haemostasis coagulation of blood
TRANSCRIPT
OBJECTIVES
Haemostasis Blood coagulation Anti-haemostatic
mechanism Bleeding disorders. Laboratory tests.
Monday, May 1, 2023
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
Monday, May 1, 2023
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
Monday, May 1, 2023
FORMATION OF TEMPORARY HAEMOSTATIC PLUG FORMATION Platelet adhesion Platelet activation Platelet aggregation Formation of
temporary haemostatic plug
Inhibition of further plug formation.
Monday, May 1, 2023
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.
Monday, May 1, 2023
PLATELET ACTIVATION Platelets secretes
ADP & Thromboxane A2
Activates other platelets & cycle continues
Monday, May 1, 2023
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.
Monday, May 1, 2023
FORMATION OF TEMPORARY HAEMOSTATIC PLUG
Platelet Adhesion
Platelet Aggregation
Fairy Loose Plug
Monday, May 1, 2023
INHIBITION OF FURTHER PLUG FORMATION.
Prostacycline from membrane phospholipids
Inhibit Thromboxane formation
Monday, May 1, 2023
FORMATION OF DEFINITIVE HAEMOSTATIC PLUG FORMATION Temporary plug
converted to definitive plug by Process of blood coagulation.
Results in formation of tight unyielding seal
Monday, May 1, 2023
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.
Monday, May 1, 2023
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
Monday, May 1, 2023
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
Monday, May 1, 2023
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.
Monday, May 1, 2023
CLOTTING FACTORS
III – THROMBOPLASTIN
Also called tissue factor or tissue thromboplastin
Released in extrinsic pathway.
Monday, May 1, 2023
CLOTTING FACTORS
V – LABILE FACTOR / PROACCLERIN
Required for formation of protrombin activator
Consumed during clotting so absent in serum.
Monday, May 1, 2023
CLOTTING FACTORS
VII – STABLE FACTOR / PROCONVERTIN
For activation of factor X in extrinsic pathway.
Monday, May 1, 2023
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.
Monday, May 1, 2023
CLOTTING FACTORS
IX – ANTI-HAEMOPHILIC FACTOR B/ PLASMA
THROMBOPLASTIC COMPONENT
First discovered in patient named Christmas.
Monday, May 1, 2023
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.
Monday, May 1, 2023
CLOTTING FACTORS
XI – PLASMA THROMBOPLASTIN
ANTICEDENT / ANTI-HAEMOPHILIC FACTOR C
Its deficiency causes hemorrhagic state.
Monday, May 1, 2023
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.
Monday, May 1, 2023
CLOTTING FACTORS
XIII – FIBRIN STABILIZING FACTOR /
FIBRINASE / LAKI LORAND FACTOR
Required for activation of fibrin polymer along with Ca.
Monday, May 1, 2023
DIFFERENCE . INTRINSIC PATHWAY.
Begins in blood itself.
Much slower take 2-6 min.
Initiated by activation of factor XII.
EXTRINSIC PATHWAY. Begins with trauma to
the vascular wall or tissue outside the vessel wall.
Explosive in nature takes 15 sec.
Initiated by activation of factor III.
Monday, May 1, 2023
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.
Monday, May 1, 2023
THROMBIN.
Monday, May 1, 2023
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
Monday, May 1, 2023
FIBRINOGEN TO FIBRIN.
Proteolysis
Polymerization .
Stabilization of fibrin polymers.
Monday, May 1, 2023
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.
Monday, May 1, 2023
ROLE OF CALCIUM.
Except for first 2 steps Ca required for all steps.
Ca removal causes Anticoagulation.
e.g. use of oxalates & citrates.
Monday, May 1, 2023
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.
Monday, May 1, 2023
ROLE OF VITAMIN K.
Deficiency causes serious hemorrhages.
Its due to
Obstructive jaundice
Newborn babies.
Chronic diarrhoea.
Side effects of antibiotics.
Monday, May 1, 2023
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
Monday, May 1, 2023
ROLE OF BLOOD VESSELS. Endothelium
Anticoagulant role. Barrier. Produces heparin & α-2
macroglobulin. Smoothness prevent
aggregation. Produces PGI2 prevent
aggregation.
Monday, May 1, 2023
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.
Monday, May 1, 2023
BLOOD IN FLUID STATE Velocity of circulation. Surface effect of
endothelium. Glycocalyx
Circulatory anticoagulants.
Fibrinolytic mechanism. Removal of activated
clotting factors.
Monday, May 1, 2023
VELOCITY OF CIRCULATION.
Blood is in constant motion due to pumping by
heart & at constant velocity
Decrease in velocity
Intravascular clotting
Monday, May 1, 2023
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
Monday, May 1, 2023
CIRCULATORY ANTICOAGULANTS.
Natural anti-coagulant.
Heparin
Antithrombin-III
Alpha 2 macroglobulin
Protein C
Monday, May 1, 2023
FIBRINOLYTIC MECHANISM. Protein C
Inactivates inhibitor of TPA
Increases Plasmin formation
Acts as Fibrinolytic
Monday, May 1, 2023
REMOVAL OF ACTIVATED CLOTTING FACTORS.
Liver plays an important role
Removes activated clotting factors
Prevents Intravascular Clotting
Monday, May 1, 2023
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.
Monday, May 1, 2023
THROMBOSIS Virchow’s triad which
predisposes to thrombus formation.
Predisposing factors Endothelial injury Alteration of blood flow Hypercoagulability of
blood
Monday, May 1, 2023
ENDOTHELIAL INJURY It occurs in Ulcerated plaques in
advanced atherosclerosis, Haemodynamic stress in
HT Arterial diseases DM Hypercholesterolemia
Monday, May 1, 2023
ALTERATION OF BLOOD FLOW Turbulence / stasis blood
flow
Platelet contact with endothelium
Initiate thrombosis
(especially venous thrombosis in leg veins after major operations)
Monday, May 1, 2023
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.
Monday, May 1, 2023
THROMBOGENESIS
Adherence of platelets
Activation of coagulation system
Entanglement of RBC with WBC – so clot mass is
mainly formed by entangled RBC & WBC.
Monday, May 1, 2023
THROMBI Red - mainly venous Soft, red & Gelatinous White – mainly arterial Pale & firm Mixed or laminated –
consists of alternate white & red Layers – Lines Of Zahn.
Monday, May 1, 2023
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
Monday, May 1, 2023
PREVENTION OF THROMBI
Drugs – decrease platelet adhesion; Aspirin,
Dextran
Anticoagulants – Heparin, Dicoumarol
Intermittent compression or electrical
stimulation of calf muscle
Monday, May 1, 2023