Abstract：
:Hemophilia A (HA) and hemophilia B (HB) are rare congenital severe bleeding disorders, that may be controlled by proper administration of adequate prophylaxis with factor VIII (FVIII), and factor IX (FIX) concentrates, respectively, to prevent joint damage due to recurrent bleeding. However, approximately 30% of patients develop inhibitory antibodies that render factor replacement therapy ineffective. Due to the high variability of patients' bleeding tendency, there is a need to "individually tailor treatment" for this unique group of patients. While replacement therapy with FVIII or FIX can be used for treating HA or HB patients with low responding inhibitors, hemophilia patients with high-responding inhibitors are treated with bypassing agents. Unfortunately, the Bethesda assay applied for inhibitor measurement in most laboratories does not fully predict either bleeding tendency or therapy response. Immune tolerance induction (ITI) may eradicate most inhibitors, yet treatment is challenging during bleeding episodes. The role of bypassing agents and their various treatment strategies still deserves attention. Recently, new nonreplacement therapies have emerged for patients with hemophilia including patients with inhibitors. Adequate monitoring of bypassing therapy and of the new nonreplacement therapies in inhibitor patients is extremely challenging, thus global hemostatic assays are increasingly used to assess clot formation. This review aims to summarize the current treatment and monitoring challenges for inhibitor patients; in this perspective, we will discuss our institutional approach for optimal decision-making and individual therapy tailoring.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Barg AA,Livnat T,Kenet Gdoi
10.1055/s-0037-1612626subject
Has Abstractpub_date
2018-09-01 00:00:00pages
544-550issue
6eissn
0094-6176issn
1098-9064journal_volume
44pub_type
杂志文章,评审abstract：:Thromboembolic complications are leading causes of both maternal and fetal morbidity and mortality. To reduce the incidence of venous thromboembolism (VTE) in pregnancy and improve outcomes, a wider understanding of the risk factors involved and better identification of women at risk of thrombosis are required. Optima...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2002-34072
更新日期：2002-08-01 00:00:00
abstract：:Site-directed thrombin inhibitors are being currently assessed clinically for their antithrombotic efficacy. Although these agents are claimed to be specific and direct thrombin inhibitors, their mechanism of inhibition varies. The objective of these studies was to compare four such agents in in vitro systems and to a...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-2007-1000393
更新日期：1995-01-01 00:00:00
abstract：:The average age of the US population continues to increase. Age is the most important determinant of disease and disability in humans, but the fundamental mechanisms of aging remain largely unknown. Many age-related diseases are associated with an impaired fibrinolytic system. Elevated plasminogen activator inhibitor-...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0034-1387883
更新日期：2014-09-01 00:00:00
abstract：:The management of childhood acute idiopathic thrombocytopenic purpura is controversial, with recent guidelines highlighting the lack of suitable evidence upon which to base management decisions. Three European centers have used an expectant policy and results over the past decade demonstrate that this is safe and conv...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2001-15256
更新日期：2001-06-01 00:00:00
abstract：:Prophylactic treatment from ages 2 to 18 years could prevent the development of hemophilic arthropathy if the concentration of the patient's deficient factor is kept from falling below 1% of normal. Early treatment is of paramount importance because the immature skeleton is very sensitive to the complications of hemop...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2003-37942
更新日期：2003-02-01 00:00:00
abstract：:Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing ...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-0036-1585076
更新日期：2017-02-01 00:00:00
abstract：:Platelet-type von Willebrand disease (PT-VWD) and type 2B von Willebrand disease (2B-VWD) are rare bleeding disorders characterized by increased ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin. Diagnosis of either condition is not easy and the differential diagnosis between the two e...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-0033-1364183
更新日期：2014-03-01 00:00:00
abstract：:Analogues of L-arginine that are chemically modified at the terminal guanidino nitrogen group, such as Nomega-monomethy-L-arginine (L-NMMA), have been used for nitric oxide synthase inhibition. However, L-NMMA and other methylated L-arginine analogues are also endogenously formed. Among these, asymmetric dimethylargin...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2000-13210
更新日期：2000-01-01 00:00:00
abstract：:Morbidity and mortality for cardiovascular disease are likely to be lower in patients with hemophilia than in the general male population. However, their clinical impact is increasing in parallel with the increase of life expectancy due to modern safe replacement treatments and the improvement of comprehensive care of...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0030-1248728
更新日期：2010-02-01 00:00:00
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journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1722307
更新日期：2021-01-22 00:00:00
abstract：:The polymorphism in the composition and actions of heparin and the parallel complexity of the thrombotic process have led to the design of a cautious, methodical, and pragmatic program of development of the first low molecular heparin fraction presently available in France (CY 216). The main idea was always to present...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 临床试验,历史文章,杂志文章,随机对照试验
doi：10.1055/s-2007-1002737
更新日期：1989-10-01 00:00:00
abstract：:Heparanase is an endo-β-glucuronidase that enzymatically cleaves heparan sulfates (HS) and heparan sulfate proteoglycan (HSPG) structures. Heparanase expression levels by tumors were correlated with cell invasion, angiogenic activity, and poor prognosis. Heparanase can also possess pro-tumorigenic effects independent ...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-0035-1544229
更新日期：2015-03-01 00:00:00
abstract：:Patients with unprovoked venous thromboembolism (VTE) may harbor occult cancer. Whether an extensive diagnostic work-up for cancer has additional value over a more limited screening for detection of underlying malignancy in these patients is controversial. We performed a randomized multicenter trial to assess if in pa...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1055/s-0036-1592335
更新日期：2016-11-01 00:00:00
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journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-0028-1104538
更新日期：2008-10-01 00:00:00
abstract：:Three commercial prothrombin complex concentrates (PCC) were compared in vitro. Differences in the activities or contents, respectively, of the PCC factors FII, FVII, FIX, FX and the proteins C, S, and Z (antigen) in particular were found. Global tests of activated factors did not reveal marked differences between the...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-2007-995838
更新日期：1998-01-01 00:00:00
abstract：:Thrombocytosis is frequently (10 to 57%) observed in cancer patients. Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity, growth factors, platelet-derived microparticles, and factors released from bone marrow endothelial cells as well...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2007-991540
更新日期：2007-10-01 00:00:00
abstract：:Thrombophilia includes multiple inherited and acquired risk factors that determine a shift in the balance of procoagulant and anticoagulant factors promoting hypercoagulability, which is associated with an increased risk of venous thromboembolism (VTE). VTE is characterized by more common clinical manifestations, such...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2007-985754
更新日期：2007-09-01 00:00:00
abstract：:Immune thrombocytopenic purpura (ITP) is a bleeding disorder and is traditionally divided in acute and chronic forms based on the duration of the disease. Chronic ITP is characterized by a persistence of thrombocytopenia for more than 6 months. Ten to 20% of children with ITP and almost all adults will develop the chr...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2007-996054
更新日期：1998-01-01 00:00:00
abstract：:Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 ...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-0039-3402430
更新日期：2020-06-01 00:00:00
abstract：:The present study revises the criteria of the Polycythemia Vera Group (PVSG) for the diagnoses of essential thrombocythemia (ET) and polycythemia vera (PV) in view of accumulating data on in vitro cultures of hematopoietic progenitors and by adding histopathology from bone marrow biopsies. The majority of ET patients ...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 指南,杂志文章,实务指引
doi：10.1055/s-2007-996107
更新日期：1997-01-01 00:00:00
abstract：:Systolic heart failure is a common syndrome whose incidence is expected to increase. Several treatment modalities, such as beta-blockers and angiotensin-converting enzyme inhibitors, improve survival. Whether antithrombotic treatment is effective remains to be elucidated, although observations suggest a prothrombotic ...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0029-1234145
更新日期：2009-07-01 00:00:00
abstract：:Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0037-1598062
更新日期：2017-06-01 00:00:00
abstract：:Numerous studies have shown that early radiation injury is characterized by vascular damage and that the initial site of damage appears to be the EC lining of the vessel wall. Chronic irreversible tissue reactions to radiation include thrombotic occlusion of capillaries, enhanced atherosclerosis in larger vessels, inf...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-2007-1002708
更新日期：1989-04-01 00:00:00
abstract：:A prospective management decision analysis for the exclusion and diagnosis of pulmonary embolism (PE) based on pre-test clinical probability (PCP) estimation for PE, a rapid ELISA D-dimer test, perfusion lungscan (P-scan), CUS, spiral CT, and pulmonary angiography is proposed. The modified PCP model for PE of Wells et...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2007-996031
更新日期：1998-01-01 00:00:00
abstract：:There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefectur...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,多中心研究
doi：10.1055/s-2006-955468
更新日期：2006-11-01 00:00:00
abstract：:The three-dimensional structures of several forms of the factor XIII A subunit have been determined using single crystal x-ray diffraction methods. Our crystallographic studies have provided the first detailed structural view of the factor XIII A subunit and information that is useful for understanding transglutaminas...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章
doi：10.1055/s-2007-999035
更新日期：1996-01-01 00:00:00
abstract：:Platelets possess three P2 receptors: two (P2Y (1) and P2Y (12)) are receptors for adenosine diphosphate (ADP), and one (P2X1) is a receptor for adenosine triphosphate (ATP). The P2Y (1) receptor, which is coupled to Gq and phospholipase C-beta, is responsible for mobilization of ionized calcium from internal stores a...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2005-869522
更新日期：2005-04-01 00:00:00
abstract：:The increase of circulating tissue factor pathway inhibitor (TFPI) in plasma by heparins is thought to contribute to their overall antithrombotic activity. In a clinical study in healthy volunteers, we recently found that the specific potency of a heparin to mobilize TFPI from the vessel wall increases with its molecu...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1055/s-2001-17952
更新日期：2001-10-01 00:00:00
abstract：:Thrombotic events are very frequent and represent the main cause of morbidity and mortality in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), mainly polycythemia vera and essential thrombocythemia. Pathogenesis of blood clotting activation in these diseases is multifactorial, and i...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0034-1370794
更新日期：2014-04-01 00:00:00
abstract：:In addition to the criteria of the Polycythemia Vera Study Group, positive markers for essential thrombocythemia (ET) include spontaneous BFU-E, splenomegaly, and megakaryocyte morphology in bone marrow smears and biopsy material. The hematologic features of 11 reported cases of ET in childhood showed platelet counts ...
journal_title：Seminars in thrombosis and hemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-2007-996102
更新日期：1997-01-01 00:00:00
