Describe the role of vascular spasm in haemostasis.

After a vessel is cut or ruptured, the wall contracts due to trauma. This reduces
blood flow from the vessel. Contraction results rom nervous reflexes initiated by
the pain, local smooth muscle spasm and local chemical factors produced by
traumatised tissues.
For smaller vessels, platelets are important as they release the vasoconstrictor
substance, thromboxane A
2
. Thromboxane A
2
helps to control the bleeding. The
greater is the contraction, the greater the degree of spasm.
Local vascular spasm lasts for many minutes or even hours.
Describe how a platelet plug is formed.
Platelets.
Platelets are formed in bone marrow from megakaryotes. They are round and
contain mitochondria, smooth endoplasmic reticulum and cytoplasmic granules but
no nuclei. They cannot reproduce.
They live for 8 days and are eliminated by macrophages.
Platelets have glycoprotein coat so that they can past normal vessel walls and stick
to injured areas. They also have secretory vesicles containing adrenaline,
serotonin, ADP and thromboxane A
2
.
Formation of platelet plug.
When a vessel is damaged, it disrupts the endothelium and exposes the connective
tissues and collagen. Platelets in circulatory blood comes across the area of
endothelial damage, and swells up to form irregulous shapes with numerous
pseudopods and attach to exposed collagen underneath the damaged tissue.
Platelets accumulate. The first player of platelet is platelet adhesion. Contractile
proteins in the platelet release substances from granules such as serotonin and
adrenaline. They cause vasoconstrictions and reduce blood loss.
ADP is also released and causes platelets nearby to become sticky and adhere to
the first row of platelets. This means that the platelets pile up (platelet aggregation)
and forms the platelet plug.
Platelet aggregation is promoted by the release of thromboxane A
2
from platelets
because it triggers the release of more ADP from platelet granules.
The platelet plug is only limited to the site of injury and does not extend further
into normal endothelium because healthy endothelial cells continuously release
prostacyclin. Prostacyclin inhibits platelet aggregation and causes vasodilation.
The balance between thromboxane A
2
and prostacyclin limits the spread of platelet
plugs to only damaged walls.


Describe the 3 major stages of blood coagulation including the intrinsic and
extrinsic pathways.
If there is a large hole, blood clot, in addition to the platelet plug, is required to
stop the bleeding. Coagulation is the transformation of blood into solid gel, clot of
thrombus. It consists mainly of protein polymer called fibrin and clotting occurs
around platelet plug to reinforce the plug.
50 substances have been identified that affects coagulation. Some that promotes
are procoagulant while those that inhibits are anticoagulants. Anticoagulants
usually predominates until there is injury where procoagulants then predominates
Firstly, injury to the vessel calls causes a cascade of chemical reactions involving
chemical factors. This form forms a complex of substances called prothrombin
activator. In the second stage, the prothrombin activator catalyses the conversion
of prothrombin to the enzyme, thrombin. In the last stage, thrombin acts as an
enzyme to convert fibrinogen to fibrin fibres that trap platelets, blood vessels and
plasma to form a clot.
The formation of the prothrombin activator is the rate-limiting step in blood
coagulation. It can be formed by the extrinsic pathway that involves factors present
in damaged tissues, or by the intrinsic pathway involving factors already present in
plasma.
In both pathways, clotting or coagulation factors (plasma proteins) play major role.
Most of them are inactive but are converted to active forms, causing a next cascade
of activation. When prothrombin activator is active, their enzymatic actions cause
the next cascading reactions of the clotting process.
Intrinsic clotting pathway.
Factor XII becomes activated by foreign substances in damaged tissues. Factor XII
activated causes Factor Xi to activate, which in turn activates Factor IX when in
the presence of Ca
2+
ions.
Activated Factor IX then complexes with Ca
2+
, platelet factor 3 and activated
Factor VII to activate Factor X. Activated Factor X activates with Factor V
(complemented by Ca
2+
, platelet factor 3 and tissue phospholipids) to form the
prothrombin activator.






Extrinsic clothing pathway.
Tissue damage begins and comes into contact with blood. Traumatic tissue release
Factor III. Factor III complexes with Factor VII, Factor V and with Ca
2+
to
produce the extrinsic thromboplastin. In the presence of Ca
2+
, extrinsic
thromboplastin will then activate Factor X. Activated Factor X reactions with
Factor V, Ca
2+
and the extrinsic thromboplastin to form the prothrombin activator.

Common pathway.
Even though the intrinsic and extrinsic pathway start from separate places, they
eventually merge at the formation of the prothrombin activator (or specifically, the
activation of factor X).
Prothrombin activator catalyses the reaction of prothrombin converting to
thrombin. In the presence of Ca
2+
, thrombin catalyses fibrinogen and convert it to
fibrin.
4
PROTHROMBIN ACTIVATOR
Formation of this is the rate limiting step in blood coagulation!
Prothrombin activator formed in two ways
- by the extrinsic pathway involving factors
present in damaged tissue
- by the intrinsic pathway involving factors
already present in plasma
In both pathways, clotting or coagulation factors (plasma
proteins) play major roles.
When active, their enzymatic actions cause the next cascading
reactions of the clotting process.
INTRINSIC CLOTTING PATHWAY
EXTRINSIC CLOTTING PATHWAY
COMMON PATHWAY
4
PROTHROMBIN ACTIVATOR
Formation of this is the rate limiting step in blood coagulation!
Prothrombin activator formed in two ways
- by the extrinsic pathway involving factors
present in damaged tissue
- by the intrinsic pathway involving factors
already present in plasma
In both pathways, clotting or coagulation factors (plasma
proteins) play major roles.
When active, their enzymatic actions cause the next cascading
reactions of the clotting process.
INTRINSIC CLOTTING PATHWAY
EXTRINSIC CLOTTING PATHWAY
COMMON PATHWAY

Conversion of fibrinogen to fibrin.
Thrombin changes fibrinogen into a smaller fibrin monomer. Fibrin builds the
structure of the clot by polymerizing with other fibrin monomers to form a loose
network of strands held together by weak hydrogen bonds. This means that it can
be broken easily.
However, the meshwork is stabilized by the formation of covalent linkages
between strands, a reaction catalysed by fibrin stabilizing factor that adds strength
to the fibrin network.
The final clot is composed of a meshwork of fibrin fibres that entrap blood cells,
platelets and plasma. Fibrin fibres adhere to damaged blood vessels and prevent
further blood loss.
Understand clot retraction.
Platelets contain actin and myosin. They release them, causing vessels of damaged
vessels to be pulled together. In this shrinkage of platelets, serum (plasma
without fibrinogen) is exuded.
Understand how a clot is replaced with fibrous tissue.
The clot is a temporary protection until there is permanent repair of vessels. When
permanent repair of vessels occur, the clot needs to be dissolved.
Plasminogen is a precursor and is an anticlotting plasma protein. It is converted to
the enzyme, plasmin. Plasmin digests fibrin and other clotting factors and so it
dissolves the clot.
Platelets secrete a protein, which stimulates growth of arterial smooth muscle and
skin fibroblasts. Serotonin stimulates secretion of collagen by fibroblasts, and the
clot is converted into fibrous tissue. The process takes 1-2 weeks.

4
PROTHROMBIN ACTIVATOR
Formation of this is the rate limiting step in blood coagulation!
Prothrombin activator formed in two ways
- by the extrinsic pathway involving factors
present in damaged tissue
- by the intrinsic pathway involving factors
already present in plasma
In both pathways, clotting or coagulation factors (plasma
proteins) play major roles.
When active, their enzymatic actions cause the next cascading
reactions of the clotting process.
INTRINSIC CLOTTING PATHWAY
EXTRINSIC CLOTTING PATHWAY
COMMON PATHWAY