HEAMOSTASIS & FIBRINOLYSIS 1 HAEMOSTASIS & FIBRINOLYSIS DR B L Mtinangi DEPARTMENT OF PHYSIOLOGY Hubert Kairuki Memorial University December 3, 2015

HEAMOSTASIS & FIBRINOLYSISHEAMOSTASIS & FIBRINOLYSIS 11

HAEMOSTASIS & FIBRINOLYSISHAEMOSTASIS & FIBRINOLYSIS

DR B L MtinangiDR B L Mtinangi

DEPARTMENT OF PHYSIOLOGYDEPARTMENT OF PHYSIOLOGY

Hubert Kairuki Memorial UniversityHubert Kairuki Memorial University

December 3, 2015December 3, 2015

Physiology Dept

A SUMMARY OF PLATELETS A SUMMARY OF PLATELETS FORMATIONFORMATION


SUMMARY OF BLOOD COAGULATION

BV Injury

PlateletPlateletAggregation

PlateletActivation

Blood VesselBlood Vessel Constriction

CoagulationCoagulation Cascade

Stable Hemostatic Plug

Fibrin formation

Reduced

Blood flow

Contact/ Tissue Factor

Primary hemostatic plug

Neural



HAEMOSTATISHAEMOSTATISHaemostasis is prevention of blood Haemostasis is prevention of blood loss after rupture or injury/trauma of loss after rupture or injury/trauma of blood vesselsblood vesselsIt is achieved through: It is achieved through: – Vascular spasmsVascular spasms– Formation of platelet plug formationFormation of platelet plug formation– Blood coagulation i.e. Development of Blood coagulation i.e. Development of

insoluble fibrin clotinsoluble fibrin clot– Clot retractionClot retraction– Clot dissolutionClot dissolution


Vascular spasms (vasoconstriction)Vascular spasms (vasoconstriction)

Vascular spasms is due to:Vascular spasms is due to:– Nervious reflex due to painNervious reflex due to pain– Effects of local and humoral mechanismEffects of local and humoral mechanism– Thromboxane A2 (prostaglandin) cause Thromboxane A2 (prostaglandin) cause

vasoconstritionvasoconstrition

All generate an Action Potential and All generate an Action Potential and cause Myogenic spasm cause Myogenic spasm (constriction) and REDUCE blood (constriction) and REDUCE blood flowflow

The spasm last less than 1 minThe spasm last less than 1 min


FORMATION OF PLATELET PLUGFORMATION OF PLATELET PLUGInitiated when the platelet come into Initiated when the platelet come into contact with damaged vascular surface or contact with damaged vascular surface or collagen fiberscollagen fibers

Platelets adhere and aggregate to the Platelets adhere and aggregate to the damaged sitedamaged site

Platelets secrete large quantity of ADP and Platelets secrete large quantity of ADP and Thromboxane A2 (prostaglandin) Thromboxane A2 (prostaglandin)

Endothetal cells secrete a Von Willebrands Endothetal cells secrete a Von Willebrands factor (a small protein molecule)factor (a small protein molecule)– Usually attached to factor VIIIUsually attached to factor VIII– Bridges the platelets to exposed collagenBridges the platelets to exposed collagen


CONT.CONT.Aggregated platelets activate Aggregated platelets activate coagulation factorscoagulation factors

Finally convert FIBRINOGEN to FIBRINFinally convert FIBRINOGEN to FIBRIN– Stabilizing the PLATELET PLUGStabilizing the PLATELET PLUG

Platelets normal count 150,000-Platelets normal count 150,000-400,000/400,000/µl µl

Platelets maintain normal vascular Platelets maintain normal vascular integrityintegrity


MECHANISMS OF BLOOD COAGULATIONMECHANISMS OF BLOOD COAGULATION

Two mechanismsTwo mechanisms

1.1. Procoagulant-promote coagulationProcoagulant-promote coagulation

Predominate during injuryPredominate during injury

2.2. Anti coagulant – inhibit coagulationAnti coagulant – inhibit coagulation

In normal condition it is In normal condition it is predominatpredominat


CLOTTING FACTORS AND THEIR CLOTTING FACTORS AND THEIR ROMANS SYNONYMSROMANS SYNONYMS

Fibrinogen: factor IFibrinogen: factor IProthrombin: factor IIProthrombin: factor IITissue thromboplastin: factor IIITissue thromboplastin: factor IIICalcium: factor IVCalcium: factor IVProaccelerin: (labile factor V)Proaccelerin: (labile factor V)Prothrombin: factor VIIProthrombin: factor VIIAntihaemophilic: factor (AHF VIII)Antihaemophilic: factor (AHF VIII)Plasma thromboplastin component PTC: Plasma thromboplastin component PTC: factor IXfactor IX


CONT.CONT.Stuart: factor X Stuart: factor X

Plasma thromboplastin antecedent Plasma thromboplastin antecedent PTA: factor XIPTA: factor XI Hegman factor XII (Hegman factor XII (contact factor)contact factor)

Fibrin stabilizing: factor XIIIFibrin stabilizing: factor XIII

NB: Factor II, VII, IX & X requires vit NB: Factor II, VII, IX & X requires vit K for their synthesis IN THE LIVER, K for their synthesis IN THE LIVER, thereforetherefore

Vit K deficiency & liver diseases leads Vit K deficiency & liver diseases leads to bleeding tendenciesto bleeding tendencies


Factor Trivial Name(s) Pathway Characteristic

Prekallikrein Fletcher factor Intrinsic

High molecular weight kininogen (HMWK)

contact activation cofactor; Fitzgerald, Flaujeac Williams factor

Intrinsic

I Fibrinogen Both-

II Prothrombin BothContains N-term. gla segment

III Tissue Factor Extrinsic

-

IV Calcium Both-

V Proaccelerin, labile factor, accelerator (Ac-) globulin

Both Protein cofactor

VI (Va) Accelerin This is Va, redundant to Factor V

VII Proconvertin, serum prothrombin conversion accelerator (SPCA), cothromboplastin

Extrinsic

Endopeptidase with gla residues

VIII Antihemophiliac factor A, antihemophilic globulin (AHG)

Intrinsic

Protein cofactor

IXChristmas Factor, antihemophilic factor B,plasma thromboplastin component (PTC)

Intrinsic

Endopeptidase with gla residues

X Stuart-Prower Factor BothEndopeptidase with gla residues

XI Plasma thromboplastin antecedent (PTA) Intrinsic

Endopeptidase

XII Hageman Factor Intrinsic

Endopeptidase

XIII Protransglutaminase, fibrin stabilizing factor (FSF), fibrinoligase

Both Transpeptidase


INITIATION OF COAGULATIONINITIATION OF COAGULATION

Initiation of coagulation by either: Initiation of coagulation by either:

1.1. Trauma/injury to the tissue – Trauma/injury to the tissue – extrinsic pathwayextrinsic pathway

2.2. Trauma/injury to the blood – intrinsic Trauma/injury to the blood – intrinsic pathwaypathway

3.3. Contact of blood with damaged Contact of blood with damaged endothelial and collagenendothelial and collagen

A SUMMARY OF COAGULATION PATHWAYA SUMMARY OF COAGULATION PATHWAY



COAGULATION is also regulated by several COAGULATION is also regulated by several natural anticoagulantsnatural anticoagulantsAntithrombin III inactivate coagulation Antithrombin III inactivate coagulation factors& it neutralizes thrombinfactors& it neutralizes thrombinAntithrombin III activity is enhanced by Antithrombin III activity is enhanced by heparinheparinProtein C receptor combine Protein C receptor combine thrombomodulin – inhibits thrombin and thrombomodulin – inhibits thrombin and several coagulation factorsseveral coagulation factorsProtein S accelerate the action of protein CProtein S accelerate the action of protein CDeficiency of the above factors leads to Deficiency of the above factors leads to HYPERCOAGULOPATHY states leading to HYPERCOAGULOPATHY states leading to increased THROMBOEMBOLISMincreased THROMBOEMBOLISM


CLOT RETRACTIONCLOT RETRACTION

Clot retraction requires large Clot retraction requires large numbers of platelets ie consolidate numbers of platelets ie consolidate the clotthe clot

This contributes to haemostasis by This contributes to haemostasis by joining the edges of the broken joining the edges of the broken vesselsvessels


SUMMARY OF FIBRINOLYSIS


FIBRINOLYSIS (CLOT DISSOLUTIONFIBRINOLYSIS (CLOT DISSOLUTION))

Dissolution of a blood clot begins Dissolution of a blood clot begins shortly after its formationshortly after its formation

Plasma – contains a globulin Plasma – contains a globulin PLASMINOGEN incooperated in a large PLASMINOGEN incooperated in a large amount in the CLOTamount in the CLOT

PLASMINOGEN is activated byPLASMINOGEN is activated by Thrombin, factor XIII, and some lysosomal Thrombin, factor XIII, and some lysosomal

enzymes to PLASMIN with A PROTEOLYTIC enzymes to PLASMIN with A PROTEOLYTIC like actionlike action


PLASMINPLASMINPlasmin digest formed fibrin thread/clotPlasmin digest formed fibrin thread/clot

(FIBRINOLYSIS)(FIBRINOLYSIS)Plasmin also digest a number of clotting Plasmin also digest a number of clotting factors like Factor I, II, V & VIIfactors like Factor I, II, V & VIIalpha2 antiplasmin is always present in blood alpha2 antiplasmin is always present in blood whichwhichBinds with plasmin and inhibit its actionBinds with plasmin and inhibit its actionFibrinolysis system is therefore important for Fibrinolysis system is therefore important for removing small clot from tiny peripheral removing small clot from tiny peripheral vessels-preventing occlusion or blockage and vessels-preventing occlusion or blockage and thromboembolismthromboembolism

Thank you


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HEAMOSTASIS & FIBRINOLYSIS 1 HAEMOSTASIS & FIBRINOLYSIS DR B L Mtinangi DEPARTMENT OF PHYSIOLOGY Hubert Kairuki Memorial University December 3, 2015