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L6 Haemostasis II – Coagulation
Platelet aggregate forms after blood vessel damage to plug the hole (doesn’t completely stop leakage)
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Blood vessel response – vasoconstriction
Primary haemostasis - Activation of platelets and formation of platelet plug
Secondary haemostasis – blood coagulation – intrinsic and extrinsic pathways
Clot retraction and fibrinolysis

Thrombin is the key molecule it cleaves fibrinogen to fibrin
Initiation of stage coagulation – Extrinsic pathway
 Damage to blood vessel wall  exposure of tissue factor (TF or FVII)
 TF binds to circulating FVII  activation of FVII = FVIIa
 FVIIa binds to FX and presence of Ca2+ activates FXa
 FXa important – generates active thrombin from prothrombin (using Phosphatidyl serine, Ca2+, FVa)
 Extrinsic pathway is the spark to generate small amount of thrombin
Amplification stage of coagulation – Intrinsic pathway
 Tissue damage  FXIIFXIIa
 FXIIa acts on FXI converts it  FXIa
 FXIa acts on FIX converts it  FIXa
 FIXa + FXIIa (+ Ca2+ + phosphatidyl serine) act FX, convert it  FXa
 Intrinsic pathway allows for generation of large amounts of thrombin
Thrombin can activate intrinsic pathway – Activates F5, 7, 8, 11, 13
So more thrombin  more production of thrombin
The end results of coagulation – fibrin and the common pathway
 Fibrinogen sticks to platelets and helps them stick together
 Fibrin holds platelet clots
 Thrombin activates FXIII  FXIIIa, which crosslinks fibrin into
fibrin mesh
Platelets and the coagulation cascade:
 Thrombin is an agonist binds to PAR receptors - activates
platelets
 Platelets provide a pro-coagulant surface – phosphatidylserine
flipping
o Phosphatidylserine normally found on inside of platelet membrane
o Phosphatidylserine gets flipped to outside of membrane upon activation
o Phosphatidylserine is now available to act with FXa and FVa to make thrombin
Pathological thrombus formation
 Conditions that give rise to pathological thrombus formation described by Rudolf Virchow – known as Virchow
Triad
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Endothelial injury (e
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atherosclerotic plaque
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Full blood counts
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Platelet production problems
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Inherited – inherited thrombocytopenia
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Certain medications, hypersplensim, autoimmune disorders, pregnancy, bacterial
infection in the blood, thrombotic thrombocytopenic purpura (TTP)
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High platelet count – thrombocytosis/thrombocythemia
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g
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Inherited - mutations in haematopoietic pregenitors (e
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MPL, TPO, JAK2)
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Platelet size and number can be independent of each other
Platelet function testing – light transmission aggregometry:
 LTA is the gold standard test of platelet function
o Cells will block some of the light from getting to the detector
o When resting the cells are all over the place so not much light will
get through
o When activated (form aggregates) so more light will reach the
detector
o B – at first cells become spiky = let even less light in
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Block
integrins needed for aggregation
o Range of agonists used to activate platelets

o
o

Arachadonic acid (platelets secrete) is the
precursor for thromboxane
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e

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