Acute Coronary Syndrome
Platelet activation and acute thrombosis in ACS:
Atherosclerosis is a chronic inflammatory process initiated by endothelial injury. It starts off
with fatty streaks and foam cell formation followed by intimal thickening then an atheroma.
Vulnerable plaque is one which has a thin fibrous cap, lipid rich and necrotic core as well as
inflammatory cell infiltrates. This breaks more easily, and fat exposed which is foreign.
Stable plaque is one which has more smooth muscle proliferation so a thicker fibrous cap
and a lipid-poor core. This is safer and has a lower risk of getting MI.
Statins taken help to increase the thickness of the cap and make it more stable so it’s safer.
, Above shows vulnerable plaque which narrows the blood vessel causing stable angina. This
over time will grow and obstruct the vessel even more as the plaque becomes more stable
or it can rupture where the lipid core and collagen is exposed so attracts platelets so platelet
aggregation occurs which could either heal into a more obstructed vessel or a thrombus can
form which either partially or fully blocks the vessel causing severe ischaemia – leading to
unstable angina/MI/death.
When you have erosion of the plaque platelet adhesion occurs via p-selectin (released by
platelet from vesicles formed when activated) to the endothelium as they are activated by
chemicals and develop a fuzzy look. Then the glycoprotein IIb-IIIa (exposed on platelet
surface) and ICAM-1 allow the platelet to stick together via fibrin (so coagulation cascade
needed to form this too – hence it’s all occurring at the same time).
Some parts of the
platelet clot can break off and go downstream (microembolisation) and as they are
activated, they release various molecules such as TXA2 which cause vasoconstriction, so
circulation reduced in small blood vessels which results in ischaemia. The thrombus itself can
block off a blood vessel – thromboembolism.
Anti-platelet therapies are used in ACS as plaque has ruptured and thrombus formation is
likely which will block large amount of the vessel – reduced blood supply to heart. Inhibiting
platelets aggregation and activation prevents onset of thrombus formation and vessel isn’t
as likely to get fully blocked.
Various parts of platelet and its activation pathway are targeted by drugs. Aspirin is used
which inhibits the COX domain so preventing formation of TXA2 so decreased platelet
aggregation and vasoconstriction. There are also drugs which act in the P2Y receptor (ADP
binds to this activating platelets) e.g. clopidogrel, prasugrel and ticagrelor. In situation e.g.
MI patient about to be given a stent, two anti-platelets will be given including aspirin and
one of the P2Y antagonists. To prevent the platelet aggregation, target the GP IIb-IIIa
Platelet activation and acute thrombosis in ACS:
Atherosclerosis is a chronic inflammatory process initiated by endothelial injury. It starts off
with fatty streaks and foam cell formation followed by intimal thickening then an atheroma.
Vulnerable plaque is one which has a thin fibrous cap, lipid rich and necrotic core as well as
inflammatory cell infiltrates. This breaks more easily, and fat exposed which is foreign.
Stable plaque is one which has more smooth muscle proliferation so a thicker fibrous cap
and a lipid-poor core. This is safer and has a lower risk of getting MI.
Statins taken help to increase the thickness of the cap and make it more stable so it’s safer.
, Above shows vulnerable plaque which narrows the blood vessel causing stable angina. This
over time will grow and obstruct the vessel even more as the plaque becomes more stable
or it can rupture where the lipid core and collagen is exposed so attracts platelets so platelet
aggregation occurs which could either heal into a more obstructed vessel or a thrombus can
form which either partially or fully blocks the vessel causing severe ischaemia – leading to
unstable angina/MI/death.
When you have erosion of the plaque platelet adhesion occurs via p-selectin (released by
platelet from vesicles formed when activated) to the endothelium as they are activated by
chemicals and develop a fuzzy look. Then the glycoprotein IIb-IIIa (exposed on platelet
surface) and ICAM-1 allow the platelet to stick together via fibrin (so coagulation cascade
needed to form this too – hence it’s all occurring at the same time).
Some parts of the
platelet clot can break off and go downstream (microembolisation) and as they are
activated, they release various molecules such as TXA2 which cause vasoconstriction, so
circulation reduced in small blood vessels which results in ischaemia. The thrombus itself can
block off a blood vessel – thromboembolism.
Anti-platelet therapies are used in ACS as plaque has ruptured and thrombus formation is
likely which will block large amount of the vessel – reduced blood supply to heart. Inhibiting
platelets aggregation and activation prevents onset of thrombus formation and vessel isn’t
as likely to get fully blocked.
Various parts of platelet and its activation pathway are targeted by drugs. Aspirin is used
which inhibits the COX domain so preventing formation of TXA2 so decreased platelet
aggregation and vasoconstriction. There are also drugs which act in the P2Y receptor (ADP
binds to this activating platelets) e.g. clopidogrel, prasugrel and ticagrelor. In situation e.g.
MI patient about to be given a stent, two anti-platelets will be given including aspirin and
one of the P2Y antagonists. To prevent the platelet aggregation, target the GP IIb-IIIa
