Blood coagulation cascade. Brief outline of blood clotting cascade with information on tests. Over view for medical laboratory scientist program and for ASCP certification test
2. Medical Laboratory
Scientist
Hematology
Part 4 of 4: Blood coagulation
Brief overview
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Presented by
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Scientist
Founder and CEO
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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
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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
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Damaged vessel
Intrinsic system
Activated by chemicals, collagen,
exposed endothelium, platelets
Extrinsic system
Blood escapes from
vascular system
Contact damaged tissues
Release phospholipoproteins
and organelle membrane
Derives tissue thromboplastin
or
Tissue Factor
Factor XII Factor XIIa
XI XIa
X
IXa
VIIIa
PL
Ca++
VIIa
VIIIX
Xa
Prothrombin Thrombin
XIII
Fibrinogen
Soluble fibrin
monomer
Ca++
VIIIa
PL
Ca++
Va
PL
Ca++
XIIIa
Fibrin clot
PL = Platelet Phospholipids
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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
10
Damaged vessel
Intrinsic system
Activated by chemicals, collagen,
exposed endothelium, platelets
Extrinsic system
Blood escapes from
vascular system
Contact damaged tissues
Release phospholipoproteins
and organelle membrane
Derives tissue thromboplastin
or
Tissue Factor
Factor XII Factor XIIa
XI XIa
X
IXa
VIIIa
PL
Ca++
VIIa
VIIIX
Xa
Prothrombin Thrombin
XIII
Fibrinogen
Soluble fibrin
monomer
Ca++
VIIIa
PL
Ca++
Va
PL
Ca++
XIIIa
Fibrin clot
PL = Platelet Phospholipids
aPTT
PT
TT
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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
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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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Notes de l'éditeur
The 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.
Citrated plasma, an activating agent, and phospholipid are added together and incubated at 37°C. Calcium is added, and the time necessary for the clumping of kaolin is measured.
The normal time is usually reported as less than 30 to 35 seconds (25 to 35 seconds), and decreased values ("short") may be abnormal.
This test is abnormal in the presence of reduced quantities of factors XII, IX, XI, VIII, X, V, prothrombin, and fibrinogen (all integral parts of the "intrinsic" and "common" pathway.
It is usually prolonged if a patient has less than approximately 30% normal activity. It can also be abnormal in the presence of a circulating inhibitor to any of the intrinsic pathway factors.
The differentiation of inhibitors from factor depletion is important and can best be accomplished by a mixing study in which patient and normal plasma are combined in a 1:1 ratio and the test is repeated on the mixed sample. If the abnormal value is corrected completely, the problem is factor deficiency. If the result does not change or the abnormality is corrected only partially, an inhibitor is present. This difference stems from the above mentioned fact that the aPTT will be normal in the presence of 50% normal activity
Since platelet factors are necessary for the cascade to function normally, the test is performed in the presence of a phospholipid emulsion that takes the place of these factors. The classic partial thromboplastin time depends on contact with a glass tube for activation. Since this is considered a difficult variable to control, the "activated" test uses an external source of activation.
Inherited deficiency of factor VII is a rare bleeding disorder - a prolonged PT and a normal aPTT. The PT completely corrects when mixed with normal plasma.
Acquired deficiencies are usually related to liver disease, warfarin therapy, or depletion secondary to consumptive coagulopathy, severe bleeding, or massive transfusion.
Circulating inhibitors are most often directed at factor X or thrombin. Most common are heparin or products of fibrinolysis. In their presence the prolonged PT cannot be completely corrected to normal in a 1:1 mixing study.
