2. What is the difference between
coagulation and hemostasis?
• Coagulation (or clotting) is the process through
which blood changes from a liquid and becomes
thicker, like a gel. Coagulation is part of a larger
process called hemostasis, which is the way that the
body makes bleeding stop when it needs to.
3. What is the process of hemostasis and
coagulation?
• The mechanism of hemostasis can divide into four
stages.
• 1) Constriction of the blood vessel.
• 2) Formation of a temporary “platelet plug." 3)
Activation of the coagulation cascade.
• 4) Formation of “fibrin plug” or the final clot.
4. What is hemostasis called?
• Hemostasis refers to normal blood clotting in
response to an injury. However, your body can also
have too much clotting, known as hypercoagulability.
That can cause many blood clots to form
spontaneously and block normal blood flow. When
blood clots form inside your blood vessels, this is
known as thrombosis
5. Homeostatis
• Definition. Hemostasis is the mechanism that leads
to cessation of bleeding from a blood vessel. It is a
process that involves multiple interlinked steps
6. Purpose
• Hemostasis facilitates a series of enzymatic
activations that lead to the formation of a clot
with platelets and fibrin polymer,This clot
seals the injured area, controls and prevents
further bleeding
7. Cellular Level
• Endothelium. Clotting factors III and VIII originate
from the endothelial cells while the clotting
factor IV comes from the plasma
• Platelets. These are non-nucleated disc-like cells
created from megakaryocytes that arise from the
bone marrow. They are about 2 to 3 microns in
size
• Hepatocytes. The liver produces the majority of
the proteins that function as clotting factors and
as anticoagulants
8. Development
• Embryology. The development of the
coagulation system begins in the fetus. The various
clotting factors and the coagulation proteins initially
get expressed in the endothelial cells during early
gestation.
9. Organ Systems Involved
The physiology of hemostasis involves the:
• Vasculature
• Liver
• Bone marrow
All of these systems help with the production of the
clotting factors, vitamins, and cells for appropriate
functionality of hemostasis.
10. Mechanism
1. Vaso Constriction. Within about 30 minutes of
damage/trauma to the blood vessels, vascular
spasm ensues, which leads to vasoconstriction. At
the site of the disrupted endothelial lining, the
extracellular matrix (ECM)/ collagen becomes
exposed to the blood components.
11. 2.Platelet Adhesion. This ECM releases
cytokines and inflammatory markers that lead to
adhesion of the platelets and their aggregation
at that site which leads to the formation of a
platelet plug and sealing of the defect.
12. 3.Platelet Activation. The platelets that have adhered
undergo very specific changes. They release their
cytoplasmic granules that include ADP, thromboxane
A2, serotonin, and multiple other activation factors.
They also undergo a transformation of their shape into
a pseudopodal shape which in-turn leads to release
reactions of various chemokines. P2Y1 receptors help
in the conformational changes in platelets
13. 4.Platelet Aggregation. With the mechanisms
mentioned above, various platelets are
activated, adhered to each other and the
damaged endothelial surface leading to the
formation of a primary platelet plug.
14. 5.xtrinsic Pathway. The tissue factor binds to factor VII
and activates it. The activated factor VII (factor VIIa)
further activates factor X and factor IX via proteolysis.
Activated factor IX (factor IXa) binds with its cofactor –
activated factor VIII (factor VIIIa), which leads to the
activation of factor X (factor Xa). Factor Xa binds to
activated factor V (factor Va) and calcium and generates
a prothrombinase complex that cleaves the
prothrombin into thrombin.
15. 6.Intrinsic Pathway. With thrombin production, there
occurs conversion of factor XI to activated factor XI
(factor XIa). Factor XIa with activated factor VII and
tissue factor converts factor IX to activated factor IX
(factor IXa). The activated factor IX combines with
activated factor VIII (factor VIIIa) and activates factor X.
Activated factor X (factor Xa) binds with activated
factor V (factor Va) and converts prothrombin to
thrombin. Thrombin acts as a cofactor and catalysis and
enhances the bioactivity of many of the
aforementioned proteolytic pathways.
16. 7.Fibrin Clot Formation. The final steps in the
coagulation cascade involve the conversion of
fibrinogen to fibrin monomers which polymerizes and
forms fibrin polymer mesh and result in a cross-linked
fibrin clot. This reaction is catalyzed by activated factor
XIII (factor XIIIa) that stimulates the lysine and the
glutamic acid side chains causing cross-linking of the
fibrin molecules and formation of a stabilized clot
17. 8.Clot Resolution (Tertiary Hemostasis). Activated
platelets contract their internal actin and myosin fibrils
in their cytoskeleton, which leads to shrinkage of the
clot volume. Plasminogen then activates to plasmin,
which promotes lysis of the fibrin clot; this restores the
flow of blood in the damaged/obstructed blood vessels
18. various tests have undergone development for platelet
testing; they include
• Bleeding time (BT)
• Light transmission platelet aggregation
• Impedance platelet aggregation
• Global thrombosis test
19. Clinical Significance
• Cardiovascular. There has been increased incidence
of bleeding while on antiplatelet agents and
anticoagulant agents for recent myocardial
infarction, stroke
• Renal. Pathological conditions like end-stage renal
disease can lead to uremic platelet dysfunction
which can be corrected with dialysis and renal
replacement therapy.
20. • Immunological. Replenishing the deficient
clotting factors, removing the antibodies
against the clotting factors, use of medications
to enhance or ameliorate functionality of the
clotting cascade-
• Pharmacological. Prudent use of the
antiplatelet agents such as aspirin,
