| |
| CLOT-ED Terminology for Professionals |
|
| The definitions provided in this
Terminology section of the CLOT-ED web site have either been
written by the web site author or collated from material extracted
completely or in part or paraphrased from any of the following
sources: Applicable Guidelines from the National Commission
of Clinical Laboratory Standards (NCCLS), Wayne, PA; Dorland's
Illustrated Medical Dictionary, 30th Edition, Elsevier Science,
2003 (www.mercksource.com);
Stedman's Medical Dictionary, 27th Edition, 2000; The American
Heritage Dictionary of the English Language, Fourth Edition,
2000 (www.bartleby.com);
Miriam-Webster's Eleventh New Collegiate Dictionary, 2003 (www.m-w.com);
The Merck Manual of Medical Information-Second Home Edition,
2003 (www.mercksource.com);
On-Line Medical Dictionary (www.cancerweb.ncl.ac.uk);
University of Edinburgh, Biology Teaching Organization Genetics
Glossary (www.helios.bto.ed.ac.uk);
Hemostasis and Thrombosis Basic Principles & Clinical Practice,
J.B. Lippincott, 1982; Hemostasis and Thrombosis Basic Principles
& Clinical Practice, 4th Edition, Lippincott Williams &
Wilkins, 2001; Hematology 2002, American Society of Hematology
Education Program Book, 2002; Consultative Hemostasis and Thrombosis,
WB Saunders, 2002; Blood Components and Pharmacologic Agents,
AABB Press, 2000 |
| |
| A - B
- C - D - E
- F - G - H
- I - J - K
- L - M - N
- O - P - Q/R
- S - T - U/V/W
- X/Y/Z |
| |
| -A- |
| |
| Activated
Partial Thromboplastin Time Test (APTT) |
| |
| A global assay that measures all procoagulant
proteins with the exception of Factor
VII. The test is used primarily as a screening tool
for deficiencies (some of which may cause bleeding) in the intrinsic
pathway of coagulation. Two other uses for the assay
are in monitoring unfractionated heparin
and in the laboratory detection of the Lupus
Anticoagulant. The APTT is the time in seconds required
for a fibrin clot to form in a platelet
poor plasma sample after an optimal amount of activating
agent, phospholipid, and calcium
chloride have been added. The
slide show entitled Intrinsic
Pathway-APTT shows which coagulation
factors are tested by the APTT. |
| |
| Accuracy
|
| |
| Closeness of agreement between the result of a measurement
and a true value of the analyte measured.
Ability of a test to return a correct result compared with an
external standard. |
| |
| Activated Protein C (APC) |
| |
| Protein C in the presence of Thrombin
and Thrombomodulin is converted
to Activated Protein C. APC is a natural anticoagulant
that dampens coagulation by inactivating FVIIIa
and FVa (cofactors for the tenase and
prothrombinase complexes, respectively). The
slide show entitled Activation
of Protein C by Thrombin shows the relationship amongst
these components. |
| |
| Activated Protein C Resistance-APCR |
| |
| A phenotype in which patients have
a limited response to Activated Protein C
leading to an increased risk for thrombosis.
If inherited, APCR is associated with a mutation
in the factor V gene (Factor V Leiden).
The APCR phenotype may also be acquired. |
| |
| Aggregometry |
| |
| Quantitative assessment of platelet
function following addition of stimulating agents (agonists).
Aggregation can be monitored in two ways: 1) light transmission
through stirred platelet rich
plasma (PRP) using a photometer or 2) electrical resistance
in whole blood or PRP using an impedance method. Platelet
secretion of ATP from dense granules can be simultaneously monitored
as luminescence during the course of agonist induced aggregation
provided luciferin-luciferase is initially added to a whole
blood or PRP suspension in a lumiaggregometer. |
| |
| Allele |
| |
| One of two different forms of
a gene that exits at a specific location
on a single chromosome. |
| |
| Amino
Acids |
| |
| Amino acids are a class of organic
molecules that contain an amino group and combine to form proteins.
There are twenty common amino acids (three and one letter abbreviations
are noted after each): alanine (Ala or A), arginine (Arg or
R), aspargine (Asn or N), aspartic acid (Asp or D), cysteine
(Cys or C), glutamic acid (Glu or E), glutamine (Gln or Q),
glycine (Gly or G), histidine (His or H), isoleucine (Ile or
I), leucine (Leu or L), lysine (Lys or K), methionine (Met or
M), phenylalanine (Phe or F), proline (Pro or P), serine (Ser
or S), threonine (Thr or T), tryptophan (Trp or W), tyrosine
(Tyr or Y), and valine (Val or V). |
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| Analyte |
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| Any compound or substance chosen to undergo analysis. |
| |
| Angina
(Angina Pectoris) |
| |
| Angina is a type of chest pain
that results from the heart not getting enough oxygen due to
narrowed coronary
arteries . There are two types of angina: 1) stable wherein
the existing pain is not changing in severity, duration, or
frequency or 2) unstable when existing chest pain increases
in severity, duration, or frequency in response to progressively
less exercise or stimuli. |
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| Antibody
|
| |
| An immunoglobulin having a specific
amino acid sequence allowing it to interact only with the antigen
that induced its synthesis. Alloantibodies are those produced
against an exogenous substance (hemophiliacs make antibodies
to exogenously introduced FVIII found in FVIII concentrates).
Autoantibodies are those produced against “self” proteins (patient
makes antibodies to their own (endogenous) FVIII). |
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| Anticoagulant |
| |
| An agent that prevents coagulation
of blood or blood products. Sodium
citrate is the anticoagulant of choice for samples (blood
becomes hypocalcemic) used in coagulation testing. Pharmacological
anticoagulants such as coumarin derivatives,
heparin, LMWH,
and hirudin are used in the prophylaxis and treatment of thrombotic
disorders. The body also has naturally occurring anticoagulants
(Antithrombin and Activated
Protein C). |
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| Antifibrinolytic |
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| Antifibrinolytic refers to a
process, protein, or drug that does not allow for the breakdown
of fibrin. If fibrin can not be destroyed,
a clot remains. For a bleeding patient,
the use of antifibrinolytic agents is beneficial. In a procoagulant
state, the inability to break down a thrombus
could be detrimental. |
| |
| Antigen |
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| Any substance (protein, bacteria,
virus, toxin) that under appropriate conditions can induce an
immune response after a latent period. Antigens react with antibodies,
that is, products of that response. |
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| Antithrombin
|
| |
| Serine protease inhibitor
(serpin) that neutralizes Thrombin
by forming a 1:1 stoichiometric complex between the two proteins
by way of antithrombin's reactive site (arginine) and Thrombin's
active center (serine) site. Binding of heparin
to antithrombin accelerates this interaction nearly 1000 fold.
Antithrombin also inactivates hemostatic
enzymes of the intrinsic
pathway of coagulation (factors IXa,
Xa, XIa,
and XIIa) by a similar mechanism.
|
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| Arteries
|
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| Thick-walled, muscular, pulsating
blood vessels that carry oxygenated blood away from the heart.
Pulmonary and umbilical arteries do not contain oxygenated blood.
Arteries that carry oxygen directly to heart tissue are called
coronary arteries. |
| |
| Atherosclerotic
Plaque |
| |
| A buildup of lipid deposits in
the intima of large and mid-sized arteries
that leads to narrowing of the lumen and subsequent reduction
in blood flow. Atherosclerosis is the most common form of arteriosclerosis
(hardening of the arteries). |
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| Atrium
(plural form is Atria) |
| |
| Atria are the two upper chambers
(left atrium & right atrium) of the heart that pump blood
into the two lower chambers (ventricles). |
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| Autosomal
|
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| Term that relates to the non-sex
chromosomes (22 inherited from either
the female or male). |
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| -B-
|
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| Base
Pair |
| |
| Four nucleotides,
(Adenine [A], Guanine [G], Thymine [T], and Cytosine [C]), are
joined in pairs (always A & G and T & C). The complimentary
bases are found one in each strand of DNA
(male & female) and together they form a base pair. There
are approximately 3.2 billion bases in the human genome.
|
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| Bethesda
Inhibitor Assay (Titer) |
| |
| Assay that quantifies the titer
of antibodies that a patient has made
to Factor VIII (Hemophilia
A) or Factor IX (Hemophilia
B). The unitage is expressed in Bethesda Units (BU). One
BU is the amount of antibody that, after two hours incubations
at 37o C, inactivates
50% of FVIII present in normal pooled plasma. |
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| Bleeding
Time |
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| A test performed on a patient's
arm that measures the time needed to stop bleeding from a standardized
cut. Historically the test was used as a screening test for
Von Willebrand Disease or for defects in
platelet function. The test has generally
been replaced by a test performed in the laboratory on a blood
sample. |
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| Blood
Collection Device |
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| For coagulation testing, an evacuated
tube, syringe, or other device with a non-activating surface. |
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| Blood
Collection System |
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| A system consisting of several components
used for blood collection, such as catheter, luer lock, syringe,
needle and evacuated collection device. |
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| Blood
Pressure |
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| Force or tension that circulating
blood exerts on walls of arteries.
It is measured as diastolic (pressure during heart relaxation)
or systolic (pressure during heart contraction). Normal blood
pressure is referred to as normotension whereas high blood pressure
is known as hypertension.
|
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| -C-
|
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| Carriers
|
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| Individuals who carry the gene
for a condition but who themselves do not have the condition. |
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| Catalyst
|
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| A catalyst is a substance that
can alter the speed of a chemical reaction but itself does not
participate in the reaction or is changed by it. |
| |
| Cholesterol |
| |
| The most abundant steroid in
animal tissues. It is found in bile and circulates in blood
complexed with various lipoproteins. It is also found in foods
such as animal fats, animal oils, milk, and egg yolks. Too much
cholesterol is termed hypercholesterolemia and may lead to deposits
in artery walls called plaque
(atherosclerosis). |
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| Chromosomes |
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| Chromosomes are threadlike structures
inside the nucleus of a cell that contain thousands of genes.
Each cell in the human body contains 46 chromosomes (23 pairs)
that are inherited
from each parent (22 from the female plus either an X or
Y chromosome [sex chromosome] and 22 from the male plus a Y
chromosome). A chromosome can reproduce its physical and
chemical structure through successive cell divisions (generation
to generation). |
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| Citrate
(Sodium Citrate) |
| |
| Chemical (salt or ester of citric
acid) agent used as the anticoagulant
in blood collection tubes (“blue top”) used for coagulation
laboratory testing. |
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| Clone
(Cloning, Cloned) |
| |
| clone is a group of cells, which
derived by asexual division, are genetically identical to a
single common ancestor. |
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| Clot (Blood
Clot) |
| |
| Consists of fibrin gels in which the
formed elements of the blood, principally the red cells, are
passively trapped. Clots are derived from extravascular
coagulation whether that occurs in vitro
(laboratory testing), by shedding (initiated by vessel injury)
of blood into tissues or body cavities, or after death (postmortem
clot). Clots are dark red, elastic, and moist with a glistening
surface. Though
commonly used as interchangeable terms, blood clot and thrombus
are not synonymous. |
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| Coagulation
(Clotting) |
| |
| The process by which a clot
is formed in whole blood or plasma.
It is divisible into three stages: extrinsic
pathway, intrinsic pathway
(includes contact activation), and common
pathway. The divisions are useful for laboratory testing.
Coagulation and clotting are similar terms. |
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| Coagulation
Cascade |
| |
| Theory that blood coagulation
takes place as a series of activation steps, each of which involves
the proteolytic conversion of a zymogen
to the corresponding active serine
protease (enzyme). These reactions
were viewed historically as a "waterfall" or "cascade"
leading to fibrin clot formation.
The slide show entitled
Coagulation
Pathways (All Components) shows these reactions in detail. |
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| Coagulation
Factors |
| |
| Components of the blood coagulation
system that include the following factors: |
| |
-
-
-
-
-
-
-
Factor
VIII (Factor VIII:C, antihemophilic globulin
[AHF], antihemophilic factor A)
-
Factor
IX (Christmas factor, antihemophilic factor
B)
-
-
-
Factor
XII (Hageman factor, surface factor, contact
factor)
-
-
|
| |
| The slide show entitled Coagulation
Pathways (All Components) shows how all these factors relate
to each other. |
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| Coagulopathy |
| |
| A disorder, either congenital
or acquired, that prevents the normal clotting
of blood. |
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| Common
Pathway of Coagulation |
| |
| Upon FXa formation by either the
extrinsic or intrinsic
pathway of coagulation, FXa catalyzes the conversion of prothrombin
to Thrombin with subsequent fibrin
formation. Both the APTT
and PT are affected by components
(FX, FV,
FII, FI)
of the common pathway. The
slide show entitled Tissue
Factor Pathway (Extrinsic) with Common Pathway (PT) shows
which components are part of this pathway. |
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| Congenital
|
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| A trait, disease, or anomaly
that exists at birth regardless of causation. This contrasts
to conditions obtained through life (acquired). |
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| Contact
Activation |
| |
| A process that initiates the intrinsic
pathway of coagulation. In
vitro FXII can be activated
to FXIIa through contact with a variety of negatively charged
surfaces such as kaolin, sulfatides, micronized silica, or ellagic
acid. Key players are FXII and Prekallikrein
both of which require HK
as a cofactor in their conversions from zymogens
to active serine proteases. |
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| Control
Plasma |
| |
| A preparation of fresh, frozen, or lyophilized
plasma collected from human or animal
blood or artificially derived material, intended for use in
the quality control process. Control plasmas are used
to monitor all aspects of the laboratory test system, including
reagents, instruments, reconstituting and diluting fluids, and
pipettes. Normal control plasmas should give test results
within the reference
interval. Abnormal control plasmas should give values
within a clinically relevant abnormal range. |
| |
| Coumarin |
| |
| Pharmacological agent that serves as
an anticoagulant by inhibiting
the hepatic synthesis of four vitamin
K-dependent procoagulant proteins
(FII, FVII,
FIX, FX).
The most common coumarins (or derivatives) in use are warfarin
sodium, acenocoumarol, and phenprocoumon. Coumarins are
routinely used in the clinical management of thrombosis and
are monitored by the PT (INR)
test. |
| |
| Cryoprecipitate |
| |
| Cryoprecipitate (“cold precipitate”)
is prepared from fresh frozen plasma
that has been thawed at 4 oC and from which the supernatant
has been removed. The precipitate is rich in Fibrinogen,
Factor VIII (for treating Hemophilia
A), Factor XIII (treating FXIII deficiencies), and Von
Willebrand Factor (treating Von Willebrand
Disease). |
| |
| -D- |
| |
| Deep Vein
Thrombosis (DVT) |
| |
| Formation of thrombi
in veins located deep within muscles of
the extremities such as the legs. |
| |
| Deoxyribonucleic
acid (DNA) |
| |
| DNA is the fundamental substance
that makes up genes. It is an antiparallel
double helix of nucleotides (having
deoxyribose as their sugars) linked by phosphodiester (sugar-phosphate)
bonds to adjacent nucleotides in the same chain and by hydrogen
bonds to complementary nucleotides in the opposite chain. |
| |
| Desmopressin
Acetate (DDAVP) |
| |
| DDAVP is a synthetic drug similar
to the natural pituitary antidiuretic hormone, 8-arginine vasopressin.
It is given to patients with mild Hemophilia
A or Von Willebrand Disease to arrest
bleeding. The drug stimulates endogenous release of Factor
VIII and Von Willebrand
Factor from storage granules in endothelial cells and platelets.
This causes a temporary increase in these proteins (2-5 times
over baseline values at 1 hour after administration). The drug
can be given intravenously, subcutaneously,
or by intranasal spray. |
| |
|
Diagnostic
Sensitivity
|
| |
| Ability of a test to identify affected
individuals (those with disease). Clinical sensitivity
at 100% indicates that all persons with disease are correctly
classified by the results of a measurement as having disease
(positive/abnormal). |
| |
| Diagnostic
Specificity |
| |
| Ability of a test to identify unaffected
individuals (those without disease [well]). Clinical specificity
at 100% indicates that all persons without disease are correctly
classified by the results of a measurement as well (negative/normal).
|
| |
| Disseminated
Intravascular Coagulation (DIC) |
| |
| A consumptive thrombohemorrhagic disorder.
DIC is not a specific disease but a manifestation of a pathologic
process. DIC is characterized by a stimulus that is massive,
sustained, and/or not neutralized. Accordingly the resulting
procoagulant process soon overwhelms
physiologic inhibitors and by that leads to free, circulating,
unopposed Thrombin and Plasmin,
the two key players in DIC. Processes that may lead to
DIC include: tissue damage (trauma), neoplasia, infections,
and obstetric complications. |
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| Dominant |
| |
| Inheritance
is said to be dominant when an allele
produces the same phenotype whether
inherited with a homozygous or heterozygous
allele. For example, if brown hair is a dominant trait then
offspring will have brown hair regardless if one or both brown
hair alleles are inherited from the parents. A trait controlled
by a dominant allele is also referred to as dominant. |
| |
| Dysfibrinogenemia |
| |
| An autosomal
dominant disorder in which Fibrinogen
is quantitatively normal but qualitatively abnormal due to mutations
in the fibrinogen gene. Patients with this abnormality can either
bleed or thrombose. A key laboratory finding is prolongation
of the Thrombin Time test. |
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| -E-
|
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| Embolism |
| |
| Embolism is the firmly lodging
in of an embolus
into a blood vessel that can lead to obstruction or occlusion
of the vessel. |
| |
| Embolus
(plural form is Emboli) |
| |
| Emboli are fragments of thrombi
that have been physically detached from a vessel and have moved
from their origins to another site. For example, thrombi originating
from the deep veins (DVT) may break away
and travel to the pulmonary circulation, lodge therein, and
result in a pulmonary embolism. The formation
and release of the embolus into the circulation is termed embolization. |
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| Endogenous |
| |
| Developing or originating from within.
Any factor or mechanism acting or derived from the system from
which the analytical sample is taken. |
| |
| Enzyme |
| |
| Enzymes are biological catalysts
(induce changes in other substances while themselves remain
unaltered). The reactants of enzyme-catalyzed reactions are
termed substrates. Enzymes are
specific in character because they act on particular substrates
to produce particular products. |
| |
| Exogenous
|
| |
| Developing or originating from outside
a system. Any factor or mechanism added to the sample
either in vivo or to the sample
in vitro. |
| |
| Exon |
| |
| Exons are regions of a gene
that function in coding for protein
synthesis. Exons make up the messenger RNA (mRNA) that is translated
into protein. |
| |
| Extrinsic
Pathway of Coagulation |
| |
| Initiating pathway of in
vitro coagulation. For in
vivo considerations, the pathway is also referred to
as the tissue factor pathway. Physiologically Tissue
Factor from extravascular sources and FVII
from blood are key components and the resulting complex, when
assembled on activated monocytes or perturbed endothelial cells,
has two substrates: FX and FIX.
For in vitro testing, a thromboplastin
reagent is the source for Tissue Factor (complexed with phospholipid).
The PT is affected by FVII
and components in the common pathway
of coagulation. The slide
show entitled Tissue
Factor Pathway (Extrinsic) with Common Pathway (PT) shows
the components of this pathway. |
| |
| -F-
|
| |
| Factor II |
| |
| See Prothrombin
|
| |
| Factor
V (FV) |
| |
| A glycoprotein
synthesized in liver and megakaryocytes which functions in the
common pathway of coagulation.
Approximately 25% of FV in blood is present in the alpha granules
of platelets. When activated
by Thrombin, activated Factor
V (FVa) serves as a cofactor in the FXa
conversion of prothrombin to Thrombin
in the presence of phospholipid
and calcium (prothrombinase complex). FVa is inhibited
by Activated Protein C.
The slide show entited Activation
of Protein C by Thrombin shows the relationship amongst
these components. See also the slide shows entitled Tissue
Factor Pathway (Extrinsic) with Common Pathway (PT)
and Intrinsic
Pathway-APTT. |
| |
| Factor
V Leiden |
| |
| Genotype underlying
most causes of Activated Protein
C Resistance. A single point mutation
in the Factor V gene leads to a substitution at position 506
in the Factor V protein (arginine replaced by glutamine).
This mutation disrupts the cleavage site for APC and produces
a cofactor that cannot be completely inactivated. The
continued procoagulant activity
of this abnormal cofactor confers a lifelong risk of thrombosis. |
| |
| Factor
VII (FVII) |
| |
| A glycoprotein
synthesized in the liver which contains 10 Gla
residues that are dependent on vitamin
K for biosynthesis. The zymogen,
FVII, is converted to a serine
protease (FVIIa) by limited proteolysis. In the presence
of Tissue Factor and calcium,
FVIIa converts FX to FXa in the initiation
phase of blood coagulation. Similarly FVIIa in the presence
of tissue factor and calcium converts FIX
to FIXa allowing for additional Thrombin
generation (amplification phase). FVII participates in
the extrinsic pathway of
coagulation (Tissue Factor pathway).
The slide show entitled Coagulation
Pathways (All Components) shows how FVII relates to the
other coagulation factors.
See also the slide shows entitled Tissue
Factor Pathway (Extrinsic) with Common Pathway (PT). |
| |
| Factor
VIII (FVIII) |
| |
| A glycoprotein synthesized
primarily in the liver and circulating in blood complexed with
Von Willebrand Factor. FVIII participates in the intrinsic
pathway of coagulation. It functions as a cofactor
by accelerating the conversion of FX
to FXa in the presence of FIXa, phospholipid,
and calcium (tenase complex). FVIII must undergo limited
proteoysis by Thrombin in order to
demonstrate cofactor activity (FVIIIa). The gene
for FVIII is X-linked and mutations
in the gene give rise to a bleeding disorder, Hemophilia
A. The slide show
entitled Coagulation
Pathways (All Components) shows how FVIII relates to the
other coagulation factors.
See also the slide show entitled Intrinsic
Pathway-APTT. |
| |
| Factor
IX (FIX) |
| |
| A glycoprotein
synthesized in the liver which contains 12 Gla
residues that are dependent on vitamin
K for biosynthesis. The zymogen,
FIX, is converted to a serine protease
(FIXa) by the enzyme FXIa. FIXa
participates in the intrinsic
pathway of coagulation by converting FX to FXa in the presence
of FVIIIa, phospholipid,
and calcium (tenase complex). The gene
for FIX is X-linked and mutations
in the gene give rise to a bleeding disorder, Hemophilia
B. The slide show entitled
Coagulation
Pathways (All Components) shows how FIX relates to the other
coagulation factors.
See also the slide show entitled Intrinsic
Pathway-APTT. |
| |
| Factor
IX Concentrates |
| |
| Blood products derived from cryoprecipitate,
virally inactivated, and harvested in a manner such that very
little or no coagulation factors other than FIX
are in the material. These products are used for replacement
treatment in patients with Hemophilia
B (FIX deficiency). |
| |
| Factor
X (FX) |
| |
| A vitamin K-dependent
glycoprotein containing 11 Gla residues
that participates in the common
pathway of coagulation. FX is synthesized in the liver
and secreted into blood as a precursor to a serine
protease (FXa). The conversion of FX to FXa involves
a single peptide bond whether brought about by the concerted
actions of FIXa, FVIIIa,
phospholipid & calcium (tenase
complex) or by the FVIIa /
Tissue Factor complex. The
latter reaction gives rise to an initial burst of Thrombin
whereas the tenase complex formed via FIXa brings about a subsequent
explosive generation of Thrombin. The
slide Coagulation
Pathways (All Components) shows how FX relates to the other
coagulation factors.
See also the slide shows entitled Tissue
Factor Pathway (Extrinsic) with Common Pathway (PT)
and Intrinsic
Pathway-APTT. |
| |
| Factor
XI (FXI) |
| |
| A glycoprotein
synthesized in the liver, secreted as a zymogen,
and circulating in blood complexed with high
molecular weight kininogen (HK). Unlike other coagulation
serine proteases, FXIa has
two active catalytic sites. FXI participates in the intrinsic
pathway of coagulation by converting FIX
to FIXa. FXI can be activated either by Thrombin
in a feedback mechanism to amplify further Thrombin generation
or by autoactivation in the presence of negatively charged materials.
In vitro, FXI can be activated
by FXIIa in the presence of
HK and a negatively charged surface. The
slide show entitled Coagulation
Pathways (All Components) shows how FXI relates to the other
coagulation factors.
See also the slide show entitled Intrinsic
Pathway-APTT. |
| |
| Factor
XII (FXII) |
| |
| FXII is a member of the contact
activation proteins. It is an activator of both the
coagulation and kinin systems. FXII circulates as an inactive
zymogen that can be converted to FXIIa,
a serine protease, either by
autoactivation through contact with negatively charged surfaces
or proteolytic cleavage by kallikrein. FXIIa can activate
Prekallikrein and FXI.
In vitro it participates in
the intrinsic pathway of
coagulation. The slide show
entitled Coagulation
Pathways (All Components) shows how FXII relates to the
other coagulation factors.
See also the slide show entitled Intrinsic
Pathway-APTT. |
| |
| Factor
XIII (FXIII) |
| |
| FXIII (fibrin-stabilizing factor) is
a heterotetramer (consists of 2 alpha and 2 beta subunits) that
circulates in blood in association with Fibrinogen.
In the presence of fibrin, Thrombin
converts the FXIII proenzyme to FXIIIa, the active transglutaminase.
FXIIIa catalyzes the formation of intermolecular (e(g-glutamyl)
lysyl) bonds between various substrates such as fibrin monomers,
a2-plasmin inhibitor, fibronectin, and collagen.
Accordingly FXIII is involved in hemostasis,
wound healing, and maintenance of pregnancy. The
slide show entitled Fibrinolytic
Pathway shows how FXIII relates to the
other coagulation factors. |
| |
| Fibrin |
| |
| Fibrin is an insoluble polymer resulting
from Thrombin action on Fibrinogen.
The conversion is a three step process: Thrombin catalyzed release
of fibrinopeptide A from Fibrinogen, non-covalent fibrin monomer
association to produce protofibrils that continue to grow laterally
with release of fibrinopeptide B, and covalent stabilization
by FXIIIa. Mature fibrin fiber
may contain approximately 100 protofibrils. |
| |
| Fibrinogen
(FI) |
| |
| A key protein involved in the coagulation
process that circulates in the blood as a soluble dimeric molecule
consisting of three-pairs of disulfide-bonded polypeptide chains
(Aa, Bb, and g). Fibrinogen serves as the substrate for
the enzyme Thrombin. Thrombin
cleavage results in the release of fibrinopeptides A & B
and fibrin monomer formation. Subsequent noncovalent assembly
of fibrin monomers and covalent stabilization
by FXIIIa gives rise to
a stabilized, insoluble fibrin mesh. |
| |
| Fibrinogen Assay |
| |
| Assay for fibrinogen concentration measured
by the rate at which Fibrinogen is
converted to fibrin by the action of
Thrombin. |
| |
| Fibrinolysis |
| |
| Controlled regulatory mechanism for
thrombus dissolution in order to preserve
vascular patency. The process of vascular occlusion (coagulation)
is the principal stimulus for simultaneously setting into motion
the process of fibrinolysis. Local activation and control
of fibrinolysis is due in large measure to the properties of
the thrombus. The key enzyme of the fibrinolytic system
is Plasmin. The
slide show entitled Fibrinolytic
Pathway shows the major players in fibrinolysis. |
| |
| -G- |
| |
| Gene
|
| |
| A gene is the basic unit of hereditary
that carries information from one generation to the next. It
is an ordered sequence of nucleotide
bases that makes up a segment of DNA and
contains chemical instructions necessary to make a product such
as a protein (Factor VIII). Genes are located on chromosomes. |
| |
| Gene
Locus (plural form is Loci) |
| |
| Specific location on a chromosome
where a gene can be found. |
| |
| Gene
Mutation |
| |
| The resulting product of a process
whereby a change or changes occur within the structure of a
gene. This gives rise to a gene that differs
from “normal” (wild-type) |
| |
| Gene
Sequence |
| |
| Order of base
pairs in a gene. |
| |
| Gene
Therapy |
| |
| Gene therapy is a method that
corrects a gene mutation by adding
an intact (normal) gene or changing one
that is already present. |
| |
| Genetics |
| |
| Genetics is the study of genes,
variation in genes, and the impact of this variability on the
transmission of inherited traits. |
| |
| Genetic
Markers |
| |
| Genetic markers are unique pieces
of DNA that are
easy to identify and by that are used as probes to track other
genes. These markers may in no way be related to a gene that
is being examined. |
| |
| Genome |
| |
| The genome is all the genetic
material in a chromosome set (all
46 chromosomes). |
| |
| Genotype
|
| |
| Represents the specific allelic
composition of a cell. It is the genetic makeup of an organism. |
| |
| GLA
Domains |
| |
| Common to all vitamin
K-dependent proteins are 9-12 glutamic
acid (GLU) residues at the N-terminal ends of the molecules.
Addition of an extra carboxyl group gives rise to a novel amino
acid called gamma carboxyglutamic acid (GLA). This post-translational
conversion of GLU to GLA is catalyzed by a microsomal vitamin
K-dependent carboxylase and is inhibited by coumarins.
Formation of GLA allows proteins to bind calcium, one calcium
with the two carboxyl groups of a GLA domain to serve as a bridge
for the proteins to bind to a phospholipid
surface. |
| |
| Glycoprotein |
| |
| Group of proteins
containing covalently linked carbohydrates. Glycoproteins that
are O glycosylated are bonded through the hydroxyl (OH) group
of either serine or threonine whereas N glycosylation occurs
via the amide (NH2)
of asparagine. |
| |
| -H- |
| |
| Hemarthrosis |
| |
| Hemarthrosis is the accumulation
of blood in a joint or joint cavity. The joint is the most common
bleeding site in patients with severe hemophilia.
|
| |
| Hematoma |
| |
| A mass of coagulated
blood, confined to a tissue or organ, which results from a break
in the wall of a blood vessel. |
| |
| Hemophilia
A |
| |
| Hemophilia A is an X-linked
bleeding disorder. Approximately 30% of cases may occur from
a spontaneous gene mutation. Mutations
in the FVIII gene
lead to a deficiency/abnormality in Factor VIII. Hemophilia
A is classified as severe, moderate, or mild depending on the
amount of protein present. |
| |
| Hemophilia
B |
| |
| Hemophilia B is an X-linked
bleeding disorder and like Hemophilia
A almost exclusively affects males. Mutations
in the FIX gene
lead to a deficiency of Factor IX. Hemophilia B is classified
as severe, moderate, or mild depending on the amount of protein
present. Hemophilia B is also referred to as Christmas Disease. |
| |
| Hemorrhage |
| |
| Loss of blood from the intravascular
space. |
| |
| Hemostasis |
| |
| The control of bleeding by the physiological
processes of vasoconstriction, coagulation
factors, and platelets or by surgical procedures (compression,
ligation) that result in the preservation of blood vessel integrity
and prevention of hemorrhage.
Hemostasis is the controlled activation of clot
formation and clot lysis (fibrinolysis)
without inappropriate clotting (thrombosis). |
| |
| Heparin-Unfractionated |
| |
| A mixture of sulfated glycosaminoglycans
released from mast cells lying beneath the vascular endothelium.
Pharmaceutical heparins are extracted from pig intestinal mucosa
or bovine lung both of which are sources for mast cells.
Pharmaceutical, unfractionated (standard) heparins have molecular
weights that vary between 3,000 to 35,000 daltons. Heparins
have no direct anticoagulant effect but act through Antithrombin. |
| |
| Hereditary Disease |
| |
| A disease that is passed down
through a family. |
| |
| Heterozygous
|
| |
| An individual is heterozygous
for a genetic trait if each allele at
the same genetic location is different. |
| |
| High
Molecular Weight Kininogen (HK) |
| |
| Critical protein involved in assembly
of the contact system on cell membranes. HK is found in
platelets, granulocytes, and endothelial cells and is a substrate
for kallikrein. Cleavage
by kallikrein releases bradykinin, a bioactive peptide that
contributes to vessel patency. HK functions as an antithrombotic
(inhibits thrombin-induced platelet activation), antiadhesive
(prevents adhesion of neutrophils to artificial surfaces), and
profibrinolytic (allows binding of prekallikrein and its activation.
The slide show entitled Coagulation
Pathways (All Components) shows how HK relates to the other
coagulation factors.
See also the slide show entitled Intrinsic
Pathway-APTT. |
| |
| Homozygous |
| |
| An individual is homozygous for
a genetic trait if both alleles at the
same genetic location are identical. |
| |
| Hypertension |
| |
| Hypertension, popularly known
as high blood pressure, is either a transitory or sustained
elevation of systemic arterial blood pressure to a level that
may cause cardiovascular damage or cerebral vascular disease
and stroke. The term generally implies diastolic hypertension. |
| |
| Hypofibrinogenemia |
| |
| A lower than normal amount of
Fibrinogen in the blood. A key laboratory
finding is prolongation of the Thrombin
Time est. |
| |
|
-I- |
| |
| Inheritance
|
| |
| Characteristics, qualities, or
traits that are transmitted from parent to offspring by coded
genetic material. |
| |
| Inhibitor
|
| |
| A substance that depresses the
activity of another substance. In the context of hemostasis,
an inhibitor is an antibody that negatively
affects the action of an enzyme (such
as an antibody to FVIII) or a molecule
that in a positive way controls an enzyme (such as Activated
Protein C retarding the action of activated [functional]
factors V and VIII).
|
| |
| INR-International
Normalized Ratio (PT-INR) |
| |
| Represents Prothrombin
Time (PT) Ratio that would have been obtained if the primary
World Health Organization (WHO) reference thromboplastin (IRP
67/40) had been used to perform the PT
test using a manual tilt-tube technique. Normalizes PT
Ratio by mathematically considering differences in PT reagents
(thromboplastin component).
INR is a universal or common scale for reporting PT results.
Mathematically the INR is derived from the PT ratio raised to
the ISI as an exponential power. |
| |
| Intrinsic
Pathway of Coagulation |
| |
| Pathway in which coagulation
is initiated by components contained within the vascular system
(independent of Tissue Factor).
In vitro the contact
system is exploited for testing purposes (particulate matter
used for activation) however its role in
vivo is questionable. Physiologically the intrinsic
pathway results in the activation of FIX by FXIa in the presence
of calcium ions whereas FIX activation by FVIIa
requires Tissue Factor. The APTT
is affected by all coagulation proteins in the intrinsic pathway
(FXII, FXI,
FIX, FVIII)
and those of the common pathway.
The slide show entitled Intrinsic
Pathway-APTT shows the components of this pathway. |
| |
| Intron |
| |
| Introns are intervening sequences
in a gene that interrupt coding sequences
(exons). These sequences of DNA
are removed from the primary transcript by a splicing mechanism
and are not found in mRNA. |
| |
| Inversion |
| |
| A mutation
that involves the removal of a piece of chromosome,
turning it 180 degrees, and putting it back in the same place.
This segment can no longer be “read” properly and no protein
is made. Approximately 50% of mutations in severe Hemophilia
A are of this type. |
| |
| In
vitro |
| |
| The term means “within glass”
and refers to testing or observations that are done outside
the body and under artificial conditions. |
| |
| In
vivo |
| |
| The term means “in life” and
refers to testing or observations made on tissues not removed
from the body. |
| |
| Ischemia |
| |
| Ischemia is the deficiency of
blood and oxygen to a part of the body due to constriction or
obstruction of a blood vessel. When specifically applied to
the heart, it indicates that there is a deficiency of blood
supply (and oxygen) to the heart muscle due to obstruction or
constriction of the coronary arteries. |
| |
| ISI-International
Sensitivity Index |
| |
| Sensitivity or "responsiveness"
of thromboplastin reagent used
for Prothrombin Time testing
to reduction in vitamin K-dependent
proteins. The ISI represents the slope of a regression
line when comparing Prothrombin Time results from normal and
coumarin plasmas using both an international
reference thromboplastin reagent and a working thromboplastin.
The ISI is used to determine the INR
for patient specimens. |
| |
| -J- |
| |
| There are no words in this
dictionary that begin with the letter J |
| |
| -K- |
| |
| There are no words in this
dictionary that begin with the letter K |
| |
| -L- |
| |
| Low Molecular
Weight Heparin (LMWH) |
| |
| LMWH preparations are derived from standard porcine heparin
by chemical or enzymatic degradation to yield fragments between
1,000 to 10,000 daltons. LMWHs are used for the prevention
and treatment of thrombosis.
Similar to standard heparin, LMWH preparations produce their
major anticoagulant effect by catalyzing
Antithrombin. Due to their
smaller size (generally less than 18 saccharides), LMWH preparations
have a higher anti-Xa to anti-IIa ratio than standard heparin
(between 2-4 times more anti-Xa activity). As such LMWH
preparations generally do not (or minimally so) prolong the
APTT and
therefore are monitored, if necessary, by an anti-Xa assay. |
| |
| Lupus
Anticoagulant (LA) |
| |
| Antibodies (IgG, IgM, or IgA) that interfere with one or more
in vitro phospholipid
dependent coagulation reactions. Due to their heterogeneity
no single laboratory test is capable of identifying every LA.
LA are grouped into a family of antibodies known as antiphospholipid
antibodies. Non-transitory LAs are usually associated
with an increased risk for venous and arterial thrombosis. |
| |
| -M-
|
| |
| Menorrhagia |
| |
| Excessive uterine bleeding (generally
defined as exceeding 80 milliliters per menstrual cycle) that
occurs at the regular intervals of menstruation. |
| |
| Mutation |
| |
| See Gene
Mutation |
| |
| Myocardial
Infarction (MI) |
| |
| Sudden insufficiency of arterial
blood supply to a segment of heart muscle (myocardium) usually
due to an occlusion of a coronary artery.
The most common cause of MI is thrombosis
of an atherosclerotic
coronary artery. |
| |
| -N- |
| |
| Non-activating
Surface |
| |
| A surface that does not activate coagulation
factors, specifically the contact
activation factors. The PT
and/or APTT
are not shortened or lengthened. |
| |
| Nucleic
acids |
| |
| Nucleic acids in the form of
DNA and RNA control inheritance
and cel |
