Secondary Hemostasis

Pathways.

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

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 al^7,8 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.)

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

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

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and action on another factor, with a dashed arrow:

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Additional terms related to secondary hemostasis are as follows:

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:

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

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:

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: