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Medical Laboratory
Scientist

Hematology
Part 4 of 4: Blood coagulation
Brief overview
Presented by
Nithianandan Selliah, PhD
Scientist
Founder and CEO
of Protg Education Center, LLC Protg
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Hemostasis
Normal hemostasis is the responsibility of a complex system of three
individual components:
Platelets - in the circulation
Endothelial cells line the wall of the blood vessel
Blood-clotting proteins circulate in the blood

The process of hemostasis occurs in three phases:


1. Vascular platelet phase: primary hemostasis

2. Activation of the coagulation cascade: formation of the clot

3. Activation of a series of control mechanisms: stop the


propagation of the clot and limit activation of the coagulation
cascade to the region of endothelial rupture Protg Education Center, LLC
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Mechanisms of Blood Coagulation
Primary hemostasis:

1. Vasoconstriction: When injury occurs, vessel walls constrict,


causing reduced blood flow to the site of injury.

2. Platelet plug: Platelets aggregate to the site of the injury. They


stick together acting as a "plug."

Secondary hemostasis
3. Platelets activate the process which causes a fibrin clot to form.

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Clotting Cascade
Extrinsic Pathway
The extrinsic pathway is activated by external trauma that
causes blood to escape from the vascular system. This pathway
is quicker than the intrinsic pathway. It involves factor VII.

Intrinsic Pathway
The intrinsic pathway is activated by trauma inside the vascular
system, and is activated by platelets, exposed endothelium,
chemicals, or collagen. This pathway is slower than the extrinsic
pathway, but more important. It involves factors XII, XI, IX, VIII.

Common Pathway
Both pathways meet and finish the pathway of clot production in
what is known as the common pathway. The common pathway
involves factors I, II, V, and X.

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Coagulation Cascade
Damaged vessel

Intrinsic system
Extrinsic system
Activated by chemicals, collagen, Blood escapes from
exposed endothelium, platelets vascular system

Contact damaged tissues


Factor XII Factor XIIa
Ca++ Release phospholipoproteins
VIIa
and organelle membrane
XI XIa
VIIIa
PL Derives tissue thromboplastin
Ca++
IX IXa VII or
VIIIa Tissue Factor
PL
PL = Platelet Phospholipids Ca++
X Xa
Va
PL
Ca++
XIII
Prothrombin Thrombin
XIIIa

Soluble fibrin Fibrin clot


Fibrinogen
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Activated Partial Thromboplastin Time
(aPTT)

aPTT measures the time necessary to generate


fibrin from initiation of the intrinsic pathway.
Activation of factor XII is accomplished with an
external agent (e.g., kaolin) capable of activating
factor XII without activating factor VII.

The normal time is usually reported as less than


30 to 35 seconds (25 to 35 seconds), and
decreased values ("short") may be abnormal.

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Prothrombin Time (PT)
PT measures the time necessary to
generate fibrin after activation of factor VII.
It measures the integrity of the "extrinsic"
and "common" pathways (factors VII, V, X,
prothrombin, and fibrinogen).
A prolonged PT may reflect either factor
deficiency or a circulating inhibitor of
coagulation.
The test is more sensitive than the aPTT for
deficient levels of factors, and a relatively
small drop in factor VII levels may prolong
the PT.
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Thrombin Time (TT)
TT is the time to drive the reaction of fibrinogen
to fibrin in the presence of thrombin

It measures the integrity of this reaction and


isolates an abnormality to either a decrease in
normal fibrinogen or an inhibitor to its activation.

Abnormalities can be: deficient fibrinogen (< 100


mg/dl), abnormal fibrinogen, or an inhibitor to the
reaction.

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Coagulation Cascade
Damaged vessel

Intrinsic system
Extrinsic system
Activated by chemicals, collagen, Blood escapes from
exposed endothelium, platelets vascular system

aPTT
Contact damaged tissues
Factor XII Factor XIIa
Ca++ Release phospholipoproteins
VIIa
and organelle membrane
XI XIa
VIIIa PT
PL Derives tissue thromboplastin
Ca++
IX IXa VII or
VIIIa Tissue Factor
PL
PL = Platelet Phospholipids Ca++
X Xa
Va
PL
Ca++
XIII
Prothrombin Thrombin
TT XIIIa

Soluble fibrin Fibrin clot


Fibrinogen
monomer Protg Education Center, LLC
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Antithrombin III Test
This test is done if repeated blood clots oocur or if blood
thinning medicine does not work.

Lower-than-normal AT III can have an increased risk of clotting.

Lower than normal AT III may be due to:


Bone marrow transplant
DIC (disseminated intravascular coagulation)
AT III deficiency, an inherited condition causing lower blood
clotting protein levels
Liver cirrhosis
Nephrotic syndrome

Higher than normal AT III may be due to:


Use of anabolic steroids
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Factor VIII assay
This test is used to find the cause of too much bleeding (decreased
blood clotting), or if a family member is known to have hemophilia A

A normal value is 50 - 200% of the laboratory control or reference value.

Decreased levels may be due to:


Disseminated intravascular coagulation (DIC)
Hemophilia A
Presence of a Factor VIII inhibitor (antibody)
Von Willebrand's disease

Increased levels may be due to:


Advanced age
Diabetes
Liver disease
Inflammation
Pregnancy
Obesity
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