Blood components?
Heterogenous colloidal suspension, containing numerous cell types, proteins, lipoproteins and immunoglobulins.
% composition plasma?
plasma (comprises around 55% of the total blood content).
45% is made of blood cells namely erythrocytes (red blood cells), leukocytes (white blood cells) and thrombocytes (platelets).
define Haemostasis:
Impermeable platelet and fibrin plug or clot is formed at the site of the vessel injury.
- all components already present within the blood so that they are immediately available when required.
define thrombosis?
pathophysiological clotting of blood [i.e. within the lumen or the walls of a blood vessel that is not ruptured].
Physiological anticoagulants- Tissue factor pathway inhibitor (TFPI)
modulates initiation of coagulation induced by tissue factor (TF).
TF is physiological initiator of coagulation
Physiological anticoagulants - protein c
In the presence of its co-factor, protein S, activated protein C (APC) degrades factors Va and VIIIa.
Antithrombin?
inactivates factors IIa, IXa and Xa.
physiological anti-coagulants - Plasmin?
initiates fibrinolysis but its activity is therefore tightly regulated by α2-antiplasmin.
‘white thrombus’?
Clot tends to form within an atherosclerotic plaque and this gives rise to a thrombus composed mainly of platelets and leukocytes
‘red thrombus?
Venous thrombosis - Mainly composed of fibrin and erythrocytes with a small platelet component.
Virchow’s triad - pathological clots?
- The rate of blood flow: slow or static blood flow is more likely to coagulate, whilst turbulent blood flow is more likely to cause endothelial damage (see point 3)
- The constituents of the blood: Alterations in the components.
- The blood vessel wall integrity: damage to the glycocalyx or the endothelium will increase the likelihood clotting
Process of coagulation - cell-based model - initiation?
initiation phase involves the small scale production of thrombin mediated by tissue factor bearing cells
Process of coagulation - cell-based model - amplification?
- When TF- bearing cells come into contact with:
- Platelets which are only present within blood vessels
- The factor VIII/ von Willebrand factor (vWF) complex, which is only released when the vascular endothelium is damaged.
- The amplification phase sets the stage for subsequent large-scale thrombin production and involves thrombin-mediated activation of factors V, VIII, IX on the surface of platelets.
Process of coagulation - cell-based model - Propagation?
- Propagation
The phase predominantly occurs on the surface of the platelets that have been recruited to the site of injury.
* Large scale production of thrombin on the surface of activated platelets resulting in the formation of fibrin strands, which are key constituents of a blood clot.
anti-coagulants - MOA?
drugs that directly or indirectly target the zymogen clotting factors are known as anti-coagulants and these will affect all three stages of coagulation
The anti-platelet drugs - MOA?
affect processes involved in platelet aggregation and these drugs will only act on stages 2 & 3 of the cell-based theory of coagulation
thrombolytic (or fibrinolytic) drugs?
dissolve the fibrin strands holding the clot together and these drugs will only affect the final stage of coagulation.
Platelet activation and aggregation - MOA?
- Thrombin binds to Protease activated receptor (PAR).
- CA2+ influx - exocytosis of ADP granules.
- Autocrine activation of P2Y12 receptor.
- Liberation of Arachnidonic acid from cell membrane
- COX converts AA to Thromboxane A2 = expression of GPIIb receptors/IIia integrin receptors.
= Platelt aggregation.
Clopidogrel - MOA?
ADP (P2Y12 antagonist) - inhibits activation and aggregation.
Aspirin - MOA?
inhibits COX - inhibits production TXA2.
Abciximab?
Inhibits platelet aggregation - binds to GPIIB/GPIIIa
Thrombosis stages?
- TF bearing cells activate Factor 10a/Va = prothrombinase complex.
- Prothrombinase complex - activates factor ptothrombin to thrombin
- Antithrombin (ATIII) - inactivates thrombin (FIIa) and F10A
Dabigataran - MOA?
Inhibits Factor IIa
Rivaroxiban - MOA?
Inhibits - Fxa
