Chapter 36: Hemostasis and Blood Coagulation
Guyton and Hall, Textbook of Medical Physiology, 12th edition
Events in Hemostasis
• Vascular Constriction
a. Local myogenic spasm-most effective
b. Local autacoid factors
c. Nervous reflexes-from pain receptors
• Formation of a Platelet Plug
a. Small cut in a vessel; have a plug
instead of the complete clotting
mechanism
Events in Hemostasis
• Platelets
a.
b.
c.
d.
e.
f.
g.
h.
Fragmented megakaryocytes
150,000-300,000
Do not have nuclei and cannot reproduce
Contain actin and myosin (thrombosthenin)
Produce ATP
Release prostaglandins
Release endothelial cell growth factor
Surface glycoproteins for adherence to damaged
vessels
i. Half-live of 8-12 days
Events in Hemostasis
• Mechanism of the Platelet Plug
a.
b.
c.
d.
Platelets swell; irregular shape with pseudopods
Become sticky and adhere to collagen
Thromboxane A2 and ADP enhance adherence
Damaged wall activates increasing numbers of
platelets
e. Important in closing small tears or ruptures in very
small vessels
Blood Coagulation
• Basic Theory
a. Depends on the activation of 50 or more possible
blood procoagulants
b. Formation of prothrombin activator
c. Conversion of prothrombin to thrombin
d. Conversion of fibrinogen to fibrin
Fig. 36.2
Blood Coagulation
• Conversion of Prothrombin to Thrombin
a. Prothrombin activator is formed as a result of
damage to a blood vessel
b. In the presence of Ca++ causes the conversion
of prothrombin to thrombin
c. Thrombin causes the polymerization of
fibrinogen molecules into fibrin fibers
d. Prothrombin attaches to receptors on platelets
e. Prothrombin is a plasma protein formed
continually by the liver
f. Vitamin K is required for the production of
prothrombin
Blood Coagulation
• Conversion of Fibrinogen into Fibrin
a. Fibrinogen is produced by the liver
b. In the early stages of polymerization, the molecules
are held together by hydrogen bonds
c. Fibrin-stabilizing factor is released by platelets;
acts as an enzyme to form covalent bonding and
multiple cross-linkages
Blood Coagulation
• Blood Clot
a. Meshwork of fibrin fibers running in all directions
and entrapping blood cells, platelets, and plasma
b. Within a few minutes the clot contracts and
expresses fluid (serum)
c. Platelets contribute directly by activation
thrombosthenin and myosin (contractile proteins)
• Positive Feedback of Clot Formation
Blood Coagulation
• Initiation of Coagulation
a. Trauma to the vascular wall and adjacent tissues
b. Trauma to the blood
c. Contact of the blood with damaged endothelial
cells or collagen and other tissue elements
d. All lead to the formation of prothrombin activator
Blood Coagulation
• Extrinsic Pathway
a. Release of tissue factor
b. Activation of Factor X-role of Factor VII and tissue
factor
c. Effect of Xa to form prothrombin activator-role of
Factor V in the presence of calcium to split
prothrombin to thrombin
Fig. 36.3 Extrinsic pathway for initiating blood clotting
Blood Coagulation
• Intrinsic Pathway
a. Blood trauma causes activation Factor XII and
release of platelet phospholipids
b. Activation of Factor XI
c. Activation of Factor IX by activated XI
d. Activation of Factor X-role of Factor VIII
e. Action of activated Factor X to form prothrombin
activator-role of Factor V
Fig. 36.4 Intrinsic pathway for initiating blood clotting
Blood Coagulation
• Role of Calcium in Extrinsic and Intrinsic Pathways
a. Except for the first two steps in the intrinsic
pathway, calcium ions are required for promotion
or acceleration of all blood clotting reactions
b. Normally, calcium levels do not fall low enough to
affect blood clotting mechanisms
Blood Coagulation
• Interaction Between Extrinsic and Intrinsic Pathways
a. Clotting occurs by both pathways simultaneously
b. Extrinsic pathway is more explosive and faster (as little
as 15 seconds)
a. Intrinsic is slower requiring 1-6 minutes
Blood Coagulation
• Intravascular Anticoagulants- prevention of blood
clotting in the normal vascular system
a. Endothelial surface factors-smoothness, glycocalyx,
thrombomodulin (binds thrombin), protein C (inhibits
Factors V and VIII
b. Antithrombin action of fibrin and antithrombin III
c. Heparin-released by basophils and mast cells
d. Plasmin-digests fibrin fibers and other clotting factors
(from plasminogen-serum protein trapped in clot)
Excessive Bleeding
• Decreased Prothrombin, Factors VII, IX, and X Caused
By Vitamin K Deficiency
• Hemophilia
• Thrombocytopenia