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
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. Don’t 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 there’s fewer
V
X
steps to remember, and this is
lucky, so the lucky PT pathway
uses lucky Factor 7 to activate
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.
Heparin’s 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.
Coumadin’s 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
