Understanding the Mechanism of Platelet Thrombus Formation under Blood Flow Conditions and the Effect of New Antiplatelet Agents

2004 ◽  
Vol 2 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Shinya Goto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Flow Conditions ◽  
Platelet Thrombus

A MODEL OF ACUTE PLATELET THROMBUS FORMATION IN STENOSED CORONARY AND CAROTID ARTERIES

1987 ◽  
Author(s):  
J D Folts
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Unstable Angina ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Metabolic Inhibitors ◽  
Coronary Artery Bypass Grafts ◽  
Chewing Tobacco ◽  
Significant Difference ◽  
Platelet Thrombus

There is currently a great deal of interest in the diagnosis and treatment of unstable angina and silent ischemia.Many feel that these syndromes are due, in part, to periodic accumulation of platelet thrombi which subsequently embolize.In addition, anti-piatelet therapy is also considered necessary for patients after coronary artery bypass grafts (CABG'S), balloon angioplasty, and thrombolysis. Currently the two antiplatelet agents most commonly prescribed for the patient conditions mentioned above are aspirin (ASA), alone or in combination with dipyridamole (Dip). ASA reduces cardiac events in patients with unstable angina, and prolongs CABG graft patency. The addition of Dip to ASA therapy is very confusing since most studies done compared ASA + Dip to placebo. In several studies however,when an ASA group was compared to an ASA + Dip group there was no significant difference.We have developed and will describe ananimal model of coronary artery stenosis in the dog and the pig, or carotid arterystenosis in the monkey and the rabbit, with intimal damage, that simulates some ofthe conditions that exist in patients with coronary or carotid artery disease. The artery to be studied is dissected outand blood flow is continuously measured with an electromagnetic flowmeter probe. As acute platelet thrombus formation (APTF) developes in the stenosed lumen, the blood flow declines to low levels, producing ischemia until the thrombus emobolizesdistally resulting in abrupt restoration of blood flow. These cyclical flow reductions (CFR's), when they occur in the coronaries, produce ECG changes identical to those observed in patients with silent ischemia and unstable angina. They also produce significant transient regional dyskinesis of the ventricular wall, which resolves when blood flow is restored. Histologic examination of myocardial tissue in the bed distal to the stenosis shows focal areas of ischemic change presumably caused by the embolized platelet emboli.We have examined factors which exacerbate the size and frequency of these CFR"ssuch as; IV infusion of epinephrine (E) 0.4 μg/kg/min for 15 min, ventilating the animals with cigarette smoke, infusing nicotine IV, or placing chewing tobacco under the tongue.We have examined four groups of agentswhich prevent APTF in our model.1. Antiplatelet agents including ASA, indomethacin, ibuprofen and several other NSAI agentsas well as several experimental thromboxane synthetase inhibitors. These agents all block the production of TXA2and inhibit APTF in our model. Unfortunately the IV infusion of E reinstates APTtemporarily (by another biochemical pathway) until the E is metabolized. High (2-4 mg/kg) doses of Dip, alone or with sub threshold dose of ASA does nothing to I APTF.However,0.6mg/kg of chi orpromaz i ne abolishes APTF in all four species and protects agents renewal of APTF by E.2. Dietary Substances In our model, caffeine 10 mg/kg, or the extract from two garlic cloves, or enough ethanol to achieve a blood alcohol level of 0.07 mg% all significantly inhibit or abolish APTF in our model.3. Metabolic Inhibitors POCA, an oral hypoglycemic agent, which inhibits mitochondrial beta oxidation of fatty acids also inhibits APTF in our model possibly by reducing ATP production in the platelet.4. We have studied a monoclonal antibody(developed by Dr. Barry Coller) to the platelet I Ib�I I la glycoprotein receptor where fibrinogen binds platelets into aggregates and ultimately leads to APTF. This antibody 0.3 mg/kg/completely inhibits APTF, and also strongly inhibits in vitro platelet aggregation in response to either ADP or collagen given alone or each combined with E. This antibody is the most potent inhibitor of APTF that we have studied.

Continuous mathematical model of platelet thrombus formation in blood flow

2012 ◽  
Vol 27 (2) ◽  
Author(s):  
A. Tokarev ◽  
I. Sirakov ◽  
G. Panasenko ◽  
V. Volpert ◽  
E. Shnol ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Blood Flow ◽  
Thrombus Formation ◽  
Platelet Thrombus

Absence of Fibrinogen in Afibrinogenemia Results in Large but Loosely Packed Thrombi under Flow Conditions

2001 ◽  
Vol 85 (04) ◽  
pp. 736-742 ◽  
Author(s):  
Ya-Ping Wu ◽  
Martin IJsseldijk ◽  
Jaap Zwaginga ◽  
Jan Sixma ◽  
Philip de Groot ◽  
...  
Keyword(s):  
Morphological Analysis ◽  
Surface Coverage ◽  
Thrombus Formation ◽  
Flow Conditions ◽  
Thrombotic Complications ◽  
Platelet Thrombus ◽  
The Difference ◽  
Adhesive Proteins ◽  
Lamellipodia Formation

SummaryWe studied the role of fibrinogen in platelet thrombus formation under flow on adhesive proteins using afibrinogenemic blood (LMWH anticoagulated) in a perfusion system. Perfusions with afibrinogenemic blood showed strong increased surface coverage and thrombus volume that normalized upon addition of fibrinogen. Similar studies using citrate anticoagulated blood showed that this was due to fibrinogen and not fibrin. Morphological analysis showed that afibrinogenemic thrombi were loosely packed and consisted mainly of dendritic platelets that contacted one another through filopodia. However, in the presence of fibrinogen, platelets formed lamellipodia and spread out on top of one another. Studies with radiolabeled platelets showed similar numbers of platelets in both conditions demonstrating that the difference is one of packing and the larger size is due to absence of lamellipodia formation and spreading. The found increased thrombus size and loosely packed platelets might help to understand thrombotic complications sometimes seen in afibrinogenemia patients.

scholarly journals The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo

2021 ◽  
Vol 10 (22) ◽  
pp. 5349
Author(s):  
Lydie Crescence ◽  
Markus Kramberg ◽  
Martine Baumann ◽  
Markus Rey ◽  
Sebastien Roux ◽  
...  
Keyword(s):  
Blood Flow ◽  
Guinea Pigs ◽  
Thrombus Formation ◽  
P2y12 Receptor ◽  
Early Application ◽  
Acute Thrombosis ◽  
Thrombosis Model ◽  
Platelet Thrombus ◽  
Platelet Thrombi

Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl3-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice. In addition, in a modified Folts thrombosis model in guinea pigs, selatogrel prevented a decrease in blood-flow, indicative of the inhibition of ongoing thrombosis, approximately 10 min after subcutaneous injection. Selatogrel fully normalised blood flow; therefore, we speculate that it may not only prevent, but also dissolve, platelet thrombi. Thrombus dissolution was investigated using real-time intravital microscopy in mice. The infusion of selatogrel during ongoing platelet thrombus formation stopped growth and induced the dissolution of the preformed platelet thrombus. In addition, platelet-rich thrombi were given 30 min to consolidate in vivo. The infusion of selatogrel dissolved the preformed and consolidated platelet thrombi. Dissolution was limited to the disintegration of the occluding part of the platelet thrombi, leaving small mural platelet aggregates to seal the blood vessel. Therefore, our experiments uncovered a novel advantage of selatogrel: the dissolution of pre-formed thrombi without the disintegration of haemostatic seals, suggesting a bipartite benefit of the early application of selatogrel in patients with acute thrombosis.

Measurement of the Platelet Response to Laserinduced Microvascular Injury

1974 ◽  
Vol 32 (02/03) ◽  
pp. 695-703 ◽  
Author(s):  
T Hovig ◽  
F. N McKenzie ◽  
K.-E Arfors
Keyword(s):  
Blood Flow ◽  
Internal Structure ◽  
Blood Cells ◽  
Thrombus Formation ◽  
Platelet Response ◽  
Microvascular Injury ◽  
Ultrastructural Studies ◽  
Laser Injury ◽  
Complete Destruction ◽  
Platelet Thrombus

SummaryMicrovascular injury was produced in rabbit mesentery and ear chamber preparations using a biolaser. Ultrastructural studies of the injury sites revealed damage to the endothelium which showed cytoplasmic swelling and flocculation. Complete destruction of the endothelium was not observed, indicating that sub endothelial structures were not exposed to blood flow. Microvascular thrombi which occurred at the sites of injury were composed of platelets which in general were loosely packed and showed minor alterations in shape and internal structure. Erythrocytes appeared to be heavily damaged by the laser injury. Fibrin was not observed. It is concluded that ADP may be released from red blood cells, and possibly from other sources, as a result of the laser injury, and that the platelet thrombus formation is induced by ADP.

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