Platelets, Vessel Wall, and the Coagulation System

1997 ◽  
pp. 585-618 ◽  
Author(s):  
R. Heller ◽  
E. M. Bevers
Keyword(s):  
Vessel Wall ◽  
Coagulation System

Oxidative Stress and Atherosclerosis: Its Relationship to Growth Factors, Thrombus Formation and Therapeutic Approaches

1999 ◽  
Vol 82 (S 01) ◽  
pp. 32-37 ◽  
Author(s):  
Karlheinz Peter ◽  
Wolfgang Kübler ◽  
Johannes Ruef ◽  
Thomas K. Nordt ◽  
Marschall S. Runge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factors ◽  
Vessel Wall ◽  
Inflammatory Responses ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Vascular Lesion ◽  
Coagulation System ◽  
Therapeutic Approaches ◽  
Causative Relationship

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.

scholarly journals Fibrinopeptide a Measurements in the Study of Thrombosis

1977 ◽  
Author(s):  
H.L. Nossel
Keyword(s):  
Arterial Thrombosis ◽  
Vessel Wall ◽  
Heparin Therapy ◽  
Coagulation System ◽  
Fibrinopeptide A ◽  
Elevated Plasma ◽  
Normal Range ◽  
Diseased Vessel ◽  
Relationship Of ◽  
The Relationship

Elevated plasma fibrinopeptide A (FPA) levels have been found in all patients with acute (symptoms for 5 days or less) venous or arterial thrombosis and/or embolism studied in our institution. Heparin therapy results in a decline of fibrinopeptide A levels to the normal range. In most instances the normal level is attained within 15 minutes of the start of therapy but in some instances return to normal is delayed for up to 72 hours.FPA levels have not been tested in a formal study on the prediction of thrombosis. The results will be presented of serial FPA measurements and the relationship of FPA elevations to recurrence of symptoms and. extension of the disease in patients with thrombo-embolism. The usefulness of FPA tests in the diagnosis of prethrombotic states will depend on the pathophysiology of these states.Measurement of FPA levels may be useful in predicting thrombosis under circumstances in which activation of the coagulation system precedes thrombosis. When thrombosis results from the reaction of normal blood with diseased vessel wall FPA levels will not be useful in prediction.Since- the pathogenesis of thrombosis is likely to vary in different syndromes, the pathophysiology of these syndromes will have to be investigated separately to answer questions as to the usefulness of such tests in prediction.

scholarly journals Reversible thrombocytopenia during hibernation originates from storage and release of platelets in liver sinusoids

2021 ◽  
Vol 191 (3) ◽  
pp. 603-615
Author(s):  
Edwin L. de Vrij ◽  
Hjalmar R. Bouma ◽  
Maaike Goris ◽  
Ulrike Weerman ◽  
Anne P. de Groot ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Blood Flow ◽  
Vessel Wall ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Coagulation System ◽  
Liver Sinusoids ◽  
Platelet Dynamics ◽  
Interleukin 1Α

AbstractImmobility is a risk factor for thrombosis due to low blood flow, which may result in activation of the coagulation system, recruitment of platelets and clot formation. Nevertheless, hibernating animals—who endure lengthy periods of immobility—do not show signs of thrombosis throughout or after hibernation. One of the adaptations of hemostasis in hibernators consists of a rapidly reversible reduction of the number of circulating platelets during torpor, i.e., the hibernation phase with reduction of metabolic rate, low blood flow and immobility. It is unknown whether these platelet dynamics in hibernating hamsters originate from storage and release, as suggested for ground squirrel, or from breakdown and de novo synthesis. A reduction in detaching forces due to low blood flow can induce reversible adhesion of platelets to the vessel wall, which is called margination. Here, we hypothesized that storage-and-release by margination to the vessel wall induces reversible thrombocytopenia in torpor. Therefore, we transfused labeled platelets in hibernating Syrian hamster (Mesocricetus auratus) and platelets were analyzed using flow cytometry and electron microscopy. The half-life of labeled platelets was extended from 20 to 30 h in hibernating animals compared to non-hibernating control hamsters. More than 90% of labeled platelets were cleared from the circulation during torpor, followed by emergence during arousal which supports storage-and-release to govern thrombocytopenia in torpor. Furthermore, the low number of immature platelets, plasma level of interleukin-1α and normal numbers of megakaryocytes in bone marrow make platelet synthesis or megakaryocyte rupture via interleukin-1α unlikely to account for the recovery of platelet counts upon arousal. Finally, using large-scale electron microscopy we revealed platelets to accumulate in liver sinusoids, but not in spleen or lung, during torpor. These results thus demonstrate that platelet dynamics in hibernation are caused by storage and release of platelets, most likely by margination to the vessel wall in liver sinusoids. Translating the molecular mechanisms that govern platelet retention in the liver, may be of major relevance for hemostatic management in (accidental) hypothermia and for the development of novel anti-thrombotic strategies.

The molecular mechanism of mechanotransduction in vascular homeostasis and disease

2020 ◽  
Vol 134 (17) ◽  
pp. 2399-2418
Author(s):  
Yoshito Yamashiro ◽  
Hiromi Yanagisawa
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Cell Interactions ◽  
Aortic Aneurysms ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Vascular Homeostasis ◽  
Matrix Cell

Abstract Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.

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

1994 ◽  
Vol 71 (06) ◽  
pp. 737-740 ◽  
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.

The Hemostatic Mechanism after Open-Heart Surgery

1978 ◽  
Vol 39 (02) ◽  
pp. 474-487 ◽  
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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