摘要:

Changes in endothelial cell physiology are now an accepted component of inflammatory and atherosclerotic vascular disease. This communication will review the scientific and clinical evidence that supports this statement, which may be demonstrated by in vivo arterial manipulations or by measuring plasma levels of endothelial cell-specific products. The former invasive approach has provided useful insights into the pharmacology of blood flow and blood pressure regulation whilst the latter has provided epidemiological evidence that endothelial cell injury can lead to an increased risk of morbidity and mortality. In addition, studies based on both techniques have demonstrated that treatment or reversal of the risk factors for atherosclerosis can be beneficial to the endothelium, validating the theory that the endothelium is the prime target for the disease process. Blood Coag Fibrinol 9:297–306 © 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The cellular components of the blood, which become associated with fibrin through specific cellular adhesive processes, play a significant role in the breakdown of fibrin. Fibrinolysis by neutrophil elastase and cathepsin G occurs in a manner distinct from that produced by plasmin. This study demonstrates that neutrophil lysosomal enzyme activity further degrades the end products of plasmic fibrin degradation into low-molecular-weight material, followed by reassembly of higher-molecular-weight products in a process dependent on calcium and factor XIII. Although one of the reformed products has a similar molecular weight to D-dimer and is recognized by a monoclonal antibody raised against D-dimer, its isoelectric point indicates it to be distinctly different from plasmin-derived D-dimer. Processing of the end products of plasmic fibrin degradation by neutrophils may have the potential for modulating the immune response as well as compromising the predictive value of tests measuring D-dimer. Blood Coag Fibrinol 9:307–313 © 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The serum thrombopoietin (TPO) levels in 61 idiopathic thrombocytopenic purpura (ITP) patients were found to be slightly increased compared with those of 29 normal subjects. The TPO levels of the 15 ITP patients who had a poor response to steroid therapy (i.e. an unchanged platelet count) were higher than those of the 22 ITP patients who had a good response to steroid therapy (i.e. an increased platelet count) and the normal subjects. The TPO levels in the 15 ITP patients whose platelet count was higher than 10 × 104/$mUl after the discontinuation of steroid therapy significantly higher than those of the normal subjects. The platelet-associated immunoglobulin G (PAIgG) levels in the ITP patients who had a poor response to steroid therapy were slightly increased compared with the normal subjects and the ITP patients who had a good response to the steroid therapy and the nine ITP patients who did not undergo the steroid therapy. The serum TPO level was negatively correlated only with the megakaryocyte count in the ITP patients, and the megakaryocyte count in the ITP patients who had good responses to the steroid therapy was higher than that in those who had poor responses. These data suggest that serum TPO levels might be important for the prediction of the outcome of ITP patients who receive steroid therapy. Blood Coag Fibrinol 9:315–321 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The activation of factors XII (FXII) and VII (FVII) has been shown to occur on the surface of lipoproteins in the presence of lipoprotein lipase and may be modulated by β2glycoprotein-1 (β2GP1). In the postprandial state FVII is activated without apparent activation of FXII in plasma. We investigated whether β2GP1, FXIIa and FVIIa are associated with triglyceride-rich lipoproteins in the fasting and postprandial state. Six normal subjects were studied while fasting and 1, 2 and 4 h after ingestion of 100 g fat. We confirmed that plasma FVIIa activity, but not FXIIa antigen, was increased in the postprandial period. FXIIa, FVIIa and β2GP1 were associated with chylomicra-rich lipoproteins, and lipase or Triton X-100 treatment caused an increase in FXIIa in plasma and chylomicra without an increase in FVIIa. This suggests that FXIIa may be formed in the postprandial period, but its antigenic determinants are masked by the association with lipoprotein particles, although it could still express proteolytic activity. Alternatively a FXII-independent mechanism or surface other than triglyceride-rich lipoproteins may be responsible for FVII activation in the postprandial state. Blood Coag Fibrinol 9:323–332 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Real-time biospecific interaction analysis based on optical detection by surface plasmon resonance was used to develop an accurate one-step method for the direct measurement of free protein S in human plasma. This assay was validated, compared with classical immunological methods and shown to be suitable for the routine clinical diagnosis of protein S deficiency. The method relies on the specific capture of free protein S directly from plasma by a monoclonal antibody (mAb), 34G2, immobilized on a sensor chip surface. A calibration curve was established with serial dilutions of standard plasma (working range 5–50%) and a linear relationship was found to exist between the relative response in resonance units (RU) and the concentration of free protein S expressed as percentage plasma dilution (r = 0.99). The specificity of the assay was confirmed using purified human protein S and polyethylene glycol treated plasma. In addition, it could be demonstrated that no dissociation of C4b-BP-protein S complexes occurred under the chosen experimental conditions. The technique was reproducible with inter-assay, intra-assay and inter-sensor chip variation coefficients of 1.5–5.4%, 2–3.1% and 4.4–4.9%, respectively, as evaluated in two different plasma samples. Since all tests are automatic and long series of analyses can be performed with the same sensor chip, the method was applied to the determination of free protein S antigen in plasma from 20 normal blood donors and 38 thrombophilic patients. Results displayed excellent correlation with those of free protein S enzyme-linked immunosorbent assay (r = 0.99) and rocket immunoelectrophoresis of polyethylene glycol-treated plasma (r = 0.93). Blood Coag Fibrinol 9:333–341 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Seventeen women with previously verified thromboembolism were included in a pharmacokinetic evaluation of dalteparin during the third trimester of pregnancy. The bioavailability of morning subcutaneous administration of dalteparin (crossover study) was also compared with that in the evening. Fifteen women injected themselves subcutaneously with 5000 IU and two with 2500 IU dalteparin once daily. An anti-FXa activity of 0.20–0.40 IU/ml 3 h after injection was obtained. The means × SD, when comparing morning and evening doses for 5000 IU, were: Cmax 0.21 × 0.05 and 0.20 × 0.05 IU anti-FXa/ml, AUC 0–24 h 1.97 × 0.46 and 1.93 × 0.55 IU × h/ml and tmax 3.71 × 0.89 and 4.32 × 1.60 h, respectively (NS). The two regimens were equivalent. A measurable anticoagulant effect was still observed 16 h after injection of 5000 IU dalteparin. The half-lives after a morning and an evening dose of 5000 IU dalteparin were 4.92 × 2.80 and 3.87 × 1.15 h, respectively (NS). There were no changes in thrombin marker levels during the two pharmacokinetic measurements. Blood Coag Fibrinol 9:343–350 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We present the protein C gene analysis of a patient with homozygous protein C deficiency. The patient was referred with purpura fulminans 3 h after birth. Skin necroses had developed on the scalp, abdomen and upper extremities when he was two days old. His protein C activity was 0.03–0.05 IU/ml and the levels in his consanguineous parents were 0.32 and 0.40 IU/ml. He was treated initially with fresh frozen plasma, and later with daily oral anticoagulants, for two episodes of skin necrosis. He had three more episodes of skin necroses that were treated with intravenous protein C concentrate. He is now two years old and under treatment with daily coumarin 0.1–0.2 mg/kg per day to keep the International Normalized Ratio between 2.0–4.5. DNA analysis showed that he is homozygous for a double variant bearing His 202 to Tyr and Ala 346 to Thr mutations. His parents were each heterozygous for the double variant and were consanguineous. This mutation has been reported previously in an Austrian patient but this is the first homozygous case for this double variant. Blood Coag Fibrinol 9:351–354 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Activated protein C (APC) resistance is related to a single point mutation in the factor V gene (FV:Q506) and appears to be the most common inherited risk factor for venous thromboembolism. A reliable screening test is therefore useful. We aimed to evaluate a new APC resistance test, on the basis of the procoagulant activity present in one snake venom of a crotalidae family: STA Staclot APC-R. We studied 36 consecutive patients with an acute deep venous thrombosis (DVT) confirmed by compression ultrasonography and carrying the FV:Q506allele, assessed by DNA analysis, 103 of their family members and 35 consecutive patients with a proven DVT but who did not carry the FV:Q506allele. Blood samples were collected within 24 h of admission for the DVT cases and on the day of medical registration for the family members. Tests were performed blind. The STA Staclot APC-R test, using a cut-off value of 0.80, had an overall sensitivity of 100% (95% CI, 95–100) and a specificity of 98.8% (95% CI, 92.0–99.6). An acute thrombosis process did not influence the performance of the test. We conclude that this test is easy and rapid to perform in every day practice and fulfills the criteria for a screening test. Blood Coag Fibrinol 9:355–359 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effects of the infusion of a human recombinant von Willebrand factor (vWF) preparation in pigs homozygous for von Willebrand disease (vWD) were evaluated on serial measurements of von Willebrand factor antigen and activity, FVIII activity, vWF multimer analysis, in-vivo bleeding time and platelet adhesion and thrombus formation on collagen at high shear rates in an ex-vivo model of experimental thrombosis. Plasma-derived human and porcine vWF were used for comparison. Before infusion, the pigs were characterized by undetectable plasma vWF levels, a low level of FVIII, prolonged bleeding time, severely impaired platelet adhesion and thrombus formation. After infusion of the human recombinant vWF, in-vivo recovery of vWF activity ranged from 58% to 82%, depending on the dose infused, and its half-life was longer than for the plasma-derived concentrates. The highest-molecular-weight forms of human recombinant vWF were removed from the circulation gradually. Infusion of the three vWF concentrates produced inconsistent effects on bleeding time and moderate improvement of platelet adhesion and thrombus formation. After infusion, a prolonged increase of FVIII (> 48 h) was observed, suggesting that human recombinant vWF is able to bind and to stabilize porcine factor VIII and that porcine vWD is a good model for studying such interactions. Blood Coag Fibrinol 9:361–372 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Evidence suggests that an allelic variation in the β fibrinogen gene may confer an increased risk of coronary artery disease and stroke. The role of the β fibrinogen gene polymorphism and fibrinogen levels in ischemic stroke has not been determined in Japanese, who are more prone to stroke than to coronary artery disease compared with Caucasians. We investigated the associations between ischemic stroke, plasma fibrinogen level, and a HaeIII restriction fragment length polymorphism (G/A-455) located at −455 bp from the start of transcription of the β fibrinogen gene in 85 hypertensive patients with ischemic stroke (stroke group), 85 hypertensive patients without ischemic stroke (nonstroke group) and in 84 normotensive subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive group). The frequency of non-cutting allele (designated A-455allele) in the control group was 0.07 [95%CI: 0.03–0.11]; this value was significantly lower than that previously reported in Caucasians (0.19–0.26). The A-455allele frequency of the nonstroke group and stroke group were 0.08 [95% CI: 0.04–0.12] and 0.15 [95% CI: 0.10–0.21]. A-455allele frequency of the stroke group was significantly higher than that of the control group (x2= 5.63, P = 0.018) and the nonstroke group (x2= 4.00, P = 0.043). The mean × SD fibrinogen level was significantly higher in the stroke group than that in the normotensive group (277 × 64 mg/dl versus 257 × 52 mg/dl, P < 0.03), but that of the nonstroke group was not significantly different compared with both normotensive and stroke groups. In conclusion, the positive association between the fibrinogen genotype G/A-455and ischemic stroke in hypertensive patients was independent of other risk factors. These results suggest that fibrinogen A-455allele may be an independent risk factor for ischemic stroke in the Japanese population. Blood Coag Fibrinol 9:373–379 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID