Abstract:
:Therapies engineered to prolong clotting factor protein circulation time, manipulate the balance of pro-coagulant and anti-coagulant proteins, or introduce new genetic material to enable endogenous factor protein production dominate the clinical trial landscape of hemophilia. The availability of clotting factor concentrates and the establishment of primary prophylaxis have dramatically improved health outcomes for hemophilia patients. But, the burden of hemostatic therapy remains significant, and many barriers to consistent longitudinal use of prophylaxis exist. Several types of emerging therapeutics including engineered factor concentrates, substitutive therapies, rebalancing therapies, and gene transfer/editing all aim to reduce the challenges of current hemophilia treatment. Emerging treatment options may reduce treatment frequency or need for intravenous administration. They may also introduce new challenges in laboratory assessment of hemostasis. These novel therapies must not introduce significant new health risks and continue to support similar or improved outcomes. The potential ramifications of rebalancing the coagulation cascade, particularly in a stress or inflammatory state, or introduction of new genetic material are not trivial. The focus of this review is to provide an overview of active and recently completed clinical trials as well as emerging preclinical data investigating new therapeutic possibilities for hemophilia patients and potentially other rare bleeding disorders.
journal_name
Am J Hematoljournal_title
American journal of hematologyauthors
Croteau SE,Wang M,Wheeler APdoi
10.1002/ajh.26018subject
Has Abstractpub_date
2021-01-01 00:00:00pages
128-144issue
1eissn
0361-8609issn
1096-8652journal_volume
96pub_type
杂志文章,评审abstract::Platelet antibodies are detectable in only about 50% of patients with chronic autoimmune thrombocytopenia (AITP). We determined platelet antibodies against GPIa/IIa, GPIb/IX, GPIIb/IIIa, and GPV and reticulated platelets in three female patients with AITP, before and after immunoadsorption treatment. None of the three...
journal_title:American journal of hematology
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abstract::By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no informa...
journal_title:American journal of hematology
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更新日期:1998-10-01 00:00:00
abstract::Total body irradiation (TBI) has been thought to promote donor cell engraftment in allogeneic hematopoietic cell transplantation (HCT) from alternative donors. However, recent progress in HCT strategies may affect the clinical significance of TBI on neutrophil engraftment. With the use of a Japanese transplant registr...
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journal_title:American journal of hematology
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journal_title:American journal of hematology
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更新日期:1998-08-01 00:00:00
abstract::Mast cell disease (MCD), a proliferation of mast cells (MC), is occasionally associated with hematologic malignancies. Neoplastic MC have activating c-kit mutations. c-kit is a receptor tyrosine kinase required for the development, proliferation, and survival of MC. Interaction of c-kit with its ligand stem cell facto...
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journal_title:American journal of hematology
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pub_type: 杂志文章,多中心研究
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journal_title:American journal of hematology
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doi:10.1002/ajh.2830050307
更新日期:1978-01-01 00:00:00
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journal_title:American journal of hematology
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更新日期:2015-01-01 00:00:00
abstract::Immune thrombocytopenia is frequently encountered in medical practice and is generally accepted as being caused by an IgG antibody. The capability of detecting platelet-bound IgG as a diagnostic and therapeutic modality is critical for appropriate care and management of patients with idiopathic thrombocytopenic purpur...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830090402
更新日期:1980-01-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:2016-03-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830070205
更新日期:1979-01-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830210110
更新日期:1986-01-01 00:00:00
abstract::Defective fibrinolysis due to decreased tissue-type plasminogen activator (t-PA) activity is a well-established finding in patients with systemic lupus erythematosus (SLE). The possibility that this decrease in t-PA activity may be related to the presence of autoantibodies directed against t-PA, and the possible role ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830490203
更新日期:1995-06-01 00:00:00
abstract::A 75-year-old female patient with agranulocytosis caused by ticlopidine is reported. She took the drug at 200 mg/day for 30 days to prevent recurrence of cerebral infarction. The leukocyte count at the nadir was 500/microliters on the 34th day since she started to take the drug. Complete recovery of her peripheral leu...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830370405
更新日期:1991-08-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is considered to be a pleuripotential stem cell disorder with the capacity to differentiate into myeloid, erythroid, megakaryocytic, and lymphoid cell lines. Consequently, blast crisis (BC) involving each of the above lineages has been well described. Among lymphoblastic crises, differen...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830360204
更新日期:1991-02-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830020210
更新日期:1977-01-01 00:00:00
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2015-05-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章,多中心研究
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journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830410305
更新日期:1992-11-01 00:00:00
abstract::The effect of short-chain aliphatic acids on [3H]deoxythymidine incorporation into DNA was studied in human mitogen-stimulated lymphocytes. Butyric acid at 1-2 mM level was strongly inhibitory; however, its hydroxy or amino derivatives were ineffective. Valeric and propionic acids were less inhibitory. Formic, acetic,...
journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:1982-09-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:1983-08-01 00:00:00
abstract::In this study, we analyzed a thiotepa-based conditioning regimen for allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia, using the EBMT database. A total of 323 patients were identified. The median age was 43 years. Disease status at transplant was first complete remission (CR1) in 48.9%,...
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2017-01-01 00:00:00
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journal_title:American journal of hematology
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abstract::Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was moni...
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更新日期:2012-02-01 00:00:00
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abstract::Idiopathic thrombocytopenic purpura is an autoimmune disease which involves opsonization of platelets by autoantibodies directed against different surface glycoproteins, leading to their premature destruction by the reticuloendothelial system. Management of patients with refractory ITP is difficult. Recent studies hav...
journal_title:American journal of hematology
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更新日期:2005-04-01 00:00:00
abstract::In light of the relationship between immune system dysregulation and multiple myeloma (MM) risk, we investigated whether genetic variation in 92 immune function genes among 77 gene regions are associated with MM susceptibility in a population-based case-control study (108 cases and 482 controls) conducted among Caucas...
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更新日期:2010-08-01 00:00:00