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 plasma-derived products containing FXIII (fresh frozen plasma, cryoprecipitate, and plasma-derived FXIII concentrates), all of which contain both subunits. Despite the increased safety of plasma-derived products, concern remains regarding potential viral safety issues. This review describes the development, from concept to clinical use, of a recombinant FXIII molecule (containing subunit A only; rFXIII-A2) for congenital FXIII-A subunit deficiency. Unmet needs and ongoing challenges in congenital FXIII deficiency are also discussed. Despite the challenges in developing a product for a very rare bleeding disorder, the information gathered on efficacy, safety, and pharmacokinetics of FXIII replacement therapy represents the largest dataset on congenital FXIII-A subunit deficiency in the world. It also provides evidence for the safety and efficacy of monthly prophylaxis with 35 IU/kg of rFXIII-A2 in patients with FXIII-A subunit deficiency. The issues encountered and overcome, along with lessons learned, may be applied to and encourage the development of new recombinant products for other rare bleeding disorders.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Carcao M,Fukutake K,Inbal A,Kerlin B,Lassila R,Oldenburg J,Garly ML,Nugent Ddoi
10.1055/s-0036-1585076subject
Has Abstractpub_date
2017-02-01 00:00:00pages
59-68issue
1eissn
0094-6176issn
1098-9064journal_volume
43pub_type
杂志文章abstract::Natural inhibitors of coagulation, in other words, antithrombin (AT), the protein C system, and tissue factor pathway inhibitor (TFPI), play an important role in controlling the activation of coagulation during disseminated intravascular coagulation (DIC). Furthermore, they may not only influence coagulation but also ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2001-18871
更新日期:2001-12-01 00:00:00
abstract::Antithrombin activity should probably be determined in persons with early onset of recurrent thrombosis, especially if a family history is present. The initial screening test should be a heparin cofactor assay optimized to reduce the contribution of heparin cofactor II. If the heparin cofactor assay is low, an antigen...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1002664
更新日期:1990-04-01 00:00:00
abstract::Acute promyelocytic leukemia (APL), once highly fatal, has emerged as the most curable subtype of acute myeloid leukemia in adults. Cure is now expected in approximately 70 to 90% of patients when treatment includes all- TRANS retinoic acid (ATRA) combined with anthracycline-based chemotherapy. Early mortality most of...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-976168
更新日期:2007-06-01 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 article explores the application of viscoelastic tests (VETs) in trauma-induced coagulopathy and trauma resuscitation. We describe the advantages of VETs over conventional coagulation tests in the trauma setting and refer to previous disciplines in which VET use has reduced blood product utilization, guided prohe...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0040-1702171
更新日期:2020-03-01 00:00:00
abstract::Fibrin formed from fibrinogen is the main component of thrombi. Clot structure is characterized by fiber thickness and pore size, which differs within a given clot and between individuals. Plasma clot architecture is largely determined by the quantity and quality of fibrinogen. Plasma fibrinogen concentrations are mos...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1579636
更新日期:2016-06-01 00:00:00
abstract::A new in vitro system for the detection of platelet dysfunction, PFA-100, has been developed. It provides a quantitative measure of platelet function in anticoagulated whole blood. The system comprises a microprocessor-controlled instrument and a disposable test cartridge containing a biologically active membrane. The...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0032-1313612
更新日期:1995-01-01 00:00:00
abstract::Biological rhythms are a universal phenomenon in living organisms and serve to help organisms adapt within a circadian cycle to the 24-hour-oscillating environment. The rhythmic modulation of selective pathways thus enables organisms to optimize their ability to store and generate chemical energy, to minimize environm...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1214145
更新日期:2009-02-01 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::The articular problems of patients with hemophilia begin in infancy when minor injuries result in hemarthroses. Early continuous prophylaxis (from cradle to college) is of paramount importance because the immature skeleton is very sensitive to the complications of hemophilia; severe structural deficiencies may develop...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2005-922223
更新日期:2005-11-01 00:00:00
abstract::The increasing use of antiplatelet therapy, particularly aspirin and oral P2Y12 inhibitors, in the prevention and management of arterial thrombosis, has stimulated extensive pharmacodynamic studies and research into tailored antiplatelet regimens. Many different methodologies have been studied for monitoring antiplate...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1597298
更新日期:2017-04-01 00:00:00
abstract::A diagnosis of hemophilia A or hemophilia B begins with clinical assessment of the patient and is facilitated by laboratory testing. The influence of the latter on a diagnosis of hemophilia A or hemophilia B is clear-a diagnosis cannot be made without laboratory confirmation of a deficiency of factor FVIII (FVIII) or ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0033-1356573
更新日期:2013-10-01 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::Development of inhibitory antibodies (inhibitors) to factor VIII (FVIII) is the most serious adverse event in replacement therapy of hemophilia A patients. The etiology and management of this condition remain major challenges for both researchers and clinicians. In the present review, we discuss recent advances in und...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1245106
更新日期:2009-11-01 00:00:00
abstract::Near-infrared spectroscopy (NIRS) has been used as a noninvasive method for monitoring the real-time oxygenation status in areas such as the brain and striated muscle. Because the oxygenation status of the placenta is closely related to the fetal condition, monitoring placental oxygenation through the maternal abdomen...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2005-872435
更新日期:2005-06-01 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::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::A series of sulfated bis-lactobionic acid amides was prepared. The compounds comprise highly charged poly-anions of very low molecular weight. Usually, the compounds contain 16 sulfate groups per molecule and are homogeneous, monodisperse substances. The molecular weights range from 2388 to 2514. The compounds were ev...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::The pharmacokinetics of heparin differ markedly from those of its fractions both in man and in experimental animal models. The route of administration determines the relative availability of different molecular species that exert the anti-Xa, anti-IIa, fibrinopeptide A generation inhibiting actions and the release of ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1004360
更新日期:1985-01-01 00:00:00
abstract::Arterial and venous thromboses are sustained by development of intraluminal thrombi, respectively, within the venous and arterial systems. The composition and structure of arterial and venous thrombi have been historically considered as being very different. Arterial thrombi (conventionally defined as "white") have be...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1607202
更新日期:2018-04-01 00:00:00
abstract::The international classification of functioning (ICF) has provided a basic framework for the measurement of outcomes in any health condition. This includes the assessment of the level of activity, participation, and the quality of life of an individual with hemophilia. The measure of activity is an assessment of the i...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0035-1552564
更新日期:2015-11-01 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::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::Severe trauma is the leading cause of death globally. Though improved resuscitation, particularly early initiation, has reduced the 24-hour mortality rate, the overall morbidity and 30-day mortality remain high mostly due to massive hemorrhage and head injury in the early stages and sepsis and multiorgan failure later...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0039-3402428
更新日期:2020-03-01 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
abstract::For most cells the nucleus takes center stage. Not only is it the largest organelle in eukaryotic cells, it carries most of the genome and transcription of DNA to RNA largely takes place in the nucleus. Because transcription is a major step in gene regulation, the absence of a nucleus is limiting from a biosynthetic s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2004-833484
更新日期:2004-08-01 00:00:00
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; s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2003-37935
更新日期:2003-02-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to evaluate the genetic variability of selected single nucleotide polymorphisms (SNPs) within GAS6 and PEAR1 genes and explore the association between selected SNPs and risk for fetal loss in women with sticky platelet syndrome (SPS). MATERIALS AND METHODS:We examined 23 female p...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0034-1395351
更新日期:2015-04-01 00:00:00
abstract::Molecular linkages between von Willebrand factor (VWF) and the alternative complement pathway (AP) have recently been discovered. Endothelial cell (EC)-anchored ultra-large (UL) VWF multimeric strings function as an activating surface for the AP. C3 (in active C3b form) binds to the EC-anchored ULVWF strings, and prom...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0034-1383547
更新日期:2014-07-01 00:00:00
abstract:UNLABELLED:We present 25-year experience with inhibitors in previously untreated patients (PUPs) with severe hemophilia A in Slovakia, where safe factor VIII (FVIII) concentrates have been used since 1990. A prospective study focused on inhibitor incidence in PUPs was established in 1997. Out of a total 61 PUPs born be...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-0036-1581107
更新日期:2016-07-01 00:00:00