4. Hemostasis
• Prevention of blood loss
• Involves three mechanisms
– Vascular constriction
– Formation of a platelet plug
– Formation of a blood clot & Growth of fibrous
tissues
5. 1. Vascular Constriction
• Due to
– Myogenic spasm
– Autacoid factors
– Nervous reflexes
• For the smaller vessels, the platelets are responsible for
much of the vasoconstriction by releasing thromboxane A2
6. 2. Formation of the Platelet Plug
• If the cut in the blood vessel is very small it is often sealed
by a platelet plug, rather than by a blood clot
• Platelets (thrombocytes)
– Are minute discs 1 to 4 µm in diameter
– Are formed in the bone marrow from megakaryocytes
– 150,000 and 300,000 per microliter
7. Characteristics of Platelets
• Actin, myosin and thrombosthenin
• Endoplasmic reticulum and the Golgi apparatus
• Mitochondria
• Fibrin-stabilizing factor
• growth factor
• glycoproteins
• phospholipids
8. Mechanism of the Platelet Plug
• Platelets damaged vascular surface change their
own characteristics
• Swell and release granules
• Platelets + collagen + von Willebrand factor
• Secrete thromboxane A2 and ADP
– Act on nearby platelets to activate them as well
– Stickiness of these additional platelets causes them to adhere to
the original activated platelets
– Form a platelet plug
9. 3. Blood Coagulation
• Formation of the blood clot
• Begins in 15 to 20 second or 1 to 2 minutes
• Activator substances from the traumatized vascular wall, platelets, and blood
proteins adhering to the traumatized vascular wall to initiate clotting process
• Within 3 to 6 mints after rupture of a vessel the entire opening of the vessel
is filled with clot
• After 20 mints to an hour, the clot retracts and this closes the vessel still
further
10. Mechanism of Blood Coagulation-1
• Basic theory
– More than 50 important substances that cause blood
coagulation have been found in the blood and in the tissues
– Procoagulants and Anticoagulants
– In the blood stream, the anticoagulants normally predominate,
so the blood does not coagulate
– But when a vessel is ruptured, Procoagulants from the area of
tissue damage become “activated” and override the
anticoagulants, and then a clot does develop
11. Mechanism of Blood Coagulation-2
• General Mechanism
Clotting takes place in three essential steps:
I. Formation of a prothrombin activator
II. Prothrombin activator catalyzes conversion of prothrombin in to
thrombin
III. Thrombin acts as an enzyme to convert fibrinogen into fibrin fibers
that enmesh platelets, blood cells, and Plasma to form the clot
12. Mechanism of Blood Coagulation-3
Pathway for Initiating clotting
mechanism
– Extrinsic Pathway
– Intrinsic Pathway
• Leads to the formation of
prothrombin activator, which then
causes prothrombin conversion to
thrombin
Guyton and Hall 12 th ed Chapter 36 pg 453
13. Mechanism of Blood Coagulation-3
https://www.quora.com/What-are-the-similarities-between-intrinsic-and-extrinsic-pathways-of-blood-coagulation
14. Intravascular Anticoagulants-1
1. Endothelial Surface Factors
– Smoothness
– Glycocalyx layer--repels clotting factors and platelets
– Thrombomodulin
• binds thrombin
• activate Protein C
15. Intravascular Anticoagulants-2
2. Antithrombin Action of Fibrin and Antithrombin III
– While a clot is forming, about 85 to 90 percent of the thrombin
formed from the prothrombin becomes adsorbed to the fibrin fibers
as they develop
– Thrombin that does not adsorb to the fibrin fibers combines with
antithrombin III
16. Intravascular Anticoagulants-3
3. Heparin
– Powerful anticoagulant, but its concentration in the blood is
normally
– It has little or no anticoagulant properties, but when it combines
with antithrombin III
– The effectiveness of antithrombin III for removing thrombin
increases by a hundredfold to a thousand fold
– This compound also removes Factors XII, XI, X, and IX
Question to ask;;; why large quantities of heparin might be needed in
the lungs and liver??
17. Thromboembolic Conditions in the Human Being-1
• Thrombus: An abnormal clot that develops in a blood vessel
• Emboli: freely flowing clots within the plasma
• Emboli that originate in large arteries or in the left side of the heart can
flow peripherally and plug arteries or arterioles in the brain, kidneys, or
elsewhere
• Emboli that originate in the venous system or in the right side of the
heart generally flow into the lungs to cause pulmonary arterial
embolism
18. Thromboembolic Conditions in the Human Being-2
Reasons!!!!
– Any roughened endothelial surface of a vessel
– Very slowly flowing of the blood through blood vessels
19. Fibrinolysis
• Enzymatic breakdown of fibrin in blood clots
t-PA
• Plasminogen Plasmin
• Plasmin digests fibrin fibers and some other protein
coagulants such as fibrinogen, Factor V, Factor VIII,
prothrombin, and Factor XII
22. Vitamin K deficiency
• Affect prothrombin, Factor VII, Factor IX, Factor X, and
protein C,
Y?
• Source?
• Absorption?
23. Hemophilia
• Males bleeding disease
• Two types
– Hemophilia A or classic hemophilia
• Lack of VIII
• 85%
• Treatment is by injection of purified Factor VIII
– Hemophilia b
• Lack of factor IX
• 15%
24. Von willebrand’s disease ( VWD)
• Inherited bleeding disorder due to lack or defective of von
willebrand factor (VWF)
• Some time associated with a deficiency of VIII
25. Types of VWD-1
–Type 1
–This is the most common (85%) and mildest form of VWD, in which a
person has lower-than-normal levels of VWF
–low levels of factor VIII
– Type 2
–Body makes normal amounts of the VWF, the factor does not work the
way it should
–Subtypes―2A, 2B, 2M, and 2N.....go and study
26. Types of VWD-2
• Type 3
– This is the most severe form of VWD, in which a person
has very little or no VWF and low levels of factor VIII
27. Thrombocytopenia
• Numbers of platelets in the
circulating blood
• Bleeding from many small venules
or capillaries
• Thrombocytopenic purpura –
displaying of many small purplish
blotches on the surface of the skin
• Normal 150,000 to 300,000/μl
28. Go and study
• DIC ( Disseminated intravascular coagulation)
– Meaning
– Causes
– Types
• Acute and Chronic
• DIC in pregnancy
30. DIC - 1
• Is a condition in which blood clots form throughout the
body, blocking small blood vessels OR
• Is a serious disorder in which the proteins that control
blood clotting become overactive
• Presence of large amounts of traumatized or dying tissue
in the body that releases great quantities of tissue factor
into the blood
31. DIC - 2
• Underlying causes
– Infection
– Inflammation
– Cancer
– Pregnancy.....go and study DIC in pregnancy??
32. Effects of DIC
• Form small blood clots in the blood vessels
– Some of these clots can clog the vessels and cut off the normal blood
supply to organs such as the liver, brain, or kidneys
– Lack of blood flow can damage and cause major injury to the organs
• Consumes the clotting proteins in the blood
– High risk of serious bleeding, even from a minor injury without injury
injury
