Haemostasis Flashcards
What are the functions of haemostasis?
- Respond to tissue injury
- Curtail blood loss
- Restore vascular integrity and promote healing
- Limits infection
What is Von Willebrand Factor (VWF)?
Large multimeric glycoprotein present in blood plasma and produced in endothelium
What are the 3 stages of the haemostatic system?
Primary haemostasis
Secondary haemostasis
Fibrinolysis
What are the 3 steps of haemostasis?
- Vasoconstriction
- Platelet Plug
- Coagulation
How long does the coagulation cascade approximately take?
The whole process occurs in less than 30 minutes
What happens to the reactive subendothelium elements when the blood vessel is damaged?
Damaged vessel => endothelium damaged
so collagen exposed to platelets and VWF
What is the prothrombin activator?
Complex of blood coagulation factors catalysing the conversion of prothrombin into thrombin activated by Ca2+
Describe how the coagulation cascade works
- Blood vessel damaged
- Nearby platelets activated, releasing prothrombin
activator - Prothrombin activator converts prothrombin into enzyme thrombin requiring Ca2+ release
- Thrombin facilitates conversion of fibrinogen -> fibrin
fibres - Fibrin threads wind around platelet plug, forming
interlocking network & framework for clot - Net of fibres traps and holds platelets, rbc and other
molecules to injury- functioning as the initial temporary clot
- Clot tightened as platelets shrink drawing vessels
closer together
What is vasoconstriction?
Reflex in which blood vessels narrow to increase blood pressure
What factors are required for the coagulation cascade reactions to occur?
- Ca2+
- Phospholipids
- Specific co factors
What is fibrinogen?
A plasma protein converted to insoluble long fibres of fibrin protein
What is coagulation?
A complex cascade in which a fibrin mesh is cleaved from fibrinogen
What is tissue factor?
aka Platelet tissue Factor, Factor III or CDI42
is a transmembrane receptor for Factor VII/VIIa present in subendothelial tssue
How does fibrinolysis occur?
Plasminogen is converted to plasmin via tissue plasminogen activator
Describe what platelet plug formation is
Involves the activation, aggregation and adherence of platelets into a plug that serves as a barrier against blood flow
What is the role of tissue factor?
Drives coagulation by forming complexes with FVIIa co factor, recruiting Fx and forming thrombin
What are weibel palade bodies?
Storage granules of endothelial cells that store and release VWF and P- selectin
What are the 4 stages of platelet plug formation (primary haemostasis)?
- Adhesion
- Secretion
- Aggregation
- Contraction
How is homeostasis achieved in blood vessels?
Homeostasis achieved when there are equal amounts of Fibrinolytic factors,
anticoagulant proteins and coagulation factors, platelets
What is fibrin?
Protein that acts as a molecular glue during clot formation holding the platelet plug together
What is thrombosis?
Formation of blood clots in a blood vessel obstructing blood flow through circulatory system
What is plasmin?
Enzyme in the blood that degrades fibrin clots
Outline the stages of the cell based model of coagulation
- Subendothelial tissue exposed to circulation at injury
site- subendothelial tssue expresses Tissue factors which
bind to endogenous activated FVII
- subendothelial tssue expresses Tissue factors which
- Complex binds small no. of Fx and Fv to exposed
surface producing thrombin - Thrombin activates platelets and other plasma-borne
clotting factors - Activated factors (including FVIIa & FIX) enable Fx + Fv
to bind to platelets, exposing their reaction sites - Leads to thrombin burst
- Thrombin causes fibrinogen conversion to fibrin
forming clot
What are the components of a blood clot?
- fibrin mesh
- platelets
- red blood cells
What products are formed from the breakdown of fibrin?
D dimers are generated when cross-linked fibrin is degraded
FDP (fibrin degradation products) generated when non cross-linked fibrin or fibrinogen is degraded
Where is VWF synthesised?
Synthesised in endothelial cells’ weibel palade bodies and α-granules of platelets in megakaryotes and subendothelial connective tissue
What is plasminogen?
The inactive precursor of plasmin enzyme
Outline the stages of blood clot formation
- Tissue injury
- Vasoconstriction
- Platelet activation
- Haemostatic plug
- Coagulation
- Stable clot formation
- Clot dissolution
What type of molecules are prothrombin and fibrinogen?
Proteins produced and deposited in blood by the liver
What is the consequence of no VWF?
Loss of VWF function results in bleeding disorders
Describe and explain levels of vasoconstriction within an intact blood vessel
Endothelial cells express fibrinolytic heparin molecule and thrombomodulin
these prevent platelet aggregation -> stop coagulation
What are the functions of Von Willebrand factor?
- Forms bridge between damaged blood vessel wall with
collagen and platelets - Stabilises and protects Factor VIII from rapid clearance
During homeostasis what is the fate of reactive elements in the subendothelium ?
Triggers and cofactors are separated
- Platelets, Von Willebrand Factors + Clotting factors in
blood (lumen)
- Collagen and tissue factors in subendothelium
Name the main clotting factors involved in coagulation cascade
FII prothrombin, thrombin and FI fibrinogen are the main clotting factors involved
What changes occur during coagulation?
Blood changes from liquid -> gel
Clotting factors undergo cascade of chemical reactions, creating a fibrin mesh
Each clotting factor has a specific function
What are the functions of fibrinolysis?
- Clot limiting mechanism
- Repair and healing mechanism
What occurs during primary haemostasis?
Vasoconstriction occurs immediately
Platelet adhesion happens within seconds
Platelet aggregation and contraction occurs after a few minutes
How does vasoconstriction affect an injured blood vessel?
Endothelial cells stop secreting anticoagulants & aggregation inhibitors
They secrete Von Willebrand factors instead
Causes platelet adherence
Vasoconstriction occurring is a brief reflexive contraction causing decreased blood flow to injured area
What is the role of thromboxane A2?
Activates other platelets
What does secondary haemostasis consist of?
Coagulation factors are activated within seconds
Fibrin formation occurs in minutes
How does coagulation occur?
When platelets stick to thrombin in the vessel wall, their secretory granules degranulate, releasing products:
- ADP
- Serotonin
- Thromboxane A2
What is the role of secondary haemostasis?
Fibrin mesh binds and stabilises platelet plug and other cells
What occurs during fibrinolysis?
Fibrinolysis is activated in minutes
Lysis of the plug occurs after a few hours
When does the coagulation cascade take place?
If the platelet plug is not enough to stop bleeding, secondary haemostasis occurs, including coagulation cascade and fibrinolysis
Which enzymes are involved in fibrinolysis?
- plasminogen
- Tissue plasminogen activator (tPA)
- Urokinase (U-PA)
- Plasminogen activator inhibitor 1 and 2
- α2 plasmin inhibitor
What is fibrinolysis?
The process of clot dissolution in a series of tightly regulated enzymatic steps
When does bleeding occur?
Increased fibrinolytic factors and anticoagulant protein
Decreased platelets and coagulation factors
What are the 4 key components of haemostasis?
- Endothelium
- Platelets
- Coagulation
- Fibrinolysis
How does thrombosis occur?
Increased coagulation factors & platelets
Decreased anticoagulant proteins and fibrinolytic factors
What is the conseuqence of increased thrombosis?
Can go on to cause chronic veinous insufficiency
- atrophic changes
- hyperpigmentation
- ulceration
- infection
What is the significance of the vessel wall?
Normal endothelium
- inhibits coagulation
- prevents platelet aggregation
- provides a barrier to reactive elements in the
subendothelium (collagen + tissue factor)
What is the role of the platelet plug?
The plug of activated platelets, localised to injury site, provides phospholipid surface on which secondary haemostasis occurs
What is haemostasis?
Formation of blood clots by slowing down blood flow
It’s a protective process evolved in order to maintain a stable physiology
Outline the stages of platelet plug formation
- Vessel wall damaged; signalling molecules tissue factor
and collagen exposed - Tissue factor produces local thrombin (thromboxane)
initiating coagulation - Exposed signalling molecules attract circulating
platelets which adhere to the exposed subendothelial
tissue - Platelets become activated via thrombin, releasing
more VWF, attracting more platelets - Platelets aggregate forming loose platelet plug
- Loose plug contracts to form dense adherant plug
