摘要:

beta 2 glycoprotein 1 (β2GP1) is a phospholipid-binding protein implicated in the development of antiphospholipid antibodies, associated with thromboembolic complications and fetal morbidity and death, and is thought to corrrelate better than anticardiolipin (aCL) assays. We analysed the role of β2GP1 in assessing 86 patients being investigated for antiphospholipid syndrome. Thirty-nine patients had 3 tests: [lupus anticoagulant (LA), aCL and β2GP1], and a further 46 had aCL and β2GP1. Sixty-one patients had completely negative tests. Five patients had β2GP1 as the only positive result. 80% of this group had recurrent miscarriage suggesting that β2GP1 may be an useful adjunct to aCL and LA testing in patients with a significant obstetric history.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We have developed a model of a pre-thrombotic state in rats based on venous stasis induced by partial ligature of the inferior vena cava. The degree of stenosis was calibrated by using variations in upstream venous pressure. Different degrees of stasis were tested in order to obtain a pre-thrombotic state. Increasing doses of thromboplastin were infused. The thrombogenic potential of this model was evaluated by measuring thrombus weight and by the increase in levels of thrombin–antithrombin complexes. A pre-thrombotic state was induced by 2 h of exposure to a 40% stasis obtained by increasing by 40% the upstream venous pressure (mean thrombus weight, 0.2 ± 0.6 mg). In these conditions of stasis, low doses of thromboplastin induced venous thrombosis (mean weight, 23 ± 20 mg;P<0.05). The increase in thrombus size was correlated to the rise in thrombin–antithrombin levels (r= 0.53,P<0.001). In conclusion, we have developed the first animal model in which venous stasis can be calibrated by varying the degree of stenosis of the inferior vena cava. This model could be used to study the kinetics of biological markers of hypercoagulability, to study the pathogeny of thrombosis or to evaluate the therapeutic efficacy of new drugs in pre-clinical trials.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Patients with deep venous thrombosis (DVT) treated out of hospital usually start warfarin with the recommended 5 mg loading dose and have their International Normalized Ratio (INR) test performed every 2–3 days. Thus, achievement of the therapeutic range may be more difficult than for inpatients, possibly resulting in extended duration of low molecular weight heparin (LMWH) treatment. We retrospectively examined the charts of 55 DVT outpatients (mean age, 61.4 years; 30 males) to assess the actual duration of LMWH treatment and to identify predictors of a slow achievement of the INR range. Thirty patients (54.4%) reached the therapeutic INR range and stopped LMWH within 7 days, and 25 patients (45.6%) had to continue for an average of 10.5 days. The latter group was significantly younger than the former (57 and 65 years, respectively;P= 0.039). Patients younger than 60 years old had an odds ratio for an extended treatment of 4.92 (P= 0.0057). Algorithms with different loading doses of warfarin according to age should be proposed for outpatient treatment of DVT.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-6), viral load, CD4+T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-α (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A relationship may exist between endothelial-mediated vasodilation and tissue-type plasminogen activator (t-PA) release. However, the existing evidence is mainly based upon exogenous agonist administration, and needs testing under more physiological conditions. We evaluated the link between t-PA, the key fibrinolytic factor in man, and forearm reactive hyperemia, a model of endogenous endothelial-mediated vasodilation, in 13 uncomplicated hypertensive subjects and six elderly hypertensive patients with atherosclerotic peripheral vascular disease and hypercholesterolemia (i.e a group in whom post-ischemic hyperemia was probably defective because of dysfunctional endothelium). To characterize further the phenomenon, 29 additional uncomplicated hypertensive patients underwent intra-arterial drug infusions. Study variables were forearm blood flow (strain-gauge plethysmography), arterial and venous concentrations of t-PA mass concentrations, and calculated net release (forearm plasma flow × veno-arterial differences). Reactive hyperemia was induced by inflating a cuff midway between systolic and diastolic pressure for 10 min; blood and forearm blood flow were sampled before and after cuff release. Post-ischemic t-PA release increased in uncomplicated hypertensives, and did not change in hypercholesterolemic atherosclerotic patients in whom post-ischemic vasodilation was negligible. Local adenosine (n= 9), acetylcholine (n= 12) and bradykinin (n= 8) vasodilated similarly, but only bradykinin increased t-PA release. Thus, reactive hyperemia stimulates t-PA release, and that relationship is altered when endothelium is dysfunctional. Release of t-PA is independent of forearm vasodilatationper se, adenosine or biological products of muscarinic stimulation and may, perhaps, be related to the activity of the endogenous kininogen/kinin system.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We found no prospective studies on dental extraction in anticoagulated patients in the literature, even though most authors suggest that there is no need to change anticoagulant treatment and to utilize a local haemostatic measure after extraction. In the present study, we have verified the incidence of bleeding complications after dental extraction in a group of 250 consecutive anticoagulated patients. Two hundred and fifty non-anticoagulated subjects requiring dental extraction represented the control group. In all patients, anticoagulant treatment was not changed (International Normalized Ratio, 1.8–4) and local haemostatic measures (fibrin sponge, silk suture and a gauze saturated with tranexamic acid) were used. All procedures were performed in an outpatient clinic setting. We registered four bleeding complications in the group of anticoagulated patients and three in the control group. The difference of bleeding complications in the two groups was not statistically different (relative risk, 1.14; 95% confidence interval, 0.29–6.04;P= 0.7). None of the post-operative late bleeding required hospitalization and/or blood transfusions, and further local measures were sufficient to stop the bleeding. The protocol proposed in the present study makes dental extractions in anticoagulated patients possible on an outpatient basis with a cost reduction for the community and minor discomfort for the patients.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

This is the first laboratory evaluation of a new instrument, designed to test both platelet function and thrombolytic activity from a native blood sample,in vitro. The inventor assumed that the reduction and arrest of blood flow was due to activation, aggregation and stabilized thrombus formation by shear-activated platelets, and that re-establishment of flow was due to thrombolysis. Morphologic and functional studies presented here confirm these mechanisms.In vitrotests provided incontestable evidence for the principal role of platelets in the obstruction of flow (occlusion time) and for thrombolysis as the principal mechanism underlying the restoration of blood flow (lysis time). In addition to aggregation, it is the explosive generation of thrombin by shear-activated platelets that results in the formation of an occlusive haemostatic thrombus. Anticoagulation of blood completely prevented occlusion. Platelet-rich thrombus formation (occlusion time) was dose-dependently inhibited by monoclonal antibody against platelet glycoprotein (GP) Ib (6B4 and 12E4), aurin tricarboxylic acid, monoclonal antibody against platelet GPIIb/IIIa (MA-16N7C2 and abciximab), a synthetic GPIIb/IIIa antagonist (TAK-029), thrombin inhibitor (argatroban), and anti-von Willebrand factor, but not by anti-fibrinogen. Plasminogen activator streptokinase (Varidase) and tissue-type plasminogen activator (Monteplase) dose-dependently enhanced thrombolysis (lysis time) without affecting platelet function (occlusion time). The test is specific for thrombolysis. The plasmin inhibitor tranexamic acid prevented plasminogen activator-induced thrombolysis, while inhibition of clot retraction by cytochalasin B did not affect the lysis time. This rapid and sensitive global test of platelet function and thrombolytic activity could be of great value both in research and in clinical practice.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The influence of several eicosanoids of the lipoxygenase pathway was examined in anex vivosystem of human whole blood subjected to stimulation by lipopolysaccharide (LPS). Exogenously added leukotriene B4[5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4)] or 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly (P<0.05) enhanced LPS-evoked expression of monocyte tissue factor (TF) activity in a concentration-dependent manner. 15(S)-HETE, on the other hand, exerted such activity only when added at certain concentrations, whereas 5(S)-HETE was devoid of any apparent activity. LPS-induced TF activity was inhibited by the lipoxygenase inhibitors nordihydroguaiaretic acid, CGS 23885 and ZM 230487, by 59, 32 and 88%, respectively. Furthermore, the production of LTB4in LPS-stimulated whole blood was investigated, in the absence or presence of either tumor necrosis factor α (TNFα) or phorbol-12-myristate-13-acetate (PMA). LPS alone induced a moderate time-dependent and concentration-dependent release of LTB4, reaching the maximum concentration (1260 ± 202 pg/ml) within 90 min at 5 ng/ml LPS. The prior and concurrent presence of PMA (5 ng/ml) or TNFα (10 ng/ml) further enhanced the LTB4production approximately twofold (P<0.05). TNFα added alone evoked approximately twice the LTB4production seen when LPS (2200 ± 243 versus 1260 ± 203 pg/ml) was added alone. Considering these results, LPS and TNFα emerge as important agonists of LTB4production in whole blood. LTB4in turn appears to be of importance for the expression of TF in monocytes, potentially amplifying the thrombogenic potential of these cells.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Factor V Leiden is a well-known risk factor for venous thrombosis. The dual role of factor V as a coagulatory and anticoagulatory cofactor permits the assumption that further mutations in the factor V gene are of importance in the study of the risk of thrombosis. Relevant studies to date have given rise to a controversy over this risk for the HR2 haplotype. For the G allele, defined in our work group as a G at the nucleotide positions 2391, 2663, 2684 and 2863, there have been to date no other investigations of thrombotic risk. In a case–control study on 347 patients with deep venous thrombosis (DVT) and 282 controls, we investigated the association of the HR2 haplotype and the G allele with DVT. We found no association between HR2 haplotype and DVT [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.58–1.30;P= 0.537]. The frequency of the G allele was, on the contrary, higher in the control group than among the patients (OR 0.68, 95% CI: 0.53 to 0.89;P= 0.005). The factor V activity of the HR2 carriers was lower than that of the wild type and G allele carriers. The HR2 haplotype exhibited a moderate influence on activated protein C response. This study presented no evidence of thrombotic risk for the HR2 haplotype alone. The results here permit the assumption of a protective effect of the G allele. The source of a possible protective influence of the G allele on thrombotic risk is at present unclear.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The role of thrombophilia in the elevated risk of thromboembolism during oral contraceptive use has been established. We performed a cross-sectional study among young women to survey the occurrence of antiphospholipid antibodies among users and non-users of oral contraceptives. Serum levels of immunoglobulin (Ig)G, IgA and IgM isotypes of anti-β2-glycoprotein I and anticardiolipin antibodies were measured by validated enzyme-linked immunosorbent assay methods. Combining all types of antiphospholipid antibodies, pill-users had an elevated antibody titre more than twice as frequently as non-users (odds ratio, 2.3; 95% confidence interval, 1.1–5.1). The higher frequency of elevated antibody titre was related most commonly to IgG type anti-β2-glycoprotein I antibodies. Oral contraceptive use increases the risk of elevated antiphospholipid antibody levels among asymptomatic young women.

ISSN:0957-5235    

出版商:OVID    

年代:2003

数据来源: OVID