COAGULATION SYSTEM
Hematology 2 (Laboratory)
Introduction to Hemostasis
A. Primary Hemostasis - all of the following are involved:
1. Vascular system and platelets - it starts when platelets come in
contact with exposed collagen, microfilaments, and the basement
membrane of endothelial tissue.
2. Small blood vessels contracts - allowing platelets to adhere to
exposed tissue, which causes:
• ADP/ATP release - promotes platelet aggregation, acts as
an energy source.
• thromboxane A2 synthesis from arachidonic acid -
promotes activation, release, and aggregation.
3. Platelets begin to aggregate - which causes the release of
additional ADP, ATP, and serotonin (substance that
promotes vasoconstriction).
4. Platelet receptor sites are exposed, which allows binding of
coagulation proteins from secondary hemostasis (e.g.,
fibrinogen binds at the glycoprotein IIb/IIIa receptor)
B. Secondary Hemostasis -
1. The goal is generation of sufficient thrombin to convert
fibrinogen to fibrin clot. It involves the following:
a. Activation of intrinsic coagulation pathway factors
b. Activation of extrinsic coagulation pathway factors
c. Activation of common coagulation pathway factors
2. Fibrin clot includes:
a. platelet plug formed in primary hemostasis &
b. fibrin formed in secondary hemostasis
C. Tertiary Hemostasis - otherwise known as “fibrinolytic system” and involves
normal fibrinolysis which refers to the enzymatic pathway of clot
dissolution in which plasmin is the key enzyme responsible for breaking
down bonds in the fibrin polymer and releasing fibrin degradation
products (FDP).
SECONDARY HEMOSTASIS:
a. Intrinsic pathway system:
• Is activated when coagulation proteins are exposed to subendothelial collagen.
• Refers to the path of the coagulation cascade which includes the following that
involved in the formation of a fibrin clot:
1. Prekallikrein (Fletcher factor)
2. Heavy-molecular-weight kininogen (Fitzgerald
factor) 3. Factors XII (Hageman factor)
4. Factor XI (plasma thromboplastin antecedent)
5. Factor IX (plasma thromboplastin component/Christmas
factor)
6. Factor VIII (antihemophiliac factor)
• In the laboratory, the APTT is used to test the coagulation cascade.
SECONDARY HEMOSTASIS:
b. Extrinsic pathway system:
• Otherwise known as “dominant in vivo pathway” • Starts with the
release of tissue factor from injured blood vessel endothelial cells and
subendothelium.
• Tissue factor (factor III) is found in most tissue, organs, and large blood vessels. It
is the primary activator of factor VII to VIIa.
• Factor VII (stable factor) which is a potent serine protease, is in
this pathway.
• In the laboratory, the PT is used to test the coagulation cascade
SECONDARY HEMOSTASIS:
c. Common pathway system:
• Begins with factor X activation by either the extrinsic (main in vivo) or
intrinsic pathway.
• It includes factors:
1. Factor X (Stuart-Prower factor)
2. Factor V (proaccelerin/labile factor)
3. Factor II (prothrombin factor)
4. Factor I (fibrinogen)
• In the laboratory, the APTT and PT is used to test the coagulation
cascade.
COAGULATION SYSTEM COAGULATION FACTORS
(Coagulation Proteins)
1. Coagulation factors - are also known as enzyme precursors or zymogens.
• They are found in the plasma, along with nonenzymatic cofactors and calcium.
2. Zymogens - are substrate having no biologic activity until converted by enzymes to active
forms called serine proteases.
a. Zymogens - include II, VII, IX, X, XI, XII and prekallikrein.
b. Serine proteases - include IIa, VIIa, IXa, Xa, XIa, XIIa and
kallikrein.
3. Cofactors - assist in the activation of zymogens and include V, VIII, tissue factor, and
high molecular weight kininogen (HMWK).
4. In its active form, factor XIII is a transglutaminase.
5. Fibrinogen is the only substrate in the cascade that does not become an activated enzyme.
COAGULATION SYSTEMCOAGULATION GROUPS
1. Contact group - includes prekallikrein, HMWK, and factor XI and XII
• It is produced in the liver and all play a role in intrinsic coagulation activation. •
It requires contact with a foreign surface for activation (e.g., collagen in vivo and
kaolin in vitro)
2. Prothrombin group - includes factors II, VII, IX and X.
• It is produced in the liver and otherwise known as vitamin K-dependent
factors. • This group depends on vitamin K metabolism to be completely
functional. • Vitamin K is required for synthesis of functional factors, with
calcium binding sites necessary for binding to phospholipid (PF3) surface.
3. Fibrinogen group - includes factors I, V, VIII, and XIII.
• It is produced in the liver and consumed in the clotting process.
• Conversion of fibrinogen to fibrin in a three-step process:
A. Fibrinogen alpha and beta fibrinopeptides are cleaved by thrombin,
forming soluble fibrin monomers.
B. Fibrin monomers spontaneously polymerize, forming soluble fibrin
polymers. This is the end point for clot-based tests.
C. Clot stabilization occurs, requiring thrombin activation of XIII and calcium.
COAGULATION SYSTEM COAGULATION FACTOR MNEMONICS:
