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 Clinical and Laboratory Standards Institute (CLSI), 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; University of Edinburgh, Biology Teaching Organization Genetics Glossary; 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
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.
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.
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.
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.
One of two different forms of a gene that exits at a specific location on a single chromosome.
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). See also the slide Nucleotide sequencesof RNA Codons Encoding for Amino Acids.
Any compound or substance chosen to undergo analysis.
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 where in 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.
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).
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).
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.
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.
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.
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.
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).
Atria are the two upper chambers (left atrium & right atrium) of the heart that pump blood into the two lower chambers (ventricles).
Term that relates to the non-sex chromosomes (22 inherited from either the female or male).
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.
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.
Systematic difference between the result of a measurement and the conventional true value, which is the net result of a constant component, mainly caused by insufficient analytical specificity of the test procedure, and a proportional component, caused by incorrect calibration.
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.
For coagulation testing, an evacuated tube, syringe, or other device with a non-activating surface.
A system consisting of several components used for blood collection, such as catheter, luer lock, syringe, needle and evacuated collection device.
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.
Individuals who carry the gene for a condition but who themselves do not have the condition.
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.
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).
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).
Chemical (salt or ester of citric acid) agent used as the anticoagulant in blood collection tubes (“blue top”) used for coagulation laboratory testing.
clone is a group of cells, which derived by asexual division, are genetically identical to a single common ancestor.
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.
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.
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.
Components of the blood coagulation system that include the following factors:
Factor IV (calcium)
Other factors: (Prekallikrein [Fletcher factor], High Molecular Weight Kininogen [Williams Fitzgerald factor)
The slide show entitled Coagulation Pathways (All Components) shows how all these factors relate to each other.
A disorder, either congenital or acquired, that prevents the normal clotting of blood.
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.
A trait, disease, or anomaly that exists at birth regardless of causation. This contrasts to conditions obtained through life (acquired).
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.
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.
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 (“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).
Formation of thrombi in veins located deep within muscles of the extremities such as the legs.
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.
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.
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).
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.
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.
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.
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.
Developing or originating from within. Any factor or mechanism acting or derived from the system from which the analytical sample is taken.
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.
Developing or originating from outside a system. Any factor or mechanism added to the sample either in vivo or to the sample in vitro.
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.
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.
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.
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).
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.
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.
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).
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.
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.
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.
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 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.
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.
Assay for fibrinogen concentration measured by the rate at which Fibrinogen is converted to fibrin by the action of Thrombin.
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.
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.
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)
Order of base pairs in a gene.
Gene therapy is a method that corrects a gene mutation by adding an intact (normal) gene or changing one that is already present.
Genetics is the study of genes, variation in genes, and the impact of this variability on the transmission of inherited traits.
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.
The genome is all the genetic material in a chromosome set (all 46 chromosomes).
Represents the specific allelic composition of a cell. It is the genetic makeup of an organism.
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.
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.
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.
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 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 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.
Loss of blood from the intravascular space.
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).
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.
A disease that is passed down through a family.
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.
Hirudin is a naturally occurring peptidein the salvary glands of medicinal leeches (such as Hirudo medicinals) that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin. The slide entitled Amino Acid Structure of Natural Hirudin gives an overview of the Amino Acid Structure of Natural Hirudin.
An individual is homozygous for a genetic trait if both alleles at the same genetic location are identical.
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.
A lower than normal amount of Fibrinogen in the blood. A key laboratory finding is prolongation of the Thrombin Time test.
Systematic difference between the result of a maesurement and the conventional true value, which is the net result of a constant component, mainly caused by insufficient analytical specificity of the test procedure, and a proportional component, caused by incorrect calibration.
Characteristics, qualities, or traits that are transmitted from parent to offspring by coded genetic material.
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.
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.
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.
The term means “within glass” and refers to testing or observations that are done outside the body and under artificial conditions.
The term means “in life” and refers to testing or observations made on tissues not removed from the body.
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.
There are no words in this dictionary that begin with the letter J
There are no words in this dictionary that begin with the letter K
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.
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.
Excessive uterine bleeding (generally defined as exceeding 80 milliliters per menstrual cycle) that occurs at the regular intervals of menstruation.
See Gene Mutation
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.
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 in the form of DNA and RNA control inheritance and cellular function. Nucleic acids are many nucleotides linked together (by 3′, 5′ phosphodiester linkages). In DNA, the sugar group is deoxyribose and the bases consist of the nucleotides, adenine, guanine, thymine and cytosine. RNA, ribonucleic acid, has ribose as the sugar and nucleotides adenine, guanine, cytosine and uracil (replaces thymine).
Nucleotides are the basic building blocks (alphabet) of nucleic acids. There are five nucleotides (bases), Adenine (A), Guanine (G), Thymine (T), Cytosine (C), and Uracil (U). They are made up of a nitrogen-containing purine or pyrimidine base linked to a sugar (ribose or deoxyribose) and a phosphate group.
There are no words in this dictionary that begin with the letter O
The observable physical appearance of an organism. Characteristics result from interactions between genotype and the environment.
Phosphate containing lipids found in membranes of cells such as platelets and endothelial cells. The phospholipid membrane surfaces of these cells serve as cofactors in coagulation. Both PT and APTT require addition of phospholipids in order for the coagulation reaction to occur in vitro.
The fluid portion of anticoagulated whole blood obtained by centrifugation or sedimentation. Plasma differs from serum in that the anticoagulant would not allow whole blood to clot. Therefore plasma contains Fibrinogen and serum does not. Plasma is used for coagulation laboratory testing.
Plasmapheresis is a procedure in which whole blood is separated into cells and plasma by a device known as a cell separator. The cells are returned to the person undergoing treatment, while the plasma that contains harmful substances (antibodies for example) is discarded and replaced with other fluids such as fresh frozen plasma, albumin and/or plasma substitute. The procedure is often referred to as plasma exchange.
Plasminogen is synthesized in the liver as the zymogen precursor of Plasmin, the main enzyme in the fibrinolytic system. Kringle regions 1 & 5 of Plasminogen bind to fibrin in order to localize fibrinolysis and for fibrin to serve as a cofactor in the activation of the zymogen to the active serine protease, Plasmin. Endogenous activators of plasminogen include tissue plasminogen activator (tPA) and Urokinase, or the exogenous activator, Streptokinase. Plasmin can degrade both Fibrinogen and fibrin into soluble products that can be cleared. One of these degraded products is the fragment D-dimer. The slide show entitled Fibrinolytic Pathway shows how Plasminogen participates in fibrinolyisis.
Platelets (thrombocytes) are small disc-like, anucleated cells that derive from the cytoplasm fragmentation of megakaryocytes. Platelets normally circulate in blood for approximately seven days. Platelets are the primary defense against bleeding by forming the initial plug when a blood vessel is injured. Platelets also participate in blood coagulation by providing the phospholipid surface on which the coagulation reactions occur. In order to become functional, platelets must be activated. Physiologically Thrombin is the most potent platelet activator (agonist). The slide show entitled Activation of Platelets by Thrombin shows how a platelet is affected by Thrombin.
Plasma containing less than 10 x 109 platelets per liter. PPP is prepared by centrifuging anticoagulated whole blood at greater than 1500 g forces for a minimum of 15 minutes using a centrifuge with a swing-out bucket rotor. PPP is used in coagulation testing.
Plasma obtained by centrifugation of anticoagulated whole blood that ensures retention of a maximum number of platelets minus any white or red cell contamination. Platelet count of PRP closely matches that of the original whole blood sample. PRP is used for platelet aggregation studies.
Prekallikrein is a member of the contact activation proteins. It is a zymogen that when activated by FXIIa becomes the active serine protease, kallikrein. Kallikrein shows proteolytic activity towards FXII, HK, and urokinase.
A determination of the disease that produces symptoms in a child before it is born.
The term may be used in two ways: 1) describes the inactive form of any coagulation factor (FVII is the procoagulant form of FVIIa, the active form) or 2) applies to any agent that promotes coagulation or thrombosis (for example, activated platelets are considered procoagulant)
The prevention of disease or a process that can lead to disease.
A large class of organic compounds, found in plants and animals, which contain carbon, hydrogen, oxygen, sulphur, and most notably nitrogen. Proteins are essentially a combination of various amino acids that are linked together. Twenty different types of amino acids are commonly found in proteins and each protein has a unique, genetically defined amino acid sequence that determines how it functions. The coagulation proteins serve as enzymes.
A glycoprotein, synthesized in the liver, containing 10 Gla residues that are dependent on vitamin K for biosynthesis. It is the zymogen for the serine protease, Thrombin, and participates in the common pathway of coagulation. Conversion of Prothrombin to Thrombin is catalyzed by FXa in the presence of the cofactor FVa, calcium ions, and phospholipid (prothrombinase complex). The slide Coagulation Pathways (All Components) shows how FII relates to the other coagulation factors. See also the slide shows entitled Tissue Factor Pathway (Extrinsic) with Common Pathway (PT) and Intrinsic Pathway-APTT.
A test used for evaluation of the extrinsic and common coagulation pathways and for monitoring oral anticoagulant therapy. The PT is the time in seconds required for a fibrin clot to form after thromboplastin and an optimal amount of calcium chloride have been added to the sample (citrated platelet poor plasma).
Manner for reporting the Prothrombin Time. The PT Ratio is the PT of a test plasma (numerator) divided by the geometric mean (denominator) of the reference interval.
Pulmonary embolism is the lodging (getting stuck) of an embolus in the pulmonary artery of a lung. Pulmonary emboli travel by way of the venous circulation from veins in the lower extremities (DVT). Once they come to rest in the pulmonary artery the emboli can cause severe respiratory dysfunction (shortness of breath, rapid heart & respiration rate).
Substance used to detect or measure another substance or to convert one substance into another by means of the reaction that it causes.
A receptor is a specific molecular structure on or within a cell that can bind to another molecule and cause a specific effect or action after the binding has taken place.
Inheritance is said to be recessive when an allele gives rise to a phenotype only when present in the homozygous form. In the heterozygous state its outward effect (phenotype) will be hidden by dominant alleles.
Process uses genetically engineered or cloned material to make blood products that do not come from human or animal plasma. With additional elimination of human or animal products used for product stabilization, the risk of viral transmission is nearly nil. Currently recombinant coagulation factors that are available for patient use are FVII (rFVIIa), FVIII (rFVIII), and FIX (rFIX).
Range of values between and including the lower to upper reference limits (usually 95% confidence limits or +2SD) found in an apparently healthy population (one not afflicted with a discernable illness).
An enzyme that recognizes a specific target nucleotide sequence in DNA and cleaves the DNA at that site.
Material prepared from a patient specimen and used to obtain information by means of a specific laboratory test. For coagulation testing the sample is citrated platelet poor plasma.
Proteins containing a catalytic domain (serine protease) that includes the three principal amino acids participating in catalysis: serine, histidine, and aspartic acid. These proteins circulate as inert zymogens, upon activation selectively hydrolyze bonds containing arginine or lysine, and are regulated by inhibitors termed serpins. Serine proteases involved in hemostasis include coagulation factors FII, FVII, FIX, FX, FXI, FXII, and Prekallikrein, as well as the fibrinolytic pathway proteins Plasminogen and tissue Plasminogen Activator (t-PA).
Serum is the clear yellowish fluid that remains after whole blood, that is not anticoagulated, is allowed to clot and sediment. The solid portion consists of cells. Serum differs from plasma in that serum contains no Fibrinogen (Fibrinogen is consumed as blood clots).
A discrete portion of body fluid or tissue taken for examination, study, or analysis of one or more qualities or characteristics. For coagulation testing, the specimen is whole blood that upon collection is anticoagulated with sodium citrate.
Ability of a system, when kept under specified conditions, to maintain a stated property value within specified limits for a specified period of time.
Stagnation of normal blood flow in a vessel.
Located beneath the layers of skin
A substance that is acted upon and changed by an enzyme. The enzyme accelerates the chemical transformation of this substance. For example the enzyme Thrombin acts upon Fibrinogen (one of its substrates) to convert it to fibrin.
The key enzyme in hemostasis that originates from a zymogen precursor, Prothrombin. Thrombin possesses distinct binding sites for substrates, inhibitors, cofactors, and sodium ions. In addition to the coagulation reaction (Thrombin conversion of Fibrinogen to fibrin), Thrombin is involved in several other proteolytic processes that maintain hemostasis: 1) activation of FXIII to further strengthen fibrin, 2) activation of FXI providing a positive feedback mechanism for additional Thrombin generation, 3) activation of cofactors FVIII and FV, 4) activation of Protein C to form Activated Protein C, a powerful anticoagulant, 5) cleavage of TAFI to form TAFIa which inhibits Plasmin (inhibits fibrinolysis), 6) cleavage of platelet PAR-1 receptor allowing for activation of platelets. The slide Coagulation Pathways (All Components) shows how Thrombin relates to the other coagulation factors. For other slide shows highlighting the critical role of Thrombin, see: Activation of Protein C by Thrombin, Activation of TAFI by Thrombin, Fibrinolytic Pathway, and Activation of Platelets by Thrombin.
A test used to evaluate the final steps of coagulation. Test result represents the time in seconds required for a fibrin clot to form in a sample after a known amount of Thrombin has been added. Prolonged times are due to heparin or heparin like anticoagulants, hyofibrinogenemia, dysfibrinogeneimia, or fibrin degradation products.
A decrease in the number of platelets in the blood leading to a potential for increased bleeding.
Formation of thrombi in blood resulting from an imbalance between thrombogenic factors and protective mechanisms. Thrombogenic influences that tip this balance in favor of thrombosis include: perturbation of endothelial cells, exposure of subendothelium, activation of platelets, activation of coagulation, inhibition of fibrinolysis, and stasis. Protective mechanisms include: antithrombotic properties of endothelium, neutralization of activated coagulation factors by endothelial cell-bound components, inhibition of coagulation factors by plasma protease inhibitors, dilution of activated coagulation factors by unimpeded blood flow, and dissolution of fibrin by the fibrinolytic system. A diminution of these protective mechanisms will also lead to thrombus formation.
Transmembrane protein present on the surface of endothelial cells. Thrombin loses its procoagulant activity after it binds with thrombomodulin. The thrombin-thrombomodulin complex initiates the Protein C anticoagulant pathway by activating the zymogen Protein C.
Egeberg coined this term in 1965 to describe a tendency to develop venous thrombosis in a Norwegian family with Antithrombin deficiency. The term now includes any disorder, whether inherited or acquired, associated with an increased tendency to venous thromboembolism.
A phospholipid / Tissue Factor preparation used for performing the Prothrombin Time. Source material for thromboplastin (Tissue Factor, factor III) is human brain or placenta (homologous sources), rabbit brain, lung or bovine brain (heterologous sources), or prepared by recombinant technology. Thromboplastins vary in their sensitivity to reductions in vitamin K-dependent proteins (FII, FVII, FIX, and FX).
Formation of a thrombus. Thrombosis can occur in veins or arteries, systemically (Disseminated Intravascular Coagulation), or in cardiac chambers.
Thrombus (plural form is Thrombi)
A solid mass or plug formed intravascularly (in the living heart or vessels) from constituents of the blood (Welch, 1899). Hemodynamic factors influence the composition of a thrombus. Arterial thrombi (white thrombi) are formed under conditions of high flow (sites of rupture of an atherosclerotic plaque) and are composed mainly of platelet aggregates bound together by thin fibrin strands. Venous thrombi (red thrombi) form in areas of stasis and are composed of red cells and with a large amount of interspersed fibrin and relatively few platelets. Though commonly used as interchangeable terms, blood clot and thrombus are not synonymous.
Synonyms for Tissue Factor include thromboplastin, CD142, and coagulation factor III. TF is an integral membrane glycoprotein associated with phospholipid and distributed in cells that synthesize it. TF is absent in all cells that are in direct contact with blood but is present in the adventitial cell layer that surrounds all blood cells, keratinocytes in the skin, and a number of epithelial cell types found in mucous membranes and many organ capsules. This distribution has been referred to as a protective “hemostatic envelope”. Atherosclerotic plaques contain TF (found in monocytes and smooth muscle cells). Exposure of TF to blood results in assembly of the cofactor TF with FVIIa. This complex is the most potent activator of the coagulation cascade and in laboratory testing is referred to as the extrinsic pathway of coagulation. The slide show entitled Coagulation Pathways (All Components) shows how TF relates to the other coagulation factors. See also the slide shows entitled Tissue Factor Pathway (Extrinsic) with Common Pathway (PT).
-U, V, W-
See Angina Pectoris
Blood vessel that carries blood to the heart. All veins, except the pulmonary vein carry oxygen-poor blood.
The lower chambers of the heart.
Any of several fat-soluble compounds that are found in alfalfa, green leafy vegetables, fish-meal, and green tea and are essential for production and function of the vitamin K-dependent coagulation proteins (FII, FVII, FIX, FX).
Von Willebrand Factor is a large, multimeric glycoprotein involved in platelet adhesion (binding to its receptor, platelet GPIb) and in stabilization of circulating FVIII. VWF also binds to heparin, collagen, and platelet GPIIb/IIIa (platelet aggregation). VWF is synthesized in endothelial cells and megakaryocytes. A deficiency or abnormality in VWF leads to a bleeding diathesis termed Von Willebrand Disease, the most common inherited bleeding disorder in humans.
The most common inherited bleeding disorder in humans. It is inherited in an autosomal fashion and by that affects both males and females equally. In VWD, Von Willebrand Factor is quantitatively and/or qualitatively abnormal. FVIII levels will also be affected by levels of VWF, since the latter serves to carry and protect the former.
-X, Y, Z-
Traits resulting from genes present on the X chromosome. Sex-linked traits are due to genes present on either X or Y chromosomes.
Precursor of an enzyme that requires some type of modification in order for it to become functional. Also termed proenzyme.