormalities, ranging from mild laboratory changes to clinically relevant thrombotic or bleeding manifesta...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Vescovi PP,Favaloro EJ,Lippi G,Garofano M,Montagnana M,Manzato F,Franchini M

    更新日期:2011-02-01 00:00:00

  • Platelets and endothelial cells.

    abstract::The pathogenesis of atherosclerosis, the leading cause of morbidity and mortality in industrial countries, is multifactorial. Atherogenesis, the development of atherosclerotic lesions, is initiated by a mechanical or functional injury of the endothelium. The function of the endothelium is influenced by multiple factor...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Siegel-Axel DI,Gawaz M

    更新日期:2007-03-01 00:00:00

  • Recent Advances in the Molecular Imaging of Atherosclerosis.

    abstract::Atherosclerosis is the major underlying cause of cardiovascular diseases, the prevalence of which is continuously increasing, thus currently standing as the leading global cause of death. This pathology gradually develops over the course of 50 or more years throughout the life of an individual under the influence of a...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Larivière M,Bonnet S,Lorenzato C,Laroche-Traineau J,Ottonès F,Jacobin-Valat MJ,Clofent-Sanchez G

    更新日期:2020-07-01 00:00:00

  • Inhibition of platelet function: does it offer a chance of better cancer progression control?

    abstract::Thrombocytosis is frequently (10 to 57%) observed in cancer patients. Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity, growth factors, platelet-derived microparticles, and factors released from bone marrow endothelial cells as well...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Sierko E,Wojtukiewicz MZ

    更新日期:2007-10-01 00:00:00

  • Morbidity and mortality in the catastrophic antiphospholipid syndrome: pathophysiology, causes of death, and prognostic factors.

    abstract::The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastr...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Espinosa G,Bucciarelli S,Asherson RA,Cervera R

    更新日期:2008-04-01 00:00:00

  • New insights into the role of erythrocytes in thrombus formation.

    abstract::The role of erythrocytes in thrombus formation has previously been regarded as passive by their influence on rheology. Erythrocytes are known, due to their abundance and size, to push platelets to the vascular wall (laminar shearing). This results in an increased platelet delivery at the vascular wall enabling platele...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Du VX,Huskens D,Maas C,Al Dieri R,de Groot PG,de Laat B

    更新日期:2014-02-01 00:00:00

  • Hyperhomocysteinemia and thrombosis.

    abstract::Homocysteine has been identified as an independent risk factor for atherosclerotic and thrombotic disease. Both arterial (cerebrovascular, carotid, coronary, and peripheral arterial) and veno-occlusive disease, jointly termed vascular occlusive disease (VOD) in this review, have been associated with hyperhomocysteinem...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Guba SC,Fonseca V,Fink LM

    更新日期:1999-01-01 00:00:00

  • Anticoagulation in the older adult: optimizing benefit and reducing risk.

    abstract::The risk for both arterial and venous thrombosis increases with age. Despite the increasing burden of strokes related to atrial fibrillation (AF) and venous thromboembolism (VTE) among older adults, the use of anticoagulant therapy is limited in this population due to the parallel increase in risk of serious hemorrhag...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Ko D,Hylek EM

    更新日期:2014-09-01 00:00:00

  • Laboratory Testing for von Willebrand Disease: The Past, Present, and Future State of Play for von Willebrand Factor Assays that Measure Platelet Binding Activity, with or without Ristocetin.

    abstract::von Willebrand disease (VWD) was first described nearly a century ago in 1924 by Erik Adolf von Willebrand. Diagnostic testing at the time was very limited and it was not until the mid to late 1900s that more tests became available to assist with the diagnosis and classification of VWD. Two of these tests are based on...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Just S

    更新日期:2017-02-01 00:00:00

  • Pharmacological profiling of recombinant tissue factor pathway inhibitor.

    abstract::Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine protease inhibitor found within the vascular system that is known to be released upon heparin administration. Tissue factor pathway inhibitor regulates the extrinsic pathway by inhibiting both factors VIIa and Xa. The role of TFPI in the prevention of thro...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Jeske W,Hoppensteadt D,Callas D,Koza MJ,Fareed J

    更新日期:1996-01-01 00:00:00

  • Membrane cofactor protein and factor I: mutations and transplantation.

    abstract::Mutations in the genes for three complement regulators-complement factor H (CFH), membrane cofactor protein (MCP), and factor I (IF)-have now been described in patients with atypical HUS. The functional effects of these mutations have been studied in detail and have been shown to affect secretion, expression, and regu...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Kavanagh D,Goodship TH

    更新日期:2006-03-01 00:00:00

  • Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-analysis.

    abstract::Severe acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Onorato D,Pucci M,Carpene G,Henry BM,Sanchis-Gomar F,Lippi G

    更新日期:2021-01-22 00:00:00

  • Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome Microangiopathy in Pregnancy.

    abstract::Thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) are thrombotic microangiopathies (TMAs) that can present in pregnancy. The presentation can be with typical microangiopathic features and thrombocytopenia, but there is also a significant risk of in-utero fetal loss. TTP presents m...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Scully M

    更新日期:2016-10-01 00:00:00

  • Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo.

    abstract::Endothelial phenotypic heterogeneity plays an important role in the susceptibility of the cardiovascular system to disease. Arteries and heart valves are susceptible to chronic inflammatory disease in regions of blood flow disturbance that implicates hemodynamic forces and transport characteristics as prominent influe...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Davies PF,Civelek M,Fang Y,Guerraty MA,Passerini AG

    更新日期:2010-04-01 00:00:00

  • Outcome of Major Hemorrhage at a Major Cardiothoracic Center in Patients with Activated Major Hemorrhage Protocol versus Nonactivated Protocol.

    abstract::This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data we...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Chang KW,Owen S,Gaspar M,Laffan M,Arachchillage DRJ

    更新日期:2021-02-01 00:00:00

  • Coacute heparin: a new simple monotest for monitoring heparin treatment.

    abstract::Anti-factor Xa methods have been generally accepted for the monitoring of heparin treatment mainly due to their sensitivity to LMWH and excellent performance on automated equipment. When such equipment is not available, as in small laboratories or on the night shift, there is a need for a simple manual method. In the ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Friberger P,Krig E,Eriksson-Skoog L,Svensson S,Isacson C

    更新日期:1993-01-01 00:00:00

  • Clinical utility of the PFA-100.

    abstract::The PFA-100 (platelet function analyzer) is a relatively new tool for the investigation of primary hemostasis. This article reviews the history of the PFA-100 and details its clinical utility in several settings. The PFA-100 was first introduced to us in 1995 in an issue of Seminars in Thrombosis And Hemostasis, which...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Favaloro EJ

    更新日期:2008-11-01 00:00:00

  • Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin.

    abstract::A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Bergqvist D,Burmark US,Frisell J,Guilbaud O,Hallböök T,Horn A,Lindhagen A,Ljungner H,Ljungström KG,Mätzsch T

    更新日期:1990-10-01 00:00:00

  • The role of tissue factor pathway inhibitor in tumor growth and metastasis.

    abstract::Clotting activation occurs frequently in cancer. Tissue factor (TF), the most potent initiator of coagulation, is expressed aberrantly in many types of malignancy and is involved not only in tumor-associated hypercoagulability but also in promoting tumor angiogenesis and metastasis via coagulation-dependent and coagul...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Amirkhosravi A,Meyer T,Amaya M,Davila M,Mousa SA,Robson T,Francis JL

    更新日期:2007-10-01 00:00:00