1. Basic Principles of Hemostasis

2. Objectives:
Describe the 4 steps of hemostasis
Describe platelets, their normal count, development, and functions.
Describe the process of coagulation & the role of Vit K in it
Define normal coagulation time
List the natural anti-coagulants present in blood
Define hemophilia and list possible symptoms of hemophilia
Explain normal bleeding time and define Purpura

3. Steps of Hemostasis 1. Vascular spasm (vasoconstriction)
2. Platelet plug formation
3. Clot formation (blood clotting)
4. Clot retraction

4. Platelets Platelets (Thrombocytes) Count 150,000-400, 000 /μL
Origin: megakaryocytes in bone marrow develop under influence of “Thrombopoeitin”
Disc shape- with vesicles
2-4 μ in size
No nucleus
Residues of ER, Golgi apparatus
Mitochondria
Enzyme systems
Contain granules which secrete chemicals:
i. Serotonin; ii. endothelial growth
factor; iii. Prostaglandins; iv. phospsholipids (membrane)
v. Fibrin stabilizing factor
vi. Platelet Derived Growth factor
Natural destruction by macrophages in spleen
Platelets

5. Functions of platelets:
Help in hemostasis (stoppage of bleeding) by
1. producing vasoconstriction
2. becoming sticky (activated) to form a platelet plug to close small holes in blood vessels
3. initiate coagulation
Clinical implications
Low dose Aspirin reduces platelet adhesiveness:
Rationale for use in “blood thinning”
Low platelet count (< 50,000/μL) causes bleeding disorder
Simple investigation: Bleeding time measurement by finger prick.
Normal bleeding time 3-6 minutes
Disease when platelet count is low: Thrombocytopenic purpura

6. Vascular spasm Contraction of vascular smooth muscle because of
i. muscle damage; ii. serotonin from platelets
Platelet plug formation
1. Platelet adhesion to damaged
endothelium
2. Platelet release reaction:
ADP: increase platelet
adhesiveness (stickiness)
3. Serotonin & TXA2 : vasoconstriction
4. Platelets stick to one another
to form a plug: Adhesion which is
good enough to stop a small puncture
from bleeding
(Prostacyclin from endothelium
opposes (يعارض) stickiness)

7. Blood coagulation: factors involved

8. Principles of Hemostasis
Blood coagulation
Prothrombin activator
PROTHROMBINASE)
(Factor Xa + Ca
Phospholipid + Factor V)
Vit K
-Source: dietary, large intestine bacteria
-Fat soluble;
-Synthesis of
prothrombin, factors VII, IX, X,
Protein C
Prothombin
thrombin
Thrombin:
Accelerates prothrombinase formation
fibrinogen
fibrin
F XIII
Serum (straw yellow in colour) =
blood – clotting factors
Clot retraction
+ RBC = clot

9. + 1 PROTHROMBINASE THROMBIN 2 STRENGTHENED 3 FIBRIN THREADS
Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway
(b) Intrinsic pathway
Activated XII
Ca2+
platelets
Platelet
phospholipids
Activated X
Activated
PROTHROMBINASE V
Prothrombin
(II)
THROMBIN
Loose fibrin
threads
STRENGTHENED
FIBRIN THREADS
Activated XIII
Fibrinogen
(I)
XIII
(c) Common
pathway 1 2 3 +

10. (Prothrombin activator)
Prothrombinase
(Prothrombin activator)

11. Breakup/limitation of clot: Fibrinolysis
Clot contains
Plasminogen
Thrombin,
Active Factor XII
Tissue –plasminogen activator
(pTA)
activate
Plasmin
clot lysis
(clot breaks up
Prostacyclin
Inhibits platelet adhesiveness

12. Natural anticoagulants:
A. Endothelial surface factors B. Anticoagulants present in the blood which
remove THROMBIN
C. Anticoagulants may be used
1. Smoothness of endothelial wall:
so has glycocalyx which
repels clotting factors
1. Fibrin itself
2. Antithrombin III
-antithrombin (α globulin)
+ heparin
-removes activated factors
XII, XI, X
-removes thrombin
2. Protein C :inactivates
factors V and VIII
3. Thrombomodulin- a protein bound
to endothelium -combines with
thrombin to reduce clotting.
In patients:
i. Heparin
ii. Vit K antagonists
Outside the body:
Heparin
Calcium antagonists
4. This combination also
activates Protein C

13. Normal coagulation time: 3-7 minutes (finger prick method)
Clinical implications
Coagulation disorders :
i. not enough coagulations factors--?
(Hemophilia (factor VIII deficiency)
transmitted by female to males. Only males suffer)
ii. Not enough Vit K -

14. Summary Steps of hemostasis Platelets and their role in hemostasis
Normal bleeding time and its abnormality
Coagulation factors
The clotting cascade and formation of prothrombinase
Natural anti-coagulation
Anticoagulation in treatment
Normal clotting time and abnormalities