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 assess their relative anticoagulant efficacy. The four agents utilized in these studies were argatroban, Efegatran, hirulog, and hirudin. While hirulog and hirudin are specific irreversible inhibitors of thrombin, argatroban and Efegatran are reversible. All four agents were found to have a concentration-dependent anticoagulant effect when supplemented into normal human plasma, as assessed in the global clotting tests (PT, APTT, and Heptest). The most potent anticoagulant on a molar basis was hirudin in all three tests. The other three agents had similar anticoagulant actions. All four agents were also capable of inhibiting the generation of thrombin and factor Xa as determined by an amidolytic method after intrinsic or extrinsic activation of fibrinogen-deficient human plasma. Except for hirulog, all agents inhibited the extrinsic generation of thrombin, with hirudin being the most potent agent. The intrinsic generation of thrombin was blocked by the reversible thrombin inhibitors (argatroban and Efegatran) but not by the irreversible inhibitors (hirulog and hirudin). While all agents were capable of inhibiting the intrinsic generation of factor Xa at very low concentrations, only Efegatran was capable of blocking the extrinsic generation of the same factor.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Callas DD,Hoppensteadt D,Fareed Jdoi
10.1055/s-2007-1000393subject
Has Abstractpub_date
1995-01-01 00:00:00pages
177-83issue
2eissn
0094-6176issn
1098-9064journal_volume
21pub_type
杂志文章abstract::Thrombotic microangiopathy (TMA) after hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation is a serious complication that may be associated with diverse clinical conditions. The reported incidence varies widely, in part due to different diagnostic criteria. Currently, the diagnosis is based m...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2005-925475
更新日期:2005-12-01 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::Most patients with atrial fibrillation need anticoagulant treatment with vitamin K antagonists for prevention of thromboembolism, in particular ischemic stroke. Many studies show the efficacy of this treatment but also that it is difficult to keep patients who use vitamin K antagonists in the proper treatment range. B...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1240016
更新日期:2009-09-01 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::Currently, in Germany, there is a successful program where patients monitor their own coagulation status through self-testing. The advent of a new generation of coagulometers has allowed more and more patients to use self-testing to monitor their coagulation status. The development of a structured training program by ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-996423
更新日期:1999-01-01 00:00:00
abstract::Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to widespread deposition of fibrin in the circulation. There is ample experimental and pathological evidence that the fibrin deposition contributes to multiple organ failure. The massive...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2001-18862
更新日期:2001-12-01 00:00:00
abstract::Self-control and self-management of oral anticoagulant therapy have become more and more attractive for patients undergoing long-term treatment. In our training center, we examined 50 patients who took part in a standardized training course for self-management. Patients (36 men, 14 women) were preselected according to...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-996433
更新日期:1999-01-01 00:00:00
abstract::Coagulation management requires the balancing of different components that contribute to clot formation. These components include the interactions between platelets, procoagulant, anticoagulant, and fibrinolytic factors. The cause of bleeding or thrombotic events is often multifactorial; however, the tests clinicians ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1265286
更新日期:2010-10-01 00:00:00
abstract::The extrinsic pathway is probably the predominant pathway in initiating blood coagulation in inflammatory lung diseases. Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor of factor VIIa/tissue factor in the presence of factor Xa. As it has been shown recently that TFPI plasma levels are increa...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-996069
更新日期:1997-01-01 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:: ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 社论,历史文章
doi:10.1055/s-0038-1677460
更新日期:2019-02-01 00:00:00
abstract::Platelet aggregometry has been the reference method employed to detect, diagnose, and monitor qualitative platelet disorders since the early 1960s. Lumiaggregometry and impedance-based whole blood lumiaggregometry have advantages over light transmittance aggregometry in that they provide for enhanced specimen manageme...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1220325
更新日期:2009-03-01 00:00:00
abstract::The liver is the main site of synthesis and/or clearance of proteins involved in fibrinolysis. Therefore, chronic liver disease, including cirrhosis, leads to altered plasma levels of fibrinolytic proteins. Historical studies using in vitro clot lysis assays suggested that patients with chronic liver disease had accel...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0035-1550437
更新日期:2015-07-01 00:00:00
abstract::Thrombotic events are uncommon disorders in childhood but increasingly recognized due to the progress made in the understanding of the hemostasis system and the importance of thromboembolic disorders in children. Multiple clinical underlying conditions and prothrombotic disorders contribute to the development of throm...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-951457
更新日期:2006-10-01 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::Physiologic regulation of fibrinolysis plays an important role in the control of hypercoagulable states and thrombogenesis. Both the hereditary and acquired conditions leading to fibrinolytic deficit result in thrombotic complications leading to arterial and venous occlusive disorders. Several changes in physiologic s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-994940
更新日期:1999-01-01 00:00:00
abstract::Hemophilia A and B gene therapy requires long-term and stable expression of coagulation factor VIII (FVIII) or factor IX (FIX), respectively, and would need to compare favorably with protein replacement therapy. Onco-retroviral and lentiviral vectors are attractive vectors for gene therapy of hemophilia. These vectors...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2004-825632
更新日期:2004-04-01 00:00:00
abstract::Despite long-standing knowledge about the relationship between thrombosis and atherosclerosis, the specific role of thrombin in modulating atherosclerosis and the response to vascular injury is not well understood. Thrombin receptor stimulation in vitro signals many cellular events that are associated with the respons...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-999001
更新日期:1996-01-01 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::Life expectancy for persons with hemophilia (PWH) has considerably increased in the last decades as a direct result of the availability of modern therapies to control the clotting defect. Because their life expectancy now matches that of the general population, PWH are experiencing age-related comorbidities, such as, ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0033-1354424
更新日期:2013-10-01 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
abstract::Through in depth studies, the biochemical pathways of hemostasis-related systems have been elucidated in terms of well-defined molecular mechanisms. The interrelationships of coagulation, fibrinolytic, kallikrein-kinin, platelets, prostaglandins, blood vessel, and complement systems are now well understood. Methods ar...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1983-10-01 00:00:00
abstract::Heparin preparations have been used for prophylaxis and treatment of deep vein thrombosis for many years. Several biologic effects of heparin are known. Since 1978, there have been several reports about reversible elevation in serum values of AST and ALT in patients and healthy volunteers given heparin in small and hi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1055/s-2007-1002654
更新日期:1991-10-01 00:00:00
abstract::Protamine sulfate has been used for many years to reverse the effects of unfractionated heparin, but it can cause hemodynamic changes and other serious side effects. Platelet factor 4 (PF4) is a naturally occurring protein synthesized in megakaryocytes and eventually stored in the alpha granules of platelets for later...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章,随机对照试验,评审
doi:10.1055/s-2004-831050
更新日期:2004-06-01 00:00:00
abstract::Despite numerous past and ongoing efforts, there remains significant variation in results from assays for the major antiphospholipid antibodies (aPL), namely anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulant (LA). There is therefore a need to produce comprehensive guidelines on ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0028-1085479
更新日期:2008-06-01 00:00:00
abstract::Mutations in the genes for three complement regulators-complement factor H (CFH), membrane cofactor protein (MCP), and factor I (IF)-have now been described in patients with atypical HUS. The functional effects of these mutations have been studied in detail and have been shown to affect secretion, expression, and regu...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-939771
更新日期:2006-03-01 00:00:00
abstract::The delicate biochemistry of coagulation and anticoagulation is greatly affected by deviations from the optimal temperature required for the interactions between various coagulation enzymes, cellular receptors, and intracellular mechanisms. Hyperthermia will lead to a prothrombotic state and, if sufficiently severe su...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1648231
更新日期:2018-10-01 00:00:00
abstract::The number of hip fractures in anticoagulated patients is predicted to increase, due to people living longer. However, evidence regarding urgent perioperative management of elderly patients with hip fracture who take oral anticoagulants (vitamin K antagonists or direct oral anticoagulants) is scarce. In this article, ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0039-1678718
更新日期:2019-03-01 00:00:00
abstract::These results show that heparin and dextran sulfate protect endothelial cells from oxygen-free radicals. Heparan sulfate and dermatan sulfate showed mild protection when measuring cell viability but none when examining the presence of LDH in media. These GAGs are obviously not as effective as heparin and dextran sulfa...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00