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

2. A SUMMARY OF PLATELETS FORMATION
HEAMOSTASIS & FIBRINOLYSIS

3. SUMMARY OF BLOOD COAGULATION
BV Injury
Platelet
Aggregation
Activation
Blood Vessel
Constriction
Coagulation
Cascade
Stable Hemostatic Plug
Fibrin formation
Reduced
Blood flow
Contact/ Tissue Factor
Primary hemostatic plug
Neural

7. HEAMOSTASIS & FIBRINOLYSIS

8. HEAMOSTASIS & FIBRINOLYSIS
HAEMOSTATIS
Haemostasis is prevention of blood loss after rupture or injury/trauma of blood vessels
It is achieved through:
Vascular spasms
Formation of platelet plug formation
Blood coagulation i.e. Development of insoluble fibrin clot
Clot retraction
Clot dissolution
HEAMOSTASIS & FIBRINOLYSIS

9. Vascular spasms (vasoconstriction)
Vascular spasms is due to:
Nervious reflex due to pain
Effects of local and humoral mechanism
Thromboxane A2 (prostaglandin) cause vasoconstrition
All generate an Action Potential and cause Myogenic spasm (constriction) and REDUCE blood flow
The spasm last less than 1 min
HEAMOSTASIS & FIBRINOLYSIS

10. FORMATION OF PLATELET PLUG
Initiated when the platelet come into contact with damaged vascular surface or collagen fibers
Platelets adhere and aggregate to the damaged site
Platelets secrete large quantity of ADP and Thromboxane A2 (prostaglandin)
Endothetal cells secrete a Von Willebrands factor (a small protein molecule)
Usually attached to factor VIII
Bridges the platelets to exposed collagen
HEAMOSTASIS & FIBRINOLYSIS

11. HEAMOSTASIS & FIBRINOLYSIS
CONT.
Aggregated platelets activate coagulation factors
Finally convert FIBRINOGEN to FIBRIN
Stabilizing the PLATELET PLUG
Platelets normal count 150, ,000/µl
Platelets maintain normal vascular integrity
HEAMOSTASIS & FIBRINOLYSIS

12. MECHANISMS OF BLOOD COAGULATION
Two mechanisms
Procoagulant-promote coagulation
Predominate during injury
Anti coagulant – inhibit coagulation
In normal condition it is predominat
HEAMOSTASIS & FIBRINOLYSIS

13. CLOTTING FACTORS AND THEIR ROMANS SYNONYMS
Fibrinogen: factor I
Prothrombin: factor II
Tissue thromboplastin: factor III
Calcium: factor IV
Proaccelerin: (labile factor V)
Prothrombin: factor VII
Antihaemophilic: factor (AHF VIII)
Plasma thromboplastin component PTC: factor IX
HEAMOSTASIS & FIBRINOLYSIS

14. HEAMOSTASIS & FIBRINOLYSIS
CONT.
Stuart: factor X
Plasma thromboplastin antecedent PTA: factor XI
Hegman factor XII (contact factor)
Fibrin stabilizing: factor XIII
NB: Factor II, VII, IX & X requires vit K for their synthesis IN THE LIVER, therefore
Vit K deficiency & liver diseases leads to bleeding tendencies
HEAMOSTASIS & FIBRINOLYSIS

15. HEAMOSTASIS & FIBRINOLYSIS
Factor
Trivial Name(s)
Pathway
Characteristic
Prekallikrein
Fletcher factor
Intrinsic
High molecular weight kininogen (HMWK)
contact activation cofactor; Fitzgerald, Flaujeac Williams factor I
Fibrinogen
Both - II
Prothrombin
Contains N-term. gla segment
III
Tissue Factor
Extrinsic IV
Calcium V
Proaccelerin, labile factor, accelerator (Ac-) globulin
Protein cofactor
VI (Va)
Accelerin
This is Va, redundant to Factor V
VII
Proconvertin, serum prothrombin conversion accelerator (SPCA), cothromboplastin
Endopeptidase with gla residues
VIII
Antihemophiliac factor A, antihemophilic globulin (AHG) IX
Christmas Factor, antihemophilic factor B,plasma thromboplastin component (PTC) X
Stuart-Prower Factor XI
Plasma thromboplastin antecedent (PTA)
Endopeptidase
XII
Hageman Factor
XIII
Protransglutaminase, fibrin stabilizing factor (FSF), fibrinoligase
Transpeptidase
HEAMOSTASIS & FIBRINOLYSIS

16. INITIATION OF COAGULATION
Initiation of coagulation by either:
Trauma/injury to the tissue – extrinsic pathway
Trauma/injury to the blood – intrinsic pathway
Contact of blood with damaged endothelial and collagen
HEAMOSTASIS & FIBRINOLYSIS

19. A SUMMARY OF COAGULATION PATHWAY
HEAMOSTASIS & FIBRINOLYSIS

20. HEAMOSTASIS & FIBRINOLYSIS
COAGULATION is also regulated by several natural anticoagulants
Antithrombin III inactivate coagulation factors& it neutralizes thrombin
Antithrombin III activity is enhanced by heparin
Protein C receptor combine thrombomodulin – inhibits thrombin and several coagulation factors
Protein S accelerate the action of protein C
Deficiency of the above factors leads to HYPERCOAGULOPATHY states leading to increased THROMBOEMBOLISM
HEAMOSTASIS & FIBRINOLYSIS

21. HEAMOSTASIS & FIBRINOLYSIS
CLOT RETRACTION
Clot retraction requires large numbers of platelets ie consolidate the clot
This contributes to haemostasis by joining the edges of the broken vessels
HEAMOSTASIS & FIBRINOLYSIS

22. HEAMOSTASIS & FIBRINOLYSIS

23. SUMMARY OF FIBRINOLYSIS

24. FIBRINOLYSIS (CLOT DISSOLUTION)
Dissolution of a blood clot begins shortly after its formation
Plasma – contains a globulin PLASMINOGEN incooperated in a large amount in the CLOT
PLASMINOGEN is activated by
Thrombin, factor XIII, and some lysosomal enzymes to PLASMIN with A PROTEOLYTIC like action
HEAMOSTASIS & FIBRINOLYSIS

25. HEAMOSTASIS & FIBRINOLYSIS
PLASMIN
Plasmin digest formed fibrin thread/clot
(FIBRINOLYSIS)
Plasmin also digest a number of clotting factors like Factor I, II, V & VII
alpha2 antiplasmin is always present in blood which
Binds with plasmin and inhibit its action
Fibrinolysis system is therefore important for removing small clot from tiny peripheral vessels-preventing occlusion or blockage and thromboembolism
HEAMOSTASIS & FIBRINOLYSIS

26. HEAMOSTASIS & FIBRINOLYSIS
Thank you
HEAMOSTASIS & FIBRINOLYSIS