Haemostasis and Thrombosis Flashcards
What is primary haemostasis?
The formation of a primary platelet plug
Describe the process of primary haemostasis
1) Damaged endothelium exposes collagen to the plasma components
2) vWF in the circulation binds to exposed collagen
3) Circulating platelets bind to the collagen-bound-vWF via glycoprotein 1b on their membrane. This binding causes release of agonists such as ADP, thromboxane and serotonin and causes the exposure of the platelet 2b and 3a glycoproteins which act as a 2nd site for vWF binding or binding to circulating fibrinogen to assist coagulation
4) vWF allows the platelets to bind to each other leading to platelet aggregation and the formation of the primary platelet plug.
What are platelets?
Platelets are non-nucleated cytoplasmic fragments that are derived from megakaryocytes in the bone marrow. These fragments can survive between 8-14 days and are removed from the circulation by the reticuloendothelial system.
How are platelets removed from the circulation?
Reticuloendothelial system
What do the delta granules/dense bodies of the platelets contain?
ADP
What do the alpha granules of the platelets contain?
vWF, fibrinogen and plasminogen activator inhibitor-1.
What is secondary haemostasis?
The formation of a stable clot due to fibrin mesh formation
Describe the process of secondary haemostasis
Whether it is by the extrinsic or intrinsic pathway, prothrombin cleavage is stimulated by factor Xa. Thrombin then acts to convert soluble fibrinogen into insoluble fibrin. Thrombin also activates factor XIII which then aids crosslink formation between platelets to create a meshwork to form the stable clot.
What is factor II in the coagulation cascade?
Prothrombin
What is factor I in the coagulation cascade?
Fibrinogen
Describe the extrinsic pathway of the coagulation cascade (secondary haemostasis)
- Factor III (tissue factor) is found in the sub-endothelial tissue and is exposed in vascular injury causing it to be activated to Factor IIIa
- Factor IIIa (activated tissue factor) then activates factor VII
- Factor IIIa (tissue factor) and factor VIIa combine to form the extrinsic ten-ase complex to form factor X
- Factor X is then activated to form factor Xa and this acts to cleave prothrombin into thrombin with the help of factor V (which can then cleave fibrin from fibrinogen and lead to the formation of a stable mesh and a stable clot)
Describe the intrinsic pathway of the coagulation cascade (secondary haemostasis)
- Factor XII is activated to become factor XIIa
- Factor XI is activated to become factor Xia
- Factor IX is activated to become factor IXa
- Factor IXa and factor VIII combine to form intrinsic ten-ase complex
- The formed factor X (intrinsic ten-ase complex) is then activated to become factor Xa which acts to cleave prothrombin into thrombin with the aid of factor V
What is factor III in the coagulation cascade?
Tissue factor
Describe the common pathway of the coagulation cascade (secondary haemostasis)
Both the extrinsic and intrinsic pathways converge when factor Xa cleaves prothrombin into thrombin
- Factor X is activated to become factor Xa (sum of 8 and 9 in intrinsic and 7 + 3 in extrinsic)
- Factor Xa then causes the cleavage of prothrombin to form thrombin, with the aid of factor V
a. Thrombin production also stimulates the activation of factor XIII - Thrombin then allows the cleavage of fibrinogen and fibrin with the aid of factor XIIIa
How does thrombin enhance the coagulation cascade?
It enhances the ctivity of: factor V, VIII, IX and XIII i.e. the two factors involved in producing the intrinsic ten-ase complex, the molecule that aids in the cleavage of prothrombin to thrombin and the factor which aids in the formation of a stable fibrin clot from fibrin.
