Coagulation System/Physiology

SummaryThe initiating event of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction. This is followed by key features of atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodeling of the vasculature, finally leading to vascular lesion formation, plaque rupture, thrombosis and tissue infarction. A causative relationship exists between these events and oxidative stress in the vessel wall. Besides leukocytes, vascular cells are a potent source of oxygen-derived free radicals. Oxidants exert mitogenic effects that are partially mediated through generation of growth factors. Mitogens, on the other hand, are potent stimulators of oxidant generation, indicating a putative self-perpetuating mechanism of atherogenesis. Oxidants influence the balance of the coagulation system towards platelet aggregation and thrombus formation. Therapeutic approaches by means of antioxidants are promising in both experimental and clinical designs. However, additional clinical trials are necessary to assess the role of antioxidants in cardiovascular disease.

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Markers of Hypercoagulability in Patients with Hemophilia B Given Repeated, Large Doses of Factor IX Concentrates during and after Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642515 ◽

1994 ◽

Vol 71 (06) ◽

pp. 737-740 ◽

Cited By ~ 18

Author(s):

E Santagostino ◽

P M Mannucci ◽

A Gringeri ◽

G Tagariello ◽

F Baudo ◽

...

Keyword(s):

High Risk ◽

Ex Vivo ◽

Factor Ix ◽

Hemophilia B ◽

Coagulation System ◽

Prolonged Treatment ◽

Orthopedic Procedures ◽

Factor X ◽

Prothrombin Complex Concentrates ◽

Increased Risk

SummaryPurer factor IX (FIX) concentrates have been produced for the treatment of hemophilia B in the attempt to reduce the risk of thrombotic complications associated with the use of prothrombin complex concentrates. To evaluate ex vivo whether or not FIX concentrates activate the coagulation system in conditions associated with a high risk for thrombosis, we measured markers of hypercoagulability in 10 patients with hemophilia B who underwent surgery, mainly orthopedic procedures, covered by multiple concentrate infusions (40-80 U/kg/day). Postinfusion plasma levels of prothrombin fragment 1+2 and factor X activation peptide did not differ significantly from the presurgical levels, neither before nor after each concentrate dose. Therefore, it appears that prolonged treatment of patients with hemophilia B undergoing high risk surgical procedures with high doses of FIX concentrate does not cause systemic activation of coagulation. This suggests that purified FIX concentrates are preferable to prothrombin complex concentrates for conditions associated with an increased risk of thrombosis.

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The Hemostatic Mechanism after Open-Heart Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646707 ◽

1978 ◽

Vol 39 (02) ◽

pp. 474-487 ◽

Cited By ~ 2

Author(s):

E R Cole ◽

F Bachmann ◽

C A Curry ◽

D Roby

Keyword(s):

Extracorporeal Circulation ◽

Heart Surgery ◽

Polyacrylamide Gel Electrophoresis ◽

Open Heart Surgery ◽

Coagulation System ◽

Open Heart ◽

Time Activity ◽

Post Surgery ◽

Plasma Fractions ◽

The Mean

SummaryA prospective study in 13 patients undergoing open-heart surgery with extracorporeal circulation revealed a marked decrease of the mean one-stage prothrombin time activity from 88% to 54% (p <0.005) but lesser decreases of factors I, II, V, VII and X. This apparent discrepancy was due to the appearance of an inhibitor of the extrinsic coagulation system, termed PEC (Protein after Extracorporeal Circulation). The mean plasma PEC level rose from 0.05 U/ml pre-surgery to 0.65 U/ml post-surgery (p <0.0005), and was accompanied by the appearance of additional proteins as evidenced by disc polyacrylamide gel electrophoresis of plasma fractions (p <0.0005). The observed increases of PEC, appearance of abnormal protein bands and concomitant increases of LDH and SGOT suggest that the release of an inhibitor of the coagulation system (similar or identical to PIVKA) may be due to hypoxic liver damage during extracorporeal circulation.

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Premature Arterial Disease Associated with Familial Antithrombin III Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645677 ◽

1990 ◽

Vol 63 (01) ◽

pp. 013-015 ◽

Cited By ~ 15

Author(s):

E J Johnson ◽

C R M Prentice ◽

L A Parapia

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Potential Risk ◽

Antithrombin Iii ◽

Arterial Disease ◽

Coagulation System ◽

Early Age ◽

Arterial Thromboembolism ◽

Potential Risk Factors ◽

Antithrombin Iii Deficiency

SummaryAntithrombin III (ATIII) deficiency is one of the few known abnormalities of the coagulation system known to predispose to venous thromboembolism but its relation to arterial disease is not established. We describe two related patients with this disorder, both of whom suffered arterial thrombotic events, at an early age. Both patients had other potential risk factors, though these would normally be considered unlikely to lead to such catastrophic events at such an age. Thrombosis due to ATIII deficiency is potentially preventable, and this diagnosis should be sought more frequently in patients with arterial thromboembolism, particularly if occurring at a young age. In addition, in patients with known ATIII deficiency, other risk factors for arterial disease should be eliminated, if possible. In particular, these patients should be counselled against smoking.

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A Re-Appraisal of the Role of Blood Coagulation and Platelets in the Generalized Shwartzman Phenomenon

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649455 ◽

1966 ◽

Vol 15 (03/04) ◽

pp. 519-538 ◽

Cited By ~ 10

Author(s):

J Levin ◽

E Beck

Keyword(s):

Blood Coagulation ◽

The State ◽

Coagulation System ◽

Renal Lesions ◽

Intravascular Coagulation ◽

Renal Glomeruli ◽

Coagulation Mechanism ◽

Shwartzman Phenomenon ◽

Do So

SummaryThe role of intravascular coagulation in the production of the generalized Shwartzman phenomenon has been evaluated. The administration of endotoxin to animals prepared with Thorotrast results in activation of the coagulation mechanism with the resultant deposition of fibrinoid material in the renal glomeruli. Anticoagulation prevents alterations in the state of the coagulation system and inhibits development of the renal lesions. Platelets are not primarily involved. Platelet antiserum produces similar lesions in animals prepared with Thorotrast, but appears to do so in a manner which does not significantly involve intravascular coagulation.The production of adrenal cortical hemorrhage, comparable to that seen in the Waterhouse-Friderichsen syndrome, following the administration of endotoxin to animals that had previously received ACTH does not require intravascular coagulation and may not be a manifestation of the generalized Shwartzman phenomenon.

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Cold Promoted Activation of Factor VII

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649052 ◽

1972 ◽

Vol 28 (02) ◽

pp. 155-168 ◽

Cited By ~ 20

Author(s):

H Gjønnæs

Keyword(s):

Coagulation Factors ◽

Oral Contraception ◽

Factor Vii ◽

Coagulation System ◽

Plasma Coagulation ◽

Main Effect

SummaryThe cold promoted shortening of the thrombotest-times occuring in the plasmas of the majority of women on oral contraception or in the last trimester of pregnancy when incubated overnight at 0°–4° was investigated.The short thrombotest-times were caused by activation of factor VII in a time consuming reaction. Activation was also revealed in the intrinsic coagulation system, but the changes in the activities of coagulation factors other than factor VII were small.Comparison was made between clot promoting effects of cooling and contact, and it was concluded that while contact apparently exerted its main effect in the intrinsic system, cooling predominately activated the extrinsic plasma coagulation system.The cold promoted activation of factor VII seemed to be brought about by an activator.

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A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650089 ◽

1980 ◽

Vol 44 (02) ◽

pp. 081-086 ◽

Cited By ~ 8

Author(s):

C V Prowse ◽

A E Williams

Keyword(s):

Platelet Rich Plasma ◽

Thrombus Formation ◽

Factor Ix ◽

Coagulation System ◽

In Vitro Tests ◽

Clinical Use ◽

Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

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