Dr Mere Kende
MBBS, MMED (Path), MACTM, MAACB, MACRRM
Lecturer: SMHS, UPNG

What is Hemostasis?

Factors Involved in Hemostasis?

Role of Blood Vessel in Hemostasis

Role of Platelet in hemostasis

Fibrin in thrombus

Coagulation Cascade

Extrinsic and Intrinsic Pathway

Fibrinolysis & Tissue Repair

List of Disorders of Hemostasis & Investigation
 STOP
BLEEDING
 Prevent
entry of micro-organisms
 Initiate
Repair & Healing of damaged
tissue
 Vessel
Wall (collagen)
 Platelets
 Coagulation
Factors
1.
Blood Vessels Contract
2.
Platelet Activation
3.
Fibrin Clot Formation
 Vessel
Wall Damage & Contract
 Temporary
Platelet Plug
 Activation
of coagulation system
 Stabilisation
 Clot
of Fibrin Clot
Retraction
 Fibrinolysis
& Repair
 Damaged


Blood Vessel
Injury: trauma,
Cholesterol plug,/Hypertension//smoking,
 Vasoconstriction
 Compression
 Collagen
(serotonin, TXA2, adrenaline)
(spilled blood/tissue swelling)
exposed

Activation of platelet (exposed collagen)

Adhesion (vWF, GpIb/IX)

Activation

Aggregation via fibrinogen links (gp IIb & IIIa)

Glansman’s Thromboaesthenia)

Secretion (ADP, TXA2, serotonin, thrombin)

Activation of more platelets/initiate clot
Formation
Fibrinogen
 In
a normal individual, coagulation is
initiated within 20 seconds after an injury
occurs to the blood vessel damaging the
endothelial cell.
 Platelets
immediately form a haemostatic
plug at the site of injury. This is called
primary haemostasis.
 Time
required for ceiling of bleeding by
‘platelet plug’ after vessel damage
 Normal:
2-6 minutes
 Replaced
by
more firm fibrin
clot
 Extrinsic
& Intrinsic Pathways
 I(fibrinogen)
 II
(prothrombin)
 Tissue factor 3/Tissue Thromboplastic
 Calcium
 V(proaccelerin, labile factor)
 VI
 VII (stable factor)
 VIII(antihemophilic factor)
 IX(Christmas factor)
 X(Stuart-Prower factor)
 XI(plasma thromboplastin antecedent)
 XII(Hageman factor)
 XIII(fibrin-stabilizing factor)
 von Willebrand factor
Prothrombin
Xa
Va
Thrombin
Fibrinogen
Fibrin
Extrinsic Pathway
TF3
(Endothelium)
Prothrombin
VIIa
Xa
Va
Thrombin
Fibrinogen
Fibrin
Intrinsic pathway
Kallikrein & HMW Kininogen
cofactors Activated by PLT
phospholipids & exposed collagen
XIIa
Extrinsic Pathway
TF3
(Endothelium)
XIa
Prothrombin
IXa
VIIIa
VIIa
Xa
Va
Thrombin
Fibrinogen
Fibrin
Intrinsic pathway
Kallikrein & HMW Kininogen
cofactors Activated by PLT
phospholipids & exposed collagen
XIIa
Extrinsic Pathway
TF3
(Endothelium)
XIa
Prothrombin
IXa
VIIIa
Fibrinogen
VIIa
Ca++
Xa
Va
Thrombin
Soft clot
Fibrin
XIIIa
Fibrin
Hard clot
Extrinsic-7
(PT)
Intrinsic 12,11,9,8
(aPTT-)
Sequential
Activation of
inactive
Proteases
Common Path (TT)
FX  FXa
Prothrombin Thrombin
Fibrinogen  Fibrin
 For
Purposes monitoring
 PT-
tests extrinsic pathway
 aPTT-tests

intrinsic
There are many points of interaction
between 2 pathways
 Thrombin
activated via extrinsic pathway is
cofactor for VIII (intrinsic pathway)
activation
 Thrombin
enhances V & VIII, plaletlet &
endothelial activity
 Factor
VIIa (extrinsic) can activate XI
(intrinsic)
 Factor
XIa, XIIa, Xa, and thrombin (IIa) can
activate VII (extrinsic)
Kallikrein
/HMWK
Collagen/PLT
phospholipids
(Tissue)
Factor III
PF-3
PF-3
Platelet
&endothelium
 Thrombin
enhances PLT & endothelium cells
 Fibrin
monomer (unstable, non-covalent)
 Fibrin
Polymers (stable, covalent bond)
 Stabilization
Factor (XIII)
Liver epoxide reductase
Fibrinogen
Thrombin
Fibrin Mononer
Fibrin Polymer
F-XIIIa
Cross Linked
Fibrin
 Within
minute-hours of clot formation
 Large
fraction of serum is extruded during
the process
 Requires
Platelet
 Prevents
clot breakdown and enhances
healing
 Pro-coagulants
Vessel Endothelium
 Platelets
 Clotting Factors

 Anti-coagulants





Prostacyclin
Anti-thrombi III
Protein C & S
Plasminogen/Plasmin
Tissue Plasminogen Activator
 Tissue
Plaminogen Activator
 Protein
C & S (enhances fibrinolysis)
 Anti-thrombin
III
 Heparin
is cofactor
 Inactivates
 Enhances
Thrombin (V,VII indirectly)
Fibrinolysis
 Inactivates
Va & VIIIa
 Binds
endothelial thrombomodulin -----
Activates Protein C
 Protein

C + cofactor (protein S)
Enhances Fibrinolysis/Proteolysis via inactivation
of Va & VIII & Inhibiting TPA inhibitor
 Endothelial
cell proliferation &
differentiation
 Fibroblast
cells (Fibroblast Growth factor)
 Smooth
muscles cells
 Growth
factors (VEGF, PDGF)
 Angiogenesis
 OPERATES
TO:

LIMIT CLOTS TO SITE OF INJURY & PREVENT
ABNORMAL CLOTS (THROMBOEMBOLYTIC DISEASE)

MAINTAINS PHYSIOLOGICAL BALANCE

BREAKS DOWN CLOT FORMED TO ENHANCE
HEALING PROCESS (proliferation, differentiation
of endothelium, fibroplast)
 Disordered
 BLEEDING

regulatory system
DISORDERS (HAEMOPHILIA)
THROMBOTIC DISORDERS (DVT/PE/STROKE)

Vascular disorders –


Platelet disorders



Scurvy, easy bruising, Henoch-Schonlein purpura,
vasculitis.
Quantitative - Thrombocytopenia
Qualitative - Platelet function disorders –
Glanzmans
Coagulation disorders


Congenital - Haemophilia (A, B), Von-Willebrands
Acquired - Vitamin-K deficiency, Liver disease

Mixed/Consumption: DIC

Thromboembolic Diseases (PE/DVT)
SKIN BRUISES/EASY BRUSING:


A bruise (layman's term), also called a
contusion (medical term), is a type of
hematoma of tissue in which capillaries
and sometimes venules are damaged by
trauma
Ecchymosis ->10mm


Purpura

(bleeding disorders)
purple/red discolouration, do not
blanch (3mm-10mm) (typical
vascilitis)
Petechiae <3mm

(typical Platelet disorder)
 BLANCHES
on
pressure
 Capillary
dilatation

Eg contact
dermatitis/allergy
/sunburn
 Easy
Bruising
 Menorrhagia
 Generalised
mucosal Bleeding (nose bleeds)
 FBE/PLATELET
 BLEEDING
COUNT
TIME
 PROTHROMBIN
 ACTIVATED
TIME (PT)
PARTIAL THROMBOPLASPTIN TIME
(aPTT/PTT)
 Coagulation
 VWF
Factor Assay (VIII)
Assay
 Snake
Venom Tests
 Thrombophilia
Screen (Protein C, S, factor V
Leiden, Ant-thrombin III activity,
Phospholipid Asssay)
Condition
PT
PTT
Bleeding Time
Platelet
Count
Vitamin K deficiency
prolonged
prolonged
normal
normal
Warfarin Rx
Prolonged
Prolonged
Normal
Normal
DIC
Prolonged
Prolonged
Prolonged
decrease
vWD
normal
Prolonged
Prolonged
Normal
Liver Disease (early)
Prolonged
Normal
Normal
Normal
Uremia (low PLT)
Normal
Normal
Prolonged
Normal
Thromobocytopenia
Normal
Normal
prolonged
decreased
Hemophilia A & B
Normal
prolonged
Normal
Normal
Factor V & X deficiency
Prolonged
Prolonged
Normal
Normal
Glasmans Thromboasthenia
(GPIIb/IIIa)
Normal
Normal
prolonged
Normal
Bernard Soulier Syndrome (GPIb)
Normal
Normal
prolonged
decreased
BV Injury
Tissue
Factor
Neural
Blood Vessel
Platelet
Coagulation
Constriction
Activation
Activation
Primary hemostatic plug
Reduced
Blood flow
Plt-Fusion
Thromibn,
Fibrin
Stable Hemostatic Plug
 Harrisons
Principle of Internal Medicine 17th Edition
 PJ.
Gallagher, GA Tanner. Medical Physiology, 2nd
edition
 A.
Despopoulous, S. Silbenagl. Colour Atlas of
Physiology, 5th Edition