Platelet Biochemistry Flashcards
What is thrombosis?
Formation of a clot inside a blood vessel
Play a central role in causing heart attacks and strokes
Atherogenesis definition?
Atherothrombosis definition?
Atherosclerosis definition?
Formation of fatty deposits in the arteries
A progressive disease characterised by the formation of a blood clot with in an artery as a result of atherosclerosis
Atherosclerosis = condition where arteries become blocked with atheroma (plaque)
Atherogenisis and atherothrombosis cause?
They cause blood vessels to narrow which at first has no side effects as they narrow further around the heart they can cause angina and if the atheroma/plaque ruptures it will clot and cause thrombosis — Heart attack, stroke etc
Overview of thrombosis:
- Usually endothelin, NO and prostacyclin Rae secreted by endothelium wall.
Endothelin is a vasoconstrictor and NO and prostacyclin are vasodilators. The VD usually have more of an effect.
During damage to the endothelium wall vasodilators are not made and hence vasoconstriction takes place.
- Platelets are found free in the blood. They carry 2 key granules (alpha and dense) and also have 2 key receptors glycoprotein Ib and IIbIIIa.
NO and prostacyclin usually stop platelets sticking to the walls of the endothelium however there is less and so platelets come closer to the walls.
At the site of injury endothelial cells secrete Von Williebrand factor which when exposed to collagen in the wall binds. It also binds to the GPIb receptor on the platelet, which activates the platelet.
Activation leads to the platelet changing shape, and activates its GPIIbIIIa receptor. The platelet granules are also released into the blood during activation.
The alpha granule contains fibrinogen and VWF and the dense granule contains serotonin, ADP
And Ca2+.
Seretonin is a vasoconstrictor and ADP activates platelets and promotes aggregation.
The activated platelets then release thromboxinA2 which further causes platelet aggregation and activation.
The GP2b3a receptors bind to fibrinogen which binds to more platelets and forms the platelet plug.
- Via the coagulation cascade fibrinogen is converted to fibrin. (Each coagulation factor activates another until thrombin is produced which produces fibrin from fibrinogen).
The intrinsic pathway is activated by collagen exposure to blood - this triggers a set of coagulation factors.
The extrinsic pathway is activated by endothelial cells releasing thromboplastin/tissue factor.
The fibrin produced binds to the platelets to form a stable clot.
What is fibrinolysis?
The breakdown of a clot
Usually a dynamic interaction between fibrinolytic and antifibrinolytic factors designed to cause haemostasis without thrombosis.
Definitions:
Agonist
Plasminogen and plasmin
Monocyte
PAI - 1
= a substance that initiates a physiological response when combined with a receptor
Plasminogen = inactive precursor of plasmin Plasmin = involved in the dissolution of fibrin blood clots
Monocyte = static phagocyte
PAI- 1 = plasminogen activator inhibitor 1 - stops/inhibits the process of fibrinolysis
Definitions:
Dense platelet granules =
Platelet alpha granules =
Coagulation factors
Hepatocyte =
Cytokines =
Dense platelet granules = release ADP, serotonin, Ca2+ - ADP activated P2y1 and P2y12 receptors which in turn activates platelets
Platelet alpha granules = release VWF and fibrinogen
Coagulation factors = proteins in the blood that help to stop bleeding they work together in the coagulation cascade.
Hepatocyte = functional liver cell - produce fibrinogen
Cytokines = small proteins involved in cell signalling
What happens during platelet activation?
Activation leads to the platelets changing shape (smooth discoid — spiculated and pseudopodia) along with its GP2b3a receptor which enables it to bind fibrinogen which binds to more platelets forming a platelet plug.
It also causes the release of the alpha and dense granules. The dense releases ADP which activates and promotes aggregation of more platelets.
The platelets also release thromboxinA2 - again causing more pallet aggregation and activation.
Pathway for thromboxaneA2
Arachidonic acid converted into a thomboxane A2 via a seres of steps one of them being mediated by COX-1.
ThromboxaneA2 — platelet aggregation and vasoconstriction.
A low dose of aspirin inhibits COX -1 only and hence decreases chances of a clot forming
How are P2Y1 and P2y12 receptors activated and what is the consequence?
Both receptors are found on the surface of the platelet. They are activated by ADP from dense granules. There activation leads to shape changes of the platelets and hence more aggregation.
Prothrombin what is it and how is it converted into thrombin?
The precursor to thrombin.
PAR-1, translocase and scramblase are all involved in its production.
Once produced both used to activate platelets and also in the coagulation cascade.
Anticoagulant drugs overview:
Often block thrombin and hence decreases pallet activation and also the coagulation cascade.
