Overview Of Hemostasis; Abnormalities Of The Hemostatic; Platelet Function; Formation Of The Primary Hemostatic - Chrono-Log 490 4+4 Instruction Manual

patients are not routinely screened for platelet defects despite
the fact that many cases of platelet dysfunction are discovered
only after excessive or recurrent post-surgical bleeding.
In 1962, Born described the aggregation of platelets by ADP and
modified a colorimeter to monitor continuously this aggregation
in platelet rich plasma. These modifications included incubation
at 37°C, stirring and recording the change in light transmission
over time on a pen recorder. 1

OVERVIEW OF HEMOSTASIS

Hemostasis - from the Greek word for blood; and, the Greek word
meaning standing - is a complex, delicately balanced system of
interactions that keeps blood circulating as a fluid through the
blood vessels. A simplified representation of the process is shown
below.
There are three elements of the hemostatic mechanism:
• Blood vessels
• Plasma proteins known as coagulation factors
• Platelets
A defect or abnormality in the interactive process of hemostasis
may lead to abnormal bleeding or to inappropriate clotting.
Abnormalities of the hemostatic mechanism
Blood vessels - abnormalities of the endothelial cell lining of the
blood vessels can arise from injury, inflammation, infection or
atherosclerosis. The endothelium may lose its normal anti-
thrombotic properties and begin to synthesize and release
compounds that promote thrombosis.
result in abnormal blood vessel support structures may contribute
to disordered hemostasis.
Coagulation proteins - abnormal levels of coagulation factor
levels or defective function of the coagulation factors can disturb
Document # 49044IM1
Revision 7.5
Dated February 16, 2017
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Vascular disorders that
hemostatic balance. These defects can be hereditary or they can
be acquired, through a pathological process, for example.
Platelets - disorders of the platelet component of hemostasis can
arise from abnormal numbers of platelets (quantitative defects)
or functional impairment (qualitative defects). Defects in the
platelet component of the hemostatic system can also be
acquired or inherited.

Platelet function

The platelets (or thrombocytes) are small, discoid cells that
circulate in the blood along with red cells and leukocytes. The
cell's nucleus is lost during the maturation process. Platelets have
cytoplasmic granules known as dense granules and alpha
granules. These contain compounds that amplify the platelet
response if they are exocytosed (released, secreted).
The main function of platelets is the maintenance of blood vessel
integrity by prevention of red cell migration through the vessel
wall. Platelets also prevent vascular leakage by plugging any sites
of damage or injury. In the case of damage or injury that exposes
the subendothelium and/or basement membrane, circulating
platelets are recruited to the site to form a platelet aggregate.
This physiologic reaction is known as formation of the primary
hemostatic plug. 15
Formation of the primary hemostatic plug
Platelets adhere and aggregate at any site of sub endothelial
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exposure. Exposure of the subendothelium results in the
unmasking of the structural protein collagen. Collagen is a
platelet stimulus.
Platelets adhere to the now exposed collagen fibrils. The platelets
change shape and pseudopods are formed. The shape change
and pseduopods result in closer contact with other individual
platelets. Granule contents are exocytosed. More platelets are
recruited and stimulated to undergo shape change, pseudopod
formation and granule release. This aggregated mass physically
prevents leakage at the site.
Von Willebrand factor (found in the alpha granules of the platelet
and circulating in the blood in association with Factor VIII) is
classified as an adhesive protein. It interacts with a binding site
on the platelet membrane and acts to strengthen the platelets'
adherence to the endothelium.

Qualitative platelet function disorders

Defective adhesion
•
Von Willebrand Disease -quantitative or qualitative
o
defect in plasma von Willebrand Factor (vWF)
Bernard-Soulier Syndrome (BSS) -lack of platelet
o
membrane glycoprotein Ib (GPIb)
• Defective aggregation
Afibrinogenemia - deficiency of plasma fibrinogen
o
Glanzmann's Thrombasthenia -defective or deficient
o
platelet membrane glycoprotein IIb-IIIa (GP IIb-IIIa)
• Defective platelet granule secretion
Storage pool deficiency (SPD) -deficiency in dense
o
granule contents (ADP, ATP and/or serotonin)
Gray platelet syndrome -deficiency in alpha granule
o
contents [platelet factor 4 (PF4), platelet vWF,
thrombospondin, and platelet derived growth factor
(PDGF)]
Arachidonic acid metabolic pathway abnormalities
o
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