2001B07 Explain the main differences between the intrinsic and the extrinsic pathways of coagulation.

 

 

Extrinsic

Intrinsic

Meaning

Requires a component extrinsic to blood

Spontaneous clotting possible without extravascular exposure

Main function

Initiation

Amplification

Triggers

Tissue factor (a tissue protein)

Charged surface

-In vivo: subendothelial collagen

-In vitro: glass

Factors: VIII, XI, XII

Factors involved

VII (and common pathway)

XII, XI, IX, VIII (and common pathway)

Speed

15 seconds to activate

“Thrombin burst”

1-6 minutes to activate

Amplification, importance

Less

More

Dampening

TFPI

AT3

(see diagramme)

TFPI

AT3

Protein C

(see diagramme)

Interactions

Xa activates TFPI, inhibiting TF/VIIa

Thrombin -> activation of XI, VIII

TF/VIIa -> activation of IX

Implication of deficiencies

?

Factor IX: haemophilia A

Factor XI: haemophilia B

Test

INR = (PTpatient/PTnormal)ISI

ISI: adjustment factor for each laboratory

Citrated blood + TF + Ca2+

Time taken to clotting

aPTT

Citrated blood plus partial thromboplastin (phospholipid), Ca2+, silicate.

Time taken to clotting

Inhibitors

Warfarin (Vitamin K epoxide reductase inhibitor; prevents γ-glutamyl carboxylation of factors II/VII/IX/X, prot C&S

Heparin (potentiates AT3 effect on II and X)

Effect of sepsis

↑[VII]

↑[kallikrein], [XI], [XII]

 

 

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