HAEMOSTASIS &
FIBRINOLYSIS
DR B L Mtinangi
DEPARTMENT OF PHYSIOLOGY
Hubert Kairuki Memorial University
December 3, 2015
HEAMOSTASIS & FIBRINOLYSIS
1
A SUMMARY OF PLATELETS
FORMATION
HEAMOSTASIS & FIBRINOLYSIS
2
SUMMARY OF BLOOD COAGULATION
BV Injury
Contact/
Tissue
Factor
Neural
Blood Vessel
Constriction
Platelet
Aggregation
Coagulation
Cascade
Primary hemostatic plug
Reduced
Platelet
Activation
Blood flow
Stable Hemostatic Plug
Fibrin
formation
HEAMOSTASIS & FIBRINOLYSIS
7
HAEMOSTATIS
Haemostasis is prevention of
blood loss after rupture or
injury/trauma of blood vessels
It is achieved through:
– Vascular spasms
– Formation of platelet plug formation
– Blood coagulation i.e. Development
of insoluble fibrin clot
– Clot retraction
– Clot dissolution
HEAMOSTASIS & FIBRINOLYSIS
8
Vascular spasms (vasoconstriction)
Vascular spasms is due to:
– Nervious reflex due to pain
– Effects of local and humoral
mechanism
– Thromboxane A2 (prostaglandin)
cause vasoconstrition
All generate an Action Potential
and cause Myogenic spasm
(constriction) and REDUCE blood
flow
The spasm last less than 1 min
HEAMOSTASIS & FIBRINOLYSIS
9
FORMATION OF PLATELET PLUG
Initiated when the platelet come into
contact with damaged vascular surface
or collagen fibers
Platelets adhere and aggregate to the
damaged site
Platelets secrete large quantity of ADP
and Thromboxane A2 (prostaglandin)
Endothetal cells secrete a Von
Willebrands factor (a small protein
molecule)
– Usually attached to factor VIII
– Bridges the platelets to exposed collagen
HEAMOSTASIS & FIBRINOLYSIS
10
CONT.
Aggregated platelets activate
coagulation factors
Finally convert FIBRINOGEN to
FIBRIN
– Stabilizing the PLATELET PLUG
Platelets normal count 150,000400,000/µl
Platelets maintain normal vascular
integrity
HEAMOSTASIS & FIBRINOLYSIS
11
MECHANISMS OF BLOOD COAGULATION
Two mechanisms
1. Procoagulant-promote coagulation
Predominate during injury
2. Anti coagulant – inhibit coagulation
In normal condition it is
predominat
HEAMOSTASIS & FIBRINOLYSIS
12
CLOTTING FACTORS AND
THEIR ROMANS SYNONYMS
Fibrinogen: factor I
Prothrombin: factor II
Tissue thromboplastin: factor III
Calcium: factor IV
Proaccelerin: (labile factor V)
Prothrombin: factor VII
Antihaemophilic: factor (AHF VIII)
Plasma thromboplastin component
PTC: factor IX
HEAMOSTASIS & FIBRINOLYSIS
13
CONT.
Stuart: factor X
Plasma thromboplastin
antecedent PTA: factor XI
Hegman factor XII (contact factor)
Fibrin stabilizing: factor XIII
NB: Factor II, VII, IX & X requires
vit K for their synthesis IN THE
LIVER, therefore
Vit K deficiency & liver diseases
leads to bleeding tendencies
HEAMOSTASIS & FIBRINOLYSIS
14
Trivial Name(s)
Pathway
Prekallikrein
Fletcher factor
Intrinsic
High molecular weight
kininogen (HMWK)
contact activation cofactor; Fitzgerald, Flaujeac Williams
factor
Intrinsi
c
I
Fibrinogen
Both
II
Prothrombin
Both
III
Tissue Factor
Extrins
ic
IV
Calcium
Both
V
Proaccelerin, labile factor, accelerator (Ac-)
globulin
Both
VI (Va)
Accelerin
VII
Proconvertin, serum prothrombin conversion
accelerator (SPCA), cothromboplastin
Antihemophiliac factor A, antihemophilic globulin
(AHG)
Factor
VIII
Characteristic
-
Contains N-term. gla
segment
-
Protein cofactor
This is Va, redundant to
Factor V
Extrins
ic
Endopeptidase with gla
residues
Intrinsi
c
Protein cofactor
IX
Christmas Factor,
antihemophilic factor B,plasma thromboplastin component
(PTC)
Intrinsi
c
Endopeptidase with gla
residues
X
Stuart-Prower Factor
Both
Endopeptidase with gla
residues
XI
Plasma thromboplastin antecedent (PTA)
Intrinsi
c
Endopeptidase
XII
Hageman Factor
Intrinsi
c
Endopeptidase
XIII
Protransglutaminase,
fibrin stabilizing factor (FSF), fibrinoligase
Both
Transpeptidase
HEAMOSTASIS & FIBRINOLYSIS
15
INITIATION OF COAGULATION
Initiation of coagulation by either:
1. Trauma/injury to the tissue –
extrinsic pathway
2. Trauma/injury to the blood –
intrinsic pathway
3. Contact of blood with damaged
endothelial and collagen
HEAMOSTASIS & FIBRINOLYSIS
16
A SUMMARY OF COAGULATION PATHWAY
HEAMOSTASIS & FIBRINOLYSIS
19
COAGULATION is also regulated by
several natural anticoagulants
Antithrombin III inactivate coagulation
factors& it neutralizes thrombin
Antithrombin III activity is enhanced by
heparin
Protein C receptor combine
thrombomodulin – inhibits thrombin and
several coagulation factors
Protein S accelerate the action of
protein C
Deficiency of the above factors leads
to HYPERCOAGULOPATHY states
leading to increased
THROMBOEMBOLISM
HEAMOSTASIS & FIBRINOLYSIS
20
CLOT RETRACTION
Clot retraction requires large
numbers of platelets ie
consolidate the clot
This contributes to haemostasis
by joining the edges of the broken
vessels
HEAMOSTASIS & FIBRINOLYSIS
21
HEAMOSTASIS & FIBRINOLYSIS
22
SUMMARY OF FIBRINOLYSIS
FIBRINOLYSIS (CLOT DISSOLUTION)
Dissolution of a blood clot begins
shortly after its formation
Plasma – contains a globulin
PLASMINOGEN incooperated in a
large amount in the CLOT
PLASMINOGEN is activated by
Thrombin, factor XIII, and some
lysosomal enzymes to PLASMIN with
A PROTEOLYTIC like action
HEAMOSTASIS & FIBRINOLYSIS
24
PLASMIN
Plasmin digest formed fibrin thread/clot
(FIBRINOLYSIS)
Plasmin also digest a number of clotting
factors like Factor I, II, V & VII
alpha2 antiplasmin is always present in
blood which
Binds with plasmin and inhibit its action
Fibrinolysis system is therefore important
for removing small clot from tiny peripheral
vessels-preventing occlusion or blockage
and thromboembolism
HEAMOSTASIS & FIBRINOLYSIS
25
Thank you
HEAMOSTASIS & FIBRINOLYSIS
26