摘要:

Snake venom toxins are now regularly used in the coagulation laboratory for assaying haemostatic parameters and as coagulation reagents. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen and fibrinogen breakdown product assay as well as detecting dysfibrinogenaemias. Significantly, because SVTLE are not inhibited by heparin, they can be used for defibrinating samples that contain the anticoagulant before assay of haemostatic variables. Prothrombin activators are found in many snake venoms and are used in prothrombin assays, for studying dysprothrombinaemias and preparing meizothrombin and non-enzymic prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains a number of compounds useful in the assay of factors V, VII, X, platelet factor 3 and lupus anticoagulants. Activators from the taipan, Australian brown snake and saw-scaled viper have been used to assay lupus anticoagulants. Protein C and activated protein C resistance can be measured by means of RVV and Protac®, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with Botrocetin® fromBothrops jararacavenom. Finally, phospholipase A2enzymes and the disintegrins, a family of Arg-Gly-Asp (RGD)-containing proteins found in snake venoms, show great potential for the study of haemostasis including, notably, platelet glycoprotein receptors GPIIb/IIIa and Ib.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Endothelium-derived nitric oxide formed by endothelial constitutive nitric oxide synthase (ecNOS) mediates endothelium-dependent vasodilation and antithrombotic action. We analyzed the distribution of a polymorphism of ecNOS (27-bp repeat in intron 4) in 127 ischemic stroke patients (18 with atherothrombotic, 58 with lacunar, and 51 with silent lacunar stroke) and 91 control subjects. When we assigned the four repeats as allele a, and five repeats as allele b, there was no significant difference between the genotype distribution and allele frequencies in the stroke group and in the control group (0.862 versus 0.868 for the b allele frequency). Moreover, there was also no significant difference in the genotype distribution or allele frequencies among the three stroke subgroups (b allele frequency: 0.889 for atherothrombotic stroke; 0.862 for lacunar stroke; 0.853 for silent lacunar stroke). These findings suggest that there is no overt association between this ecNOS gene polymorphism and ischemic stroke. We found no evidence that this polymorphism may be a genetic factor for the onset of cerebrovascular disease in this Japanese population.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Staphylokinase (SAK), a protein with known profibrinolytic properties, has recently given encouraging results in acute myocardial infarction and in peripheral arterial occlusion. The aims of this study were to compare SAK with alteplase (recombinant tissue plasminogen activator rt-PA) in a rabbit arterial thrombosis model, in terms of femoral blood flow kinetics during and after thrombolysis, and to examine the biological effects of systemic fibrinolysis invivo.We compared two modes of intravenous rt-PA administration, two modes of intravenous SAK administration and three different SAK dose regimens in a rabbit model of femoral artery thrombosis. The main finding was that the infusion of SAK following a single bolus administration gave statistically higher blood flow values than the infusion of the same dose of rt-PA following a single bolus administration (P< 0.05). In this experimental model, we also confirmed that SAK is a fibrin-specific and plasminogen-saving fibrinolytic agent at doses below 0.5mg/kg. However, at higher doses (1.0 and 1.5mg/kg), which are above usual therapeutic doses, SAK significantly reduced fibrinogen levels in a dose- and time-dependent manner (P< 0.05). These results indicate that SAK compares favorably with rt-PA in an rabbit arterial thrombosis model, yielding higher blood flow values. Moderate-dose SAK seems to be a fibrin-specific plasminogen activator, but in our model very high doses were associated with a decrease of fibrinogen.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process which may contribute to the maintenance of a fresh blood clot. We have examined the inactivation of scu-PA by thrombin in a plasma milieu to get more insight in the physiological relevance of this phenomenon. Citrated pooled normal plasma was treated with thrombin in the absence and presence of thrombomodulin. After an incubation period of 30 min the concentrations of scu-PA and tcu-PA/T were measured using specific bioimmunoassays. The inactivation of scu-PA in citrated plasma was found to be stimulated fourfold by thrombomodulin. Kinetic experiments showed that the inactivation of scu-PA by thrombin in the absence and presence of thrombomodulin occurred rapidly and declined within 1 min as a result of rapid inhibition by antithrombin III (ATIII) and other possible inhibitors. Calcium had no direct effect on the inactivation of scu-PA by exogenously added thrombin in the absence and presence of thrombomodulin. However, recalcification of plasma induced significant inactivation of scu-PA in plasma as a result of endogenous thrombin generation through the contact activation system. This calcium-induced inactivation of scu-PA was completely abolished in the presence of thrombomodulin, most likely as a result of activation of protein C by the complex formed between thrombomodulin and endogenously generated thrombin. Thrombomodulin thus appeared to play a dual role both by stimulating the inactivation of scu-PA by thrombin, and by inhibiting calcium-induced inactivation of scu-PA in plasma. In the plasma from a patient heterozygous for protein C deficiency, thrombomodulin could not prevent calcium-induced generation of tcu-PA/T, whereas the stimulating effect of thrombomodulin predominated instead. This result implied that disturbance of the protein C pathway may lead to the inactivation of substantial amounts of scu-PA in plasma under (patho)physiological circumstances and may provide an additional explanation for the association found between thromboembolism and deficiencies in the protein C pathway. This study shows that the amount of scu-PA that is inactivated in plasma depends mainly on the generation of thrombin and on thrombomodulin. We conclude that the inhibition of scu-PA-induced fibrinolysis appears to be regulated by activation of the coagulation system, providing a link between coagulation and fibrinolysis.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Antiphospholipid antibodies (aPL) are heterogeneous and are now accepted to be mainly phospholipid-protein-dependent antibodies. Although these antibodies are classically associated with thrombosis, their clinical relevance remains to be established. The subgroups of antibodies characterized by their proteic targets were reported to be more appropriate thrombotic markers. We analysed the prevalence of a large panel of antiphospholipid-related antibodies (aPLR), comprising antibodies directed to phospholipid-protein complexes and to different protein cofactors (β2GPI, prothrombin, annexin V and protein S), in 122 consecutive unselected patients who had experienced at least one venous thrombotic event. The presence of lupus anticoagulants was assessed with an integrated assay using hexagonal phase phospholipids. Two types of aPL (APA and anti-β2GPI-PL) were measured using a mixture of phospholipids containing cardiolipin and goat serum or human β2GPI, respectively, as a source of protein cofactor. Our results show a similar prevalence, close to 15%, of lupus anticoagulants, APA and anti-β2GPI-PL. In contrast, antibodies to β2GPI were detected in only 8% of the patients, and very few patients had antibodies directed to other proteins. Of the 35 patients having at least one positive aPLR, 17 were classified as severe, because they had recurrent or early onset of thrombosis (< 35 years). The distribution of aPLR between severe and mild cases was not significantly different except for lupus anticoagulants. Our results clearly indicate that lupus anticoagulant is the only aPLR test to be strongly associated with the severity of thrombosis.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In the present study we used an in-vitro technique to examine initiation and propagation of blood coagulation at the surface of tantalum coronary stents exposed to flowing platelet-rich and platelet-free plasma. The time course of factor IXa production at the surface of the stent was not influenced by platelets. In spite of a significant factor IXa production, no thrombin activity was detected when the tantalum stent was exposed to platelet-free plasma; only when the stent was exposed to platelet-rich plasma was extensive thrombin production observed. These findings indicate that tantalum triggers blood coagulation, but that (adherent) platelets are essential for thrombin generation. Heparin-coated tantalum stents exposed to flowing platelet-rich plasma showed that factor IXa generation was slightly reduced compared with the bare stent. However, the heparin coating drastically delayed the onset of thrombin generation and largely reduced the steady-state production of thrombin. We found a clear relationship between the antithrombin binding capacity and the antithrombogenic potential of the heparin-coated stents. The mode of action of immobilized heparin is thought to abrogate thrombin generation by inhibiting thrombin-dependent positive feedback reactions at the surface of the coronary stent.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Molecular studies have been performed on a Greek family with factor XIII-A subunit deficiency. The 15 exons of the A subunit gene were amplified by polymerase chain reaction and analysed by direct nucleotide sequencing. A homozygous single base insertion (1286insC) in exon 9 of the gene was identified in three affected family members. The insertion results in a frameshift and a premature stop signal a short distance downstream at codon 403. Any A subunit protein expressed is likely to be unstable and lack part of the catalytic core domain together with both β barrel domains towards the C-terminal of the molecule. This study contributes to our knowledge of the mutational spectrum in patients with factor XIII-A deficiency.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID