HAEMOSTASIS - I

DR NILESH KATE MBBS,MD

ASSOCIATE PROF DEPT. OF PHYSIOLOGY

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

IV – CALCIUM

Essential in all stages of coagulation.

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

Monday, May 1, 2023

MECHANISM OF COAGULATION-INTRINSIC PATHWAY.

Monday, May 1, 2023

EXTRINSIC PATHWAY.

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

Thank you.

Monday, May 1, 2023

Monday, May 1, 2023