Suppressed intrinsic fibrinolytic activity by monoclonal anti-beta-2 glycoprotein I autoantibodies: possible mechanism for thrombosis in patients with antiphospholipid syndrome.

Abstract:

:beta2-glycoprotein I (beta2GPI) bears the epitope(s) for autoimmune anticardiolipin antibodies (aCL) frequently present in patients with antiphospholipid syndrome (APS). beta2GPI is involved in coagulation and fibrinolytic systems, including inhibition of contact activation. Coagulation factor XII is an initiator of intrinsic coagulation and also of intrinsic fibrinolysis. We investigated the effect of aCL (= anti-beta2GPI antibodies), regarding intrinsic fibrinolysis using autoimmune monoclonal anti-beta2GPI antibodies derived from a patient with APS or from an NZW/BXSB-F1 mouse. We developed a chromogenic assay system to determine intrinsic fibrinolytic activity. The reaction was activated by kaolin in the euglobulin fraction. Exogenous beta2GPI slightly suppressed intrinsic fibrinolytic activity of the euglobulin fraction from normal plasma. Human monoclonal anti-beta2GPI antibody (EY2C9) and mouse monoclonal anti-beta2GPI antibody (WBCAL-1) in the presence of beta2GPI decreased the activity. In this system, the suppression remained significant in the presence of an excess of exogenous activated factor XII. Euglobulin fractions from APS patients' plasma paralleled low activities of intrinsic fibrinolysis compared with those from healthy subjects. Our results suggest that beta2GPI and anti-beta2GPI antibodies suppress intrinsic fibrinolytic activities. This suppression was not only due to inhibition of factor XII activation but was also related to function of activated factor XII (XIIa). These phenomena partly explain the mechanisms of thrombosis in APS.

journal_name

Br J Haematol

authors

Takeuchi R,Atsumi T,Ieko M,Amasaki Y,Ichikawa K,Koike T

doi

10.1046/j.1365-2141.2002.03928.x

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

781-8

issue

3

eissn

0007-1048

issn

1365-2141

pii

3928

journal_volume

119

pub_type

杂志文章
  • The effect of human T cell leukaemia virus type I infection on a herpes simplex virus-specific CD8+ cytotoxic T cell clone.

    abstract::In an effort to clarify the effect of human T cell leukaemia virus type I (HTLV-I) infection on virus-specific CD8+ cytotoxic T cells, a herpes simplex virus-specific CD8+ cytotoxic T cell clone was infected with HTLV-I in vitro. The cytotoxic activity of the clone was found to have declined early after HTLV-I infecti...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.1991.tb08576.x

    authors: Inatsuki A,Yasukawa M,Kobayashi Y

    更新日期:1991-03-01 00:00:00

  • An unusual indication for splenectomy in hairy cell leukaemia: a report of three cases with persistent splenomegaly after chemoimmunotherapy.

    abstract::We describe three cases of relapsed hairy cell leukaemia (HCL) treated with pentostatin plus rituximab. All three achieved bone marrow complete remission but had persistent splenomegaly and hypersplenism. Because of the clinical uncertainty of its significance, they were all splenectomized. The spleen histology showed...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/bjh.13767

    authors: Sarid N,Ahmad HN,Wotherspoon A,Dearden CE,Else M,Catovsky D

    更新日期:2015-12-01 00:00:00

  • The iron chelator deferasirox affects redox signalling in haematopoietic stem/progenitor cells.

    abstract::The iron chelator deferasirox (DFX) prevents complications related to transfusional iron overload in several haematological disorders characterized by marrow failure. It is also able to induce haematological responses in a percentage of treated patients, particularly in those affected by myelodysplastic syndromes. The...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/bjh.13381

    authors: Tataranni T,Agriesti F,Mazzoccoli C,Ruggieri V,Scrima R,Laurenzana I,D'Auria F,Falzetti F,Di Ianni M,Musto P,Capitanio N,Piccoli C

    更新日期:2015-07-01 00:00:00

  • Autologous haematopoietic cell transplantation in elderly patients with multiple myeloma.

    abstract::High-dose chemotherapy with melphalan followed by autologous haematopoietic cell transplantation (AHCT) is a standard of care in young patients (<65 years) with multiple myeloma. Most myeloma patients, however, are older than 65 years at the time of diagnosis, and the findings of numerous single-centre and registry st...

    journal_title:British journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/bjh.13608

    authors: Auner HW,Garderet L,Kröger N

    更新日期:2015-11-01 00:00:00

  • Two novel mutations (Pro864His, Val867Glu) causing type 2A von Willebrand disease and affecting a single restriction site in exon 28.

    abstract::We detected two transversions in two unrelated Italian patients with type 2A von Willebrand disease (VWD): a C to A at nucleotide 8821 and a T to A at nucleotide 8830, resulting in the missense mutations Pro864His and Val867Glu respectively. Both mutations were in the heterozygous form and abolished the BstXI restrict...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.1998.01064.x

    authors: Bernardi F,Casonato A,Marchetti G,Gemmati D,Bizzaro N,Pontara E,Girolami A

    更新日期:1998-12-01 00:00:00

  • How to manage invasive procedures in children with haemophilia.

    abstract::Invasive procedures can be performed safely in children with haemophilia due to the availability of factor VIII/IX for patients without inhibitors. Most guidelines are based on the experiences in adults, but still there is no established consensus on the optimal factor levels or duration of replacement therapy for adu...

    journal_title:British journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2141.2012.09089.x

    authors: Ljung RC,Knobe K

    更新日期:2012-06-01 00:00:00

  • Interaction of monocytes and T cells in the regulation of normal human megakaryocytopoiesis in vitro: role of IL-1 and IL-2.

    abstract::Autologous or allogeneic peripheral blood T cells can stimulate the human megakaryocyte progenitor cell (CFU-Meg)-derived colony formation in a dose-dependent fashion in agar cultures of nonadherent (NA), T cell-depleted (NT) bone marrow (BM) cells. Low concentrations of monocytes and T cells can collaborate in the st...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.1990.tb07830.x

    authors: Hamaguchi H,Takano N,Saito K,Enokihara H,Furusawa S,Shishido H

    更新日期:1990-09-01 00:00:00

  • Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis.

    abstract::Myeloproliferative disorders (MPD) are reported in 25-65% of patients with splanchnic vein thrombosis (SVT). Diagnostic criteria for MPD have not been fully established in this context. Using clusters of abnormal megakaryocytes in bone marrow (BM) biopsy as a reference standard for Philadelphia negative MPD, we assess...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.2005.05490.x

    authors: Chait Y,Condat B,Cazals-Hatem D,Rufat P,Atmani S,Chaoui D,Guilmin F,Kiladjian JJ,Plessier A,Denninger MH,Casadevall N,Valla D,Brière JB

    更新日期:2005-05-01 00:00:00

  • Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research.

    abstract::We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% a...

    journal_title:British journal of haematology

    pub_type: 杂志文章,多中心研究

    doi:10.1111/j.1365-2141.2007.06592.x

    authors: Panepinto JA,Walters MC,Carreras J,Marsh J,Bredeson CN,Gale RP,Hale GA,Horan J,Hows JM,Klein JP,Pasquini R,Roberts I,Sullivan K,Eapen M,Ferster A,Non-Malignant Marrow Disorders Working Committee, Center for International Bl

    更新日期:2007-06-01 00:00:00

  • Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.

    abstract::The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, na...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.1997.1722990.x

    authors: Reilly JT,Snowden JA,Spearing RL,Fitzgerald PM,Jones N,Watmore A,Potter A

    更新日期:1997-07-01 00:00:00

  • Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

    abstract::To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, defero...

    journal_title:British journal of haematology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1111/j.1365-2141.2011.08720.x

    authors: Vichinsky E,Bernaudin F,Forni GL,Gardner R,Hassell K,Heeney MM,Inusa B,Kutlar A,Lane P,Mathias L,Porter J,Tebbi C,Wilson F,Griffel L,Deng W,Giannone V,Coates T

    更新日期:2011-08-01 00:00:00

  • ATG-saporin-S6 immunotoxin: a new potent and selective drug to eliminate activated lymphocytes and lymphoma cells.

    abstract::Anti-thymocyte globulins (ATG) are currently used to prevent graft-versus-host disease in haematopoietic stem cell transplants from alternative donors and to treat and prevent acute organ rejection after transplantation. Many recent studies have demonstrated that ATG can also be beneficial in patients with myeloma, ly...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.2009.07904.x

    authors: Polito L,Bortolotti M,Farini V,Pedrazzi M,Tazzari PL,Bolognesi A

    更新日期:2009-12-01 00:00:00

  • Evaluation of erythropoiesis after bone marrow transplantation: quantitative reticulocyte counting.

    abstract::Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the re...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.1992.tb08163.x

    authors: Davies SV,Cavill I,Bentley N,Fegan CD,Poynton CH,Whittaker JA

    更新日期:1992-05-01 00:00:00

  • The management and outcome of chronic graft-versus-host disease.

    abstract::Chronic graft-versus-host disease (cGVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT). It is the leading cause of non-relapse mortality in transplant survivors and has a significant impact upon their functional status and quality of life. Despite significant advances being m...

    journal_title:British journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2141.2007.06652.x

    authors: Fraser CJ,Scott Baker K

    更新日期:2007-07-01 00:00:00

  • A variant of the EPB3 gene of the anti-Lepore type in hereditary spherocytosis.

    abstract::The EPB3 gene encodes band 3 (anion exchanger 1) of the red cell membrane. A subset of hereditary spherocytosis (HS) is associated with EPB3 gene mutations and band 3 deficiency. We report a large Italian family in which 10 of the 27 members investigated displayed an autosomal dominant HS. SDS-PAGE revealed a reductio...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.1997.1983013.x

    authors: Bianchi P,Zanella A,Alloisio N,Barosi G,Bredi E,Pelissero G,Zappa M,Vercellati C,Baronciani L,Delaunay J,Sirchia G

    更新日期:1997-08-01 00:00:00

  • Plasminogen activator inhibitor-1 is an independent diagnostic marker as well as severity predictor of hepatic veno-occlusive disease after allogeneic bone marrow transplantation in adults conditioned with busulphan and cyclophosphamide.

    abstract::We attempted to identify the diagnostic markers and severity predictors of hepatic veno-occlusive disease (VOD) in 115 adult patients who were uniformly conditioned with busulphan and cyclophosphamide and who underwent allogeneic bone marrow transplantation (BMT). A diagnosis of VOD was made according to clinical crit...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.2002.03748.x

    authors: Lee JH,Lee KH,Lee JH,Kim S,Seol M,Park CJ,Chi HS,Kang W,Kim ST,Kim WK,Lee JS

    更新日期:2002-09-01 00:00:00

  • Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse.

    abstract::Idiopathic thrombotic thrombocytopenic purpura (TTP) is characterized by frequent recurrences. Effective screening for relapses will enable intervention prior to overt episodes of TTP. The present study used a modified assay to detect ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13) ac...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.2008.07107.x

    authors: Jin M,Casper TC,Cataland SR,Kennedy MS,Lin S,Li YJ,Wu HM

    更新日期:2008-05-01 00:00:00

  • Mutation at position -12 of intron 45 (c-->t) plays a prevalent role in the partial skipping of exon 46 from the transcript of allele alphaLELY in erythroid cells.

    abstract::Allele alphaLELY is a common low-expression allele of the erythroid spectrin SPTA1 gene. It results in the aggravated expression of hereditary elliptocytosis due to SPTA1 gene mutations occurring in trans. Allele alphaLELY contains, in particular, mutations in introns 45 and 46, both in polypyrimidine tracts, and caus...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.1999.01271.x

    authors: Wilmotte R,Marechal J,Delaunay J

    更新日期:1999-03-01 00:00:00

  • Is refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T) a necessary or useful diagnostic category?

    abstract::Both the 2001 World Health Organisation (WHO) classification of haematopoietic neoplasms and the 2008 WHO classification revision include a distinctive diagnostic category, refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T), to describe those rare patients who have both >or=15% ring sideroblasts and...

    journal_title:British journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2141.2008.07526.x

    authors: Wardrop D,Steensma DP

    更新日期:2009-03-01 00:00:00

  • Analysis of the kinetics of band 3 diffusion in human erythroblasts during assembly of the erythrocyte membrane skeleton.

    abstract::During definitive erythropoiesis, erythroid precursors undergo differentiation through multiple nucleated states to an enucleated reticulocyte, which loses its residual RNA/organelles to become a mature erythrocyte. Over the course of these transformations, continuous changes in membrane proteins occur, including shif...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.2010.08268.x

    authors: Kodippili GC,Spector J,Kang GE,Liu H,Wickrema A,Ritchie K,Low PS

    更新日期:2010-09-01 00:00:00

  • The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant.

    abstract::The frequency and prognostic relevance of translocations t(11;14) and t(4;14), the most common translocations involving the immunoglobulin heavy chain (IgH) gene in multiple myeloma (MM), were investigated in 128 patients treated with intensive chemotherapy and autologous stem cell transplant. Myeloma cells were ident...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.2004.04867.x

    authors: Chang H,Sloan S,Li D,Zhuang L,Yi QL,Chen CI,Reece D,Chun K,Keith Stewart A

    更新日期:2004-04-01 00:00:00

  • Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2-year follow-up.

    abstract::35 patients with oral anticoagulant (OAC) related intracranial or intraspinal haemorrhage were studied to determine treatment received, outcome and rate of recurrent bleeding and thromboembolism after restarting OAC. All patients underwent active anticoagulant reversal and in 14 patients with prosthetic heart valves (...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.1998.01078.x

    authors: Butler AC,Tait RC

    更新日期:1998-12-01 00:00:00

  • Type II oestrogen binding sites in acute lymphoid and myeloid leukaemias: growth inhibitory effect of oestrogen and flavonoids.

    abstract::The presence of oestrogen receptors (ER) and type II oestrogen binding sites (type II EBS) have been investigated by a whole cell assay in seven cases of acute lymphoid leukaemia (ALL) and 16 cases of acute myeloid leukaemia (AML). ER were detected in 6/7 ALL patients with values ranging between 133 and 2268 sites/cel...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.1990.tb07787.x

    authors: Larocca LM,Piantelli M,Leone G,Sica S,Teofili L,Panici PB,Scambia G,Mancuso S,Capelli A,Ranelletti FO

    更新日期:1990-08-01 00:00:00

  • Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study.

    abstract::Death during the induction phase of chemotherapy remains a common event in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we ...

    journal_title:British journal of haematology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1046/j.1365-2141.2002.03565.x

    authors: Dumontet C,Mounier N,Munck JN,Bosly A,Morschauser F,Simon D,Marit G,Casasnovas O,Reman O,Molina T,Reyes F,Coiffier B

    更新日期:2002-07-01 00:00:00

  • Childhood, adolescent and young adult non-Hodgkin lymphoma: state of the science.

    abstract::The 5th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non-Hodgkin Lymphoma (NHL) was held in Varese, Italy, from 21-25 October 2015. This review represents a summary of the scientific sessions of this international symposium including childhood, adolescent and young adult (AYA) NHL in countri...

    journal_title:British journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/bjh.14035

    authors: Cairo MS,Pinkerton R

    更新日期:2016-05-01 00:00:00

  • Three unrelated Gaucher's disease patients with three novel point mutations in the glucocerebrosidase gene (P266R, D315H and A318D).

    abstract::Three novel point mutations were detected in the glucocerebrosidase gene of three unrelated Gaucher's disease patients by direct sequencing of PCR products. The first is a C to G change at position 4263 in the genomic sequence (exon 7) which results in a proline to arginine change at position 266 in the mature enzyme ...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.1995.tb05298.x

    authors: Walley AJ,Ellis I,Harris A

    更新日期:1995-10-01 00:00:00

  • The significance of TP53 in lymphoid malignancies: mutation prevalence, regulation, prognostic impact and potential as a therapeutic target.

    abstract::The tumour suppressor TP53 (previously termed p53) mediates a pathway that is considered to be one of the most important mechanisms in the maintenance of genomic stability. The function of TP53 can be abrogated by genomic deletion, mutation, or deregulation of upstream and downstream participants in the TP53 pathway. ...

    journal_title:British journal of haematology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2141.2009.07739.x

    authors: Cheung KJ,Horsman DE,Gascoyne RD

    更新日期:2009-08-01 00:00:00

  • Increased levels of tissue factor activity and procoagulant phospholipids during treatment of children with acute lymphoblastic leukaemia.

    abstract::The use of L-asparaginase (L-ASP) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with thrombotic complications. We evaluated the activities of tissue factor (TFa), thrombomodulin (TMa) and procoagulant phospholipids (PPL) in 26 consecutive children with ALL (25 B-ALL and one T-ALL) treat...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2141.2009.07958.x

    authors: Schneider P,Van Dreden P,Rousseau A,Kassim Y,Legrand E,Vannier JP,Vasse M

    更新日期:2010-02-01 00:00:00

  • Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications.

    abstract::The aim of this study was to analyse the expression of NK-associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex- and age-matched healthy volunteers w...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.1996.4651006.x

    authors: García-Sanz R,González M,Orfão A,Moro MJ,Hernández JM,Borrego D,Carnero M,Casanova F,Bárez A,Jiménez R,Portero JA,San Miguel JF

    更新日期:1996-04-01 00:00:00

  • Recombinant humanized anti-CD40 monoclonal antibody triggers autologous antibody-dependent cell-mediated cytotoxicity against multiple myeloma cells.

    abstract::Multiple myeloma (MM) is currently incurable, and novel therapies are needed. In this study, we examined a novel recombinant humanized monoclonal antibody against CD40 (rhuCD40 mAb) and demonstrate for the first time that rhuCD40 mAb induces antibody-dependent cell-mediated cytotoxicity (ADCC) against CD40-positive MM...

    journal_title:British journal of haematology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2141.2003.04322.x

    authors: Hayashi T,Treon SP,Hideshima T,Tai YT,Akiyama M,Richardson P,Chauhan D,Grewal IS,Anderson KC

    更新日期:2003-05-01 00:00:00