Coagulation cascade Flashcards
What is hemostasis?
The process of blood clot formation and dissolution
What does homeostasis require?
Platelet activation and a cascade of zymogens activation
4 phases of hemostasis
Constriction of blood vessel
Formation of a temporary “platelet plug”
Activation of the coagulation cascade
Fibrinolysis
Which steps are included in primary hemostasis?
Constriction of blood vessel
Formation of a temporary “platelet plug”
Activatio
Which step is included in secondary hemostasis?
Activation of the coagulation cascade
Which are the smallest cell in the blood?
Platelets
Where is the production of platelets?
Bone marrow
What is endothelin released by?
The endothelium
What layer of the blood vessel is destroyed during injury?
The endothelium layer
What causes platelet activation?
Collagen and basement membran exposure to blood
What does endothelin release cause?
Vasoconstriction
What are some of the signalling molecules released by platelets?
Thromboxanes
What allows adhesion of platelets to collagen?
Membran proteins like GPIb, GPIIB and GPIIIa
What is the coagulation cascade?
A series of reactions catalysed by protein enzymes known as coagulation factors
Why is blood coagulation a cascade?
A small trigger can have a bigger impact
It is very sensitive and effective
Is blood coagulation cascade regulated?
Yes highly
There are inhibitors which help with regulation
Are there more than one entry point?
Yes there are the intrinsic pathway and the extrinsic pathway
What is the extrinsic pathway triggered by?
Trauma
What is the intrinsic pathway triggered by?
Internal factors
Do the two pathways work independently?
Yes they can be triggered at the same time, both or just one
What surfaces are exposed upon future of the endothelial lining of the blood vessel?
The anionic surfaces
Example of coagulation factors
Fibrinogen
Prothrombin
Whatkind of enzymes are most of the coagulation factors?
Serine proteases
What is the final product of the coagulation cascade?
Cross-linked fibrin net
What is the activated fibrinogen?
Fibrin
What activated fibrinogen?
Thrombin
Can thrombin also activate upstream?
Yes and it is called retrograde activation
Which is the only enzyme in the coagulation cascade that is not serine protease?
Fibrin-stabilizing factor which is Ca2+ dependent transglutaminase
What triggers the intrinsic pathway?
When factor XI is converted to factor XIa by thrombin
What converts fibrinogen into fibrin?
The proteolytic removal of amino acid residues
Is vitamin k essential for blood coagulation cascade?
Yes
What gets cleaved by thrombin?
The alpha and beta tails of fibrinogen
What does factor XIIIa do?
It binds, doesn’t cleave
Is activated by thrombin
What degrades fibrin when the clot is no longer needed?
The enzyme plasmin
Is plasminogen already incorporated in the clot?
Yes and is then activated by factors
2 conditions that cause blood coagulation cascade to go wrong
Hemophilia
Thrombosis
What happens in thrombophilia?
Your blood clots more than in healthy individuals
What is haemophilia caused by a defect in?
Zymogen activation
What is a blood clot?
An Aggregate of specialised cell fragments which lack nuclei (platelets) cross-linked and stabilised by proteinaceous fibers consisting mainly of the protein fibrin
What are platelets?
Specialized cell fragments that lack nuclei
What is fibrin?
A protein
What is fibrin derived from?
The soluble zymogen fibrinogen
What are platelets differentiated by?
Hematropic cells
What does the shape change of platelets during platelet activation allow for?
Makes them able to bind to eachother
What shape does platelets change from and to?
Pancakes to more ball shape with protrusion
What kind of covalent modifications are made by th blood coagulation cascade, reversible or irreversible?
Irreversible
What are serine proteases?
Enzymes that cleave peptide bonds in proteins
What does serine serve as at the active site of the enzyme?
Nucleophilic amino acid
What is the main player in the catalytic mechanism in the serine proteases?
The catalytic triad
What does the catalytic triad consist of?
His 57
Ser 195
Asp 102
What converts fibrinogen to fibrin?
The proteolytic removal of amino acid residues
What does thrombin catalyse?
Peptide removal
What does factor XIIIa catalyse?
The formation of covalent cross-links between fibrins
What are gamma-carboxylated clotting proteins chelated to the membrane surface via?
Electrostatic interactions with calcium and negatively charged phospholipids of the platelet membrane
Is the activation of prothrombin fast or slow? and why
Slow because the activator cofactors are only present in small amounts
Which vitamin is essential for the process of clotting?
Vitamin K
What do vitamin K antagonists do?
They do not allow reduction of vitamin K
What converts fibrinogen to fibrin?
Thrombin
What is the precursor to Fibrin?
Fibrinogen
What can the fibrin monomers form when aggregated?
A soft clot
What stabalizes a soft clot?
Formation of amide bonds between the side chains of lysine and glutmine residues in different monomers
Which reactions cross-links fibrin monomers?
The transmutation reaction catalysed by factor XIIIa, transglutaminase
What ensures that clotting is regulated and limited to the site of injury?
Many mechanism:
Some factors are unstable and lose activity quickly
Clotting factors are diluted by blood flow
Some factors are digested by protein C
Protease inhibitors
Heparin
What is protein C activated by?
Thrombin
What is heparin?
Anticoagulant found in mast cells
What does heparin do?
Helps inactivate serine protease clotting factors
When does heparin cofactor II inhibit thrombin?
In its procoagulant role
When does protein C inhibit thrombin/thrombomodulin complex?
When thrombin plays an anticoagulant role
What degrades fibrin?
Plasmin
Which enzyme are clots dissolved by?
Plasmin
What is Plasmin?
An enzyme
What is plasmin formed from?
Plasminogen
What catalyses the reaction where plasminogen is made into plasmin?
Tissue-type plasminogen activator (TPA)
What does fibrinolysis involve?
Degradation of fibrin in a clot by plasmin
What kind of enzyme is plasmin?
Serine protease
What can activate plasminogen?
Tissue plasminogen activator
Urokinase
What is haemophilia?
Increased tendency to bleed
What causes haemophilia?
An abnormality of a blood-clotting factor
Defect in zymogen activation
Which is the major form of haemophilia?
Haemophilia A
What is haemophilia a caused by?
A defect of clotting factor VIII
What tests the intrinsic pathway?
Activated partial thromboplastin time
What tests the extrinsic pathway?
Prothrombin time
What tests the final common pathway?
Thrombin clotting time
What does aspirin block the formation of?
Thromboxane
What is heparan sulfate?
A heparin-like polysaccharide but attached to proteins
Which are the highest negative-charge density biomolecules?
Heparin
Heparin sulfate
How does heparin and heparin sulfate prevent blood clotting?
By activating protease inhibitor antithrombin
What happens when heparin and heparin sulfate binds to viruses and bacteria?
decreases their virulence
What does warfarin inhibit?
Vitamin K production
Different name for thrombin
Factor 2
Is fibrin soluble or insoluble in blood plasma?
Insoluble
