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Secondary Hemostasis

Chapter:
Nomenclature
Author(s):

Harriet S. Meyer

Secondary Hemostasis

Blood coagulation is the phase of clot formation dependent on plasma coagulation factors (also known as clotting factors).

Pathways.

The laboratory evaluation of plasma factor-dependent coagulation has been divided into 2 pathways (systems, phases). The following terms and synonyms are used:

Term

Synonym

intrinsic pathway

contact system-initiated pathway

extrinsic pathway

tissue factor-mediated or tissue factor-dependent pathway

Clotting Factors.

An international system of nomenclature, formulated from 1954 through 1963,4,5 clarified clotting factor terminology and, as Biggs6 observed, scientific findings in coagulation, when factors identified and named independently by different groups were shown to be the same.5 A major update to the standard nomenclature was published by Blomback et al7,8 in the early 1990s.

A number of clotting factors were named for the patients whose disorders led to their discovery. Biggs considered this practice valuable in avoiding ‘“hypothetical implication.”’5(p705)

Roman numerals are used to designate most of the major plasma coagulation factors. These designations when formulated were seen as having advantages over eponyms and functional names for comprehension by readers of non-Western languages.5 “The sequence of numbers in current terminology is … based on the historical order in which the coagulation factors were discovered.”5(p710)

The following tabulation gives roman numeral designations, descriptive names, and synonyms for the plasma coagulation factors. Asterisks indicate preferred terms. Terms that are rarely used are enclosed in parentheses. If a term other than the preferred term is used, the preferred term should be given in parentheses at the first mention of a factor. Common abbreviations appear here, but their use should conform to guidelines in 14.11, Abbreviations, Clinical, Technical, and Other Common Terms. (The term “factor VI,” originally designating activated factor V, is not used.)

Factor No.

Descriptive Name

Synonym(s)

(factor I)

fibrinogen*

factor II

prothrombin*

prethrombin

(factor III)

tissue factor

thromboplastin tissue thromboplastin tissue extract

(factor IV)

calcium*

calcium ion Ca2+

factor V*

proaccelerin

(labile factor) (accelerator globulin [AcG]) (Ac globulin) (thrombogen)

factor VII*

proconvertin

(stable factor) (serum prothrombin conversion accelerator [SPCA]) (autoprothrombin I)

factor VIII*

antihemophilic factor (AHF)

antihemophilic globulin (AHG) antihemophilic factor A (platelet cofactor 1) (thromboplastinogen)

factor IX*

plasma thromboplastin component (PTC)

Christmas factor antihemophilic factor B (autoprothrombin III) (platelet cofactor 2)

factor X*

Stuart factor

Prower factor Stuart-Prower factor (autoprothrombin III) (thrombokinase)

factor XI*

plasma thromboplastin antecedent (PTA)

(antihemophilic factor C)

factor XII*

Hageman factor

contact factor (glass factor)

factor XIII

fibrin stabilizing factor (FSF)

plasma transglutaminase fibrinoligase (Laki-Lorand factor [LLF]) (fibrinase)

prekallikrein*

Fletcher factor prokallikrein

high-molecular-weight kininogen (HMW kininogen, HMWK, HK)*

Fitzgerald factor Williams factor Flaujeac factor (contact activation factor) (Reid factor) (Washington factor)

A lowercase a designates the activated form of a factor, eg, IXa.

In diagrams of coagulation pathways, activation is indicated with a solid arrow:

and action on another factor, with a dashed arrow:

Additional terms related to secondary hemostasis are as follows:

Term

Abbreviation

γ-glutamyl carboxylic acid residues

Gla residues

tissue factor/VIIa complex

TF-VIIa complex

or

VIIa/tissue factor complex

VIIa-TF complex

active factor XII fragment

XIIf

Clotting Factor Variants.

Specific variants or abnormal forms may be named for locations, as follows:

factor V Cambridge

factor V Leiden

factor X San Antonio

fibrinogen Paris

protein C Vermont

prothrombin Barcelona

prothrombin Himi I

prothrombin Himi II

Clotting factor variants that have been characterized molecularly are specified by means of terms that indicate the molecular change, ie, nucleotide or amino acid alteration.9 The abbreviations ins (insertion), del (deletion), In (intron), Ex (exon), and ter (termination codon) are used within such terms.9 See Sequence Variations, Nucleotides, and Sequence Variations, Amino Acids, in 15.6.1, Genetics, Nucleic Acids and Amino Acids, for a more detailed description of such notation. Examples:

factor VIII Arg1689Cys

or

VIII R1689C

factor VIII Glu1987ter

or

VIII G1987ter

factor VIII Ex24-25del

A shorthand expression is permissible after the term is first defined:

The factor II resulting from the 20210G→A variant (mutation) in the prothrombin gene (factor II A20210)…

Thrombin.

The protein thrombin is the end result of the coagulation factor cascade. Related terms include the following:

α-thrombin

β-thrombin

γ-thrombin

thrombin A loop, B loop, C loop, E loop, γ loop

β-thromboglobulin

Hemophilias and Thrombophilias.

Hemophilias are bleeding disorders. Hemophilia A is associated with factor VIII deficiency, hemophilia B with factor IX deficiency, hemophilia C with factor XI deficiency, and von Willebrand disease with von Will-ebrand factor deficiency. (Factor IX was the originally named Christmas factor, after a patient’s surname. That patient went on to become an influential advocate for safe blood supply.5 Hemophilia B, known as Christmas disease, was reported in the Christmas 1952 issue of the British Medical Journal.4,5) Examples of subtypes include hemophilia A, CRM(+) variant (CRM: cross-reacting material), hemophilia B Leyden [sic], and hemophilia Bm.

Thrombophilias are excessive clot-forming disorders. One variety occurs with factor V Leiden.

See “Clotting Factor Variants” above for molecularly based nomenclature.

Von Willebrand Factor.

Because factor VIII, involved in coagulation, and von Will-ebrand factor (vWF), involved in platelet adhesion, form a noncovalent bimolecular complex, they were originally difficult to distinguish biochemically and immunologically. Original nomenclature reflected this difficulty; for instance, what was first referred to as factor VIII-related antigen (abbreviated VIIIR:Ag) was found to be the factor that is deficient in von Willebrand disease.

Factor VIII and vWF, although functionally associated, are physiologically, genetically, and clinically distinct. In 1985 the International Committee on Coagulation and Thrombosis put forth preferred terminology that was meant (1) to distinguish VIII from vWF and (2) to clarify exactly which entity was being specified (Table 12). The committee noted that it is acceptable to use the term VIII-vWF for the biomolecular complex but not for either single component.10,11

Table 12. Factor VII and von Willebrand Factor Terminology

Preferred

Synonym

Old (Avoid)

Meaning

factor VIII

antihemophilic factor (AHF)

VIII:C

factor VIII protein

VIII:Ag

factor VIII antigen

VIII:CAg

factor VIII antigen

VIII:c

factor VIII coagulant activity

vWF

von Willebrand factor

VIIIR:Ag VIII/vWF AHF-like protein

von Willebrand factor protein

vWF:Ag

VIIIR:Ag

von Willebrand factor antigen

ristocetin cofactor (RCoF)

VIIIR:RCoF VIII:R:RCo VIIIR:vWF

von Willebrand factor function, ie, platelet adhesion-promoting property of vWF in the presence of the drug ristocetin

The terms in column 1 of Table 12 are not only preferred but also familiar exactly as shown to those conversant with the field. However, for most audiences, authors should clarify the preferred term by including the synonym or an explanation (eg, column 4, “Meaning”) at first mention.

 

Von Willebrand Disease.

Variants of von Willebrand disease include the following:

Type

Sample Molecular Variants12

type I

vWF Arg854Gln, vWF Cys1149Arg

type IIA

vWF Ile865Thr, vWF Arg834Trp

type IIB

vWF Trp550Cys, vWF Arg545Cys

type III

vWF Arg1659ter, vWF Arg2635ter

Normandy 1

vWF Thr28Met

Nomenclature for sequence variants (mutations and polymorphisms) of the VWF gene is indicated according to Sequence Variations, Nucleotides, and Sequence Variations, Amino Acids, in 15.6.1, Nucleic Acids and Amino Acids, as above or as in the following examples13:

1234G>A

adenine substituted for guanine at position 1234 in VWF cDNA sequence

g1234G>A

as above, in complete VWF sequence

1234insN

nucleotide insertion after nucleotide 1234 in VWF cDNA sequence

R123G

glycine substitute for arginine at position 123 in pre-pro VWF sequence

R123del

arginine deletion at position 123 in pre-pro VWF sequence

1234A/G

adenine/guanine polymorphism at position 1234 in VWF cDNA

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