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Editorial Board / Aims & ScopeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Source Type: journals

The promise and pitfalls of gene expression studiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
“…because as we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns -- the ones we don't know we don't know.”Donald Rumsfeld
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Jerald Radich Source Type: journals

Gene expression profiling in acute myeloid leukaemia (AML)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In view of the genetic heterogeneity of acute myeloid leukaemia (AML), gene expression profiling (GEP) with the possibility of investigating the expression of tens of thousands of genes in parallel represents a promising approach to facilitate and improve the diagnostic process in this complex disorder. In the last decade, following the introduction of this methodology in leukaemia research, various studies have demonstrated that classification of the majority of known genetic subclasses in AML can be performed with high accuracy by GEP. Further, GEP allowed for detecting new biologically and prognostically relevant subcla...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Ulrike Bacher, Alexander Kohlmann, Claudia Haferlach, Torsten Haferlach Source Type: journals

The impact of gene profiling in chronic myeloid leukaemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The use of microarray technology in chronic myeloid leukaemia (CML) has increased our understanding of the biology of this disease. From early studies of gene expression profiling in BCR-ABL-positive cell lines to samples from patients in different disease phases of CML, using resting cells or cells treated with a variety of therapeutic agents, the field has now moved on to profiling microRNA and single nucleotide polymorphisms of CML cells. With the advent of tyrosine kinase inhibitors, several groups have also attempted to use microarray profiling to ascertain if particular gene expression profiles pre-existing in patien...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Agnes S.M. Yong, Junia V. Melo Source Type: journals

Gene expression profiling in lymphoma diagnosis and managementEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The classification of lymphoid malignancies has evolved from a purely morphological scheme to the current WHO (World Health Organization) classification, which takes into consideration histological, immunophenotypic, genetic and clinical information. DNA microarray technology enables the simultaneous determination of the expression levels for thousands of genes (gene expression profile; GEP) and provides a powerful approach for investigating lymphoma biology and improving disease classification. Distinct molecular signatures for many lymphomas, as well as novel lymphoma subtypes have been identified. Molecular prognosticat...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Javeed Iqbal, ZhongFeng Liu, Karen Deffenbacher, Wing C. Chan Source Type: journals

Gene expression profiling in chronic lymphocytic leukaemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The proliferation of new techniques that allow a multiparametric study of gene expression, the mutational state of genomic DNA, DNA methylation and the phosphorylation of receptor and adaptor proteins has led to an increased understanding of the origin of different cancers, the definition of new prognosis markers and the response to treatment profiles. Gene profiling studies on chronic lymphocytic leukaemia (CLL) are at the origin of new prognosis markers such as zeta-associated protein-70 (ZAP-70), LPL and CLLU1, which, at present, are under study for their application to clinical practice. An increased resolution in the ...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Carles Codony, Marta Crespo, Pau Abrisqueta, Emili Montserrat, Francesc Bosch Source Type: journals

Clinical implications of gene expression profiling in myelodysplastic syndromes: Recognition of ribosomal and translational gene dysregulation and development of predictive assaysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Myelodysplastic syndromes (MDS) are a group of haematopoietic stem cell disorders that pose a unique challenge for gene expression profiling by virtue of their inherent heterogeneity. Despite monoclonality of MDS, the marrow picture is complicated by the presence of not only stromal cells but also by varying stages of differentiating diseased cells belonging to all three lineages. Now that reproducible results can be obtained from nanograms of RNA, it is possible to derive useful information from even a limited number of cells; for example, dysregulation of ribosomal and translational genes was detected in MDS patients com...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Naomi Galili, Azra Raza Source Type: journals

MicroRNA expression profiling in acute myeloid and chronic lymphocytic leukaemiasEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Altered expression of microRNAs, a new class of noncoding RNAs that regulate messenger RNA and protein expression of target genes, has been recently demonstrated to have an essential role in the process of leukaemogenesis. Distinctive patterns of activation and/or silencing of multiple microRNAs (microRNA signatures) associated with certain cytogenetic and molecular subsets of leukaemia have been identified using genome-wide high-throughput profiling assays. This has led not only to the discovery of new molecular pathways implicated in leukaemogenesis, but also supplied prognostic information complementing that gained from...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Guido Marcucci, Krzysztof Mrózek, Michael D. Radmacher, Clara D. Bloomfield, Carlo M. Croce Source Type: journals

Gene expression changes in normal haematopoietic cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article seeks to present an organised approach to the use and interpretation of gene profiling in normal haematopoiesis and broadly illustrates the challenges of selecting appropriate controls for high-throughput expression studies.
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Jack M. Lionberger, Derek L. Stirewalt Source Type: journals

Analysis of DNA microarray expression dataEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA microarrays are powerful tools for studying biological mechanisms and for developing prognostic and predictive classifiers for identifying the patients who require treatment and are best candidates for specific treatments. Because microarrays produce so much data from each specimen, they offer great opportunities for discovery and great dangers or producing misleading claims. Microarray based studies require clear objectives for selecting cases and appropriate analysis methods. Effective analysis of microarray data, where the number of measured variables is orders of magnitude greater than the number of cases, requires...
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Authors: Richard Simon Source Type: journals

IndexEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Source: Best Practice & Research. Clinical Haematology - May 31, 2009 Category: Hematology Source Type: journals

The coagulopathy of acute promyelocytic leukaemia revisited.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since the initial description of the disease, the life-threatening coagulopathy associated with acute promyelocytic leukaemia (APL) has been the defining clinical characteristic. Historically, this uncommon subtype of acute myeloid leukaemia has been associated with a high mortality rate during induction therapy, most frequently attributable to haemorrhage. Since the introduction of all-trans retinoic acid (ATRA) into the therapy of all patients with APL, disease-free survival and overall survival have improved dramatically, such that the disease is now highly curable. However, induction mortality remains a major probl...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Stein E, McMahon B, Kwaan H, Altman JK, Frankfurt O, Tallman MS Tags: Best Pract Res Clin Haematol Source Type: journals

Antithrombotic therapy and survival in cancer patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Venous thromboembolism is a common complication in patients with malignant disease. The development of symptomatic thromboembolism is associated with a poor prognosis for patients with cancer. Retrospective analysis of studies comparing unfractionated heparin with low-molecular-weight heparin (LMWH) for the initial treatment of deep vein thrombosis indicated improved survival for cancer patients receiving LMWH therapy. Prospective studies exposing cancer patients to LMWH therapy, in the absence of established thrombosis, suggest that survival may be prolonged in these patients after LMWH exposure. Ongoing studies, with...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Kakkar AK Tags: Best Pract Res Clin Haematol Source Type: journals

Thrombotic complications after haematopoietic stem cell transplantation: early and late effects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Haematopoietic stem cell transplantation is currently the only curative option for many haematological malignancies, but is characterized by a wide spectrum of complications, including haemostatic changes. Bleeding and thrombotic events occur in the early and late phases after transplantation. In the early phase, thrombotic events have a variable clinical picture and present either as venous thrombosis, mainly at the site of central venous lines, veno-occlusive disease (also known as sinusoid occlusion syndrome) or transplant-associated microangiopathy. The latter two occur in the context of an acute graft-vs-host reac...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Tsakiris DA, Tichelli A Tags: Best Pract Res Clin Haematol Source Type: journals

Disseminated intravascular coagulation in cancer patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Disseminated intravascular coagulation (DIC) is a syndrome that may complicate a variety of diseases, including malignant disease. DIC is characterized by widespread, intravascular activation of coagulation (leading to intravascular fibrin deposition) and simultaneous consumption of coagulation factors and platelets (potentially resulting in bleeding). Clinically, DIC in cancer has, in general, a less fulminant presentation than the types of DIC complicating sepsis and trauma. A more gradual, but also more chronic, systemic activation of coagulation can proceed subclinically. Eventually, this process may lead to exhaus...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Levi M Tags: Best Pract Res Clin Haematol Source Type: journals

Thrombosis associated with angiogenesis inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances in the understanding of the pathogenesis of cancer have led to the introduction of a variety of biological agents with novel mechanisms of action into clinical trials and even into clinical practice. In particular, tumour-associated neoangiogenesis has become a major target for this new class of antineoplastic agents. Five anti-angiogenic agents (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use, and many others have entered clinical trials. Many new biological agents with anti-angiogenic properties appear to be ...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Elice F, Rodeghiero F, Falanga A, Rickles FR Tags: Best Pract Res Clin Haematol Source Type: journals

Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute lymphoblastic leukaemia (ALL) is the most common malignancy associated with venous thromboembolism (VTE) in children. The prevalence of symptomatic VTE ranges from 0% to 36%, and the variation can be explained, at least in part, by differences in chemotherapeutic protocols. The mechanism for increased risk of VTE is associated with alterations in the haemostatic system by use of L-asparaginase (ASP) alone or in combination with vincristine or prednisone, presence of central venous lines (CVLs) and/or inherited thrombophilia. The children at greatest risk are generally those receiving Escherichia coli ASP concomit...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Nowak-Göttl U, Kenet G, Mitchell LG Tags: Best Pract Res Clin Haematol Source Type: journals

Treatment of venous thromboembolism in cancer patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Monotherapy with low-molecular-weight heparin is the recommended first-line approach in cancer patients with newly diagnosed VTE, and is usually continued for a minimum of 3-6 months. Other management issues that require further research include optimal duration of anticoagulant therapy, treatment of recurrent VTE, the role of vena cava filters, the effects of VTE and its treatment on quality of life, and the impact of anticoagulants on survival. Newer anticoagulants hold promise in providing more effective and convenient ...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Lee AY Tags: Best Pract Res Clin Haematol Source Type: journals

Heparanase coagulation and cancer progression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Heparanase is an endo-beta-D-glucuronidase capable of cleaving heparan sulphate (HS) side chains of heparan sulphate proteoglycans on cell surfaces and the extracellular matrix; activity that is strongly implicated in tumour metastasis and angiogenesis. It has been shown that heparanase overexpression in human leukaemia, glioma and breast carcinoma cells results in a marked increase in tissue factor (TF) levels. In addition, TF was induced by exogenous addition of recombinant heparanase to tumour cells and primary endothelial cells; induction that was mediated by p38 phosphorylation and correlated with enhanced procoag...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Nadir Y, Brenner B Tags: Best Pract Res Clin Haematol Source Type: journals

Tissue factor in tumour progression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The linkage between activation of the coagulation system and cancer is well established, as is deregulation of tissue factor (TF) by cancer cells, their vascular stroma and cancer-associated inflammatory cells. TF is no longer perceived as an 'alternative' coagulation factor, but rather as a central trigger of the coagulation cascade and an important cell-associated signalling receptor activated by factor VIIa, and interacting with several other regulatory entities, most notably protease-activated receptors (PAR-1 and PAR-2). Preclinical studies revealed the role of oncogenic transformation and tumour micro-environment...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Rak J, Milsom C, Magnus N, Yu J Tags: Best Pract Res Clin Haematol Source Type: journals

Microparticles, thrombosis and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Microvesicles comprised of exosomes and microparticles are shed from both normal and malignant cells upon cell activation or apoptosis. Microvesicles promote clot formation, mediate pro-inflammatory processes, facilitate cell-to-cell interactions, transfer proteins and mRNA to cells, and induce cell signalling. Microparticles bearing tissue factor play a central role in coagulation initiation and thrombus formation. This chapter will review earlier studies which focus on the role of procoagulant microvesicles in cancer thrombogenicity, and discuss the effects of microvesicles on vascular cell dysfunction and angiogenes...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Aharon A, Brenner B Tags: Best Pract Res Clin Haematol Source Type: journals

Procoagulant mechanisms in tumour cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pathogenesis of the prothrombotic state of cancer patients is due, at least in part, to the ability of cancer cells to activate the coagulation system. Several complex and not fully recognized interactions between the malignant cell and the clotting system promote a shift in the haemostatic balance compared with a procoagulant state. Tumour cells possess the capacity to interact with the haemostatic system in multiple ways. The principal mechanisms include the expression of haemostatic proteins by tumour cells, the production of inflammatory cytokines by tumour and/or host cells, and the direct adhesion of tumour cells...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Falanga A, Panova-Noeva M, Russo L Tags: Best Pract Res Clin Haematol Source Type: journals

Risk stratification for cancer-associated venous thromboembolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The risk of venous thromboembolism (VTE) is elevated in cancer, and thrombosis is the second leading cause of death in patients with malignancy. Many risk factors for cancer-associated thrombosis have been identified. These include patient-associated factors such as age, obesity and medical comorbidities; cancer-associated factors such as site and stage of cancer; and treatment-associated factors, particularly chemotherapy and hospitalization. In addition, several candidate biomarkers for cancer-associated thrombosis have been identified recently. Despite the high rate and significant impact of VTE in cancer outpatient...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Connolly GC, Khorana AA Tags: Best Pract Res Clin Haematol Source Type: journals

Lessons from VTE registries: the RIETE experience.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Patients with venous thromboembolism (VTE) and active cancer are often excluded from clinical trials of anticoagulant therapy because of short life expectancy, inability or unwillingness to attend for regular laboratory monitoring during vitamin K antagonist therapy, or contraindications to therapy. As such, treatment regimens based on the results from clinical trials might not be suitable for many VTE patients with cancer. 'Registro Informatizado de la Enfermedad TromboEmbólica' (RIETE) was initiated in March 2001 to prospectively record the current clinical management of patients with symptomatic, objectively co...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Monreal M, Trujillo-Santos J Tags: Best Pract Res Clin Haematol Source Type: journals

Epidemiology of cancer-related venous thromboembolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies have better defined the epidemiology of venous thromboembolism (VTE) in cancer patients. The incidence is highest in patients who have metastatic disease at the time of presentation and who have fast growing, biologically aggressive cancers associated with a poor prognosis. The incidence is also high in patients with haematological cancers. Other specific risk factors that affect the incidence of VTE include undergoing invasive neurosurgery, the number of underlying chronic co-morbid conditions, and being of Asian/Pacific Islander decent (lower incidence). The incidence is highest in the first few months...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Wun T, White RH Tags: Best Pract Res Clin Haematol Source Type: journals

Thrombosis and cancer: Trousseau syndrome revisited.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this introductory chapter a story has been reviewed concerning the evolution of the concept of "cancer and thrombosis", since its first description by Armand Trousseau in 1865. From scattered reports on experimental material (tumor extracts) or on animal models of tumor/metastasis growth, through the progress of cell biology and experimental pharmacology, during the last 20 years interest has moved to clinical questions, such as: how to prevent and treat thrombosis, a frequent complication of both solid and hematologic malignancies? Has an occult cancer to be suspected in the majority of cases of idiopathic deep vei...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Donati MB Tags: Best Pract Res Clin Haematol Source Type: journals

Cancer and thrombosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19285267 [PubMed - in process]
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Brenner B Tags: Best Pract Res Clin Haematol Source Type: journals

Editorial Board / Aims & ScopeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Source Type: journals

Cancer and ThrombosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer and thrombosis are the two major disease states in the developed world. While the association of venous thromboembolism (VTE) with tumors has been described more than 140 years ago, clinical and basic research over the past 30 years have broadened our understanding of this association. The interactions of thrombosis and cancer are complex and involve issues related to pathogenic mechanisms, clinical presentation, prognosis and treatment.
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Benjamin Brenner Source Type: journals

Thrombosis and cancer: Trousseau syndrome revisitedEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this introductory chapter a story has been reviewed concerning the evolution of the concept of “cancer and thrombosis”, since its first description by Armand Trousseau in 1865.From scattered reports on experimental material (tumor extracts) or on animal models of tumor/metastasis growth, through the progress of cell biology and experimental pharmacology, during the last 20 years interest has moved to clinical questions, such as: how to prevent and treat thrombosis, a frequent complication of both solid and hematologic malignancies? Has an occult cancer to be suspected in the majority of cases of idiopathic deep vein...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Maria Benedetta Donati Source Type: journals

Epidemiology of cancer-related venous thromboembolismEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies have better defined the epidemiology of venous thromboembolism (VTE) in cancer patients. The incidence is highest in patients who have metastatic disease at the time of presentation and who have fast growing, biologically aggressive cancers associated with a poor prognosis. The incidence is also high in patients with haematological cancers. Other specific risk factors that affect the incidence of VTE include undergoing invasive neurosurgery, the number of underlying chronic co-morbid conditions, and being of Asian/Pacific Islander decent (lower incidence). The incidence is highest in the first few months aft...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Ted Wun, Richard H. White Source Type: journals

Lessons from VTE registries: the RIETE experienceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Patients with venous thromboembolism (VTE) and active cancer are often excluded from clinical trials of anticoagulant therapy because of short life expectancy, inability or unwillingness to attend for regular laboratory monitoring during vitamin K antagonist therapy, or contraindications to therapy. As such, treatment regimens based on the results from clinical trials might not be suitable for many VTE patients with cancer. ‘Registro Informatizado de la Enfermedad TromboEmbólica’ (RIETE) was initiated in March 2001 to prospectively record the current clinical management of patients with symptomatic, objectively confir...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Manuel Monreal, Javier Trujillo-Santos Source Type: journals

Risk stratification for cancer-associated venous thromboembolismEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The risk of venous thromboembolism (VTE) is elevated in cancer, and thrombosis is the second leading cause of death in patients with malignancy. Many risk factors for cancer-associated thrombosis have been identified. These include patient-associated factors such as age, obesity and medical comorbidities; cancer-associated factors such as site and stage of cancer; and treatment-associated factors, particularly chemotherapy and hospitalization. In addition, several candidate biomarkers for cancer-associated thrombosis have been identified recently. Despite the high rate and significant impact of VTE in cancer outpatients, p...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Gregory C. Connolly, Alok A. Khorana Source Type: journals

Procoagulant mechanisms in tumour cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pathogenesis of the prothrombotic state of cancer patients is due, at least in part, to the ability of cancer cells to activate the coagulation system. Several complex and not fully recognized interactions between the malignant cell and the clotting system promote a shift in the haemostatic balance compared with a procoagulant state. Tumour cells possess the capacity to interact with the haemostatic system in multiple ways. The principal mechanisms include the expression of haemostatic proteins by tumour cells, the production of inflammatory cytokines by tumour and/or host cells, and the direct adhesion of tumour cells to ...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Anna Falanga, Marina Panova-Noeva, Laura Russo Source Type: journals

Microparticles, thrombosis and cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Microvesicles comprised of exosomes and microparticles are shed from both normal and malignant cells upon cell activation or apoptosis. Microvesicles promote clot formation, mediate pro-inflammatory processes, facilitate cell-to-cell interactions, transfer proteins and mRNA to cells, and induce cell signalling. Microparticles bearing tissue factor play a central role in coagulation initiation and thrombus formation. This chapter will review earlier studies which focus on the role of procoagulant microvesicles in cancer thrombogenicity, and discuss the effects of microvesicles on vascular cell dysfunction and angiogenesis. ...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Anat Aharon, Benjamin Brenner Source Type: journals

Tissue factor in tumour progressionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The linkage between activation of the coagulation system and cancer is well established, as is deregulation of tissue factor (TF) by cancer cells, their vascular stroma and cancer-associated inflammatory cells. TF is no longer perceived as an ‘alternative’ coagulation factor, but rather as a central trigger of the coagulation cascade and an important cell-associated signalling receptor activated by factor VIIa, and interacting with several other regulatory entities, most notably protease-activated receptors (PAR-1 and PAR-2). Preclinical studies revealed the role of oncogenic transformation and tumour micro-environment...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Janusz Rak, Chloe Milsom, Nathalie Magnus, Joanne Yu Source Type: journals

Heparanase coagulation and cancer progressionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulphate (HS) side chains of heparan sulphate proteoglycans on cell surfaces and the extracellular matrix; activity that is strongly implicated in tumour metastasis and angiogenesis. It has been shown that heparanase overexpression in human leukaemia, glioma and breast carcinoma cells results in a marked increase in tissue factor (TF) levels. In addition, TF was induced by exogenous addition of recombinant heparanase to tumour cells and primary endothelial cells; induction that was mediated by p38 phosphorylation and correlated with enhanced procoagulant ...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Yona Nadir, Benjamin Brenner Source Type: journals

Treatment of venous thromboembolism in cancer patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Monotherapy with low-molecular-weight heparin is the recommended first-line approach in cancer patients with newly diagnosed VTE, and is usually continued for a minimum of 3–6 months. Other management issues that require further research include optimal duration of anticoagulant therapy, treatment of recurrent VTE, the role of vena cava filters, the effects of VTE and its treatment on quality of life, and the impact of anticoagulants on survival. Newer anticoagulants hold promise in providing more effective and convenient tr...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Agnes Y.Y. Lee Source Type: journals

Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute lymphoblastic leukaemia (ALL) is the most common malignancy associated with venous thromboembolism (VTE) in children. The prevalence of symptomatic VTE ranges from 0% to 36%, and the variation can be explained, at least in part, by differences in chemotherapeutic protocols. The mechanism for increased risk of VTE is associated with alterations in the haemostatic system by use of L-asparaginase (ASP) alone or in combination with vincristine or prednisone, presence of central venous lines (CVLs) and/or inherited thrombophilia. The children at greatest risk are generally those receiving Escherichia coli ASP concomitant ...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Ulrike Nowak-Göttl, Gili Kenet, Lesley G. Mitchell Source Type: journals

Thrombosis associated with angiogenesis inhibitorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances in the understanding of the pathogenesis of cancer have led to the introduction of a variety of biological agents with novel mechanisms of action into clinical trials and even into clinical practice. In particular, tumour-associated neoangiogenesis has become a major target for this new class of antineoplastic agents. Five anti-angiogenic agents (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use, and many others have entered clinical trials. Many new biological agents with anti-angiogenic properties appear to be asso...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Francesca Elice, Francesco Rodeghiero, Anna Falanga, Frederick R. Rickles Source Type: journals

Disseminated intravascular coagulation in cancer patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Disseminated intravascular coagulation (DIC) is a syndrome that may complicate a variety of diseases, including malignant disease. DIC is characterized by widespread, intravascular activation of coagulation (leading to intravascular fibrin deposition) and simultaneous consumption of coagulation factors and platelets (potentially resulting in bleeding). Clinically, DIC in cancer has, in general, a less fulminant presentation than the types of DIC complicating sepsis and trauma. A more gradual, but also more chronic, systemic activation of coagulation can proceed subclinically. Eventually, this process may lead to exhaustion...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Marcel Levi Source Type: journals

Thrombotic complications after haematopoietic stem cell transplantation: early and late effectsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Haematopoietic stem cell transplantation is currently the only curative option for many haematological malignancies, but is characterized by a wide spectrum of complications, including haemostatic changes. Bleeding and thrombotic events occur in the early and late phases after transplantation. In the early phase, thrombotic events have a variable clinical picture and present either as venous thrombosis, mainly at the site of central venous lines, veno-occlusive disease (also known as sinusoid occlusion syndrome) or transplant-associated microangiopathy. The latter two occur in the context of an acute graft-vs-host reaction...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Dimitrios A. Tsakiris, André Tichelli Source Type: journals

Antithrombotic therapy and survival in cancer patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Venous thromboembolism is a common complication in patients with malignant disease. The development of symptomatic thromboembolism is associated with a poor prognosis for patients with cancer. Retrospective analysis of studies comparing unfractionated heparin with low-molecular-weight heparin (LMWH) for the initial treatment of deep vein thrombosis indicated improved survival for cancer patients receiving LMWH therapy. Prospective studies exposing cancer patients to LMWH therapy, in the absence of established thrombosis, suggest that survival may be prolonged in these patients after LMWH exposure. Ongoing studies, with car...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: A.K. Kakkar Source Type: journals

The coagulopathy of acute promyelocytic leukaemia revisitedEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since the initial description of the disease, the life-threatening coagulopathy associated with acute promyelocytic leukaemia (APL) has been the defining clinical characteristic. Historically, this uncommon subtype of acute myeloid leukaemia has been associated with a high mortality rate during induction therapy, most frequently attributable to haemorrhage. Since the introduction of all-trans retinoic acid (ATRA) into the therapy of all patients with APL, disease-free survival and overall survival have improved dramatically, such that the disease is now highly curable. However, induction mortality remains a major problem a...
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Authors: Eytan Stein, Brandon McMahon, Hau Kwaan, Jessica K. Altman, Olga Frankfurt, Martin S. Tallman Source Type: journals

IndexEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Source: Best Practice & Research. Clinical Haematology - March 1, 2009 Category: Hematology Source Type: journals

What are the most important donor and recipient factors affecting the outcome of related and unrelated allogeneic transplantation?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several recipient and donor risk factors affect outcome after transplantation with allogeneic hematopoietic stem cells. The most important recipient risk factors are patient age, comorbidity, performance status, cytomegalovirus (CMV) status, and disease considerations, such as diagnosis, stage, and cytogenetic risk. Prior chemotherapy regimens, patient race, and IL10 promoter polymorphism also appear to have some impact, but to a lesser extent. The most important donor factor is the level of HLA mismatch. Donor gender, relation, age, and KIR genotype also affect outcome. Donor CMV serology, parity, and race do not appe...
Source: Best Practice & Research. Clinical Haematology - December 1, 2008 Category: Hematology Authors: Anasetti C Tags: Best Pract Res Clin Haematol Source Type: journals

Diagnosis and therapy of fungal infection in patients with leukemia-new drugs and immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Invasive fungal infections (IFIs) are a common problem in immunocompromised patients. Patients with leukemia, especially those undergoing stem cell transplantation, are at increased risk for IFIs, particularly invasive aspergillosis (IA). Serial monitoring with the recently approved Aspergillus galactomannan antigen test has helped to improve the diagnosis and the monitoring of treatment of IA in cancer patients. There are several new options to treat cancer patients with fungal infections. These include new antifungal agents, such as the mould-active triazoles (itraconazole, voriconazole, and posaconazole), the echino...
Source: Best Practice & Research. Clinical Haematology - December 1, 2008 Category: Hematology Authors: Anaissie EJ Tags: Best Pract Res Clin Haematol Source Type: journals

Advances in the clinical management of GVHD.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The principal cause of mortality and morbidity following hematopoietic cell transplantation (HCT) is graft-versus-host disease (GVHD). Studies in murine models have revealed that inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) promote destruction of host tissue following HCT. Elevated plasma levels of soluble TNF receptor 1 have been associated with patients with GVHD and blocking TNF-alpha in experimental models has shown a reduced incidence of GVHD. Based on this finding, patients with new onset GVHD were treated with steroids plus the TNF-alpha inhibitor, etanercept, on a previously reported p...
Source: Best Practice & Research. Clinical Haematology - December 1, 2008 Category: Hematology Authors: Ferrara JL Tags: Best Pract Res Clin Haematol Source Type: journals

What is the impact of hematopoietic cell transplantation (HCT) for older adults with acute myeloid leukemia (AML)?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute myeloid leukemia (AML) patients over the age of 55 years are generally more difficult to treat than younger patients due to intrinsic drug resistance and diminished tolerance to treatment. The unfortunate result is that conventional chemotherapy is toxic and rarely curative. Recent studies suggest a better outcome for older AML patients treated with reduced-intensity conditioning (RIC) hematopoietic cell transplantation (HCT) than those treated with conventional chemotherapy. However, there are major limitations to RIC HCT. Some of these limitations may be able to be overcome, broadening the impact of allogeneic ...
Source: Best Practice & Research. Clinical Haematology - December 1, 2008 Category: Hematology Authors: Appelbaum FR Tags: Best Pract Res Clin Haematol Source Type: journals

What is the role of arsenic in newly diagnosed APL?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute promyelocytic leukemia (APL), a highly curable subtype of acute myeloid leukemia (AML) is characterized by the chromosomal translocation t(15;17) and, consequently, the presence of the PML-RARalpha fusion transcript. Most patients are treated with all-trans retinoic acid (ATRA), which targets the RAR-alpha moiety of the PML/RAR-alpha fusion transcript, and anthracycline-based chemotherapy. Arsenic trioxide (ATO) targets the PML moiety and has different mechanisms of action at different concentrations, and induces differentiation and apoptosis. Several clinical trials have tested the combination of ATRA and ATO wi...
Source: Best Practice & Research. Clinical Haematology - December 1, 2008 Category: Hematology Authors: Tallman MS Tags: Best Pract Res Clin Haematol Source Type: journals

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