Haemostasis 160514164610

HAEMOSTASIS - I
DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
OBJECTIVES
 Haemostasis
 Blood coagulation
 Anti-haemostatic
mechanism
 Bleeding disorders.
 Laboratory tests.
Saturday, May 14, 2016

HAEMOSTASIS
 Definition – spontaneous arrest or stoppage of bleeding
from injured blood vessel by physiological process.
 3 processes
 Vasoconstriction
 Formation of temporary haemostatic plug formation
 Formation of Definitive haemostatic plug formation

VASOCONSTRICTION
 Immediate –
 Direct effect of injury
 Proportionate to the
degree of trauma.
 Later by humoral
 Release of 5- HT by
bound platelets to the
collagen

FORMATION OF TEMPORARY
HAEMOSTATIC PLUG FORMATION
 Platelet adhesion
 Platelet activation
 Platelet aggregation
 Formation of
temporary
haemostatic plug
 Inhibition of further
plug formation.

PLATELET ADHESION
 After injury platelets
contacts with collagen &
damaged endothelium
 Swell, becomes irregular &

protrudes Pseudopodia.
 Contractile proteins contracts

& releases granules.
 Platelets becomes sticky &
adhere to collagen.

PLATELET ACTIVATION
 Platelets secretes
 ADP & Thromboxane

A2
 Activates other
platelets & cycle
continues

PLATELET AGGREGATION
 Activated sticky
platelets stick to each
other & forms
Aggregation
 It is also increases by
Platelet Activating
Factor (PAF) released
by neutrophils,
Monocyte & platelets
cell membrane lipids.
FORMATION OF TEMPORARY
HAEMOSTATIC PLUG
 Platelet Adhesion
 Platelet Aggregation
 Fairy Loose Plug

INHIBITION OF FURTHER
PLUG FORMATION.
 Prostacycline from
membrane
phospholipids
 Inhibit Thromboxane
formation

FORMATION OF DEFINITIVE
HAEMOSTATIC PLUG FORMATION
 Temporary plug
converted to definitive
plug by Process of
blood coagulation.
 Results in formation of
tight unyielding seal

COAGULATION OF BLOOD
 Through out life blood – in
fluid state but when
removed or shed or
collected in container
become jelly like – clot
 Fluidity – necessary for
circulation.
 Coagulation – protect
from excessive bleeding.

COAGULATION OF BLOOD
 Clotting factors
 Mechanism of coagulation
 Role of calcium in blood coagulation.
 Role of vitamin –k, liver and vascular wall in
haemostasis and coagulation.
 Blood clot retraction
 Blood in fluid state
 Thrombosis

CLOTTING FACTORS
 I – FIBRINOGEN
 Soluble
 Mol wt – 3,40,000
Dalton
 6 polypeptide chain
 Conc. – 0.3 gm/100 ml
 It is converted into
fibrin in the presence of
enzyme thrombin

CLOTTING FACTORS
 II- PROTHROMBIN
 Inactive precursor of
thrombin.
 Mol wt 69000 dalton.
 Synthesized in liver in
the presence of vitamin
K.
 Conc. is 40 mg / 100
ml.

CLOTTING FACTORS
 III – THROMBOPLASTIN
 Also called tissue factor or tissue thromboplastin
 Released in extrinsic pathway.

CLOTTING FACTORS
 IV – CALCIUM
 Essential in all stages of coagulation.

CLOTTING FACTORS
 V – LABILE FACTOR / PROACCLERIN
 Required for formation of protrombin activator
 Consumed during clotting so absent in serum.

CLOTTING FACTORS
 VII – STABLE FACTOR / PROCONVERTIN
 For activation of factor X in extrinsic pathway.

CLOTTING FACTORS
 VIII – ANTI-HAEMOPHYLLIC FACTOR A / ANTI-
HAEMOPHLIC GLOBULIN.
 Protein of b globulin type, synthesized in liver.
 Activation of factor x
 Deficiency causes classical Haemophilia.
 Inherited disease in which CT prolonged.

CLOTTING FACTORS
 IX – ANTI-HAEMOPHILIC FACTOR B/ PLASMA
THROMBOPLASTIC COMPONENT
 First discovered in patient named Christmas.

CLOTTING FACTORS
 X –STUART-PROWER FACTOR
 Along with active factor V, Ca and phopholipid forms a
complex – Prothrombin activator.
 Formed in both extrinsic & intrinsic pathway.

CLOTTING FACTORS
 XI – PLASMA THROMBOPLASTIN
ANTICEDENT / ANTI-HAEMOPHILIC FACTOR C
 Its deficiency causes hemorrhagic state.

CLOTTING FACTORS
 XII – HAGEMAN FACTOR/ GLASS FACTOR /
CONTACT FACTOR
 Activated when comes in contact with electronegative
surface or glass or rough surface.
 Its activation initiate intrinsic pathway.

CLOTTING FACTORS
 XIII – FIBRIN STABILIZING FACTOR /
FIBRINASE / LAKI LORAND FACTOR
 Required for activation of fibrin polymer along with Ca.

MECHANISM OF COAGULATION-
INTRINSIC PATHWAY.

EXTRINSIC PATHWAY.

DIFFERENCE .
 INTRINSIC  EXTRINSIC
PATHWAY. PATHWAY.
 Begins in blood itself.  Begins with trauma to
the vascular wall or
tissue outside the
vessel wall.
 Much slower take 2-6
min.
 Explosive in nature
takes 15 sec.
 Initiated by activation
 Initiated by activation of factor III.
of factor XII.
CONVERSION OF
PROTHROMBIN TO THROMBIN
 Prothrombin –
 Inactive precursor of
thrombin.
 Mol wt 69000 dalton.
 Synthesized in liver in
the presence of
vitamin K.
 Conc. is 40 mg / 100
ml.
THROMBIN.
Proteolytic enzyme.
Amount of thrombin
produced during
clotting of 1 ml of
blood is sufficient to
coagulate 3 liters of
blood.

I – FIBRINOGEN
 Soluble
 Mol wt – 3,40,000 Dalton
 6 polypeptide chain
 Conc. – 0.3 gm/100 ml
 It is converted into fibrin in the presence of enzyme
thrombin
FIBRINOGEN TO FIBRIN.
 Proteolysis
 Polymerization .
 Stabilization of fibrin polymers.

BLOOD CLOT RETRACTION.
 Clot is meshwork of fibrin
with entrapped blood cells ,
platelets & plasma.
 Contractile proteins – Actin,
myosin & thrombosthenin.
 Compress fibrin meshwork
squeeze out serum.
 Clot reduced to 40% of
original volume.

ROLE OF CALCIUM.
 Except for first 2 steps Ca required for all steps.
 Ca removal causes Anticoagulation.
 e.g. use of oxalates & citrates.

ROLE OF VITAMIN K.
 Chemical structure.
 Naphthoquinone derivatives.
 Fat soluble , insoluble in water.
 Sources.
 Food , bacterial flora.
 Role of vitamin K
 Synthesis of coagulants like Prothrombin.
 Factor VII , IX & X & circulatory anticoagulant
protein.
ROLE OF VITAMIN K.
 Deficiency causes serious hemorrhages.
 Its due to
 Obstructive jaundice
 Newborn babies.
 Chronic diarrhoea.
 Side effects of antibiotics.

ROLE OF LIVER.
 Synthesis of procoagulants – site of synthesis of
factor V,VII,IX,X, Prothrombin & fibrinogen
 Removal of activated procoagulants.
 Synthesis of anticoagulants like – heparin, anti
thrombin III & protein C

ROLE OF BLOOD VESSELS.
 Endothelium
 Anticoagulant role.
 Barrier.
 Produces heparin & α-2
macroglobulin.
 Smoothness prevent
aggregation.
 Produces PGI2 prevent
aggregation.

ROLE OF BLOOD VESSELS.
 Coagulant role
 Von Willebrand factor
(VWF)
 Tissue factor.
 Plasminogen activator.
 Sub endothelial tissue –
collagen fibres
 Causes platelet
aggregation
 Intrinsic pathway
activation.
BLOOD IN FLUID STATE
 Velocity of circulation.
 Surface effect of
endothelium.
 Glycocalyx
 Circulatory
anticoagulants.
 Fibrinolytic mechanism.
 Removal of activated
clotting factors.
VELOCITY OF CIRCULATION.
 Blood is in constant motion due to pumping by
heart & at constant velocity
 Decrease in velocity
 Intravascular clotting

SURFACE EFFECT OF ENDOTHELIUM.
GLYCOCALYX
 Endothelial lining smoothness – prevents adhesion
& intrinsic mechanism.
 Glycocalyx --inner layer of endothelium negatively
charged repel clotting factors &Y platelets &
prevent clotting.
 Intact Endothelium – barrier between collagenous
tissue & blood
CIRCULATORY ANTICOAGULANTS.
 Natural anti-coagulant.
 Heparin
 Antithrombin-III
 Alpha 2 macroglobulin
 Protein C

FIBRINOLYTIC MECHANISM.
 Protein C
 Inactivates inhibitor of
TPA
 Increases Plasmin
formation
 Acts as Fibrinolytic
REMOVAL OF ACTIVATED
CLOTTING FACTORS.
 Liver plays an important role
 Removes activated clotting factors
 Prevents Intravascular Clotting

THROMBOSIS
 Def.– Intravascular
clotting of blood & clot
so formed is thrombus
 Thrombus – Def –
Solid mass formed in
the living heart or
blood vessel from the
constituents of blood.

THROMBOSIS
 Virchow’s triad which
predisposes to
thrombus formation.
 Predisposing factors
 Endothelial injury
 Alteration of blood flow
 Hypercoagulability of
blood

ENDOTHELIAL INJURY
 It occurs in
 Ulcerated plaques in
advanced
atherosclerosis,
 Haemodynamic stress in
HT
 Arterial diseases
 DM
 Hypercholesterolemia
ALTERATION OF BLOOD FLOW
 Turbulence / stasis blood
flow
 Platelet contact with

endothelium
 Initiate thrombosis
(especially venous
thrombosis in leg veins
after major operations)
HYPERCOAGULABILITY OF
BLOOD
 Increase Platelet count
& adhesiveness.
 Increase Coagulation
factors as fibrinogen,
prothrombin
factors,Via,VIIa,Xa
 Decrease coagulation
inhibitors – Antithrombin
III & fibrinogen
degradation product.
THROMBOGENESIS
 Adherence of platelets
 Activation of coagulation system
 Entanglement of RBC with WBC – so clot mass is
mainly formed by entangled RBC & WBC.

THROMBI
 Red - mainly venous
 Soft, red & Gelatinous
 White – mainly arterial
 Pale & firm
 Mixed or laminated –
consists of alternate
white & red Layers –
Lines Of Zahn.

EFFECTS OF THROMBI
 Ischemia and Infarction
 Clot in Intact vessel decrease blood supply (Ischemia)
 Cell death (Infarction)
 Thromboembolism
 Dislodged clot in distant vessel & block circulation
 Pulmonary & Cerebral Embolism

PREVENTION OF THROMBI
 Drugs – decrease platelet adhesion; Aspirin,
Dextran
 Anticoagulants – Heparin, Dicoumarol
 Intermittent compression or electrical
stimulation of calf muscle

Thank you.


Haemostasis 160514164610

Hochgeladen von

Dokumentinformationen

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Haemostasis 160514164610

Hochgeladen von

Copyright:

Verfügbare Formate

HAEMOSTASIS - I

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

 Swell, becomes irregular &

 Contractile proteins contracts

Saturday, May 14, 2016

 ADP & Thromboxane

Saturday, May 14, 2016

 Fairy Loose Plug

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

 V – LABILE FACTOR / PROACCLERIN

 Required for formation of protrombin activator

 Consumed during clotting so absent in serum.

Saturday, May 14, 2016

 VII – STABLE FACTOR / PROCONVERTIN

 For activation of factor X in extrinsic pathway.

Saturday, May 14, 2016

Saturday, May 14, 2016

 IX – ANTI-HAEMOPHILIC FACTOR B/ PLASMA

 First discovered in patient named Christmas.

Saturday, May 14, 2016

 Along with active factor V, Ca and phopholipid forms a

complex – Prothrombin activator.

 Formed in both extrinsic & intrinsic pathway.

Saturday, May 14, 2016

ANTICEDENT / ANTI-HAEMOPHILIC FACTOR C

 Its deficiency causes hemorrhagic state.

Saturday, May 14, 2016

 Activated when comes in contact with electronegative

surface or glass or rough surface.

 Its activation initiate intrinsic pathway.

Saturday, May 14, 2016

 XIII – FIBRIN STABILIZING FACTOR /

FIBRINASE / LAKI LORAND FACTOR

 Required for activation of fibrin polymer along with Ca.

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

 Stabilization of fibrin polymers.

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

factor V,VII,IX,X, Prothrombin & fibrinogen

 Removal of activated procoagulants.

 Synthesis of anticoagulants like – heparin, anti

thrombin III & protein C

Saturday, May 14, 2016

Saturday, May 14, 2016

Saturday, May 14, 2016

 Removes activated clotting factors

 Prevents Intravascular Clotting