HEMOSTASIS
Spontaneous arrest of bleeding by
physiological process in an injured blood
vessel.
Prevents the blood loss, maintains the blood in
fluid state.
More effective in small vessel
Mechanism :
1. Vascular spasm / blood vessel constriction .
2. Formation of platelet plug.
3. Formation of a blood clot.
4. Eventual growth of fibrous tissue in to the
clot.
BV Injury
Contact/ Tissue
Factor
Neural
Blood Vessel
Constriction
Reduced
Blood flow
Platelet adhesion,
activation
and release,
Aggregation
Primary hemostatic plug
Platelet
Activation
Stable Hemostatic Plug
Coagulation
Cascade
Fibrin formation
1. VASCULAR SPASM / CONSTRICTION :
-Trauma to the blood vessel.
Reduce the blood loss , platelets remains
longer at the site of injury
Results from: Nervous reflexes
Local myogenic spasm
Local humoral factors
Eg: 5-HT, Thromboxane A2
platelet:
Plasma membrane: specific receptors –repels normal
endothelium.
Contractile proteins: Actin ,Myosin, Thrombosthenin.
Mitochondria : ATP & ADP.
Lipids: Prostaglandins, Tromboxane.
Endoplasmic reticulum & Golgi Apparatus : Enzyme synthesis.
Protein : fibrin stabilizing protein.
Granules
1. Alpha : Fibrinogen, Von -Willebrand Factor(VWF),
factors v, Factors vii.
1. Dense: ADP,ATP,5-HT, Ca 2+.
2. MECHANISM OF PLATELET PLUG
FORMATION:
a. Platelet adhesion: exposed collagen
Von -Willebrand Factor
- Released from Endothelial cells and platelets .
b. Platelet activation and release: PAF
• Platelets activated by adhesion.
• Swells, numerous pseudopod like projections
from the surface.
• Extend projections to make contact with
each other.
• Contractile proteins thrombospondin and
thrombonectin contracts forcefully.
• Serotonin
• Increase ADP, Thromboxane A2 releaseactivate other platelets.
• Membrane phospholipids rearrange.
• Ca 2+ release.
• Serotonin/ 5-HT & Thromboxane A2 are
vasoconstrictors decreasing blood flow
through the injured vessel. ADP causes
stickiness.
c.Platelet Aggregation: PAF
ADP + Thromboxane A2
Activate, Increase the stickiness of additional
platelets
loose platelet plug
3.Formation of blood clot.
Procoagulants .
Anticoagulants.
Balance b/w Procoagulants and anticoagulants
keep the blood in fluid state .
Mechanism of clotting:
Cascade of reaction In which inactive clotting factors
are activated and this in turn activate other inactive
clotting factors = Water Fall Hypothesis
blood is transformed from a liquid to a gel
state.
Clotting factors
Factor 1 – Fibrinogen.
Factor 2 – Prothrombin.
Factor 3 –Tissue
Thromboplastin.
Factor 4 – Calcium Ion.
Factor 5 -- proaccelarin.
Factor 6 - Absent .
Factor 7 – proconvertin.
Factor 8- Anti Hemophilic
factor.
Factor 9- Christmas Factor.
Factor 10 – Stuart Prower
factor.
Factor 11-plasma
thromboplastin antecedent
Factor 12- Hageman Factor.
Factor 13- Fibrin Stabilizing
Factor.
Other factors :
Heavy molecular weight Kininogens.
Kallikreins.
Pre Kallikreins.
Platelet Phospholipids.
The final three steps of this series of
reactions are:
1. Prothrombin activator is formed.
2. Prothrombin is converted into thrombin.
3. Thrombin catalyzes the conversion of
fibrinogen into a fibrin mesh.
Prothrombin Activator
2 Pathways :
Intrinsic Pathway
Extrinsic Pathway
• Intrinsic pathway
Invivo :
Inactive clotting factor XII is activated by
surface contact with collagen.
Change in blood constituents.
Invitro:
Blood exposed to glass materials
• Extrinsic pathway – Activated by tissue
factor/tissue thromboplastin.
Injury to vessel wall.
Injury to body tissue.
Tissue thromboplastin is not a plasma
protein – released from outside the
endothelium ( Damaged tissue )
Intrinsic system
Extrinsic system
HMWK,KK
XII
XIIa
Tissue thromboplastin
HMWK
XI
XIa
VII
VIIa
Ca2+
IX
IXa
VIII
VIIIa
PL, ca2+,
X
V
Xa
Va
Prothrombin
Ca2+,Factor III,PL
X
Ca2+ PL
Thrombin
Fibrinogen
Fibrin
Ca2+,PL
Extrinsic pathway
Intrinsic pathway
Conversion of Prothrombin to Thrombin
*Prothrombin activator
Prothrombin
Thrombin
Formation of Fibrin
Fibrinogen(soluble)
Stabilized
Fibrin(Polymer)
Insoluble
Proteolysis
Stabilization
Fibrin( Monomer)
polymerization
Fibrin (Polymer)
Ca2+
XIII
XIII (a)
4. CLOT RETRACTION:
1 hour50% of the clot retracts.
Impaired if platelets are decreased or
absent.
Clot retracts – pulls the broken vessels
together, facilitates wound healing and
prevents thrombolysis
Injury to the vessel wall
Release of 5-HT &
other
vasoconstrictors
Platelet adhesion
Constriction
of injured
blood vessel
Release of
factor III
Endothelium
disrupted –
collagen exposed
Via intrinsic
system
Platelet activation
Platelet aggregation
Formation of temporary
platelet plug
Via extrinsic
system
Activation of
coagulation
Formation
of fibrin
Formation of a definitive
hemostatic plug
• FIBRINOLYSIS :
• Vascular endothelium release of
thrombomudulin
Thrombomodulin + Thrombin
Protein C
activated Protein C with protein S
activation of
plasminogen activator
Inactivates Va and VIII a
Tissue plasminogen
activator
plasminogen
Fibrin/
Fibrinogen
plasmin
Fibrin degradation
products
Why blood does not clot in the blood vessels????
1. Endothelial factors:
Smoothness of the endothelium.
Negatively charged particles on the
endothelium.
Thrombomodulin.
2. Velocity of blood circulation.
3. Presence of natural anticoagulants.
Eg: Heparin , Protein C, Protein S
4. Negative feed back by thrombin
ADP
+
Thromboxane A2
Prostacyclin &NO
Prostacyclin & NO
Vessel injury
Applied Aspects :
1. Vit K deficiency
Factor II ,Factor VII ,Factor IX ,Factor X ,
protein C.
 Diseases of Liver
 Gastro intestinal disease
 Decrease in dietary Vit K.
Treatment:
Injecting Vit K
2. Hemophilia :
It’s a clotting disorder caused due to the deficiency of
the clotting factors
Hemophilia A – deficiency of Factor VIII (85%)
Hemophilia B – deficiency of Factor IX (15%)
Hemophilia C – deficiency of Factor XI (Rare)
First detected among the British royal family
members- Royal disease.
Sex linked disorder –abnormal gene on the
X-chromosome.
Females are the carriers( No symptoms) and males
the sufferers /manifest signs of the disease.
Presence of another normal X chromosome ,the gene
acts as a recessive gene.(no signs of disease but
can transmit the disease)
Bleeding time :
Time from the onset of bleeding to the formation of the
temporary platelet plug .
Normal value: 2-5 min.
Clotting time:
Time from the onset of bleeding to the formation of the first
Fibrin thread.
Normal value: 3 -8 min
Diagnosis:
 Increase in clotting time .
 Bleeding time is normal
Carrier Female
Normal Male
X
X
X
Carrier female
Y
X
X
X
X
Y X
Normal Female
Hemophilic male
YX
Normal male
Treatment:
Fresh blood transfusion Factor VIII is lost rapidly on
storage.
Injecting factor VIII,IX prepared from fresh frozen
plasma.
3. Platelet disorder:
A. Thrombocytopenia:
Reduction in the platelet count secondary
to some other cause.
B . Idiopathic thrombocytopenia:
Reduction in the number of platelets due
to unknown cause.
C. Thromboasthenia :
Defective platelet function.
Hyper coagulable disorder:
Clot appear spontaneously in the vessels and heart:Thrombosis
Thromboembolism: clot blocks the smaller vessels.
Causes:
Antithrombin III deficiency , protein C deficiency,
plasminogen abnormalities etc
Risk factors :
Atherosclerosis, hyperlipidaemia , slow blood flow,
smoking etc
4.Defective capillary contractility:
The clinical condition in Which the capillary
abnormality results in bleeding is called PURPURA.
Characterized by spontaneous haemorrhages
beneath the skin, mucous membrane and internal
organs.
Types:
Primary (idiopathic) - congenital or hereditary and
usually occurs in children.
Secondary (symptomatic) - due to allergies,
infection.
• Thrombocytopenic Purpura:
low platelet count.
Mild: less than 50,000 cells/cumm of blood.
Moderate: less than 10,000 cells /cumm of blood.
Fulminating : less than 1000 cells/cumm of blood
Purpura develops in following condition:
Increase capillary fragility
Thrombocytopenia
Idiopathic thrombocytopenia
Thromboasthenia
Allergy, drug toxicity
ANTICOAGULANTS
Natural anticoagulants
Heparin
Protein-C, Protein S
Synthetic anticoagulants:
Heparin
Vit K antagonists
EDTA, Sodium citrate Oxalates
Aspirin
Synthetic Anticoagulants:
1.Heparin: ( In Vivo & In Vitro )
Administered after surgery to avoid
thrombosis
2.Aspirin:
Inhibit platelet aggregation
3.Vitamin K Antagonists:
Dicoumarol, Warfarin
Synthetic Anticoagulants( In Vitro)
• Heparin
• Oxalates & Citrates & EDTA
Decreases the conc. of Ca ions in the blood
Prostacyclin
& NO
ADP
Vessel injury
Thromboxane A2
Prostacyclin
& NO