Haemostasis and blood coagulation

1. Haemostasis and blood
coagulation

2. Haemostasis means stoppage
of bleeding and prevention of
blood loss when blood vessel is
injured.
It occurs by 5 mechanisms:

3.  1- Vasoconstriction (V.C.) of
injured vessel :
 This occurs as a result of :
 A) Nervous reflexes.
 B) Myogenic contraction of the
injured vessel.
 C) Release of serotonin and
thromboxane A2 from platelets.

4.  2- Formation of platelet
plug: can stop bleeding from
a small blood vessel.
 As a result of injury, the
subendothelial collagen fibers
are exposed.

5. The platelets adhere to collagen
(platelet adhesion).
The platelet adhesion is helped
by Von Willebrand factor.
Platelet activation: initiated by
binding of platelets to collagen.

6.  The activated platelets swell, developed
pseudopodia, becomes sticky and
discharge their contents (ADP).
 Platelet aggregation: platelets secrete
ADP, thromboxane A2 and platelet
activating factor (PAF) which make the
platelets sticky and attract more
platelets, forming platelet plug.

7.  3- Formation of blood clot:
the platelet plug becomes firm
when fibrin threads are
deposited and this is essential
for stoppage of bleeding from
large vessels.

8.  4- Clot retraction: platelets
release retractozyme which
causes clot retraction and
approximation of cut ends of
injured vessels.

9.  5- Repair of the damaged
blood vessel:
 Fibroblasts, vascular endothelial
and smooth muscle cells grow and
proliferate by the effect of a growth
factor secreted by the platelets
(PDGF).

11. Platelets (Thrombocytes)

12.  These are small granulated oval or
round bodies 2-4 microns in
diameter.
 They have no nuclei and normal
count ranges from 150000 to 450000
per mm3.
 Their life span averages 8 days.

13. Function of the platelet:
 The platelets are concerned with
haemostasis through performing the
following function:
 1- Formation of the primary
haemostatic plug.
 2- Release of V.C. substance.

14.  3- Release of platelet factor 3 which
is essential for blood clotting.
 4- Stabilization of the blood clot
(factor XIII) and induction of clot
retraction.
 5- Release of the PDGF which
repairs of the damaged vessel wall.

15.  The cascade mechanism of blood
clotting:
 Blood clotting involves a cascade of
reactions in which inactive enzymes
are activated, and these in turn activate
other inactive enzymes.
 These reactions proceed in 2 different
system:

16.  A) Extrinsic system:
 1- This occurs when there is damage to
the vascular wall and surrounding
tissues.
 2- It is a rapid process.
 3- The damaged tissues release factor
III and this activates factor VII.
 4- Active factor VII and factor III in
the presence of Ca++ activate factor X.

17.  5- Factor Xa converts prothrombin
to thrombin.
 6- Thrombin converts the soluble
fibrinogen into insoluble fibrin.
 7- At first, the clot is soft and loose,
then it is becoming firm and tight by
factor XIII.

19.  B) Intrinsic system:
 1- This occurs in the absence of tissues
damage both in vitro and vivo.
 2- It is a slow process.
 3- Exposure of blood to substances such
as glass or collagen fibers leads to 2
effects:
 a) Activation of factor XII.
 b) Platelet aggregation and release of PL.

20. 4- Factor XIIa activate factor XI.
5- Factor XIa activate factor IX.
6- Factor IXa forms a complex
with VIIIa, and in the presence of
PL and Ca++, it activates factor X.

23. Factors that affect blood
clotting

24.  A)Factors that accelerate clotting:
 In vitro:
 1- Warming of blood.
 2- Contact of blood to wettable
surfaces e.g. glass.
 3- Addition of foreign bodies to the
blood.

25.  In vivo:
 1- Blood stagnation.
 2- Roughening or damage of
the vascular endothelial lining.
 3- Injection of vitamin K or
adrenaline.

26.  B) Factors that slow clotting:
 In vitro:
 1- Cooling of blood to zero 0C.
 2- Collection of blood in non-wettable
surface.
 3- Blood defibrination.
 4- Addition of heparin to the blood.
 5- Decreasing the blood Ca++
concentration to very low levels.

27.  In vivo:
 1- Vitamin K deficiency.
 2- Small doses of aspirin.
 3- Administration of heparin or
dicumarol.

28. Anticoagulants
A) Anticoagulants used in vitro:
1- Sodium oxalate.
2- Sodium citrate.
 3- Heparin.

29. B) Anticoagulants used in vivo
1- Heparin:
 This is a highly negatively-charged
mixture of sulfated polysaccharides
with a strong acid reaction.
 It is a natural anticoagulant that is
formed by mast cells and basophil
leukocytes.

30. Action of heparin:
 1- Facilitate the action of antithrombin III.
 2- Heparin and heparin cofactor II inhibits
both formation of thrombin and its actions.
 3- Heparin acts as a cofactor for the
lipoprotein lipase enzyme (clearing effect).

31.  2- Dicumarol:
 This substance is of a plant
origin.
 Its structure is closely similar to
that of vitamin K.
 Its block the action of vitamin K
in the liver by competitive
inhibition.

32. Disorders of haemostasis
1- Purpura.
 a) Thrombocytopenic purpura.
 b) Thromboasthenic purpura.
2- Haemophilia.