Abstract:
:Factor (F) VIII is a large gene located near the terminus of the long arm of the X chromosome. It contains 26 exons that code for a signal peptide and a 2332 amino acid polypeptide with three different types of domains, namely A1-A2-B-A3-C1-C2. The A domains are homologous with each other and those of ceruloplasmin; substitution into the known crystal structure of the copper binding protein produces molecular models. The large, central B domain is highly glycosylated but has a variable sequence, even among FVIIIs from different species. Most of B can be deleted and the resulting recombinant protein has essentially normal survival in circulation and corrects the bleeding tendency in hemophilia A patients. The C domains are similar to each other, and the crystal structure of a recombinant human C2 domain is known, allowing construction of a molecular model of C1. The FVIII protein is secreted as a heterodimer following at least two intracellular cleavages within the B domain. In circulation it is stabilized by binding to von Willebrand factor (vWF) with a plasma half-life of about 10 hours. After specific thrombin cleavages that remove the remainder of the B domain and one of the high-affinity von Willebrand factor binding sites, FVIII becomes heterotrimeric FVIIIa, capable of enhancing intrinsic FX activation by FIXa. Inactivation of FVIIIa occurs by A2 dissociation or by specific cleavages within A1 and A2 by activated protein C. Control of intrinsic FX activation is critical for hemostasis and thrombosis.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Thompson ARdoi
10.1055/s-2003-37935subject
Has Abstractpub_date
2003-02-01 00:00:00pages
11-22issue
1eissn
0094-6176issn
1098-9064journal_volume
29pub_type
杂志文章,评审abstract::We investigated the protective effects of DX-9065a, an orally active, newly synthesized, and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a 4 hour sustained infusion of thromboplastin at a dose of 2.5 mg/kg. The rats were or...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-999016
更新日期:1996-01-01 00:00:00
abstract::Non-Shiga toxin-associated hemolytic uremic syndrome (atypical HUS) is a rare form of thrombotic microangiopathy that associates hemolytic anemia, thrombocytopenia, and acute renal failure. The disease has been demonstrated to be linked with a complement alternative pathway dysregulation due to genetic defects but als...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1262885
更新日期:2010-09-01 00:00:00
abstract::Patients undergoing surgery for malignancy are at increased risk of initial and recurrent venous thromboembolism (VTE). Several factors have been found to increase the risk of deep vein thrombosis (DVT) in cancer patients both during the first days after the operation and after discharge from hospital. Although, in ge...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2002-36701
更新日期:2002-12-01 00:00:00
abstract::Essential thrombocythemia (ET) is a clonal myeloproliferative disorder of unknown origin primarily involving the megakaryocyte/platelet lineage. In an attempt to evaluate the role of the receptor c-mpl and its ligand thrombopoietin (TPO) in ET, various studies have been undertaken, the results of which are discussed h...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-996118
更新日期:1997-01-01 00:00:00
abstract::The age of the thrombus is probably a very important determinant of the outcome of thrombolysis. The clinical potential for rapidly dissolving thrombi by thrombolytic therapy is considerable because restoration of the blood flow can rescue the jeopardized district served by the occluded vessel such as for myocardial i...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1002747
更新日期:1989-10-01 00:00:00
abstract::Vatreptacog alfa is a genetically engineered variant of recombinant factor VIIa (rFVIIa) containing three amino acid changes. Aspartic acid, valine, and glutamine residues replace valine, glutamic acid, and methionine at positions 158, 296, and 298, respectively. These substitutions result in considerable enhancement ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0032-1302442
更新日期:2012-04-01 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::The role of erythrocytes in thrombus formation has previously been regarded as passive by their influence on rheology. Erythrocytes are known, due to their abundance and size, to push platelets to the vascular wall (laminar shearing). This results in an increased platelet delivery at the vascular wall enabling platele...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0033-1363470
更新日期:2014-02-01 00:00:00
abstract::Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate amo...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2005-863810
更新日期:2005-02-01 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
abstract::Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in thi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1666823
更新日期:2018-09-01 00:00:00
abstract::Quiescent pulmonary endothelium establishes an antithrombotic, anti-inflammatory surface that promotes blood flow. However, the endothelium rapidly responds to injury and inflammation by promoting thrombosis and enabling the directed transmigration of inflammatory cells, such as neutrophils, into the alveolar airspace...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1253452
更新日期:2010-04-01 00:00:00
abstract::The purpose of this article is to review the use of blood products and hemostatic agents in the management of coagulopathy at the time of postpartum hemorrhage. Blood product administration strategies are broadly reviewed, including the role of the blood bank, the role of massive transfusion protocols, the role of lab...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1593417
更新日期:2016-10-01 00:00:00
abstract::We present three clinical cases that illustrate some of the key features of the diagnosis and management of immune-mediated heparin-induced thrombocytopenia (HIT). The importance of having a high clinical suspicion for HIT in the appropriate clinical setting is emphasized. Early therapeutic decisions should be based o...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2004-831040
更新日期:2004-06-01 00:00:00
abstract::While lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2 glycoprotein I (anti-β2GPI) antibodies represent the best available and the most widely used tests in the investigation for antiphospholipid syndrome (APS), evidence gathered in recent years indicates that other antiphospholipid antibodies (aPL)...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1601328
更新日期:2018-07-01 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::The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to the activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemo...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::External Quality Control of Diagnostic Assays and Tests (ECAT) surveys on thrombin generation rests (TGTs) have identified that various tests show a more than 30-fold difference in time to peak (TTP). The survey included pooled normal plasmas, microparticle (MP)-depleted plasmas, and factor (F)XII-deficient patient pl...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1265296
更新日期:2010-10-01 00:00:00
abstract::In this article, three cases, with antithrombin (AT) abnormality "Toyama" (type IIb), AT abnormality "Aomori" (type IIa), and congenital AT deficiency (type I) with pregnancy and delivery managed with administration of both AT concentrates and low-molecular-weight heparin, are described. Additionally, a case of AT-pro...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-996136
更新日期:1997-01-01 00:00:00
abstract::von Willebrand disease (VWD) was first described nearly a century ago in 1924 by Erik Adolf von Willebrand. Diagnostic testing at the time was very limited and it was not until the mid to late 1900s that more tests became available to assist with the diagnosis and classification of VWD. Two of these tests are based on...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0036-1592164
更新日期:2017-02-01 00:00:00
abstract::Most acute coronary syndromes result from a platelet-rich occlusion of the coronary arteries. Antiplatelet drugs are of proven efficacy in preventing myocardial infarction, unstable angina, and stroke. However, not all patients on aspirin (ASA) benefit. We studied the phenomenon of aspirin resistance with a simple and...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2005-916677
更新日期:2005-01-01 00:00:00
abstract::Neutrophils have long been known as innate immune cells that phagocytose and kill pathogens and mount inflammatory responses protecting the host from infection. In the past decades, new aspects of neutrophils have emerged unmasking their importance not only in inflammation but also in many pathological conditions incl...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0034-1370765
更新日期:2014-04-01 00:00:00
abstract::Clinicians prescribing new oral anticoagulants (OACs; dabigatran, rivaroxaban, and apixaban) should be aware of the exclusion criteria related to bleeding risks defined in published clinical studies. At least a quarter of patients currently using warfarin have an exclusion criterion that may prevent easy transition to...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0031-1300948
更新日期:2012-02-01 00:00:00
abstract::Treatment of patients with inhibitors to FVIII remains a complex clinical problem. Although characterizing the individual patient may aid in the initial development of a care plan, no treatment is uniformly reliable for all patients. Experts in the field are as likely to disagree as agree when it comes to choosing tre...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-994002
更新日期:1993-01-01 00:00:00
abstract::This epilogue represents a final summary of the issues discussed and highlighted at the International Summit on Differentiation of Low Molecular Weight Heparins (LMWHs). International scientists and physicians presented and discussed the physicochemical differences between LMWHs, and concluded that different productio...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::This report describes the first two Japanese cases of AIDS developed in patients with hemophilia. One was a 48-year-old man with hemophilia B and the other was a 62-year-old patient with hemophilia A. They had nonspecific prodromal syndromes of AIDS initially, and later developed fatal opportunistic infections with Ca...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1004393
更新日期:1985-10-01 00:00:00
abstract::The key reason behind the success of heparin in thrombosis and beyond is its polypharmacological sites of action for the prevention and treatment of multifactorial diseases that will only benefit slightly with single pharmacological mechanism-based agents. Thromboembolic disorders are driven by hypercoagulable, hypera...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-982084
更新日期:2007-07-01 00:00:00
abstract::The selection of treatment for patients with polycythemia vera (PV) still is the subject of much discussion among hematologists. It is emphasized that important physiologic and pathogenic components of the illness relate not only to the erythroid cell, but also to the megakaryocyte. Both play essential roles in causin...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-942765
更新日期:2006-06-01 00:00:00
abstract::The increased prevalence of the laboratory diagnosis of von Willebrand disease (vWD) in women presenting with menorrhagia has raised concerns regarding certain specifics in vWD testing in women, including when vWD testing should be done in relation to menses and whether testing should be done while the patient is not ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-947861
更新日期:2006-07-01 00:00:00
abstract::In the pathogenesis of vascular disease, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Tissue factor (T...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-933338
更新日期:2006-02-01 00:00:00