Abstract:
:The inhibitor titer is the most important clinical measurement in inhibitor patients, and the Nijmegen method is preferable to the original and well-established Bethesda assay for this purpose; however, both methods have high inter-laboratory variability. Monitoring inhibitor patients after treatment with bypassing agents is difficult. Treatment with recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) can be monitored with assays for FVII clotting activity or with a specific assay for FVIIa; while the latter is more reproducible, its relevance to the clinical response of individual patients remains unclear. Recent years have also witnessed a revival of global assays, which contribute useful additional information and which may be more relevant to the hemostatic state of individual inhibitor patients. One such assay currently undergoing a renaissance is the thrombin generation test (TGT). The TGT has many methodological variations--several of which have been studied in our laboratory--and shows the most promise for use in treatment monitoring. This article reviews the assays most appropriate for monitoring inhibitor patients and discusses some of the most recent developments in the use of global assays in this indication.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Barrowcliffe TWdoi
10.1053/j.seminhematol.2008.03.002subject
Has Abstractpub_date
2008-04-01 00:00:00pages
S25-30issue
2 Suppl 1eissn
0037-1963issn
1532-8686pii
S0037-1963(08)00042-5journal_volume
45pub_type
杂志文章,评审abstract::Even though the overall outcome after allogeneic transplant has improved significantly in the last decades, late infectious diseases are still the most important causes of late morbidity and mortality. Here, impaired immune reconstitution and therapy of chronic graft-versus-host disease (GVHD) represent the major risk...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2011.10.009
更新日期:2012-01-01 00:00:00
abstract::The use of combination chemotherapy has been successful in treating advanced or widespread Hodgkin's disease (HD). For patients with relapsed disease, the long-term prognosis is much poorer, despite the good rate of reinduction into a second or further remission using conventional treatments. The majority of such pati...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-07-01 00:00:00
abstract::Though peripheral T-cell lymphoma (PTCL) is an area of significant unmet therapeutic need, a number of new treatment options are available for patients, especially those with relapsed or refractory disease. A plethora of drugs are now in development for PTCL, but drugs that truly target novel disease biology are notic...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2010.01.014
更新日期:2010-04-01 00:00:00
abstract::Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhan...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-04-01 00:00:00
abstract::Both thalidomide and intermittent high-dose dexamethasone are agents with established activity against multiple myeloma. We summarized our experience with thalidomide alone, and then in combination with dexamethasone, for groups of patients with myeloma resistant or relapsing despite standard treatments. Criteria of r...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2003.09.006
更新日期:2003-10-01 00:00:00
abstract::Tumor cells from patients with B-cell malignancies exhibit a number of immunophenotypic characteristics that may be responsible for their survival. It has been shown, for example, that down-modulation of CD154 (CD40 ligand), which allows B cells to respond to T cells, may account for some of the immune defects of thes...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::Gene expression profiling of cancer began as a research tool but is rapidly moving towards clinical application. The diagnostic category of diffuse large B-cell lymphoma (DLBCL) can now be viewed as an amalgam of several different diseases that have distinct gene expression profiles, oncogenic mechanisms, and clinical...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(03)00194-x
更新日期:2003-10-01 00:00:00
abstract::Serum vitamin B12 levels are often low in human immunodeficiency virus (HIV)-infected patients. However, only a few patients appear to have actual vitamin B12 deficiency. A low red cell folate level accompanying the low vitamin B12 level makes the presence of vitamin B12 deficiency more likely. Our experience suggests...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::Purine analogues have been shown to be active in a variety of B- and T-cell malignancies. Among them, pentostatin is also a tight binding inhibitor of adenosine deaminase (ADA), a key enzyme of purine metabolism. ADA is present in all human tissues, with the highest levels in the lymphoid system. Early clinical trials...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.12.005
更新日期:2006-04-01 00:00:00
abstract::Most of the major advances in thrombosis research have occurred in the last 50 years, reflecting progress in biomedical sciences and clinical trials methodology. Improved understanding of the mechanisms of thrombogenesis has led to the discovery of a plethora of new antithrombotic agents that target many of the key st...
journal_title:Seminars in hematology
pub_type: 历史文章,杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::The availability of antibodies reactive with antigens expressed only by hematopoietic cells has provided clinical investigators with new tools for use in developing therapies for acute myeloid leukemia (AML). Studies performed to date have investigated the use of such antibodies in an unmodified state, combined with p...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::The activation, function, and development of peripheral T lymphocytes are dependent on the ability to signal properly through the surface T-cell antigen receptor (TCR)-CD3 complex. Transmission of such signals requires the activation of specific cytoplasmic protein tyrosine kinases (PTK) associated with the TCR. Recen...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 00:00:00
abstract::Recombinant factor VIIa (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) has been used for many years in the successful management of bleeding episodes in patients with hemophilia and inhibitors. More recently, rFVIIa has also shown considerable success as a hemostatic agent in trauma and surgery patients with...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2003.11.019
更新日期:2004-01-01 00:00:00
abstract::The experiments reviewed here establish that surface components and surface functions can assume predictable, asymmetric patterns within the continuous plasma membranes of mammalian leukocytes. Recent biophysical and morphological studies show that receptor redistribution can occur very rapidly and that a unique geome...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1983-10-01 00:00:00
abstract::Mechanisms that support migration of leukocytes have been studied extensively in vitro. The adhesion of neutrophils under conditions of flow at venous shear rates primarily involves members of the selectin family. E-selectin is upregulated by cytokine stimulation of endothelial cells (ECs); P-selectin is upregulated b...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelet...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2017.04.006
更新日期:2017-04-01 00:00:00
abstract::Anemia of chronic disease (ACD) or inflammation may be secondary to infections, autoimmune disorders, chronic renal failure, or malignancies. It is characterized by an immune activation with an increase in inflammatory cytokines and resultant increase in hepcidin levels. In addition, inappropriate erythropoietin level...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2013.06.006
更新日期:2013-07-01 00:00:00
abstract::Traditionally, acute myeloid leukemia (AML) has been diagnosed and classified based on the morphologic and cytochemical criteria of the French-American-British (FAB) classification system. However, more recent studies have demonstrated that the cytogenetic and molecular genetic abnormalities consistently associated wi...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::Antibody-mediated rejection (AMR) is a major risk factor for graft loss following kidney transplantation. Traditional anti-humoral therapies provide suboptimal therapy and they do not deplete plasma cells, which are the source of antibody production. Proteasome inhibitors (PI) have been shown to deplete both transform...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2012.04.008
更新日期:2012-07-01 00:00:00
abstract::Immune thrombocytopenia (ITP) is a bleeding disorder characterized by low platelet counts due to decreased platelet production as well as increased platelet destruction by autoimmune mechanisms. A shift toward Th1 and possibly Th17 cells together with impaired regulatory compartment, including T-regulatory (Tregs) and...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2013.03.011
更新日期:2013-01-01 00:00:00
abstract::Current therapeutic strategies for autoimmune diseases primarily rely on immunosuppression, but global immune suppression results in an increased risk for severe infection and malignancy. In contrast, immuomodulation is another therapeutic approach employing intrinsic or environmental regulators that exert modulatory ...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1053/j.seminhematol.2016.04.009
更新日期:2016-04-01 00:00:00
abstract::Analysis of data from 806 patients with newly diagnosed adult acute myelocytic leukemia (AML) (not including acute promyelocytic leukemia [APL] patients) treated at M.D. Anderson Cancer Center from 1995 through 1999 indicated that among patients entering a particular week of induction therapy, mortality rates were 6%,...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1016/s0037-1963(01)90042-3
更新日期:2001-10-01 00:00:00
abstract::Stem cell transplantation is a recognized treatment for many hematologic malignancies. Human leukocyte antigen (HLA) testing is a key assessment in the evaluation of potential recipients and selection of the appropriate stem cell donor. Over the past several years, technological advances have moved HLA testing from a ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90052-6
更新日期:2001-04-01 00:00:00
abstract::Psoralens plus ultraviolet A (UVA) light inactivate viruses and bacteria as well as leukocytes. A system employing the synthetic psoralen compound amotosalen hydrochloride (S-59), in combination with UVA light, is being developed to decontaminate platelet concentrates and plasma in a blood-bank setting. S-59 is a hete...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90118-0
更新日期:2001-10-01 00:00:00
abstract::The prolonged and severe myelosuppression associated with high-dose chemotherapy and autologous bone marrow transplantation is a major causative factor in patient morbidity and mortality resulting from infection and other causes. The recent molecular cloning, in vitro expression, and formulation of recombinant human c...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for th...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.30909
更新日期:2002-01-01 00:00:00
abstract::Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which the patient's immune system reacts with a platelet autoantigen(s) resulting in thrombocytopenia due to immune-mediated platelet destruction and/or suppression of platelet production. Platelet membrane proteins, for reasons that are unclea...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2007.11.002
更新日期:2007-10-01 00:00:00
abstract::Since warfarin remains the predominate drug administered for long-term anticoagulation, optimizing therapy for maximum antithrombotic effect with minimal bleeding risk continues to challenge clinicians. Genetic differences exist that affect an individual's response to warfarin. The clinician can use genetic informatio...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.34089
更新日期:2002-07-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenia and by increased progression to acute myelocytic leukemia (AML). With the exception of allogeneic stem cell transplantation, there is generally no curative treatment for these d...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2004.02.002
更新日期:2004-04-01 00:00:00
abstract::The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide wer...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.10.004
更新日期:2005-10-01 00:00:00