Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab.

Abstract:

BACKGROUND:Paroxysmal nocturnal hemoglobinuria (PNH) is associated with an increased risk of thrombosis through unknown mechanisms. DESIGN AND METHODS:We studied 23 patients with PNH, before and after five and 11 weeks of treatment with eculizumab. We examined markers of thrombin generation and reactional fibrinolysis (prothrombin fragment 1+2 (F1+2), D-dimers, and plasmin antiplasmin complexes (P-AP), and endothelial dysfunction tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), soluble thrombomodulin (sTM), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule (sVCAM-1), endothelial microparticles (EMPs), and tissue factor pathway inhibitor (TFPI). RESULTS:At baseline, vWF, sVCAM-1, the EMP count, and F1+2 and D-dimer levels were significantly elevated in the patients, including those with no history of clinical thrombosis. Treatment with eculizumab was associated with significant decreases in plasma markers of coagulation activation (F1+2, P=0.012, and D-dimers, P=0.01), and reactional fibrinolysis (P-AP, P=0.0002). Eculizumab treatment also significantly reduced plasma markers of endothelial cell activation (t-PA, P=0.0005, sVCAM-1, P<0.0001, and vWF, P=0.0047) and total (P=0.0008) and free (P=0.0013) TFPI plasma levels. CONCLUSIONS:Our results suggest a new understanding of the contribution of endothelial cell activation to the pathogenesis of thrombosis in PNH. The terminal complement inhibitor, eculizumab, induced a significant and sustained decrease in the activation of both the plasma hemostatic system and the vascular endothelium, likely contributing to the protective effect of eculizumab on thrombosis in this setting.

journal_name

Haematologica

journal_title

Haematologica

authors

Helley D,de Latour RP,Porcher R,Rodrigues CA,Galy-Fauroux I,Matheron J,Duval A,Schved JF,Fischer AM,Socié G,French Society of Hematology.

doi

10.3324/haematol.2009.016121

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

574-81

issue

4

eissn

0390-6078

issn

1592-8721

pii

haematol.2009.016121

journal_volume

95

pub_type

杂志文章,多中心研究
  • Dendritic cells: specialized antigen presenting cells.

    abstract::Renewing interest in cancer immunotherapy reflects the excellent results that have been obtained in animal models and the promising results in early clinical trails with dendritic cell (DC) based approaches. The central role that DCs play in the initiation of an immune response raises the possibility of using them to ...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: Di Nicola M,Lemoli RM

    更新日期:2000-02-01 00:00:00

  • Abnormal platelet count is an independent predictor of mortality in the elderly and is influenced by ethnicity.

    abstract::Even though alterations in platelet counts are presumed to be detrimental, their impact on the survival of patients has not been studied in large cohorts. The prevalence of thrombocytopenia and thrombocytosis was examined in a large inner city outpatient population of 36,262 individuals aged ≥65 years old. A significa...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2013.101949

    authors: Msaouel P,Lam AP,Gundabolu K,Chrysofakis G,Yu Y,Mantzaris I,Friedman E,Verma A

    更新日期:2014-05-01 00:00:00

  • Quantitation of HBF gamma-chain types by HPLC in patients with myelodysplastic syndrome.

    abstract::High levels of HbF were found in patients with myelodysplastic syndrome (MDS), as well as a possible switching of the ratio of the gamma chains from the adult to the newborn type in 25% of our patients. These abnormalities in general were not present in the parents. The possibility of having thalassemia or other hemog...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Bourantas KL,Georgiou I,Seferiadis K

    更新日期:1991-07-01 00:00:00

  • Double versus single autotransplantation in multiple myeloma; a single center experience of 100 patients.

    abstract::One hundred patients with newly diagnosed multiple myeloma (MM) were treated with high-dose chemotherapy followed by single or double autologous stem cell transplantation (ASCT). Up-front treatment with a double ASCT tended to prolong progression-free and overall survival. ...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Putkonen M,Rauhala A,Itälä M,Kauppila M,Pelliniemi TT,Remes K

    更新日期:2005-04-01 00:00:00

  • Blood cytokine concentrations in pediatric patients with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

    abstract::Patients with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma often present with B-symptoms or hemophagocytosis and generate an anti-tumor immune response. Specific serum cytokine levels or profiles may reflect the tumor burden, non-specific immune stimulation by the tumor or differences in the stre...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2017.177972

    authors: Knörr F,Damm-Welk C,Ruf S,Singh VK,Zimmermann M,Reiter A,Woessmann W

    更新日期:2018-03-01 00:00:00

  • Re-evaluation of hematocrit as a determinant of thrombotic risk in erythrocytosis.

    abstract::Here we critically evaluate the role of elevated hematocrit as the principal determinant of thrombotic risk in polycythemia and erythrocytosis, defined by an expansion of red cell mass. Since red cell volume determination is no longer readily available, in clinical practice, polycythemia and erythrocytosis are defined...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:10.3324/haematol.2018.210732

    authors: Gordeuk VR,Key NS,Prchal JT

    更新日期:2019-04-01 00:00:00

  • Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure.

    abstract::Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2012.066217

    authors: Seiki Y,Sasaki Y,Hosokawa K,Saito C,Sugimori N,Yamazaki H,Takami A,Nakao S

    更新日期:2013-06-01 00:00:00

  • Multilineage engraftment of refrozen cord blood hematopoietic progenitors in NOD/SCID mice.

    abstract::Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells, with multilineage engraftment. I...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Timeus F,Crescenzio N,Sanavio F,Fazio L,Doria A,Foglia L,Pignochino Y,Berger M,Piacibello W,Madon E,Cordero di Montezemolo L,Fagioli F

    更新日期:2006-03-01 00:00:00

  • Primary thrombocytosis in children.

    abstract::Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL mutations, while common drivers of myeloproliferative neoplasms in adult patients, are not clearly linked to pediatric disease. Management and clinical outco...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:10.3324/haematol.2013.092684

    authors: Kucine N,Chastain KM,Mahler MB,Bussel JB

    更新日期:2014-04-01 00:00:00

  • Natural killer resistance of a drug-resistant leukemia cell line, mediated by up-regulation of HLA class I expression.

    abstract:BACKGROUND AND OBJECTIVES:Drug-resistant leukemia cells may exhibit cross-resistance towards immunological effector mechanisms by alterations of apoptosis pathways. This is particularly relevant in allogeneic bone marrow transplantation for leukemia, where the graft-versus-leukemia effect acts on cells pretreated with ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Classen CF,Falk CS,Friesen C,Fulda S,Herr I,Debatin KM

    更新日期:2003-05-01 00:00:00

  • Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse.

    abstract::Monitoring minimal residual disease is an important way to identify patients with acute myeloid leukemia at high risk of relapse. In this study we investigated the prognostic potential of minimal residual disease monitoring by quantitative real-time polymerase chain reaction analysis of NPM1 mutations in patients trea...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:10.3324/haematol.2014.104133

    authors: Hubmann M,Köhnke T,Hoster E,Schneider S,Dufour A,Zellmeier E,Fiegl M,Braess J,Bohlander SK,Subklewe M,Sauerland MC,Berdel WE,Büchner T,Wörmann B,Hiddemann W,Spiekermann K

    更新日期:2014-08-01 00:00:00

  • Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia.

    abstract:BACKGROUND:Diamond-Blackfan anemia is a rare, clinically heterogeneous, congenital red cell aplasia: 40% of patients have congenital abnormalities. Recent studies have shown that in western countries, the disease is associated with heterozygous mutations in the ribosomal protein (RP) genes in about 50% of patients. The...

    journal_title:Haematologica

    pub_type: 杂志文章,多中心研究

    doi:10.3324/haematol.2009.020826

    authors: Konno Y,Toki T,Tandai S,Xu G,Wang R,Terui K,Ohga S,Hara T,Hama A,Kojima S,Hasegawa D,Kosaka Y,Yanagisawa R,Koike K,Kanai R,Imai T,Hongo T,Park MJ,Sugita K,Ito E

    更新日期:2010-08-01 00:00:00

  • Inconsistency of different methods for assessing ex vivo platelet function: relevance for the detection of aspirin resistance.

    abstract:BACKGROUND:Assays to evaluate platelet function are often interchangeably used to assess "resistance" to aspirin. We compared different platelet function assays in patients treated or untreated with aspirin. DESIGN AND METHODS:Platelet function was evaluated in 162 subjects, 85 of whom were not being treated with any ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2010.027102

    authors: Renda G,Zurro M,Malatesta G,Ruggieri B,De Caterina R

    更新日期:2010-12-01 00:00:00

  • Simultaneous occurrence of B-cell chronic lymphocytic leukemia and chronic myeloid leukemia with further evolution to lymphoid blast crisis.

    abstract::The coexistence of chronic myeloid leukemia (CML) and B-cell chronic lymphocytic leukemia (CLL) in the same patient is rare. A 71-year-old woman developed a B-lineage lymphoid blast crisis at 18 months after diagnosis of Ph-positive CML. At this time, a lymphoid cell population with morphologic and immunophenotypic fe...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: Esteve J,Cervantes F,Rives S,Rozman M,Zarco MA,Montserrat E

    更新日期:1997-09-01 00:00:00

  • Long-term cost-effectiveness of low molecular weight heparin versus unfractionated heparin for the prophylaxis of venous thromboembolism in elective hip replacement.

    abstract:BACKGROUND AND OBJECTIVE:Either low molecular weight heparin (LMWH) or unfractionated heparin (UH) may be used for the prophylaxis of post-operative venous thromboembolic disease (VTD) in elective hip replacement. This study was aimed at assessing the cost-effectiveness of LMWH over UH from the society perspective, whi...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Marchetti M,Liberato NL,Ruperto N,Barosi G

    更新日期:1999-08-01 00:00:00

  • Bone marrow morphology and proliferative activity in acquired immunodeficiency syndrome.

    abstract::Peripheral cytopenia has been reported in a number of patients with the acquired immunodeficiency syndrome (AIDS), but the mechanism of bone marrow (BM) failure is unclear. We have examined the BM morphology and cytokinetics of 16 untreated HIV-positive patients whose clinical condition ranged from asymptomatic (stage...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Danova M,Riccardi A,Brugnatelli S,Maserati R,Comolli G,Mazzini G,Castello A,Ascari E,Rondanelli EG

    更新日期:1989-07-01 00:00:00

  • Genetic modifiers of beta-thalassemia.

    abstract::As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with apparently identical genotypes can have many different clinical conditions even in simple monogenic disorders. Beta thalassemia occurs when there is a deficiency in the synthesis of beta globin chains. The clin...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: Thein SL

    更新日期:2005-05-01 00:00:00

  • Patient-derived anti-β2GP1 antibodies recognize a peptide motif pattern and not a specific sequence of residues.

    abstract::Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2017.170381

    authors: de Moerloose P,Fickentscher C,Boehlen F,Tiercy JM,Kruithof EKO,Brandt KJ

    更新日期:2017-08-01 00:00:00

  • 11q- and constitutional X trisomy in a patient with M5b acute non-lymphocytic leukemia.

    abstract::A patient with M5b acute nonlymphoblastic leukemia (ANLL) and a 47,XXX del(11) (q23) karyotype is described. Partial remission was obtained after treatment with daunorubicin, arabinosylcytosine and VP-16. Subsequently, two courses of chemotherapy for resistant ANLL were administered without achieving complete remissio...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Bigazzi C,Galieni P,Scarinci R,Vivarelli R,Bucalossi A,Biancolini G,Falbo R,Vessichelli F,Dispensa E

    更新日期:1993-05-01 00:00:00

  • Cytogenetic characterization of acute myeloid leukemia in Shwachman's syndrome. A case report.

    abstract::We report on a case of acute myeloid leukemia in a 17-year old boy affected by Shwachman Diamond syndrome (SDS). Conventional cytogenetics at diagnosis revealed an abnormal clone with complex karyotypic changes including typical myeloid aberrations, such as monosomy 5, tetrasomy of chromosome 8, trisomy 9, and deletio...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: Spirito FR,Crescenzi B,Matteucci C,Martelli MF,Mecucci C

    更新日期:2000-11-01 00:00:00

  • Heterogeneity of BCL6 rearrangements in nodular lymphocyte predominant Hodgkin's lymphoma.

    abstract:BACKGROUND AND OBJECTIVES:Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) showed recurrent rearrangement of the BCL6 which is gene detected in 48% of cases analyzed by interphase-fluorescent in situ hybridization (FISH). These findings point to a critical role for BCL6 in the development of this distinct Hodg...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Wlodarska I,Stul M,De Wolf-Peeters C,Hagemeijer A

    更新日期:2004-08-01 00:00:00

  • Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma.

    abstract::Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma,...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2016.145102

    authors: Camus V,Stamatoullas A,Mareschal S,Viailly PJ,Sarafan-Vasseur N,Bohers E,Dubois S,Picquenot JM,Ruminy P,Maingonnat C,Bertrand P,Cornic M,Tallon-Simon V,Becker S,Veresezan L,Frebourg T,Vera P,Bastard C,Tilly H,Jardin

    更新日期:2016-09-01 00:00:00

  • Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid.

    abstract::n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Ontachi Y,Asakura H,Omote M,Yoshida T,Matsui O,Nakao S

    更新日期:2005-11-01 00:00:00

  • FLU-ID (fludarabine and idarubicin) regimen as salvage therapy in pretreated low-grade non-Hodgkin's lymphoma.

    abstract::Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with promising activity in lymphoproliferative disorders and, in particular, in low-grade non-Hodgkin's lymphoma (LG-NHL). Recently, a few reports have described interesting results using FLU in polychemotherapy regimens. In order to evaluate FLU in comb...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:

    authors: Zinzani PL,Bendandi M,Gherlinzoni F,Merla E,Gozzetti A,Tura S

    更新日期:1996-03-01 00:00:00

  • Hemoglobin sickle cell disease complications: a clinical study of 179 cases.

    abstract:BACKGROUND:Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease. D...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.055202

    authors: Lionnet F,Hammoudi N,Stojanovic KS,Avellino V,Grateau G,Girot R,Haymann JP

    更新日期:2012-08-01 00:00:00

  • Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation.

    abstract::Advanced myelodysplastic syndrome harbors a high risk of progression to acute myeloid leukemia and poor prognosis. In children, there is no established treatment to prevent or delay progression to leukemia prior to hematopoietic stem cell transplantation. Azacitidine is a hypomethylating agent, which was shown to slow...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2016.145821

    authors: Waespe N,Van Den Akker M,Klaassen RJ,Lieberman L,Irwin MS,Ali SS,Abdelhaleem M,Zlateska B,Liebman M,Cada M,Schechter T,Dror Y

    更新日期:2016-12-01 00:00:00

  • Treatment of childhood acute lymphoblastic leukemia. Long-term results of the AIEOP-ALL 87 study.

    abstract:BACKGROUND AND OBJECTIVES:In March 1987 AIEOP started the AIEOP-ALL-87 study, based on the previous AIEOP-ALL-82. The aim of this new study was to evaluate, for all risk groups: a) the efficacy of treatment intensification achieved by adding a fourth drug (daunomycin) in the induction phase and a 3-drug reinduction pha...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Paolucci G,Vecchi V,Favre C,Miniero R,Madon E,Pession A,Rondelli R,De Rossi G,Lo Nigro L,Porta F,Santoro N,Indolfi P,Basso G,Conter V,Aricò M,Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

    更新日期:2001-05-01 00:00:00

  • Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts.

    abstract::The classification of myelodysplastic syndromes is based on the morphological criteria proposed by the French-American-British (FAB) and World Health Organization (WHO) groups. Accurate enumeration of blast cells, although essential for diagnosis of myelodysplastic syndrome and for assignment to prognostic groups, is ...

    journal_title:Haematologica

    pub_type: 共识发展会议,杂志文章

    doi:10.3324/haematol.13405

    authors: Mufti GJ,Bennett JM,Goasguen J,Bain BJ,Baumann I,Brunning R,Cazzola M,Fenaux P,Germing U,Hellström-Lindberg E,Jinnai I,Manabe A,Matsuda A,Niemeyer CM,Sanz G,Tomonaga M,Vallespi T,Yoshimi A,International Working Group

    更新日期:2008-11-01 00:00:00

  • Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy.

    abstract:BACKGROUND:In multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, ...

    journal_title:Haematologica

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.3324/haematol.2010.037978

    authors: van Duin M,Broyl A,de Knegt Y,Goldschmidt H,Richardson PG,Hop WC,van der Holt B,Joseph-Pietras D,Mulligan G,Neuwirth R,Sahota SS,Sonneveld P

    更新日期:2011-11-01 00:00:00

  • Influence of genetic polymorphisms in CYP3A4, CYP3A5, GSTP1, GSTM1, GSTT1 and MDR1 genes on survival and therapy-related toxicity in multiple myeloma.

    abstract::We investigated the role of single nucleotide polymorphisms in genes encoding for drug-metabolizing enzymes in 209 newly diagnosed multiple myeloma patients included in a clinical trial comparing single with double intensive therapy. We observed no significant association between polymorphisms in CYP3A4, CYP3A5, MDR1,...

    journal_title:Haematologica

    pub_type: 信件

    doi:10.3324/haematol.10618

    authors: Schilthuizen C,Broyl A,van der Holt B,de Knegt Y,Lokhorst H,Sonneveld P

    更新日期:2007-02-01 00:00:00