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Factor VII AND anticoagulants bleeding

Massimo Franchini, Pier Mannuccio Mannucci
One of the most challenging issues facing us in the treatment of haemophilia is the development of alloantibodies against infused factor VIII (FVIII) or factor IX (FIX). Inhibitors render factor replacement therapy ineffective, exposing patients to an unacceptably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in a new class of therapeutic agents which act by enhancing coagulation (i...
February 14, 2018: Blood Transfusion, Trasfusione del Sangue
José María Bastida, María Teresa Cano-Mozo, Felix Lopez-Cadenas, Victor Eduardo Vallejo, Soraya Merchán, Cecilia Santos-Montón, David González-Calle, Javier Carrillo, Ana Africa Martín, Jose Angel Torres-Hernández, Marcos González, Francisco Martín-Herrero, Pedro Pabón, Jose Ramon González-Porras
BACKGROUND: Acquired hemophilia A (AHA) is a rare bleeding disease caused by autoantibodies against factor VIII. Spontaneous bleeding symptoms usually affect the skin and muscle, while pericardial effusion is an extremely rare manifestation. In the elderly, anticoagulant treatment is frequent and bleeding symptoms are usually associated with this. CLINICAL FINDINGS: We report a hemorrhagic pericardial effusion as the AHA debut in a patient with untreated chronic lymphocytic leukemia and anticoagulated with apixaban for atrial fibrillation and chronic arterial ischemia...
November 2017: Medicine (Baltimore)
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
Hira Qadir, Anila Rashid, Salman Naseem Adil
Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient...
September 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Andrea Roxanne J Anas, Akane Mori, Mineka Tone, Chiaki Naruse, Anna Nakajima, Hirohiko Asukabe, Yoshiaki Takaya, Susumu Y Imanishi, Tomoyasu Nishizawa, Makoto Shirai, Ken-Ichi Harada
The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction...
August 30, 2017: Marine Drugs
M Dobran, M Iacoangeli, A R Scortichini, F Mancini, R Benigni, D Nasi, M Gladi, M Scerrati
AIM: Chronic subdural hematoma (CSDH) is typically in elderly and rarely in young people. To prevent complications and re-bleeding after surgical treatment of CSDH it is important to assess the risk factors as coagulation disorders especially in young patients (below 65 years) with no history of head trauma, alcohol abuse or anticoagulant therapy. PATIENTS AND METHODS: This study consists of 16 patients (12 males, 4 females) with age ranging from 27 to 59 years (median 48,25 years) operated for CSDH...
March 2017: Il Giornale di Chirurgia
Emma P DeLoughery, Thomas G DeLoughery
: When patients on anticoagulation present with intracranial bleeding, stopping the bleeding is paramount. Despite the availability of multiple options to reverse anticoagulation, no study has directly compared the effectiveness of the procoagulants recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination, and 4-factor PCC on improving patient outcomes compared with a control. This study examined the medical records of 197 warfarin patients with intracranial hemorrhage, an initial international normalized ratio (INR) greater than 1...
December 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
William Beattie, Maria Magnusson, Winita Hardikar, Paul Monagle, Vera Ignjatovic
INTRODUCTION: Chronic liver disease causes a disruption of procoagulant and anticoagulant factors, resulting in a fragile state, prone to increased rates of both bleeding and thrombosis. Currently, there is limited literature describing the changes observed in pediatric liver disease and extrahepatic portal vein obstruction or shunt. This study aimed to describe the changes that occur in children with chronic liver disease and extrahepatic portal vein obstruction or shunt. MATERIALS AND METHODS: We measured the concentration and activity of key procoagulant and anticoagulant factors in children with liver disease, children with extrahepatic portal vein obstruction or shunt, and healthy children...
March 2017: Pediatric Hematology and Oncology
Joseph Meltzer, Joseph R Guenzer
Bleeding complications are a common concern with the use of anticoagulant agents. In many situations, reversing of neutralizing their effects may be warranted. Prothrombin complex concentrate replaces coagulation factors lowered by warfarin, as does fresh frozen plasma, but in a more concentrated form. Protamine negates the effect of heparin and combines chemically with heparin molecules to form an inactive salt. It also partially reverses the effects of low-molecular-weight heparin. Recombinant activated factor VII is a nonspecific procoagulant that activates the extrinsic clotting pathway, resulting in thrombin generation, but does not directly neutralize the activity of any of the new oral anticoagulants...
June 2017: Anesthesiology Clinics
William E Dager, Linda Banares
The standard of care for oral anticoagulation therapy has primarily been warfarin, which is limited by its indirect mechanism-of-action, variable kinetics, tolerability, and routine monitoring concerns. The direct-acting oral anticoagulants (DOACs) have predictable pharmacokinetics and pharmacodynamics, and improved safety and efficacy compared to warfarin for the prevention of stroke in patients with nonvalvular atrial fibrillation and prevention or management of venous thromboembolism. Consequential bleeding is a concern with all anticoagulants...
April 2017: Hospital Practice (Minneapolis)
Nina Haagenrud Schultz, Hoa Thi Tuyet Tran, Stine Bjørnsen, Carola Elisabeth Henriksson, Per Morten Sandset, Pål Andre Holme
BACKGROUND: An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons...
2017: Thrombosis Journal
Eric Paulus, Kathy Komperda, Gabriel Park, Julie Fusco
Factor VII (FVII) deficiency is the most prevalent rare bleeding disorder in the USA and affects approximately 1 out of every 500,000 people. Warfarin inhibits the synthesis of FVII, in addition to other clotting factors. Warfarin is contraindicated in patients with bleeding tendencies or blood dyscrasias; therefore, the literature regarding the use of warfarin in FVII deficiency is very limited. We report a successful re-challenge of warfarin therapy in a patient with FVII deficiency. A 70-year-old woman with FVII deficiency experienced a significant decrease in FVII activity and subsequent vaginal bleeding roughly 5 weeks after starting warfarin for atrial fibrillation...
December 2016: Drug Safety—Case Reports
B Schenk, P Würtinger, W Streif, W Sturm, D Fries, M Bachler
BACKGROUND: In major bleeding events, the new direct oral anticoagulants pose a great challenge for physicians. The aim of the study was to test for ex vivo reversal of the direct oral anticoagulant rivaroxaban with various non-specific reversal agents: prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa), and fibrinogen concentrate (FI). METHODS: Blood was obtained from healthy volunteers and from patients treated with rivaroxaban...
November 2016: British Journal of Anaesthesia
Leyla Pourgholi, Hamidreza Goodarzynejad, Ali Mandegary, Shayan Ziaee, Azita Hajhosseini Talasaz, Arash Jalali, Mohammadali Boroumand
BACKGROUND: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. METHODS: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0-3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics...
October 15, 2016: Toxicology and Applied Pharmacology
Mareike K Körber, Elisabeth Langer, Lutz Kaufner, Michael Sander, Christian Von Heymann
BACKGROUND: A bleeding patient undergoing therapy with new oral anticoagulants is every clinician's nightmare as no specific reversal agent is available yet. This in vitro study investigated the effect of prothrombin complex concentrate (PCC), recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC) on supratherapeutic rivaroxaban concentrations using standard laboratory parameters (prothrombin time [PT], activated partial thromboplastin time [aPTT] and PT ratio) and thromboelastometry (clotting time [CT])...
2016: Blood Transfusion, Trasfusione del Sangue
Suna Kang, Hoi Soo Yoon, Eun Hye Lee
The objective of this study is to analyze the major causes of abnormal findings seen in the preoperative coagulation tests of asymptomatic pediatric patients and to discuss the usefulness of coagulation tests prior to minor surgery. Among patients who received minor surgery in Kyung Hee University Medical Center from March 2008 to April 2015, a total of 7114 pediatric patients (ages 1-18) were included in our study. Of these, 226 (3.1%) were referred to the pediatrics hematology-oncology department because of abnormal preoperative coagulation tests...
May 2016: Pediatric Hematology and Oncology
S V Mallett, A Sugavanam, D A Krzanicki, S Patel, R H Broomhead, B R Davidson, A Riddell, A Gatt, P Chowdary
The international normalised ratio is frequently raised in patients who have undergone major liver resection, and is assumed to represent a potential bleeding risk. However, these patients have an increased risk of venous thromboembolic events, despite conventional coagulation tests indicating hypocoagulability. This prospective, observational study of patients undergoing major hepatic resection analysed the serial changes in coagulation in the early postoperative period. Thrombin generation parameters and viscoelastic tests of coagulation (thromboelastometry) remained within normal ranges throughout the study period...
June 2016: Anaesthesia
K Varadi, S Tangada, M Loeschberger, P Montsch, G Schrenk, B Ewenstein, P L Turecek
INTRODUCTION: FEIBA(®) consists of zymogens and traces of activated forms of procoagulant factors II, VII, IX, X, anticoagulants protein C and TFPI, and small amounts of cofactors FV, FVIII and protein S, in a balanced ratio. As shown previously, FII-FXa complex plays a key role in FEIBA's mode of action (MoA). METHODS: Thrombin generation (TG) was measured by spiking coagulation factors, cofactors and inhibitors to high titer FVIII inhibitor plasma, and in plasma samples from patients in a phase 3 clinical study evaluating the safety and efficacy of FEIBA prophylaxis in haemophilia A patients with inhibitors...
July 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Hans-Christoph Diener, James Aisenberg, Jack Ansell, Dan Atar, Günter Breithardt, John Eikelboom, Michael D Ezekowitz, Christopher B Granger, Jonathan L Halperin, Stefan H Hohnloser, Elaine M Hylek, Paulus Kirchhof, Deirdre A Lane, Freek W A Verheugt, Roland Veltkamp, Gregory Y H Lip
The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension...
March 21, 2017: European Heart Journal
Páll T Onundarson, Charles W Francis, Olafur S Indridason, David O Arnar, Einar S Bjornsson, Magnus K Magnusson, Sigurdur J Juliusson, Hulda M Jensdottir, Brynjar Vidarsson, Petur S Gunnarsson, Sigrun H Lund, Brynja R Gudmundsdottir
BACKGROUND: Rapid fluctuations in factor VII during warfarin anticoagulation change the international normalised ratio (INR) but contribute little to the antithrombotic effect. We aimed to assess non-inferiority of anticoagulation stabilisation with a warfarin monitoring method affected only by factors II and X (Fiix-prothrombin time [Fiix-PT]) compared with standard PT-INR monitoring that includes factor VII measurement as well. METHODS: The Fiix trial was a single centre, double-blind, prospective, non-inferiority, randomised controlled clinical trial...
June 2015: Lancet Haematology
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