摘要:

The pathogenesis of thrombosis involves consideration of two processes: atherosclerosis and thrombosis. Atherosclerosis is a prolonged process in which interaction of lipids and the haemostatic system produces focal lesions at sites of turbulence in arteries. These lesions may rupture, precipitating the complication of thrombosis and leading to complete occlusion of the vessel, causing myocardial infarction, stroke, or acute ischaemia. In veins the atherosclerotic process does not occur, and thrombosis is precipitated by immobility often associated with accidental or surgical trauma. The changes in platelets, coagulation, fibrinolytic systems leading to atherosclerosis and thrombi are reviewed. The role of platelets and coagulation changes in these processes are emphasized by the beneficial effects of therapy, both antiplatelet and anticoagulant therapy. Last, the concept of hypercoagulability leading to accelerated arterial disease and the clinical value of laboratory tests used in its detection are considered.

ISSN:1424-8832    

DOI:10.1159/000216161

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216105

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

We have studied the procoagulant activity (PCA) of blood and spleen mononuclear phagocytes and the thrombomodulin activity of aortic segments in rabbits fed an atherogenic diet for 6 weeks as compared to rabbits fed a standard diet. Blood monocytes expressed negligible basal PCA (i.e., PCA measured immediately after cell isolation) both in treated and control rabbits. PCA induced by endotoxin in vitro was not different in the two groups. In contrast, dietary treatment resulted in a significant increase in the basal PCA of spleen cells (p < 0.01). Moreover, the latter produced significantly more PCA than control cells (p < 0.002) in response to endotoxin in vitro. The thrombomodulin activity associated with aortic endothelium was not different in the two groups of animals despite the presence of visible fatty streaks on the aortic endothelium of treated rabbits. When rabbits were given a single injection of endotoxin, spleen mononuclear phagocytes harvested 60 min after the injection from treated animals expressed three times more PCA (p < 0.01) than did cells from controls. In all instances PCA was identified as tissue factor. Endotoxin injection did not affect the thrombomodulin activity of thoracic aorta from both control and diet groups. It is suggested that dietary fats may cause early functional changes in mononuclear phagocytes that lead to an increased PCA production both in vivo and in vitro. These data may be relevant to an understanding of the role of monocytes-macrophages in the pathogenesis of atherosclerosis.

ISSN:1424-8832    

DOI:10.1159/000216106

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216107

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216108

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216109

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Heparin fractions and fragments are useful tools in the elucidation of the mechanism of action of heparin and similar substances. The identification of portions with low or high affinity for antithrombin III and of a ‘core’ pentasaccharide responsible for anti-factor Xa activity has been possible thanks to heparin fractionation and fragmentation procedures. The development of low molecular weight heparins led to the production of substances with a molecular weight around 5,000, considerably variable in chemical structure, anti-factor Xa and anti-factor IIa activities, and experimental antithrombotic effects. The original rationale according to which fragments with high anti-factor Xa activity and anti-factor Xa/anti-factor IIa ratio would retain optimal antithrombotic activity with greatly reduced prohemorragic actions, turned out to be an oversimplification of the problem. In fact, neither is the anti-factor Xa activity the only determinant of the antithrombotic effect, nor is the anti-factor IIa activity a good predictor of hemorrhage. Despite disaggregation of the original rationale, low molecular weight heparins have already proved to be at least as effective and safe, and more conveniently and practically administered, as unfractionated heparin in the prophylaxis of deep-vein thrombo

ISSN:1424-8832    

DOI:10.1159/000216163

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Heparins, unfractionated and low molecular weight, act primarily by their scavenging of thrombin (S-type heparins). Via the feedback effect on factor VIII this has a secondary effect on prothrombin conversion in the intrinsic pathway (activated partial thromboplastin time). The anti-Xa action of a heparin will not significantly inhibit prothrombin conversion, except in the case of ultra low molecular weight heparins (P-type heparins) that have no significant antithrombin activity. These P-type heparins need, therefore, be given at high doses to have an antithrombotic effect. In platelet-rich plasma heparins retard platelet activation by lowering thrombin levels. Activated platelets neutralize up to 0.5 U/ml of unfractionated heparin, but low molecular weight heparin is much less affected.

ISSN:1424-8832    

DOI:10.1159/000216164

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The main kinetic features of heparin and low molecular weight heparins (LMWHs) are reviewed. The complexities related to the study of a nonhomogeneous drug containing fractions with different molecular weight and pharmacological effects are discussed along with the possible bias due to the prevalent use of indirect measures of drug concentration. Available data show that LMWHs have longer half-lives with respect to that of heparin and higher bioavailabilities after subcutaneous administration; experimental and clinical evidences suggest that the kinetics of heparin and LMWHs can only be described taking into account the presence of an endogenous pool from which these drugs are released with different speeds and after various types of manipulations.

ISSN:1424-8832    

DOI:10.1159/000216165

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Monocytes are able to specifically bind heparin rapidly, reversibly, and saturably with 5.5 ± 2.6 × 106 binding sites per monocyte and a dissociation constant of 330 ± 221 nmol/l. Moreover, at least 40–50% of the cell-bound heparin can be internalized. Heparin binding by monocytes is affected by cell stimulation with an increase of the availability of binding sites after challenge with calcium ionophore, lipopolysaccharide, and interleukin 2. The interaction of heparin with monocytes reversibly decreases the expression of tissue factor on the cellular surface, so hampering the cellular procoagulant poten

ISSN:1424-8832    

DOI:10.1159/000216166

出版商:S. Karger AG    

年代:1990

数据来源: Karger