Cardio L18 Thrombosis Flashcards
Thrombosis
Formation of a solid mass from the constituents of the blood within the living circulation.
!!!Distinction from blood clot!!!
Blood clot
When blood solidifies outside the living circulation the solid and fluid components separate and form blood clots.
When a thrombus forms
The cellular and serum phases are mixed and form a series of alternating layers of cell poor and cell rich zones.
Layers of thrombus
Lines of Zahn
Arterial site thrombus type
Tiny, consisting largely of platelets (Very small dimension)
Venous site thrombus type
Small and pale; platelet and fibrin rich (Fast local blood flow)
Capillaries thrombus type
Large and red; Red cell rich (Slow local blood flow)
Virchow’s triad →
The conditions, which predispose to thrombosis, were first addressed by Virchow in the mid 19th Century.
Changes in the vessel wall
Changes in local blood flow
Changes in co-agulative qualities of the blood
Changes in the vessel wall
Loss of endothelial integrity (most common: atheroma)
Changes in local blood flow
Nature of blood flow – laminar vs. turbulent
Disturbance of blood flow allows large numbers of platelets to come into contact with endothelium.
Changes in co-agulative qualities of the blood
Alteration in coagulability of the blood Increased platelet numbers: 1. Major injury 2. Surgery 3. Post partum Increased fibrinogen concentration
→ Thrombus forms at
sites of endothelial injury.
Intact endothelium tend to discourage thrombosis by 3
- Expressing sulphated mucopolysacchardies (heparin and heparin like molecules)
- Expressing tissue plasminogen activator (TPA)
- Synthesizing prostacyclin (PGI2)
The endothelial cell surface is covered by and are potent activators ok
covered by sulphated mucopolysaccharides, which carry a large negative charge.
These molecules are potent activators of circulating antithrombotic enzymes such as anti-thrombin 3.
Heparin causes
A conformational change in the anti-thrombin molecule which enhances its activity a hundredfold.
Endothelium expresses
Tissue plasminogen activator (TPA)
Plasminogen is the
Circulating, inactive, precursor of the enzyme Plasmin which destroys thrombus.
Endothelial TPA activates
Plasminogen with the result that there is active destruction of thrombus at the endothelial surface.
Damaged endothelial cells generates
Prostacyclin (PGI2)
PGI2 function
Dilates vessels
Disaggregates platelets
Opposition to PGI2
Prostaglangin generated by platelets
Platelets description
Circulating anuclear fragments of the cytoplasm derived from megakaryocytes (multinucleate bone marrow cells, each of which will generate between 2000 & 4000 platelets).
Platelets structure
3 microns diameter
Conc – 200-400 x 10 to the 9/L
Approx 10 day life span
Platelets Contain two sorts of cytoplasmic granules
Alpha granules
Dense bodies
Alpha granules
Coagulation factors
Platelet derived growth factors
Fibrinogen
Dense bodies
Unique to platelets
Adenine nucleotides (ADP)
5 Hydroxytryptamine
Calcium
Platelet Adhesion
Rapid adherence to collagen exposed by endothelial damage
Platelet releases reaction
Degranulation of the platelets
Platelet aggregation
- Platelets rapidly clump together to cover the area of endothelial cell loos
- Mediated by ADP and Ca2+
Prostaglandins Generated from
Cell wall phospholipids, which are released when cells are injured.
Endothelial cells generate
Prostacyclin (PGI2)
Endothelial cells generating prostacyclin (PGI2) function
Dilates vessels
Disaggregates platelets
Thromboxane produced by
Platelets
Thromboxane function
Constricts vessels
Aggregates platelets
PGI2 Function
Vasodilation
Platelet disaggregation
PGI2 Derived from
EPE
PGI3
TXA3
PGI3 function
Vasodilation
Platelet disaggregation
TXA2 function
Vasoconstriction
Platelet aggregation
TXA3 function
Almost without action
Diet that reduce thromboxane activity
Diets rich in EPE, such as oily fish, evening primrose oil result in reduced thromboxane (TXA3) activity and thus have an anti-thrombotic effect.
Virchow’s Triad 2: Co-agulative qualities of the blood:
- Changes in blood constituents
a. Alteration in coagulability of the blood
b. Increased platelet numbers
i. Major injury
ii. Surgery
iii. Post partum
c. Increased fibrinogen concentration
Normal platelet numbers
200-400x10(9) /L
Platelet numbers Can increase to
900-1200 x 10 (9)/L
Risk of elevated platelets
Increased risk of thrombosis
Coagulation Cascade:
Consists of a series of circulating plasma proteins which, with the appropriate stimulus, are activated sequentially with the goal of precipitating Fibrin which forms a fibrous mesh, or scaffold, fo the formation of thrombus.
Coagulation: steps
amplification
Control
Amplification
The sequential activation of the clotting factors leads to enormous amplification of the initial signal.
Control
Antithrombin 3
Heparin
Anticoagulation
- Enhancing the action of Antithrombin 3 by adding Heparin
* Reducing the concentration of coagulation factors
Reducing the concentration of coagulation factors how
Achieved by reducing their production in the liver (using dicoumarols such as Warfarin) or by removing the clotting factors from the circulation.
Nature of blood flow
laminar vs. turbulent.
Disturbance =
allows large numbers of platelets to come into contact with endothelium.
Laminar Flow
Minimal mixing between layers
Cellular component of the blood moves in the fast flowing, lower pressure zone, in the centre of the vessel with the result that platelets have little contact with endothelium.
Turbulent Flow
With disturbance of aminar flow and the introduction of turbulence large numbers of platelets are brought into contact with the endothelial surface.
Common Sites for formation of thrombus: arterial
- Atheromatous plaque
a. Coronary arteries
b. Aorta - Endocardium
a. ‘mural thrombus’
b. following myocardial
c. infarction
Common Sites for formation of thrombus: venous
Venous side of the circulation
- Deep veins of the leg
- Pelvic veins
