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Coagulation Made Easy

Alice Ma, M.D.


University of North Carolina-Chapel Hill
Division of Hematology

Erniody, M.D.
Intensive Care - Husada Hospital
November 13, 2016
Coagulation Made Easy

The PTT Pathway The PT Pathway

Rather than thinking about the intrinsic and the


extrinsic pathways, think about the PTT and the
PT pathways.
Coagulation Made Easy

The PTT Pathway The PT Pathway

X The PT and the PTT


pathway meet at Factor X,
because X marks the
spot.
Coagulation Made Easy

The PTT Pathway The PT Pathway

V
X Factor V is a cofactor for
Factor X, and you can
remember this because V
fits into the notch of the X.
Coagulation Made Easy

The PTT Pathway The PT Pathway

V
X
Prothrombin Thrombin
Factor Xa converts prothrombin (Factor II) into
thrombin, the most important enzyme on the planet.
Coagulation Made Easy

The PTT Pathway The PT Pathway

V Thrombin, among other

X things, converts the soluble


molecule fibrinogen into a
solid fibrin clot.

Prothrombin Thrombin

Fibrinogen Fibrin
The Common Pathway = Small Bills

V+X

II = prothrombin

I = fibrinogen

You can remember the factors in the common pathway by remembering the
bills in your wallet smaller than a $20. Dont forget the $2 bill!
Coagulation Made Easy: The PT
The PT Pathway
PT has one less letter than PTT,
and PT values are shorter than
PTT values, because the
pathway is shorter. It means that 7
the PT pathway is also shorter.
This means that theres fewer
steps to remember, and this is V
lucky, so the lucky PT pathway
uses lucky Factor 7 to activate
X
Factor X.

Prothrombin Thrombin

Fibrinogen Fibrin
Coagulation Made Easy: The aPTT
The PTT Pathway
The PTT pathway has all those
XII hideous roman numerals. . .
XI How are we going to remember
them? Hmmmmm. . .
IX V
VIII X
Prothrombin Thrombin

Fibrinogen Fibrin
Coagulation Made Easy: The aPTT
The PTT Pathway
Well, just remember that the PTT
T is a basic TENET of hematology.
E
TENET stands for. . .
N
E V
T X
Prothrombin Thrombin

Fibrinogen Fibrin
Coagulation Made Easy: The aPTT

The PTT Pathway


Twelve
Eleven
Nine
Eight V
Ten X
Prothrombin Thrombin

Fibrinogen Fibrin
Coagulation Made Easy:
PT and PTT Both Prolonged

The PTT Pathway The PT Pathway

V These factors are in the

X common pathway.

Prothrombin (II)

Fibrinogen
Coagulation Made Easy:
Only PT Prolonged

Deficiency of Factor VII will prolong the PT but not the PTT.
Coagulation Made Easy:
Only PTT Prolonged

Twelve
Eleven - Deficiencies of Factors 12, 11,
9, and 8 will prolong the PTT
Nine and not the PT.
Eight - Remember that Factor 10 is in
the common pathway, and
Ten affects BOTH the PT and the
PTT.
What Matters Clinically
XII
XI
Deficiencies of Factor XI,
IX IX, VIII, VII. X, V,
prothrombin, and fibrinogen
VIII VII
are clinically significant.
X Inhibitors of these factors
are clinically significant for
V
bleeding.
Thrombin Deficiency of Factor XII,
and the presence of the
Fibrinogen Fibrin lupus anticoagulant are not.
Heparins anticoagulation mechanism and the cascade

- Antithrombin (AT) is a substance that inhibits clot formation primarily by


inactivating the activated factors of the intrinsic pathway (XII, XI, IX, II).
- Heparin does have some effect on X and VII but it is easier to associate
heparin with the intrinsic pathway.
- The activity of AT is greatly increased when it binds with heparin.
- Depending on which factor is involved (XII, XI, IX, II), the AT-Heparin
complex can be 500 to 1 million times more effective as an anticoagulant
than AT alone.
- Factors Xa and IIa (Thrombin) are most sensitive to inactivation by the AT-
Heparin complex. This is not the case when factors Xa and Thrombin are
bound within a clot. As a bound unit of a clot, the factors are protected
from inactivation by the AT-Heparin complex. The protection afforded by
clot formation is why heparin is not a clot busting drug but rather an
anticoagulant.
Heparin/AT-III complex inactivates the coagulation enzymes factor XIIa, factor XIa, factor IXa, factor
Xa, and thrombin (IIa).

Jack Hirsh et al. Circulation. 2001;103:2994-3018

Copyright American Heart Association, Inc. All rights reserved.


Coumadins anticoagulation mechanism and the cascade

- Coumadin acts on vitamin K dependent factors (II, VII, IX and X)


.
- Factors II, VII, IX and X are termed vitamin K dependent because
they require vitamin K for activation.
- Coumadin has structural components that mimic vitamin K. When
exposed to Coumadin, factors II, VII, IX and X will mistakenly
bond with the Coumadin instead of vitamin K.
- The incorporation of Coumadin will thus prevent the factors
activating.
- Coumadin also deactivates the anticoagulants protein C and S.
While the deactivation briefly causes a prothrombotic state, the
effect Coumadin has on the extrinsic pathway eventually leads to
Thank You