Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives.

Abstract:

:In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo). The new compounds have a predictable dose response and few drug-drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.

journal_name

Eur J Haematol

authors

Gómez-Outes A,Suárez-Gea ML,Lecumberri R,Terleira-Fernández AI,Vargas-Castrillón E

doi

10.1111/ejh.12610

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

389-404

issue

5

eissn

0902-4441

issn

1600-0609

journal_volume

95

pub_type

杂志文章,评审
  • Circulating extracellular vesicle-associated CD163 and CD206 in multiple myeloma.

    abstract:OBJECTIVES:Extracellular vesicles (EVs) are important for intercellular signalling in cancer. Tumour-associated macrophages, expressing the haemoglobin-haptoglobin and mannose receptors CD163 and CD206, are crucial for cancer progression. We recently identified CD163 on EVs in the circulation as a fraction of total sol...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.13371

    authors: Kvorning SL,Nielsen MC,Andersen NF,Hokland M,Andersen MN,Møller HJ

    更新日期:2020-05-01 00:00:00

  • Role of protein phosphorylation in EPO-mediated early signal transduction: analysis in the EPO-reactive cell line ELM-I-1 transfected with a c-fos-enhancer/promoter-luciferase reporter gene.

    abstract::To investigate the role of protein phosphorylation in the early phase of EPO-mediated signal transduction, we EPO-stimulated a murine erythroid cell line ELM-I-1 transformed by plasmids comprised of the c-fos enhancer/promoter linked to the luciferase gene. Using this reporter gene system, we previously showed that EP...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.1994.tb00647.x

    authors: Tsuda H,Huang RW,Takatsuki K

    更新日期:1994-04-01 00:00:00

  • Improved survival from fungaemia in patients with haematological malignancies: analysis of risk factors for death and usefulness of early antifungal therapy.

    abstract::Fourty-three episodes of fungaemia encountered from 1978 to 1991 in 43 patients with haematological malignancies are reviewed here to analyse the risk factors for death and to evaluate the efficacy of early antifungal therapy. Low serum cholinesterase and elevated serum blood urea nitrogen were significantly associate...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.1993.tb00617.x

    authors: Iwama A,Yoshida M,Miwa A,Obayashi T,Sakamoto S,Miura Y

    更新日期:1993-09-01 00:00:00

  • BAALC and WT1 expressions from diagnosis to hematopoietic stem cell transplantation: consecutive monitoring in adult patients with core-binding-factor-positive AML.

    abstract::No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML (CBF-AML) from diagnosis to hematopoietic stem cell transplantation (HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction (RQ-PCR) at diagnos...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12142

    authors: Yoon JH,Kim HJ,Shin SH,Yahng SA,Lee SE,Cho BS,Eom KS,Kim YJ,Lee S,Min CK,Cho SG,Kim DW,Lee JW,Min WS,Park CW,Lim JH

    更新日期:2013-08-01 00:00:00

  • Acute myeloid leukemia in the pregnant patient.

    abstract::Although acute myeloid leukemia (AML) mostly occurs in older patients, it could be seen in women of childbearing age. It is therefore not surprising that in some patients, the management of AML will be complicated by a coexistent pregnancy. However, the association of leukemia and pregnancy is uncommon. Its incidence ...

    journal_title:European journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/ejh.12479

    authors: Thomas X

    更新日期:2015-08-01 00:00:00

  • FLAMSA reduced-intensity conditioning is equally effective in AML patients with primary induction failure as well as in first or second complete remission.

    abstract::Reduced-intensity conditioning regimens have demonstrated lower toxicity but increased relapse rates in the context of allogeneic hematopoietic stem cell transplantation (aSCT) for patients with acute myelogenous leukemia (AML). The FLAMSA- reduced-intensity conditioning (RIC) regimen, combining a cytoreductive and a ...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12615

    authors: Holtick U,Shimabukuro-Vornhagen A,Chakupurakal G,Theurich S,Leitzke S,Burst A,Hallek M,von Bergwelt-Baildon M,Scheid C,Chemnitz JM

    更新日期:2016-05-01 00:00:00

  • Can t(8;21) oligoblastic leukemia be called a myelodysplastic syndrome?

    abstract::The new World Health Organization (WHO) classification of hematologic malignancies has incorporated t(8;21) myelodysplastic syndromes (MDS) according to the French-American-British classification into the category of acute myeloid leukemia (AML) with t(8;21)(q22;q22), while our knowledge about clinicopathological feat...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0609.2002.02770.x

    authors: Kaneda K,Kojima K,Takeuchi M,Takimoto H,Takaba S,Shinagawa K,Kobayashi H,Miyata A,Hara M,Tanimoto M

    更新日期:2002-09-01 00:00:00

  • Morphologic, flow cytometric, functional, and molecular analyses of S100B positive lymphocytes, unique cytotoxic lymphocytes containing S100B protein.

    abstract::Little is known about the S100B⁺ lymphocytes, which are unique human peripheral blood lymphocytes (PBL) containing the S100B protein. It has recently been shown that S100B is released from various types of S100B⁺ cells and exhibits varied cytokine-like activities. In this study, we precisely characterized the S100B⁺ l...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12036

    authors: Miki Y,Gion Y,Mukae Y,Hayashi A,Sato H,Yoshino T,Takahashi K

    更新日期:2013-02-01 00:00:00

  • A new exon 12 mutation in the EPAS1 gene possibly associated with erythrocytosis.

    abstract::In secondary erythrocytosis, the elevated red cell count is powered by factors outside the erythroid compartment, for instance by raised erythropoietin (EPO) synthesis based on congenital defects of the oxygen-sensing pathway. The principal transcriptional regulator of EPO synthesis is endothelial PAS domain-containin...

    journal_title:European journal of haematology

    pub_type:

    doi:10.1111/ejh.13241

    authors: Schelker RC,Herr W,Grassinger J

    更新日期:2019-07-01 00:00:00

  • Quantifying immature platelets as markers of increased platelet production after coronary artery bypass grafting surgery.

    abstract:OBJECTIVES:An increased rate of platelet production is a possible cause of reduced antithrombotic response to once-daily aspirin. Markers of immature platelets (IPs), such as immature platelet count (IPC), immature platelet fraction (IPF), and mean platelet volume (MPV) might be useful for identifying patients who have...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.13109

    authors: Xu K,Chan NC,Hirsh J,Ginsberg JS,Bhagirath V,Kruger P,Dale B,Crowther M,Whitlock RP,Li C,Eikelboom JW

    更新日期:2018-09-01 00:00:00

  • High level of full-length cereblon mRNA in lower risk myelodysplastic syndrome with isolated 5q deletion is implicated in the efficacy of lenalidomide.

    abstract::Downregulation of cereblon (CRBN) gene expression is associated with resistance to the immunomodulatory drug lenalidomide and poor survival outcomes in multiple myeloma (MM) patients. However, the importance of CRBN gene expression in patients with myelodysplastic syndrome (MDS) and its impact on lenalidomide therapy ...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12457

    authors: Jonasova A,Bokorova R,Polak J,Vostry M,Kostecka A,Hajkova H,Neuwirtova R,Siskova M,Sponerova D,Cermak J,Mikulenkova D,Cervinek L,Brezinova J,Michalova K,Fuchs O

    更新日期:2015-07-01 00:00:00

  • FCGR3A-158V/F polymorphism may correlate with the levels of immunoglobulin in patients with non-Hodgkin's lymphoma after rituximab treatment as an adjuvant to autologous stem cell transplantation.

    abstract:OBJECTIVES:Recent studies have indicated that patients who receive stem cell transplantation (SCT) and rituximab demonstrate an increased risk of developing hypogammaglobulinemia. Such hypogammaglobulinemia has been found to be due to delayed recovery of memory B cells with an abnormal cell marker expression and impair...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.2008.01174.x

    authors: Nishio M,Endo T,Fujimoto K,Yamamoto S,Obara M,Yamaguchi K,Takeda Y,Goto H,Kasahara I,Sato N,Koike T

    更新日期:2009-02-01 00:00:00

  • Viral encephalitis after haplo-identical hematopoietic stem cell transplantation: Causative viral spectrum, characteristics, and risk factors.

    abstract:OBJECTIVE:To retrospectively identify characteristics and risk factors of viral encephalitis (VE) in patients who underwent a haplo-identical hematopoietic stem cell transplant (HSCT). METHODS:A nested case-control study was designed. Cases with VE and controls were identified from a cohort composed of 1274 patients w...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12855

    authors: Zhang XH,Zhang JM,Han W,Chen H,Chen YH,Wang FR,Wang JZ,Zhang YY,Mo XD,Chen Y,Wang Y,Chang YJ,Xu LP,Liu KY,Huang XJ

    更新日期:2017-05-01 00:00:00

  • Is higher income and educational status associated with poorer outcome in patients with Hodgkin's disease?

    abstract:OBJECTIVES:The aim of the study was to determine the impact of socioeconomic status on relapse-free survival (RFS) in patients with Hodgkin's disease. METHODS:A number of factors were analyzed for their impact on relapse-free and overall survival in Hodgkin's disease using Cox regression. These factors included socioe...

    journal_title:European journal of haematology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1600-0609.2004.00315.x

    authors: Holzner B,Fischhofer M,Kemmler G,Kopp M,Sperner-Unterweger B,Krugmann J,Dirnhofer S,Greil R

    更新日期:2004-11-01 00:00:00

  • A novel gene STORP (STOmatin-Related Protein) is localized 2 kb upstream of the promyelocytic gene on chromosome 15q22.

    abstract::We generated a 100-kb map of the region 5' of the PML (promyelocytic leukemia) gene on human chromosome 15q22 and identified a new gene provisionally named STORP for stomatin-related protein. The STORP gene is positioned 2 kb upstream of the PML gene in a head-to-head configuration, and contains 7 exons spanning a gen...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0609.2000.90054.x

    authors: Gilles F,Glenn M,Goy A,Remache Y,Zelenetz AD

    更新日期:2000-02-01 00:00:00

  • Characterization of a new human plasma cell leukemia cell line UHKT-944.

    abstract:OBJECTIVE:A new interleukin-6 (IL-6)-dependent plasma cell leukemia cell line UHKT-944 was established from bone marrow cells derived from a 55-yr-old man with plasma cell leukemia. RESULTS:The cell line possesses phenotypic characteristics of plasma cells including the production of a monoclonal immunoglobulin IgA1-k...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12505

    authors: Vyhlídalová I,Uherková L,Pleschnerová M,Špička I,Březinová J,Michalová K,Čermáková K,Polanská V,Jedelský PL,Hamšíková E,Kuželová K,Stöckbauer P

    更新日期:2015-10-01 00:00:00

  • Prevalence and risk factors for Pulmonary Hypertension associated with chronic Myeloproliferative Neoplasms.

    abstract:OBJECTIVES:Pulmonary hypertension (PH) is commonly reported in Philadelphia-chromosome negative myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). PH may be diagnosed directly by right heart catheterization (RHC) or estimated by transthoracic ec...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.13543

    authors: Ferrari A,Scandura J,Masciulli A,Krichevsky S,Gavazzi A,Barbui T

    更新日期:2021-02-01 00:00:00

  • Discrepant ratios of arterial vs. venous thrombosis in hemophilias A and B as compared to FVII deficiency.

    abstract:BACKGROUND:The occurrence of a thrombotic event in congenital bleeding disorders has drawn considerable attention in recent years. Both patients with hemophilia and patients with von Willebrand disease and even those with rare coagulation disorders have been shown to present occasional thrombotic events. Little is know...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12129

    authors: Girolami A,Berti de Marinis G,Bertozzi I,Peroni E,Tasinato V,Lombardi AM

    更新日期:2013-08-01 00:00:00

  • Responsiveness of cytogenetically discrete human myeloma cell lines to lenalidomide: lack of correlation with cereblon and interferon regulatory factor 4 expression levels.

    abstract::The introduction of novel immunomodulatory drugs (IMiDs) has dramatically improved the survival of patients with multiple myeloma (MM). While it has been shown that patients with specific cytogenetic subtypes, namely t(4;14), have the best outcomes when treated with bortezomib-based regimens, the relationship between ...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12192

    authors: Greenberg AJ,Walters DK,Kumar SK,Rajkumar SV,Jelinek DF

    更新日期:2013-12-01 00:00:00

  • Neonatal isoimmune thrombocytopenia caused by type I CD36 deficiency having novel splicing isoforms of the CD36 gene.

    abstract::Neonatal alloimmune thrombocytopenia (NAIT) occurs because of transplacentally acquired maternal platelet alloantibodies. Most of the alloantibodies are against human platelet antigens, but the alloantibody against CD36 is rare. A full-term female baby was delivered by a mother who experienced two spontaneous abortion...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.2008.01093.x

    authors: Taketani T,Ito K,Mishima S,Kanai R,Uchiyama A,Hirata Y,Kumakura S,Ishikura H,Yamaguchi S

    更新日期:2008-07-01 00:00:00

  • Lenalidomide as maintenance treatment for patients with multiple myeloma after autologous stem cell transplantation: A pharmaco-economic assessment.

    abstract:OBJECTIVE:Autologous stem cell transplantation (ASCT) has improved progression-free survival (PFS) and overall survival in eligible patients with newly diagnosed multiple myeloma (NDMM); however, relapse occurs. Maintenance therapy with lenalidomide (Len-Mt) extends survival and delays relapse and the subsequent initia...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.13497

    authors: Uyl-de Groot CA,Ramsden R,Lee D,Boersma J,Zweegman S,Dhanasiri S

    更新日期:2020-11-01 00:00:00

  • Significance of cytokines and CD68-positive microparticles in immune thrombocytopenic purpura.

    abstract::We investigated the significance of cytokines (soluble interleukin-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-6, and interferon-gamma) and CD68-positive microparticles in immune thrombocytopenic purpura. Cytokines were measured by enzyme-linked immunosorbent assay and microparticles were...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.1995.tb00232.x

    authors: Nomura S,Yanabu M,Kido H,Lan XG,Ichiyoshi H,Katsura K,Miyake T,Miyazaki Y,Kagawa H,Fukuhara S

    更新日期:1995-07-01 00:00:00

  • Free iron catalyzes oxidative damage to hematopoietic cells/mesenchymal stem cells in vitro and suppresses hematopoiesis in iron overload patients.

    abstract:OBJECTIVES:Transfusional iron overload is of major concern in hematological disease. Iron-overload-related dyserythropoiesis and reactive oxygen species (ROS)-related damage to hematopoietic stem cell (HSC) function are major setbacks in treatment for such disorders. We therefore aim to investigate the effect of iron o...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12159

    authors: Lu W,Zhao M,Rajbhandary S,Xie F,Chai X,Mu J,Meng J,Liu Y,Jiang Y,Xu X,Meng A

    更新日期:2013-09-01 00:00:00

  • Hepatitis B virus infection is associated with deletion of chromosome 8p in multiple myeloma.

    abstract::Serological analyses within epidemiological cohort and case-control studies indicate to an association between HBV infection and risk of multiple myeloma (MM). To verify the relationship with an independent approach, we investigated the correlation between HBV positivity and chromosomal aberrations within 680 patients...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.12018

    authors: Becker N,Byl A,Friedrich S,Jauch A,Schnitzler P,Egerer G,Ho AD,Goldschmidt H,Neben K

    更新日期:2013-04-01 00:00:00

  • Identification and characterization of the first large deletion of the MYH9 gene associated with MYH9 disorders.

    abstract::MYH9 disorders are autosomal dominant macrothrombocytopenias with leukocyte inclusion bodies. Single point mutations in the protein-coding sequence of the MYH9 gene are the most common cause. So far no large gene deletion/insertion and splicing defects have been reported. Conventional DNA sequencing of each MYH9-codin...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.2008.01046.x

    authors: Kunishima S,Matsushita T,Hamaguchi M,Saito H

    更新日期:2008-06-01 00:00:00

  • Cardiac function during iron chelation therapy in adult non-thalassaemic patients with transfusional iron overload.

    abstract::It is well-documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion-dependent children suffering from beta-thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT-patients), iron chelation by desferrioxamine may affect the c...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.1997.tb00981.x

    authors: Jensen PD,Olsen N,Bagger JP,Jensen FT,Christensen T,Ellegaard J

    更新日期:1997-10-01 00:00:00

  • Persistent altered fusion transcript splicing identifies RUNX1-RUNX1T1+ AML patients likely to relapse.

    abstract::In acute myeloid leukemia (AML) mouse models, the RUNX1-RUNX1T1 fusion protein has failed to produce leukemia by itself, but alternative splicing of exon 9a of the RUNX1-RUNX1T1 fusion transcript (FT) has recently been shown to enhance the leukemogenic potential. We have analyzed 138 diagnosis and follow-up samples fr...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0609.2009.01371.x

    authors: Ommen HB,Ostergaard M,Yan M,Braendstrup K,Zhang DE,Hokland P

    更新日期:2010-02-01 00:00:00

  • Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies.

    abstract::Host cells are protected from the lytic effect of the complement system by complement regulatory proteins. This study was designed to investigate the expression of complement regulatory proteins on leukemic blasts which may be susceptible to the lytic effects of the complement system in the circulation. The surface ex...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0609.2000.80097.x

    authors: Guc D,Canpinar H,Kucukaksu C,Kansu E

    更新日期:2000-01-01 00:00:00

  • Clinical course and risk factors for mortality from COVID-19 in patients with haematological malignancies.

    abstract:BACKGROUND:The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported. METHODS:We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer ...

    journal_title:European journal of haematology

    pub_type: 杂志文章

    doi:10.1111/ejh.13493

    authors: Sanchez-Pina JM,Rodríguez Rodriguez M,Castro Quismondo N,Gil Manso R,Colmenares R,Gil Alos D,Paciello ML,Zafra D,Garcia-Sanchez C,Villegas C,Cuellar C,Carreño-Tarragona G,Zamanillo I,Poza M,Iñiguez R,Gutierrez X,Alonso R

    更新日期:2020-11-01 00:00:00

  • Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

    abstract:BACKGROUND:More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function. METHODS:Children with SCA enrolled in t...

    journal_title:European journal of haematology

    pub_type: 临床试验,杂志文章

    doi:10.1111/ejh.12361

    authors: Nottage KA,Ware RE,Winter B,Smeltzer M,Wang WC,Hankins JS,Dertinger SD,Shulkin B,Aygun B

    更新日期:2014-11-01 00:00:00