MLAB 1227: COAGULATION
KERI BROPHY-MARTINEZ
Overview of Hemostasis:
Part Two
FUNCTION
OF
 Surveillance


PLATELETS
of blood vessel continuity
Checks endothelial lining for gaps and breaks
Fill-in small gaps caused by separation of
endothelial cells
 Formation
of primary hemostatic plug
 Surface for coagulation factors to make
secondary hemostatic plug
 Aid in healing injured tissue
FORMATION OF PRIMARY HEMOSTATIC
PLUG
 Once
the platelets “normal” environment
is changed, they become activated or
adhesive
 Stages




of plug formation
Adhesion
Secretion
Aggregation
Stabilization
STAGE 1: PLATELET ADHESION



Platelets attach to non-platelet surfaces, such as collagen
fibers in the subendothelium
Platelets move from the blood vessels and into the tissues.
Exposure to surfaces in the tissues causes them to bind





Veins/venules- collagen
Capillaries/arterioles- von Willebrand factor ( vWF) through the
Glycoprotein Ib/IX receptor
Results in a bridge formation, which triggers a shape
change in the platelets
Reversible
No energy required
PLATELET ACTIVATION
Platelets undergo a shape change from disc to
spiny sphere with projections
 Activation required for 1O hemostatic plug
formation
++
 Activation continues until Ca
threshold met
 Platelets remain localized in injured area

Key outcome- generate active GPllb/llla
receptors to bind fibrinogen
 http://tiny.cc/abmhmw

ACTIVATION
Platelet shape change after exposure to
agonist.
Agonists include: ADP, Serotonin,
collagen, thrombin
STAGE 2: PLATELET SECRETION/ PLATELET
RELEASE REACTION

Secretion



Requires ATP
Provides a positive feedback by releasing more agonists
to stimulate more plt receptors
Release of Granule contents



Causing vasoconstriction
Release of ADP(agonist)= increased Ca+, plt release,
increase in fibrinogen receptors
Trigger a secondary aggregation which is irreversible
WHAT’S IN

A
GRANULE?
Granules consist mainly of:
 Alpha granules: Factor V, vWF, Fibrinogen,
platelet factor 4, β-thromboglobulin
Factor V: receptor on platelet surface for factor Xa &
prothrombin
 PF4: heparin neutralizing factor, promotes wound healing


Dense bodies: ATP, ADP, serotonin, Ca
SIDE

NOTE
Heparin is used on patients who clot excessively.
Endothelial cells make heparin-like molecules and
expose them on their surface. PF4 binds these
substances. Heparin can complex with bound PF4
and heparin will be neutralized.
STAGE 3: PLATELET
 Chemical
AGGREGATION
changes cause platelets to
aggregate and stick to one another
 Newly arriving platelets become activated
by agonists
 Exposure of GPIIb/IIIa sites bind
fibrinogen
 Fibrinogen + activated platelets serves as
a bridge between two platelets
 Calcium must be present
ADHESION & AGGREGATION

http://www.platelet-research.org
FINAL STAGE : STABILIZATION
OF
CLOT
AKA: primary hemostatic plug formation
 Thrombus formation
 Platelets release Factor V
 Expose factor III (TF)



Accelerating coagulation cascade
Promote activation of clotting factors
STAGES
OF 1O PLUG FORMATION
BLOOD CLOT
COAGULATION SYSTEM

Composed of 14 coagulation factors (serine proteases) which are
interdependent (Factors I through XIII – there is no Factor VI –
and PK and HMWK)
◦
◦
◦
◦

Final product is fibrin mesh or clot which completely stops bleeding
◦

Inactive form of each is an enzyme precursor which is usually designated by a
Roman numeral but also given a name – Ex. Factor I fibrinogen. Numbers
correspond to order of discovery NOT order in cascade.
Active forms are usually designated by the letter “a” after the Roman numeral and
may also have a different name – Ex. Ia Fibrin
Cofactors are needed for many reactions in the cascade – Ex. Calcium, platelet
factor 3 (PF3)
Each molecule must be present in sufficient quantity as well as functioning normally
Secondary hemostasis
Slow contraction or retraction and lysis of the clot occurs
FIBRINOLYTIC SYSTEM
Fibrin is a product formed during hemostasis,
tissue repair or inflammation
 Fibrin plays a temporary role
 Once injury heals, the fibrin clot is lysed

Plasminogen is converted to plasmin
 Plasmin enzymatically attacks the fibrin molecule
producing fibrin degradation products (FDPs,
sometimes called FSPs) that are cleared from
the circulation by macrophages

COAGULATION INHIBITION SYSTEM
Provides balance and control of clotting
mechanisms
 Natural inhibitors and anticoagulants circulate in
the plasma to:
 Prevent clotting when it’s not needed
 Limit or localize the clotting that is needed
 Examples: Protein C and S, antithrombin III

REFERENCES
McKenzie, Shirlyn B., and J. Lynne. Williams.
"Chapter 29." Clinical Laboratory Hematology.
Boston: Pearson, 2010. Print.
 Platelet Research Laboratories. Platelet
Function. Retrieved from http://www.plateletresearch.org/1/function_hemo.htm.
