Encyclopedia of Health and Medicine

136 The Blood and Lymph
in blood clotting. Clotting factors interact with
each other as well as other enzymes in the blood,
notably fibrin and thrombin, to form blood clots.
Deficiencies of specific clotting factors cause coagulation
disorders such as HEMOPHILIA (excessive
bleeding) and thrombophilia (excessive clot formation).
The LIVER produces clotting factors I (fibrinogen),
II (prothrombin), V (proaccelerin), VII
(cothromboplastin), IX (PLASMA thromboplastin),
and X (Stuart-Prower factor).
See also ANTICOAGULANT THERAPY; ASPIRIN THERAPY.
coagulation The process, also called the coagulation
cascade, through which the BLOOD forms clots.
The cells responsible for forming clots are
platelets, which interact with each other, collagen,
proteins, and other substances in the blood. Specialized
proteins in the blood, called CLOTTING FAC-
TORS, activate in cascades, with one activation
leading to another in sequence. Coagulation
begins with one of two sequences of cascading
events: either an extrinsic or an intrinsic trigger
sets off a different cascade. Each cascade culminates
in clot formation. Current research suggests
that coagulation cascades unfold at different paces
and with differing thresholds of activation according
to the type of tissue or the organ structure
involved. This way, the body manages the coagulation
process appropriately to the situation.
Coagulation is a beneficial event when it stops
bleeding and can become a hazard to health when
it occurs inside blood vessels. Insufficient clotting
allows extended bleeding, and excessive clotting
can result in HEART ATTACK, STROKE, PULMONARY
EMBOLISM, and DEEP VEIN THROMBOSIS (DVT). Though
the coagulation process includes several inherent
checks and balances that ordinarily strike a balance
between beneficial and harmful clotting,
problems with coagulation can occur and can be
life-threatening.
Coagulation disorders occur when certain clotting
factors are missing (such as in HEMOPHILIA),
which results in excessive bleeding, or when there
is an abundance of platelets in the blood (such as
in THROMBOCYTHEMIA), resulting in excessive clotting.
LIVER disease such as CIRRHOSIS or severe HEPA-
TITIS affects the liver’s ability to produce clotting
factors—especially factors II, VII, and X—and to
metabolize VITAMIN K (which participates in converting
a number of clotting factors from inactive
to active states), impairing coagulation.
Extrinsic coagulation cascade Any breach in a
blood vessel, such as a cut (even microscopic),
causes blood to come into contact with tissue factor
(clotting factor III), a protein on the surface of
epithelial cells (the cells of the SKIN, mucous membranes,
and lining of the blood vessels). Tissue factor
initiates the extrinsic coagulation cascade,
activating the release and interactions of thromboplastin,
clotting factor VII, and calcium ions to culminate
in the production of clotting factor X.
Intrinsic coagulation cascade Internal clot formation
occurs without a breach when the blood
comes into contact with a foreign substance in the
blood such as an ATHEROSCLEROTIC PLAQUE that activates
the body’s INFLAMMATION response, resulting
in the formation of collagen. Collagen’s presence
initiates the release of kallikrein and high molecular
weight kininogen (HMWK), two substances
that activate clotting factor XII. The continued
interaction among these substances draws clotting
factor XI and clotting factor IX into the process,
culminating in the production of clotting factor X.
Clot formation PLATELET AGGREGATION and clot
formation begin at the intermediate level of either
cascade, when clotting factor X initiates the conversion
of clotting factor II (prothrombin) into the
enzyme thrombin. Thrombin in turn converts
clotting factor I (fibrinogen) to fibrin, a protein
that interlaces with collagen (formed by the
IMMUNE SYSTEM’s inflammation response) to form a
clot. The clot attracts additional platelets, extending
the coagulation process until the protein
thrombomodulin activates protein C, beginning
the coagulation inhibition cascade that brings
coagulation to a halt.
See also ANTICOAGULATION THERAPY; ASPIRIN THER-
APY; CORONARY ARTERY DISEASE (CAD); C-REACTIVE PRO-
TEIN; HEALING; MEDICATIONS TO TREAT CARDIOVASCULAR
DISEASE; SCAR.