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Lysis Time (lysis + time)
Kinds of Lysis Time Selected AbstractsORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and ThrombosisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Maria Angeles Martinez-Zamora Problem, Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Method of study, Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Results, Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Conclusion, Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS. [source] Influence of factor IX on overall plasma coagulability and fibrinolytic potential as measured by global assay: monitoring in haemophilia BHAEMOPHILIA, Issue 1 2008N. A. GOLDENBERG Summary., We sought to determine the influence of factor IX (FIX) deficiency upon overall coagulative and fibrinolytic capacities in plasma using the clot formation and lysis (CloFAL) assay, and to investigate the role of this global assay as an adjunctive monitoring tool in haemophilia B. CloFAL assay parameters were measured in vitro in platelet-poor plasma in relation to FIX activity and antigen (FIX:Ag), and were determined ex vivo among FIX-deficient patients (n = 41) in comparison to healthy individuals (n = 48). Supplementation of FIX-deficient plasma with FIX in vitro demonstrated a non-linear concentration dependence of FIX upon overall plasma coagulability. Ex vivo, coagulability was significantly decreased in FIX-deficient vs. healthy subjects among adults [median coagulation index (CI): 4% vs. 104% respectively; P < 0.001] and children (median CI: 9% vs. 63%; P < 0.001). Fibrinolytic capacity was increased in adult FIX-deficient vs. healthy subjects (median fibrinolytic index: 216% vs. 125%, respectively, P < 0.001), and was supported by a trend in shortened euglobulin lysis time (ELT). Severe haemophilia B patients showed heterogeneity in aberrant CloFAL assay waveforms, influenced partly by FIX:Ag levels. Patients with relatively preserved FIX:Ag (i.e. dysfunctional FIX) exhibited a shorter time to maximal amplitude in clot formation than those with type I deficiency. During patient treatment monitoring, markedly hypocoagulable CloFAL assay waveforms normalized following 100% correction with infused FIX. The CloFAL global assay detects FIX deficiency, demonstrates differences in coagulability between dysfunctional FIX and type I deficiency, and appears useful as an adjunctive test to routine FIX measurement in monitoring haemophilia B treatment. [source] The relative kinetics of clotting and lysis provide a biochemical rationale for the correlation between elevated fibrinogen and cardiovascular diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2007P. Y. KIM Summary.,Background:,Elevated plasma fibrinogen is a well known risk factor for cardiovascular disease. The mechanistic rationale for this is not known.Objectives:,These studies were carried out to determine the fibrinogen concentration dependencies of clotting and lysis times and thereby determine whether these times rationalize the correlation between an increased risk of cardiovascular disease and elevated plasma fibrinogen.Methods:,The time courses of clot formation and lysis were measured by turbidity in systems comprising a) fibrinogen, thrombin and plasmin, or b) fibrinogen, thrombin, plasminogen and t-PA, or c) plasma, thrombin and t-PA. From the lysis times, kcat and Km values for plasmin action on fibrin were determined.Results:,The time to clot increased linearly from 2.9 to 5.6 minutes as the fibrinogen concentration increased from 1 to 9 ,M and did not increase further as the fibrinogen concentration was raised to 20 ,M. In contrast, the clot lysis time increased linearly over the input fibrinogen concentration range of 2 to 20 ,M. A similar linear trend was found in the two systems with t-PA and plasminogen. Apparent Km and kcat values for plasmin were 1.1 ± 0.6 ,M and 28 ± 2 min,1, respectively. Km values for plasmin in experiments initiated with t-PA and plasminogen were 1.6 ± 0.2 ,M in the purified system and 2.1 ± 0.9 ,M in plasma.Conclusion:,As the concentration of fibrinogen increases, especially above physiologic level, the balance between fibrinolysis and clotting shifts toward the latter, providing a rationale for the increased risk of cardiovascular disease associated with elevated fibrinogen. [source] Reversible inhibitors of TAFIa can both promote and inhibit fibrinolysisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2003M. Schneider Summary., The plasma carboxypeptidase activated thrombin-activable fibrinolysis inhibitor (TAFIa), is thermally unstable at 37 °C, with a half-life of 8 or 15 min depending on the isoform. The arginine analog, 2-guanidinoethylmercaptosuccinate (GEMSA), not only inhibits TAFIa but also slows the spontaneous inactivation of the enzyme, thereby reducing the activity of TAFIa, while extending its apparent half-life. Because, as shown in previous work, the ability of TAFIa to prolong clot lysis can be more dependent on its half-life than its concentration, in this study we determined whether reversible inhibitors of TAFIa could paradoxically prolong clot lysis. Potato tuber carboxypeptidase inhibitor (PTCI) or GEMSA were titrated into normal pooled human plasma, in the presence of soluble thrombomodulin. Both inhibitors mediate a biphasic antifibrinolytic effect, prolonging clot lysis at lower concentrations and enhancing clot lysis at higher concentrations. The antifibrinolytic effect of GEMSA is maximized at 1 mmol L,1, increasing clot lysis time from 100 min to 350 min. The antifibrinolytic effect of PTCI is maximized at 100 nmol L,1, increasing clot lysis time from 100 min to 240 min. To further characterize the nature of this biphasic effect, TAFI at various concentrations was added to TAFI-immunodepleted human plasma in the presence of PTCI or GEMSA. The magnitude of the effect depends on the concentration of TAFIa, the concentration of inhibitor, and the potency of the inhibitor. We propose that the biphasic antifibrinolytic effect is mediated by the dynamic equilibrium of free TAFIa that inactivates quickly, and TAFIa bound to inhibitor that inactivates slowly. TAFIa inhibitors used as therapeutic agents might not only enhance lysis at higher concentrations, but also stabilize fibrin clots at intermediate concentrations. [source] The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous thrombosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006C.H. Martini Summary Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis. High TAFI antigen levels are associated with an increased risk of deep venous thrombosis (DVT). Because TAFI levels are partly determined genetically, we assessed the association between three TAFI gene polymorphisms (,438 G/A, 505 A/G and 1040 C/T), TAFI antigen levels and clot lysis times and the risk of DVT. Carriers of the 505G allele, which is associated with lower TAFI antigen levels than the 505A allele, showed an increased risk of DVT. This indicates that the relationship between TAFI and venous thrombosis is more complex than previously suggested. [source] Discovery of novel mechanisms and molecular targets for the inhibition of activated thrombin activatable fibrinolysis inhibitorJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2008K. HILLMAYER Summary.,Background:,Thrombin activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis and an attractive target to develop profibrinolytic drugs. Objective:,To analyze the (inhibitory) properties of five monoclonal antibodies (mAbs) directed towards rat TAFI (i.e. MA-RT13B2, MA-RT30D8, MA-RT36A3F5, MA-RT36B2 and MA-RT82F12). Methods and results:,Direct interference of the mAb with rat activated TAFI (TAFIa) activity was assayed using a chromogenic activity assay. This revealed reductions of 79% ± 1%, 54% ± 4%, and 19% ± 2% in activity in the presence of a 16-fold molar excess of MA-RT13B2, MA-RT36A3F5, and MA-RT82F12, respectively whereas MA-RT30D8 and MA-RT36B2 had no direct inhibitory effect. Additionally, MA-RT13B2 and MA-RT36A3F5 reduced rat TAFIa half-life by 56% ± 2% and 61% ± 3%. Tissue-type plasminogen activator mediated in vitro clot lysis was determined using rat plasma. Compared to potato tuber carboxypeptidase inhibitor, MA-RT13B2, MA-RT30D8, MA-RT36A3F5, and MA-RT82F12 reduced clot lysis times by 86% ± 14%, 100% ± 5%, 100% ± 10%, and 100% ± 11%, respectively. During epitope mapping, Arg227 and Ser251 were identified as major residues interacting with MA-RT13B2. Arg188 and His192 contribute to the interaction with MA-RT36A3F5. Arg227, Ser249, Ser251, and Tyr260 are involved in the binding of MA-RT30D8 and MA-RT82F12 with rat TAFI(a). The following mechanisms of inhibition have been deduced: MA-RT13B2 and MA-RT36A3F5 have a destabilizing effect on rat TAFIa whereas MA-RT30D8 and MA-RT82F12 partially block the access to the active site of TAFIa or interact with the binding of TAFIa to the blood clot. Conclusions:,The described inhibitory mAb towards rat TAFIa will facilitate TAFI research in murine models. Additionally, we reveal novel molecular targets for the direct inhibition of TAFIa through different mechanisms. [source] The relative kinetics of clotting and lysis provide a biochemical rationale for the correlation between elevated fibrinogen and cardiovascular diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2007P. Y. KIM Summary.,Background:,Elevated plasma fibrinogen is a well known risk factor for cardiovascular disease. The mechanistic rationale for this is not known.Objectives:,These studies were carried out to determine the fibrinogen concentration dependencies of clotting and lysis times and thereby determine whether these times rationalize the correlation between an increased risk of cardiovascular disease and elevated plasma fibrinogen.Methods:,The time courses of clot formation and lysis were measured by turbidity in systems comprising a) fibrinogen, thrombin and plasmin, or b) fibrinogen, thrombin, plasminogen and t-PA, or c) plasma, thrombin and t-PA. From the lysis times, kcat and Km values for plasmin action on fibrin were determined.Results:,The time to clot increased linearly from 2.9 to 5.6 minutes as the fibrinogen concentration increased from 1 to 9 ,M and did not increase further as the fibrinogen concentration was raised to 20 ,M. In contrast, the clot lysis time increased linearly over the input fibrinogen concentration range of 2 to 20 ,M. A similar linear trend was found in the two systems with t-PA and plasminogen. Apparent Km and kcat values for plasmin were 1.1 ± 0.6 ,M and 28 ± 2 min,1, respectively. Km values for plasmin in experiments initiated with t-PA and plasminogen were 1.6 ± 0.2 ,M in the purified system and 2.1 ± 0.9 ,M in plasma.Conclusion:,As the concentration of fibrinogen increases, especially above physiologic level, the balance between fibrinolysis and clotting shifts toward the latter, providing a rationale for the increased risk of cardiovascular disease associated with elevated fibrinogen. [source] The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous thrombosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006C.H. Martini Summary Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis. High TAFI antigen levels are associated with an increased risk of deep venous thrombosis (DVT). Because TAFI levels are partly determined genetically, we assessed the association between three TAFI gene polymorphisms (,438 G/A, 505 A/G and 1040 C/T), TAFI antigen levels and clot lysis times and the risk of DVT. Carriers of the 505G allele, which is associated with lower TAFI antigen levels than the 505A allele, showed an increased risk of DVT. This indicates that the relationship between TAFI and venous thrombosis is more complex than previously suggested. [source] | ||||||||||