摘要:

We studied the effects of PRAP-1, a PAI-1-inhibiting polyclonal antibody, on tissue-type plasminogen activator (t-PA)-induced lysis of arterial-like thrombi prepared in vitro from rat and human blood in a Chandler loop device. The t-PA induced lysis of the thrombus head and tail was studied over 5 h. For thrombi prepared from rat blood, the lysis ratio head:tail was (mean × SD): 0.71 × 0.16 (platelet-poor blood), 0.49 × 0.22 (whole blood), and 0.22 × 0.12 (platelet-rich blood). PRAP-1 increased the lysis ratio to 0.68 × 0.22 for whole-blood thrombi (P < 0.01) and to 0.46 × 0.15 for platelet-rich thrombi (P < 0.001). For thrombi formed from human whole blood, PRAP-1 increased the lysis ratio head:tail from 0.61 × 0.18 to 0.95 × 0.24 (P < 0.05). These effects of PRAP-1 were due to a selective increase in the lysis of the thrombi head. The plasminogen activator inhibitor (PAI-1) activity was 7.5 × 2.8 (rat) and 3.4 × 1.3 (human) times higher in the thrombus head compared with the tail. In thrombi prepared from rat whole blood, PRAP-1 decreased the PAI-l activity of the thrombus head only by 38 × 7% (P < 0.01), while in thrombi prepared from human whole blood the PAI-1 activity of the thrombus head decreased by 83 × 4% (P < 0.001). In conclusion, the lysis resistance of the head of an arterial-like thrombus formed in vitro can be partially (rat) or totally (human) normalized by inhibition of the PAI-1 activity. The results further suggest that in rat arterial-like thrombi a t-PA-inhibiting component, different from PAI-1, is present. Blood Coag Fibrinol 9:11–18 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Bleeding is a major problem during early excision of burned skin. Therefore, 13 severely burned adult patients operated on during the first week after the trauma were studied. Blood loss was replaced with crystalloids, colloids and packed red cell concentrates (PRC). After ten infused PRCs, four fresh frozen plasma (FFP) units were given and thereafter one FFP unit with one PRC unit. Arterial blood samples were drawn before anaesthesia (S0), during operation after every four units of PRC transfusion (S1–4), 4 h postoperatively (S5) and on the first postoperative morning (S6). Prothrombin time (%) and activated partial thromboplastin time (s) were abnormal before operation (median values 67%, range 22–99% and 44 s, range 30–86 s, respectively). Prothrombin time decreased during operation and reached the critical level for normal haemostasis at S2. Thrombelastography showed decreased clot formation rate and impaired fibrin platelet interaction peri- and postoperatively. Fibrinogen and factor VIII activity were high preoperatively (median 6.1 g/1 and 253%) and the critical values for normal haemostasis were not reached. Burned patients have a consumption coagulopathy which, in combination with haemodilution during operation, results in a clinically significant deficiency of coagulation factors II, VII and X, in spite of reactive elevation of coagulation factor VIII and fibrinogen. Blood Coag Fibrinol 9:19–28 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The gC1qR is a ubiquitously expressed, 33 kDa cellular protein which recognizes the globular domains of Clq. Recent evidence suggests that the gC1qR also serves as the Zn++-dependent endothelial cell binding site for factor XII and high-molecular-weight kininogen, and activates intrinsic coagulation and kinin pathways in purified systems. In addition, activated lymphocytes have been reported to release soluble gC1qR. Thus, the present study investigated the procoagulant potential of soluble gC1qR in human plasma using the recombinant protein (rgC1qR). rgC1qR supported a dose-dependent shortening of extrinsic coagulation using the prothrombin time in the presence of diluted (1/50–1/500) thromboplastin. Maximum enhancement of the prothrombin time resulted in shortening of the clotting time from 78.8 × 0.4 s to 68.5 × 0.6 s (mean × SD, n = 8) in the presence of 50 $mUg/ml (1.5 $mUmol/1) rgC1qR. rgC1qR also enhanced the intrinsic pathway of coagulation evaluated in the absence of activators of the contact system, as demonstrated by a shortening of the plasma recalcification time from 348 × 66 s to 140 × 23 s (n = 4). rgC1qR, however, had no effect on intrinsic coagulation in the presence of undiluted kaolin or ellagic acid, and under these conditions failed to shorten the activated partial thromboplastin time of factor VIII or factor-IX-deficient plasma. rgC1qR further failed to affect thrombin and factor Xa generation assayed using chromogenic substrates, and did not enhance thrombin-induced conversion of fibrinogen to fibrin. Interestingly, the procoagulant activity of the rgC1qR was measurable in either factor-XII- or factor-XI-deficient plasma, suggesting that it was not exclusively focused on the contact system of coagulation. Although the mechanism of action of gC1qR on blood coagulation remains obscure, the data suggest a potential role for this protein in hemostatic and thrombotic events. Blood Coag Fibrinol 9:29–37 (c) 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Light-to-moderate alcohol intake is associated with a reduced incidence of ischaemic cardiovascular events, whilst heavy alcohol intake can predispose individuals to stroke. Alcohol-induced changes in coagulation and fibrinolysis may be relevant and are the subject of this controlled trial of varying alcohol intake in 55 predominantly beer-drinking men. Following 4 weeks stabilization maintaining usual drinking habits, participants were randomized to either continue usual alcohol intake or to restrict alcohol by changing to low alcohol beer for 4 weeks. In a final 4 week period, they crossed over to low or usual alcohol intake, respectively. Comparing combined low and usual alcohol periods, an increase in mean weekly alcohol intake from 92 to 410 ml (mean daily intake from 13 to 58 ml) was associated with a decrease in plasma fibrinogen (by 11%, P < 0.001) and platelet count (3%, P < 0.05), but increases in factor VII (7%, P = 0.001), tissue plasminogen activator (tPA; 16%, P = 0.01) and plasminogen activator inhibitor-1 (PAI-1; 21 %, P < 0.001). The ratio, tPA/PAI-1, fell from 0.50 to 0.44 (P = 0.02) confirming the relatively greater increase in PAI-1 with alcohol consumption. Two lipid-associated natural anticoagulants, tissue factor pathway inhibitor and β2-glycoprotein-I, did not change. The substantial reduction in plasma fibrinogen with alcohol intake may well contribute to the apparent protection alcohol confers against ischaemic coronary and cerebral events. The increase in factor VII and relatively greater increase in PAI-1 than tPA with alcohol intake may attenuate this benefit and indeed may sufficiently predispose individuals to thrombosis to contribute to the increased incidence of ischaemic stroke seen in heavier drinkers. The balance of anticoagulant and procoagulant and fibrinolytic effects in any individual may vary depending on quantity and type of alcoholic beverage ingested, as well as on genetic and other variables, all of which merit further study. Blood Coag Fibrinol 9:39–45 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozoto-cin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia. Blood Coag Fibrinol 9:47–53 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The purposes of this study were to investigate the association between carotid atherosclerosis and hemostatic markers, and to elucidate the difference in hemostatic markers between intima-media thickening and plaque formation in patients with cerebral small artery disease. We investigated carotid atherosclerosis by assessing diffuse intima—media thickness measurements and localized plaque using B-mode ultrasonography, and we measured the concentrations of plasma fibrinogen, β-thromboglobulin and platelet factor 4 as markers for platelet activation, and the activity of plasma von Willebrand factor as a marker for endothelial damage. The intima-media thickness was significantly associated with age, male sex, the concentrations of plasma β-thromboglobulin and platelet factor 4, and the activity of plasma von Willebrand factor. The plaque score showed a significant association with male sex, the concentration of fibrinogen, and the activity of plasma von Willebrand factor. These results may indicate that underlying mechanisms are not the same between the intima-media thickness and plaque formation. We suggest that hemostatic markers could reflect the severity of carotid atherosclerosis in patients with cerebral small artery disease, and that preventive antiplatelet therapies against brain infarction might be necessary for patients with severe carotid atherosclerosis. Blood Coag Fibrinol 9:55–62 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

After physical exercise monocytes have been shown to express more lipopolysaccharide (LPS)-induced tissue factor activity compared with monocytes at rest. This is in contrast to LPS-induced tumor necrosis factor (TNF)-α production, which is reduced after physical exercise. Furthermore, LPS-induced tissue factor activity in monocytes at rest has been shown to be dependent on platelets and granulocytes, whereas LPS-induced TNF-α is not affected by these cells. The aim of the present study was to test how platelets and granulocytes affect LPS-induced tissue factor activity in monocytes observed after exercise. This was done by separating the different blood cells before and after exercise, followed by recombination of the cells in plasma and quantification of LPS-induced tissue factor activity in vitro. Two groups of subjects with different aerobic endurance levels were tested to reveal possible differences as a result of physical conditioning. The results of the present study showed that the major effect of exercise was associated with a change in the reactivity of monocytes themselves, since monocytes from blood samples taken after running recombined with platelets, and granulocytes showed the greatest increase in tissue factor activity. Platelets and granulocytes stressed by physical exercise had no further enhancing effect on LPS-induced tissue factor activity other than that observed at rest. The lowest LPS-induced tissue factor activity in all combinations of blood cells was found in athletes, compared with less trained subjects, both at rest and in response to exercise. Blood Coag Fibrinol 9:63–69 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Several studies have demonstrated a higher risk of thrombosis in carriers of anticoagulant deficiencies than in non-deficient individuals from families with thrombophilia. The prevalences in Spain were established in a multicenter study (the EMET study) and all the deficient individuals were invited to recruit all available family members to be screened for the same deficiency in order to establish the risk of thrombosis in deficient individuals. Five-hundred-and-eighty-three individuals from 114 families with natural anticoagulant deficiencies were analysed. Propositi and relatives with a history of thrombosis were asked about the localization and the age at the first episode and whether or not it was spontaneous. Three families with antithrombin deficiency, 35 with protein C, 60 with protein S, four with plasminogen, four with heparin cofactor II, seven with combined deficiencies and one family with dysfibrinogenemia were included in the analysis. The risk of thrombosis was increased for individuals deficient in antithrombin (adjusted odds ratio 21.23; 95% confidence interval 5.71–78.94), protein C (adjusted odds ratio 12.62; 95% confidence interval 4.75–33.51), protein S type I (adjusted odds ratio 19.95; 95% confidence interval 7.40–53.82), protein S type III (adjusted odds ratio 8.11; 95% confidence interval 2.66–21.99) or in protein C plus protein S (adjusted odds ratio 8.99; 95% confidence interval 2.79–28.93), but not for those deficient in plasminogen or heparin cofactor II. The thrombosis-free survival was shortened for deficient individuals in antithrombin (median 30 years), protein C (median 46 years), protein S type-I (median 48 years), protein S type III (median 61 years) and combined protein C and S (median 40 years). In conclusion, individuals carrying anticoagulant deficiencies have an increased risk of thrombosis, especially those with antithrombin, protein C or type I protein S deficiencies. Blood Coag Fibrinol 9:71–78 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Since the first report by Trousseau in 1865, several experimental and clinical studies have established that activation of coagulation is common in cancer. However, the biochemical basis of the activation of coagulation in cancer patients is still not completely understood. The current most accepted opinion is that initiation of coagulation in malignancy is driven primarily by activation of the extrinsic (tissue factor-dependent) pathway. In order to further prove that such a pathogenetic mechanism is actually involved in cancer patients, we correlated the plasma levels of activated factor VIIa (FVIIa), which represent a very small fraction of plasma FVII, with some well-established markers of systemic thrombin generation. Circulating FVIIa was measured using a prothrombin time-based assay that employs a truncated form of human recombinant tissue factor, while plasma levels of the thrombin-antithrombin complex, the prothrombin fragments 1+2 and D-dimer were determined by commercially available ELISA kits. The study was carried out in 37 patients with different types of cancer and 20 healthy controls. Plasma levels of FVIIa were significantly increased while those of FVII antigen (FVIIag) were decreased in cancer patients compared with controls. Furthermore, the FVIIa/ VIIag ratio was more than two-fold higher in cancer patients than in controls. In addition, an excess of thrombin generation was observed in cancer patients. Interestingly, a positive correlation between the FVIIa/VIIag ratio and the plasma levels of either D-dimer (Spearman's r = 0.325; P = 0.027) or prothrombin fragments 1+2 (r = 0.309; P = 0.034) was observed in cancer patients. In conclusion, our study further supports the hypothesis that the tissue factor/VIIa complex is the main determinant of coagulation activation in cancer patients. Large clinical studies will be necessary to determine whether FVIIa and the FVIIa/VIIag ratio are useful prognostic factors of thromboembolic events in cancer patients. Blood Coag Fibrinol 9:79–84 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Twenty-nine clinically well-characterized, symptomatic index patients, 15 with protein C and 14 with protein S deficiency, in whom the genetic defect had been identified, were investigated for the presence of factor V Leiden. In six of 15 (40%) propositi with protein C and four of 14 (29%) with protein S deficiency, factor V Leiden was present. The age at first thrombosis was significantly lower (P < 0.001) in the ten propositi with a combined genetic defect (mean age 18.4 × 6.6 years) than in those with a single defect (mean age 32.6 × 10.4 years). Spontaneous occurrence, recurrence and site of thrombosis were similar in propositi with the single and the combined defect. Family studies led to the identification of a combined defect in 18 individuals from 11 families (11 propositi and 29 relatives), seven subjects had no abnormality, and in 15 a single defect was found. In individuals with a combined defect, thrombosis-free survival time was significantly shorter than in individuals with a single defect, even after exclusion of index patients. None of the seven individuals without genetic abnormality had experienced thrombosis. Our findings indicate a higher risk for development of thrombosis in individuals with a combined defect compared with those with a single defect. Blood Coag Fibrinol 9:85–89 × 1998 Rapid Science Ltd.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID