Abstract：
:Bypassing inhibitors in haemophilia patients is limited to activated (a) Factor(F)VII products. We introduced "FVa activity augmentation" as another bypassing strategy and studied effects of an engineered FVa variant designated superFVa. Procoagulant and clot stabilising properties of superFVa and recombinant human (rh)FVIIa, either alone or in combination, were studied in thrombin generation and clot lysis assays in normal human plasma (NHP) with or without anti-FVIII inhibitors, in haemophilia plasma, and in FVIII-deficient mice or in wild-type mice with anti-FVIII inhibitors. SuperFVa was as effective as rhFVIIa to improve thrombin generation or clot lysis. Furthermore, procoagulant effects were significantly enhanced when these compounds were combined. RhFVIIa at 40 nM (a therapeutic concentration) improved thrombin generation mildly, but markedly improved thrombin generation when combined with a low concentration (e. g. 3 nM) of superFVa. In clot lysis studies, the concentration of rhFVIIa to normalise clot lysis times could be reduced by 100-fold (e. g. from 40 nM to 0.4 nM) when combined with a low concentration (0.37 nM) of superFVa. In haemostasis studies of FVIII-deficient mice, blood loss was dose-dependently reduced by either superFVa or rhFVIIa. SuperFVa (200 U/kg) corrected mean blood loss indistinguishably from rhFVIII. Blood loss correction by rhFVIIa was greatly improved when combined with superFVa. Similar blood loss correction results were observed for therapies in wild-type mice after infusion with anti-FVIII inhibitors. Thus, superFVa may be an effective procoagulant agent in the setting of haemophilia with inhibitors and it merits further evaluation for new bypassing strategies.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Bhat V,von Drygalski A,Gale AJ,Griffin JH,Mosnier LOdoi
10.1160/TH15-07-0525subject
Has Abstractpub_date
2016-03-01 00:00:00pages
551-61issue
3eissn
0340-6245issn
2567-689Xpii
15-07-0525journal_volume
115pub_type
杂志文章abstract：:This study assessed the abundance and activity of thrombin in human thrombi. removed at autopsy or during surgery. Arterial and venous thrombus sections showed thrombin activity by in situ zymography, based on conversion of fibrinogen to fibrin. Hirudin or antibodies to thrombin abolished the activity. Thrombin activi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained ...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1994-12-01 00:00:00
abstract：:The in vitro vitamin K-dependent carboxylation of peptide- or protein-bound glutamate residues is generally studied in detergent-solubilized microsomes from rat or cow liver. Under the conditions usually employed, the efficiency of the carboxylation reaction is low (less than 1% of the carboxylatable residues is conve...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-02-03 00:00:00
abstract：:Antithrombin (AT) is a native plasma protein that acts as the main inhibitor of enzymes generated by the coagulation cascade. In extreme thrombotic conditions, consumption of plasma AT can make treatment with AT-associated heparin therapies less effective. Supplementation with recombinant human AT (rhAT) has shown pro...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-01-0062
更新日期：2009-08-01 00:00:00
abstract：:A fully representative and viable platelet population was isolated from the blood of 15 baboons by a multiwash procedure, and labelled with In-111-oxine. The recovery of the total platelet population in the circulation was 85% +/- 9. Mean platelet life span was 146 hr +/- 13. Correcting for plasma radioactivity (alway...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-06-24 00:00:00
abstract：:The cellular phospholipid, lysophosphatidic acid (LPA), released by activated platelets and fibroblasts or, at high levels, from ovarian and cervical carcinomas is a powerful serum mitogen that may modulate several signaling pathways in endothelial cells (EC). Hence, LPA could function in a paracrine manner during EC-...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:CD36, also known as GPIIIb or GPIV, is a main protein of the platelet membrane. Accumulating evidence implicates CD36 in the pathogenesis of atherosclerosis. CD36 binds to cholesteryl-hemisuccinate coupled to agarose. This binding may be of physiologic relevance since CD36 has a long extracellular hydrophobic region a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:Activated protein C resistance (APCR) is a major risk factor for venous thromboembolism (VTE). Although the factor V (FV) Leiden mutation accounts for the vast majority of APCR cases, other polymorphisms may contribute to the APCR phenotype. Genetic components of APCR and thrombophilia were investigated by two dinucle...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-06-01 00:00:00
abstract：:Although it is recognized that glycoprotein (GP) IIb-IIIa complexes are deficient in platelets in Glanzmann's thrombasthenia, little is known of the origin of the defect. We have examined the megakaryocytes in a bone marrow aspirate obtained from a thrombasthenia patient during surgery. Analysis of platelet proteins b...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-08-20 00:00:00
abstract：:Platelet microparticles (PMPs) are small vesicles released from blood platelets upon activation. The procoagulant activity of PMPs has been previously mainly characterized by their ability to bind coagulation factors VIII and Va in reconstructed systems. It can be supposed that PMPs can contribute to the development o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-03-01 00:00:00
abstract：:A robust two-way analysis of variance technique was applied to determine simultaneously the effects of method and thromboplastin on prothrombin time. A new approach to outlier detection for two-way analysis of variance was used. Focusing on the underlying error structure improved the uniformity of the grading procedur...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-10-30 00:00:00
abstract：:Current thrombolytic strategies have a number of important shortcomings including resistance to recanalization and development of acute reocclusion. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by SR 46349, a novel 5-HT2 receptor antagonist, or clo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:We report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all exons in protein C gene in this family revealed two mutations. The first abnormality, derived from the mother, was a deletion of one of four consecutive G at nucleotide number 10758...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-10-18 00:00:00
abstract：BACKGROUND: A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrel...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/a-1326-5110
更新日期：2020-12-01 00:00:00
abstract：:The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0039-1679939
更新日期：2019-05-01 00:00:00
abstract：:Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-12-0904
更新日期：2017-10-05 00:00:00
abstract：:Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin family, as it spontaneously converts into a latent conformation. However, the exact mechanism of this conversion is not known. Previous studies reported that neutralizing monoclonal antibodies as well as reversal or removal of charges on the s3...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:The clearance of radiolabeled human fibrinogen fragments X and Y was studied in the mouse model. Fragment X cleared rapidly from the circulation with less than 10% of the ligand remaining in the circulation at 4 hr. The clearance of fragment Y was somewhat slower, but was identical to the rate of clearance of fragment...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1983-04-28 00:00:00
abstract：:Sequential treatment of arterial occlusions of the leg with porcine plasmin and low dose streptokinase results in a strong systemic proteolysis as already seen in deep leg vein thrombosis. In 31 of 45 patients the blood flow through major arterial segments could be restored. Thrombolytic success is possible within the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-10-29 00:00:00
abstract：:Lupus anticoagulants (LA) are immunoglobulins directed to either prothrombin or Beta-2-glycoprotein 1(beta1GPI) bound to phospholipids. Most patients with LA have both beta2GPI- and prothrombin-dependent antibodies. Several recent reports have shown that LA is more strongly associated with thrombosis than anticardioli...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：1999-06-01 00:00:00
abstract：:Noninvasive diagnosis of deep vein thrombosis (DVT) is based on ultrasound examination of the leg veins, usually restricted to only compression of the proximal veins (CUS). Patients with negative CUS findings require a second examination or a combination with other tests, which impairs clinical efficiency. In this pro...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-02-01 00:00:00
abstract：:We have devised an improved high pressure liquid chromatographic technique whereby serotonin, nucleosides, cyclic nucleotides, namely cAMP and cGMP, and 5'mono-, 5'di-, and 5'tri-nucleotides can be analyzed. The cyclic nucleotides have been measured in picomolar quantities. All nucleotides can be quantitated in a sing...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1977-12-15 00:00:00
abstract：:Severe factor XI (FXI) deficiency is a bleeding disorder generally inherited as an autosomal recessive trait and characterized by haemorrhagic symptoms mainly associated with injury or surgery. So far, more than 150 causative molecular defects have been identified throughout the F11 gene. In the present study, we inve...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH07-12-0723
更新日期：2008-03-01 00:00:00
abstract：:In eighteen patients with fulminant hepatic failure (FHF), in grade III or IV coma, both protein C antigen and activity were significantly decreased (0.35 +/- 0.03 u/ml and 0.35 +/- 0.03 u/ml respectively). There was a significant correlation between protein C antigen and activity (r = 0.61, p less than 0.01). Protein...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-04-08 00:00:00
abstract：:In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain.We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH14-04-0305
更新日期：2015-03-01 00:00:00
abstract：:Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Warfarin induction is accomplished by titrating dosage to coagulation test results. Algorithms can guide this process but not identify the starting dose. We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction. In a randomized trial we compared a fix...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：2003-02-01 00:00:00
abstract：BACKGROUND: There have been no prior nationwide reports on the prevalence of hypertrophic cardiomyopathy (HCM) among patients suffering from atrial fibrillation (AF). It is also unclear how much stroke risk is attributable to HCM compared with other stroke risks in patients with AF. This study assessed the prevalence o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1676818
更新日期：2019-02-01 00:00:00
abstract：:Lenalidomide, a derivate of thalidomide, has recently been approved in Europe for the treatment of patients with multiple myeloma. Although the substance has a better effect/side-effect profile, especially with regard to teratogenicity and neurotoxicity, the rate of therapy-induced thrombosis seems comparable to thali...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH08-01-0009
更新日期：2008-06-01 00:00:00
