摘要:

The effect of fibrinolytic agents on platelet adhesion onto insolubilized collagen type I was evaluated. Normal human whole blood samples were incubated with agents and perfused over collagen-coated surfaces in a parallel-plate flow chamber. Platelet adhesion and aggregation were analyzed by video microscopy and image processing. When blood was perfused at 1500/s, both streptokinase and urokinase, each at 500 U/ml, caused a significantly less normalized platelet deposition, compared with controls. At 480/s, platelet deposition was not different between controls and test samples. Inhibition of platelet deposition at high flow rates was partly due to inhibition of platelet adhesion. Both ristocetin- and ADP-induced platelet aggregation were inhibited in test samples. The agents caused proteolytic degradation of plasma fibrinogen, but no degradation of platelet glycoproteins Ib and IIb–IIIa (GPIb and GPIIb–IIIa) and of plasma von Willebrand factor in test samples prior to perfusion. Post-perfusion von Willebrand factor degradation was not found. Plasmin may cause functional changes to plasma proteins and/or platelet receptors, altering their adhesive properties under flow. At high shear, fibrinogen degradation products may interfere with GPIIb–IIIa binding to insolubilized von Willebrand factor, leading to decreased platelet adhesion. Inhibition of platelet adhesion by thrombolytic agents could help maintain vessel patency after recanalization in stenosed arteries.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Reconstituted recombinant factor VIII (FVIIIrec) loses little biologic activity at room temperature for up to seven days and continuous infusion is convenient, effective hemostatically and requires less FVIIIrecconcentrate than treatment by conventional bolus injections. However, the potential for bacterial contamination, with proliferation to high levels that can cause bacteremia, is a concern with continuous infusion. We studied the growth properties at 4, 25 and 35°C in reconstituted FVIIIrec(Kogenate®) and at 25°C in 5% dextrose in water (D5%W) of three isolates each ofStaphylococcus epidermidis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia,Flavobacterium spp. andCandida albicans, species most likely to contaminate infusate during preparation or administration and which have been implicated in more than 95% of all outbreaks and sporadic cases of nosocomial bloodstream infection traced to contaminated admixtures, biologic agents or medications administered parenterally. Reconstituted FVIIIrecallowed growth of only three species at 25°C and 35°C:S. marcescens, S. maltophiliaandP. aeruginosa; logarithmic growth appeared only after 24–48 h. D5%W allowed growth of two gram-negative species,S. marcescensandB. cepacia.We conclude that reconstituted FVIIIrec(Kogenate®) is a poor growth medium for most nosocomial pathogens, comparable with D5%W. If reconstituted aseptically, continuous infusion of reconstituted FVIIIrecshould be safe, and it should not be necessary to replace the container or tubing more frequently than every 3 days, an administration schedule that can provide effective hemostasis at lower cost.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The present study was undertaken to examine the involvement of platelet-derived serotonin (5-hydroxytryptamine; 5-HT) in thromboxane A2(TXA2)-induced platelet aggregation. Pharmacological experiments with 5-HT2and TXA2inhibitors were conducted on platelet aggregation in platelet-rich plasma from cats. Exogenously added 5-HT, U-46619 (a stable TXA2analogue) and collagen caused platelet aggregation in a concentration-dependent manner. The combination of low concentrations of 5-HT and U-46619 caused full platelet aggregation, whereas each agent alone, at these concentrations, caused a transient aggregation. 5-HT-induced aggregation was inhibited by ketanserin (0.01–0.3 µmol/l), a 5-HT2receptor antagonist, in a concentrationdependent manner. Collagen-induced platelet aggregation was also inhibited by ketanserin, whereas the inhibition by indomethacin was modest even at the highest concentration tested (300 µmol/l). U-46619 triggered platelet aggregation in a biphasic manner. Ketanserin inhibited only the second phase of the aggregation. The inhibition of U-46619-induced aggregation by ketanserin occurred at a concentration range similar to that for 5-HT-induced platelet aggregation. Likewise, platelet aggregation induced by the combination of low concentrations of 5-HT and U-46619 was fully inhibited by ketanserin. These data suggest a major involvement of platelet-derived 5-HT in TXA2-dependent aggregation in cat platelets.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Ristocetin A is used clinically as a tool for the measurement of von Willebrand protein due to its ability to induce the aggregation of platelets in plasma being proportional to the concentration of von Willebrand protein. The enzymatically induced cleavage ofα- l-rhamnose from the tetrasaccharide of ristocetin A removes this ability to induce platelet aggregation in plasma, providing a possible insight into the structural basis for this effect.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The aim of this study was to compare fibrinolytic parameters in two subgroups of young survivors of myocardial infarction: group A (n= 14) with silent myocardial ischaemia and group B (n= 15) without silent myocardial ischaemia, as assessed by 24 h Holter electrocardiogram monitoring. Only men aged 33–46 years who were in a stable condition at least 6 months after the acute event were included in the survey. All patients were normolipaemic or had only mild hyperlipidaemia, non-diabetic, normotensive, noncurrent smokers and with a normal body mass index. The control group consisted of 15 age-matched healthy men. Blood samples were taken at 7.30 a.m. In the group A patients, we found higher mean levels of tissue plasminogen activator (t-PA) total antigen (11.1 versus 6.9 ng/ml,P< 0.01), its inhibitor plasminogen activator inhibitor-1 (PAI-1) antigen (58.1 versus 34.8 ng/ml,P< 0.01), PAI-1 activity (4.9 versus 3.4 U/ml,P< 0.05) and tPA-PAI-1 complexes (5.1 versus 3.5 ng/ml,P< 0.05) as well as a lower level of t-PA activity (0.5 versus 0.8 IU/ml,P< 0.01) and free t-PA antigen (0.8 versus 1.3 ng/ml,P< 0.01) compared with the controls. However, group A patients exhibited higher PAI-1 antigen levels (58.1 versus 41.6 ng/ml,P< 0.05) than those without silent ischaemia. There were no differences between group B and controls in any of the parameters measured. Our results indicate that patients with more severe disease, as revealed by silent myocardial ischaemia, had lower levels of free t-PA as a result of the excess of PAI-1.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

400 mg/dl) and in plasma from anticoagulated patients. The systematic overestimate in the latter samples could be a result of an increased fibrin gel turbidity, as shown by in-vitro experiments using purified fibrinogen clotted by different thrombin concentrations. The PFC overestimate by the prothrombin-time-derived method could also be experimentally reproduced by competitively inhibiting thrombin–fibrinogen interaction by hirudin 54–65 peptide and the fibrinogen fragment E. A similar qualitative result was also found for the prothrombin-time-derived method in the presence of the Gly-Pro-Arg-Pro peptide, which competitively inhibits the end-to-end fibrin aggregation process. Notably, under both the above experimental conditions, the Clauss method underestimated the PFC. On the other hand, the 'clot recovery' method was minimally affected by the above inhibitors. These results indicate that the prothrombin-time-derived method is accurate and precise for most routine purposes. Its precision seems inadequate, however, under those conditions where the prothrombin time is prolonged (such as anticoagulant therapy) and in the presence of high fibrinogen levels.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

von Willebrand factor antigen II (vWFAgII) is the 100 kDa propolypeptide of endothelial cell marker von Willebrand factor (vWF). Our aim was to determine the relationship between vWFAgII and mature vWF and an additional endothelial cell marker, soluble thrombomodulin, in atherosclerosis. To do this, we measured levels of all three by enzyme-linked immunosorbent assay in plasma obtained from 24 patients with peripheral vascular disease (PVD), from 25 patients who survived a myocardial infarction [i.e. had ischaemic heart disease (IHD)], and from 47 age- and sex-matched controls. We found raised levels of vWFAgII in PVD (57.3 ± 15.3 µg/dl; mean ± standard deviation) and in IHD (53.4 ± 19.2 µg/dl) compared with the controls (35.7 ± 12.0 µg/dl; analysis of varianceP< 0.001). Raised levels of vWf were found in both groups of patients but raised soluble thrombomodulin was found only in patients with PVD. Levels of vWFAgII correlated with those of vWf (r= 0.45,P< 0.001) but not with soluble thrombomodulin (r= 0.14,P= 0.17), nor any of the major risk factors for atherosclerosis. Our brief study reports raised levels of vWFAgII in atherosclerosis. This may, like that of vWf, be related to endothelial cell damage, although the incomplete correlation between the two implies different metabolic and/or release mechanisms.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A high plasma concentration of factor VII procoagulant activity is considered an independent risk factor for coronary heart disease. Recently, two polymorphisms of factor VII gene (insertion of a decanucleotide at −323 [A2], and the variant Q353) have been associated with 20–25% lower levels of this protein in plasma. In this study, the prevalence of these two factor VII polymorphisms were evaluated in relation to the development of acute thromboembolic events. Thus, we conducted three case-control studies of patients diagnosed with acute coronary syndromes, acute cerebrovascular events and deep venous thrombosis (101, 104 and 97 cases, respectively). No significant differences were detected in the prevalence of these polymorphisms between patients and controls, suggesting that the A1/A2 or R/Q alleles do not play an important role in the development of thromboembolic episodes.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A serious retroperitoneal bleeding occurred in a 56-year-old male patient receiving unfractionated heparin due to multiple pulmonary embolism. After reducing the heparin dose, the patient developed a new pulmonary embolism and a large thrombus in the right atrium. Concomitantly, the platelet count dropped to a value of 29 g/l. Heparin-induced thrombocytopenia (HIT) was confirmed by a functional assay, the heparin-induced platelet activation (HIPA) assay, whereas the results of a platelet factor 4/ heparin complex ELISA were repeatedly negative. This indicated that the patient's HIT antibodies were directed towards an antigen other than platelet factor 4/heparin complexes. For treatment of the atrial thrombus, an ultra-low-dose lysis with rt-PA (2 mg/h, intravenously) was administered for a period of 52 h, overlapping with systemic treatment with recombinant hirudin (Lepirudin, Refludan®, 0.06–0.14 mg/kg/h intravenously). The aim was to enhance lysis of the thrombus without increasing the haematoma, and at the same time keep the risk of fulminant pulmonary embolism due to thrombus fragmentation as low as possible. The cardiac thrombus disappeared within 48 h, without new signs of pulmonary embolism. Platelet counts normalized within nine days.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We present the case of a 42-year-old woman with a recently acquired bleeding tendency. Coagulation studies and response to antifibrinolytic therapy suggested primary hyperfibrinogenolysis: markedly low levels of fibrinogen and α2-antiplasmin, normal levels of antithrombin III, protein C and protein S combined with an only borderline low number of platelets without evidence of microangiopathic haemolytic anaemia. A suspected causative adenocarcinoma of the lung was demonstrated. She was treated successfully with tranexamic acid and cryoprecipitate, until the tumor progressed and hyperfibrinogenolysis progressed to diffuse intravascular coagulation. Differential diagnosis of these coagulation disorders, with similar etiology, clinical and laboratory findings is reviewed. Therapeutic implications are discussed.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID