Hemostasis and blood Hemostasis and blood coagulationcoagulation

Lecture by Lecture by

Dr SandeepDr Sandeep

23-03-0823-03-08

9:30-10:30 am9:30-10:30 am

The term hemostasis means prevention of The term hemostasis means prevention of blood loss. It is achieved by several blood loss. It is achieved by several mechanismsmechanisms

1)1) Vascular constrictionVascular constriction

2)2) Formation of platelet plugFormation of platelet plug

3)3) Formation of blood clotFormation of blood clot

4)4) eventual growth of fibrous tissue in to the eventual growth of fibrous tissue in to the blood vessel to close the holeblood vessel to close the hole

Vascular constriction:Vascular constriction: Occurs by local Occurs by local myogenic spasm, local autocoid factors, and myogenic spasm, local autocoid factors, and nervous reflexnervous reflex

Formation of platelet plugFormation of platelet plugPlatelets (Platelets (thromobocytes)thromobocytes) are 1-4 micron in are 1-4 micron in diameter.diameter.

They are formed in the bone marrow from They are formed in the bone marrow from megakaryocytesmegakaryocytes

The normal platelet count is 150,000 to The normal platelet count is 150,000 to 300,000/microliter300,000/microliter

Even though they do not have nuclei they Even though they do not have nuclei they contain active factorscontain active factors

Like Like actin myosin molecules, actin myosin molecules, they are they are contractile proteins similar in muscle cellscontractile proteins similar in muscle cells

The residues of golgi and ER helps in The residues of golgi and ER helps in synthesize various enzymes and store large synthesize various enzymes and store large quantity of calciumquantity of calcium

They also have ATP and ADPThey also have ATP and ADP

They contain They contain prostaglandinsprostaglandins

Fibrin stabilizing Fibrin stabilizing factor is present factor is present

It also contain growth factors helps in It also contain growth factors helps in regrowth of vascular smooth muscle and regrowth of vascular smooth muscle and fibroblastsfibroblasts

Mechanism of platelet plugMechanism of platelet plug

When platelet come in contact with damaged When platelet come in contact with damaged vascular surface, they stick to collagen fibers vascular surface, they stick to collagen fibers by changing their shape and characterby changing their shape and character

The contractile proteins helps in release of The contractile proteins helps in release of multiple active factors multiple active factors

They release They release ADP ADP and and thromoboxane A2 to thromoboxane A2 to attract more plateletsattract more platelets

Importance of platelet plug Importance of platelet plug formationformation

In day today life numerous microvessels In day today life numerous microvessels will rupturewill rupture

These holes will be often repaired by These holes will be often repaired by plateletsplatelets

In pathological conditions, any decrease In pathological conditions, any decrease in platelet count results in small in platelet count results in small hemorrhagic spots called “purpura”hemorrhagic spots called “purpura”

Blood coagulationBlood coagulation

More than 50 important substances that More than 50 important substances that cause or affect blood coagulationcause or affect blood coagulation

Some promote coagulation called Some promote coagulation called ““procoagulants”procoagulants” and other inhibit, and and other inhibit, and they are called as “they are called as “anticoagulants”anticoagulants”

Clotting Factors in Blood and Their SynonymsClotting Factors in Blood and Their Synonyms

Clotting FactorClotting Factor SynonymsSynonyms FibrinogenFibrinogen -- Factor IFactor I ProthrombinProthrombin -- Factor IIFactor II Tissue factorTissue factor -- Factor III; tissue Factor III; tissue

thromboplastinthromboplastin Calcium Calcium - - Factor IV Factor IV Factor VFactor V -- Proaccelerin; labile factor; Proaccelerin; labile factor; Factor VII Factor VII - Serum prothrombin - Serum prothrombin

conversion conversion accelerator accelerator (SPCA); (SPCA);

proconvertin; stable factorproconvertin; stable factor Factor VIII -Factor VIII - Antihemophilic factor Antihemophilic factor

A A

Factor IX -Factor IX - Christmas factor; Christmas factor; antihemophilic antihemophilic

factor Bfactor B Factor XFactor X - - Stuart factor; Stuart-Prower Stuart factor; Stuart-Prower

factorfactor Factor XIFactor XI - - Plasma thromboplastin Plasma thromboplastin

antecedent antecedent (PTA); (PTA); antihemophilic factor Cantihemophilic factor C

Factor XIIFactor XII - - Hageman factorHageman factor Factor XIIIFactor XIII - - Fibrin-stabilizing factorFibrin-stabilizing factor PrekallikreinPrekallikrein - - Fletcher factorFletcher factor High-molecular-weight kininogenHigh-molecular-weight kininogen - -

Fitzgerald factor; HMWK)Fitzgerald factor; HMWK) PlateletsPlatelets Protein CProtein C

Clotting takes place in 3 stepsClotting takes place in 3 steps

1)1) Formartion of prothrombin by a complex Formartion of prothrombin by a complex of activated coagulation factorsof activated coagulation factors

2)2) Prothrombin gets converted into Prothrombin gets converted into thrombinthrombin

3)3) The thrombin acts as an enzyme to The thrombin acts as an enzyme to convert fibrinogen into fibrin fibersconvert fibrinogen into fibrin fibers

Initiation of coagulationInitiation of coagulation

Prothrombin activator is generally Prothrombin activator is generally considered to be formed in two waysconsidered to be formed in two ways

1) By the 1) By the extrinsic pathwaysextrinsic pathways that begins that begins with the trauma to the vascular wall and with the trauma to the vascular wall and its surroundingsits surroundings

2) By the 2) By the intrinsic pathwaysintrinsic pathways that begins that begins in the blood itselfin the blood itself

Extrinsic pathwaysExtrinsic pathways

It starts with release of tissue factor. The It starts with release of tissue factor. The traumatized tissue releases severaltraumatized tissue releases several

This factor is composed of phospholipids This factor is composed of phospholipids plus lipoprotein complexplus lipoprotein complex

Intrinsic pathwaysIntrinsic pathways

This pathway begins with trauma to the This pathway begins with trauma to the blood itself or exposure of the blood to blood itself or exposure of the blood to collagen form the traumatized blood collagen form the traumatized blood vessel wallvessel wall

Prevention of blood clotting in Prevention of blood clotting in blood vesselsblood vessels

Normally blood is fluid in the vascular Normally blood is fluid in the vascular compartment, the most important factor compartment, the most important factor preventing clotting in the normal vascular preventing clotting in the normal vascular system aresystem are

1)1)Smoothness of the endothelial cellsSmoothness of the endothelial cells

2)2)A layer of glycocalyx on the endothelium, A layer of glycocalyx on the endothelium, which repels clotting factors and plateletswhich repels clotting factors and platelets

3)3)A protein called thrombomodulin which binds A protein called thrombomodulin which binds thrombin which slows clottingthrombin which slows clotting

Condition that causes Condition that causes excessive bleeding in human excessive bleeding in human beingsbeings

All the clotting factors are formed by the All the clotting factors are formed by the liver therefore, liver disease such as liver therefore, liver disease such as hepatitis, cirrhosis can sometime hepatitis, cirrhosis can sometime depress this depress this

Defeciency of Vit K –which is imp for Defeciency of Vit K –which is imp for synthesis of 5 factorssynthesis of 5 factors

Proteombin, Factor VII, Factor IX, Factor Proteombin, Factor VII, Factor IX, Factor X, and protein CX, and protein C

Defeciency of factor VIII – a Defeciency of factor VIII – a condition called hemophilia Acondition called hemophilia A

ThrombocytopeniaThrombocytopenia