NSC1103D Clinical Sciences: Warfarin's Role in Blood Clotting

This report provides a detailed explanation of how warfarin impacts blood clotting through its interaction with vitamin K-dependent clotting factors. The introduction outlines the coagulation cascade, highlighting the roles of various clotting factors and vitamin K. Warfarin, a vitamin K antagonist, inhibits the activation of clotting factors, disrupting the normal hemostatic balance. The report elucidates the mechanism by which warfarin blocks the enzyme VKORC1, reducing the activity of vitamin K-dependent clotting factors. A concept map visually summarizes these processes, illustrating the relationship between warfarin, vitamin K, and the coagulation cascade. The report also briefly discusses how disruptions in this system can lead to bleeding disorders and emphasizes the importance of maintaining appropriate vitamin K levels and warfarin dosage to prevent adverse effects. This assignment showcases a student's understanding, and Desklib provides access to similar resources.

Running head: CONCEPT MAP 1
Blood clotting affected by warfarin
(Author’s name)
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CONCEPT MAP 2
Introduction
The clotting system involves a process where blood forms clots following a tissue injury
to prevent further blood loss(Gee, 2018). The process follows a coagulation cascade where
various clotting factors are involved(Gee, 2018). There are two major pathways of the
coagulation which include the intrinsic and extrinsic pathways. There are several coagulation
factors that are involved in both pathways which include the tissue factor, factors XIII, XII, XI,
X, IX, VIII, VII, V, IV, III, II and I(Tshikudi, Tripathi, Hajjarian, Van Cott & Nadkarni, 2017).
Other important factors include calcium ions and vitamin K(Gee, 2018). Vitamin K is involved
in activation of various coagulation factors. Warfarin work against as vitamin K hence it can
inhibit the whole process resulting in homeostasis imbalance(Tshikudi, Tripathi, Hajjarian, Van
Cott & Nadkarni, 2017).
Blood clotting affected by warfarin
The blood clotting cascade is influenced by various clotting factors and cofactors. The
cofactors are usually the inactive form of certain factors that activates various clotting factors
into active forms(Palta, Saroa & Palta, 2014). Failure of this activation, no blood clotting can
occur(Gee, 2018). Vitamin K is one of the cofactors used to activate the clotting factors X, IX,
VII and II. An increased activation of vitamin K will lead to increase in clotting process and vise
vasa(Gee, 2018).
Therefore, VItamin K acts as an important contributing factor of the clotting process due
to its effects on its dependent factors of the coagulation cascade(Goodman, Brunton, Chabner &
Knollmann, 2012). This is due to the fact that, Vitamin K form one of the major factor that is
required by the liver microsomal enzyme known as vitamin K epoxide reductase (VKOR) that
catalyzes the conversion of the specific glutamyl precursors of the vitamin K clotting factors to

CONCEPT MAP 3
gamma-carboxyl glutamyl residues in a plasma form of these proteins(Goodman, Brunton,
Chabner & Knollmann, 2012). The product that comes from this carboxylation reaction is the 2,
3 eporoxide of Vitamin K quinone. Warfarin, which acts as the Vitamin K inhibitor is made up
of the mixture of S- and R- enantiomers(Palta, Saroa & Palta, 2014).
The S- warfarin is usually the most active type of enantiomer than the R-warfarin. Both
warfarin enantiomers inhibit the process of coagulation by blocking the enzymes encoded as
VKORC1(Malátková, Sokolová, Chocholoušová Havlíková & Wsól, 2016). This, in turn, read to
the reduction of peroxides of the vitamin K or oxidized vitamin K into an active coenzyme of the
vitamin known as hydroquinone(Goodman, Brunton, Chabner & Knollmann, 2012). Since
vitamin K serves a major cofactor of glutamyl carboxylase that serves as the catalyst in the
carboxylation process of factors X, IX, VII and II, this characteristic of Warfarin decreases the
activity of all carboxylated clotting factors that are dependent on vitamin K(Harter, Levine &
Henderson, 2015).
Calcium ions that usually activate prothrombin to thrombin normally function well in the
presence of gamma carboxyl glutamyl in order to form des-gamma-carboxyl forms of
prothrombin. Thereby, only the activated vitamin K can act as a cofactor in the conversion of
prozymogens into zymogens capable of binding with calcium ions and smoothly interacting with
phospholipids surfaces(Goodman, Brunton, Chabner & Knollmann, 2012). Therefore, the
introduction of warfarin normally reduces the blood thrombotic potential as the needed factors
are inactivated. The reduced vitamin K can be held back into normal through the intake of more
vitamins K in the body and reduced dose of warfarin(Malátková, Sokolová, Chocholoušová
Havlíková & Wsól, 2016). Below is the concept map that summarises the above whole process.

CONCEPT MAP 4
Summary Concept map
 A summary concept map usually presents a relationship between various items and facts
inform of a diagram in order to show certain concepts of knowledge.
 A concept map is meant to demonstrate an overall picture of a given topic by showing
how various interacting subunits work to bring an overall outcome.
 The diagram below demonstrate how warfarin affect the vitamin K dependant factors of
coagulation process therefore ending up affecting the clotting process.

CONCEPT MAP 5
Concept Map and the disease
 The impact of the disease process could be presented clearly be demonstrated on this
concept map by introducing a person with a fresh tissue injury for example.
 After tissue injury, the body responds to the clotting process to prevent further bleeding.
 The clotting process involves both intrinsic and extrinsic pathways where various clotting
factors are involved to enhance coagulation process.
 Oxidized Vitamin K is involved inactivation of clotting factors X, IX, VII and II, and
proteins C and S of which play a key role in the clotting process.
 The factors involved can be well be demonstrated by putting them in bold color in order
to show the exact stages of clotting process affected
 Warfarin normally reduces oxidized vitamin K into its inactive form hence the clotting
factors will not be activated. This, in turn, leads to more bleeding as the normal
homeostasis is affected.

CONCEPT MAP 6
Reference
Gee, E. (2018). Principles and nursing management of anticoagulation. Nursing
Standard, 32(23), 50-63.
Goodman, L., Brunton, L., Chabner, B., & Knollmann, B. (2012). Goodman & Gilman's
pharmacological basis of therapeutics. New York: McGraw-Hill.
Harter, K., Levine, M., & Henderson, S. (2015). Anticoagulation Drug Therapy: A
Review. Western Journal Of Emergency Medicine, 16(1), 11-17.
Malátková, P., Sokolová, S., Chocholoušová Havlíková, L., & Wsól, V. (2016). Carbonyl
reduction of warfarin: Identification and characterization of human warfarin
reductases. Biochemical Pharmacology, 109, 83-90.
Palta, S., Saroa, R., & Palta, A. (2014). Overview of the coagulation system. Indian Journal Of
Anaesthesia, 58(5), 515.
Tshikudi, D., Tripathi, M., Hajjarian, Z., Van Cott, E., & Nadkarni, S. (2017). Optical sensing of
anticoagulation status: Towards point-of-care coagulation testing. PLOS ONE, 12(8),