normal blood clotting and its abnormalities in short bleeding disorders

1. Pathophysiology
BLOOD COAGULATION
(Hemostasis)
Dr. Dina Hamdy Merzeban
Physiology lecturer
Fayoum university
www.facebook.com/merzeban physiology

2. HEMOSTASIS:
• Definition: prevention of blood loss after injury

3. STEPS OF HEMOSTASIS:
• Constriction of the Blood Vessels:
The constriction of injured blood vessel occurs immediately after injury and may be so
marked that the lumen is completely closed.
• Formation of Temporary Hemostatic Plug:
Injury stimulates the platelets to form a mechanical plug to seal the vascular injury.
If the cut in the vessel is small, the platelet plug by itself can stop blood loss Completely,
but if the cut is large, a blood clot in addition is required to stop bleeding.
• Blood coagulation:
Formation of a blood clot by the intrinsic and to stop the bleeding

4. Constriction of the
Blood Vessels:
The constriction of
injured blood vessel
occurs immediately
after injury and may
be so marked that
lumen is completely
closed.

5. Formation of Temporary
Hemostatic Plug:
• Injury stimulates the
platelets to form a
mechanical plug to seal
the vascular injury.
• If the cut in the vessel is
small, the platelet plug by
itself can stop blood loss
Completely, but if the cut
is large, a blood clot in
addition is required to
bleeding.

6. Blood
coagulation:
Formation of a
blood clot by the
intrinsic and to
stop the bleeding

8. ANTI- CLOTTING MECHANISMS

9. Anti- clotting
mechanisms
The tendency of blood
to clot is balanced in
vivo by limiting
reactions that tend to
prevent clotting inside
the blood vessels and
to break down any
formed clots.

10. A.General limiting reactions.
1. Smooth vascular endothelium, thus there is no activation of platelets.
2. Presence of heparin, which is a naturally occurring anticoagulant.

11. B. Specific limiting reactions.
1. The interaction between thromoboxane A2 and
prostacyclin:
• The interaction between the platelet-aggregating effect of
thromboxane A2, and the antiaggregating effect of
prostacyclin.
• This interaction causes a clot to form at the site of injury but
keeps the vessel lumen free of clot.
Note: aspirin increases prostacyclin prevent platelet-
aggregation , so given to prevent thrombosis.

12. B. SPECIFIC LIMITING REACTIONS.
2. FIBRINOLYTIC SYSTEM
 Intact blood vessel walls are
provided with a mechanism that
inhibit clot formation.
 Plasminogen receptors are
located on the surfaces of many
different types of cells e.g.
endothelial cells.
 When plasminogen binds to its
receptors, it becomes
activated.

13. FIBRINOLYTIC SYSTEM
 Plasminogen is converted to its active form plasmin,
by the action of tissue-plasminogen activator (t-PA).
 Plasmin (fibrinolysin) is an enzyme that lyses fibrin
and fibrinogen

14.  It is also activated by urokinase or Streptokinse.
 Human t-PA is now produced by recombinant DNA techniques for
clinical use in myocardial infarction and stroke.

15. In vivo anticoagulants:
Point of
Comparison
Heparin Dicumarol
Origin: Mast cells and
basophils.
Plant
Mode of action: blocks the activity of
some clotting factors
Inhibits formation of vitamin K
dependent clotting factors in the liver
Site of action: In vivo & In vitro Only in vivo.
Onset: Rapid onset. Slow onset
Duration: Short duration Long duration
Administration: Intravenous/
intramuscular
Orally
Antidote: Protamine sulfate 1% Vitamin K.

16. ABNORMALITIES OF HEMOSTASIS:
There are three groups of abnormalities that can occur in hemostasis:
A. Conditions that cause excessive bleeding
B. Conditions that cause excessive intravascular clotting.
C. Conditions that cause both excessive bleeding and intravascular
clotting.

17. A- CONDITIONS THAT CAUSE EXCESSIVE BLEEDING
1-Thrombocytopenic purpura:
This is due to deficiency of platelets, the symptoms appear when platelet
count decreases below 50,000/mm". It is characterized by the presence
many subcutaneous hemorrhages called petechiae and prolongation of
bleeding time.

18. A- CONDITIONS THAT CAUSE EXCESSIVE BLEEDING
2-Vitamin K deficiency:
Vitamin K is a fat soluble vitamin synthesized by the intestinal bacterial flora. It is needed
for the formation of factors, ll, VIl, IX and X by the liver. Deficiency of this vitamin leads to
decrease in the formation of these coagulation factors and thus there is prolongation of
coagulation time.
Causes:
• Absence of intestinal bacterial flora which occurs in new born infants
• Treatment with antibiotics for long periods in adults.
• Obstruction of biliary ducts which leads to absence of bile needed for absorption of the
vitamin.

19. A- CONDITIONS THAT CAUSE EXCESSIVE BLEEDING
3- Hemophilia:
• It is a congenital disease characterized by a tendency for
severe bleeding after mild trauma.
• It is a sex linked recessive disease carried by females and
manifested almost always in males.
• It causes prolongation of the whole blood coagulation
time.

20. CONDITIONS THAT CAUSE EXCESSIVE INTRAVASCULAR
CLOTTING
(THROMBOEMBOLIC CONDITIONS):
Causes:
1. Slow blood flow as occurs in leg veins due to long bed
rest after operations, or with varicose veins
2. In atherosclerosis due to roughness or vascular
endothelium.

21. CONDITIONS WITH BOTH EXCESSIVE BLEEDING AND
INTRAVASCULAR CLOTTING
Disseminated intravascular coagulation(DIC) :
• It is characterized by wide spread clotting accompanied
with bleeding tendency due to consumption of many
clotting factors.
• Causes:
• Retention of a dead fetus in the uterus for weeks
• Septicemia

22. HEMOSTATIC FUNCTION TESTS
1. Blood count and blood film: The platelet count is
reduced in thrombocytopenia.
2. Bleeding time: It is the time needed for bleeding to stop
without clotting of the blood. The normal bleeding time is
1-3 minutes and it depends on platelet count and function.
It is prolonged in thrombocytopenic purpura.
3. Tests for blood coagulation:

23. HEMOSTATIC FUNCTION TESTS
3. TESTS FOR BLOOD COAGULATION:
Whole blood coagulation time:
It is the time needed for blood to clot.
Normally, it is 3-10 minutes at 37 C. It is prolonged in both vitamin K
deficiency, hemophilia, and liver diseases.
The activated partial thromboplastin time (APTD):
Normally it is 30-40 seconds and is prolonged in hemophilia.
Prothrombin time: normal value is 15 seconds and is prolonged in
vitamin K deficiency.