AMA Manual of Style - Stacy L. Christiansen, Cheryl Iverson 2020

Hemostasis
Nomenclature

Hemostasis consists of platelet plug formation (primary hemostasis)¹ and blood coagulation (secondary hemostasis, coagulation, clotting). Hemostasis and its control involve complex interactions of numerous procoagulants and anticoagulants. Description of hemostatic processes depends on consistent use of terms.

14.7.1 Primary Hemostasis (Initiation).

Note the typography of the terms listed in Table 14.7-1, which are found in descriptions of platelet hemostasis^2,3,4 (use parenthetical abbreviated terms in accordance with 13.11, Clinical, Technical, and Other Common Terms).

Table 14.7-1. Platelet Hemostasis Terms and Abbreviations

See 14.1.2, Granulocyte Antigens and Platelet-Specific Antigens.

14.7.2 Endothelial Factors.

Structures and products of endothelial cells—the cells lining blood vessels—maintain blood fluidity by preventing excessive clotting and prevent bleeding by promoting clotting. The endothelium-associated terms listed in Table 14.7-2 are presented as a guide to style.

Three glycoprotein complexes are synonymous with 3 integrins and take part in hemostasis:

Table 14.7-2. Endothelium-Associated Terms and Abbreviations

14.7.3 Secondary Hemostasis (Amplification and Propagation).

Blood coagulation (secondary hemostasis¹) is the phase of clot formation dependent on plasma coagulation factors (also known as clotting factors).

14.7.3.1 Pathways.

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

14.7.3.2 Clotting Factors.

An international system of nomenclature, formulated from 1954 through 1963,^6,7 clarified clotting factor terminology. A major update to the standard nomenclature was published by Blomback et al⁸ in the early 1990s.⁹

A number of clotting factors were named for the patients whose disorders led to their discovery.

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.⁷ “The sequence of numbers in current terminology is . . . based on the historical order in which the coagulation factors were discovered.”^7(p710)

Table 14.7-3 gives roman numeral designations, descriptive names, and synonyms for the plasma coagulation factors. 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 13.11, Clinical, Technical, and Other Common Terms. (The term factor VI, originally designating activated factor V, is not used.)

Table 14.7-3. Roman Numeral Designations, Descriptive Names, and Synonyms for the Plasma Coagulation Factors

^a Terms in parentheses are rarely used.

^b Preferred term.

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:

Examples of additional terms related to secondary hemostasis are as follows:

14.7.3.3 Clotting Factor Variants.

Some specific variants or abnormal forms have been named for locations where they were discovered, as follows:

factor V Cambridge

factor V Leyden [sic]

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).¹⁰ The abbreviations ins (insertion), del (deletion), In (intron), Ex (exon), ter (termination codon), MAF (maximum allele frequency), LD (linkage disequilibrium), and SNV (single nucleotide variation; formerly SNP [single-nucleotide polymorphism]) are used within such terms.¹⁰ See 14.6.1.1.1, Sequence Variation, Nucleotides for a more detailed description of such notation. Examples are as follows:

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) . . .

14.7.3.4 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

14.7.3.5 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 Willebrand factor deficiency. (Factor IX was originally named Christmas factor, after a patient’s surname. Hemophilia B is known as Christmas disease and was reported in the Christmas 1952 issue of the BMJ.^6,7) 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 Leyden.

See 14.7.3.3, Clotting Factor Variants, for molecularly based nomenclature.

14.7.3.6 von Willebrand Factor.

Because factor VIII, involved in coagulation, and von Willebrand 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 terms that were meant (1) to distinguish factor VIII from VWF and (2) to clarify exactly which entity was being specified (Table 14.7-4). The committee noted that it is acceptable to use the term VIII-VWF for the biomolecular complex but not for either single component.^11,12

Table 14.7-4. Factor VIII and von Willebrand Factor Terms

The terms in column 1 of Table 14.7-4 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.

14.7.3.7 von Willebrand Disease.

Variants of von Willebrand disease^13,14,15,16 include, but are not limited to, the following:

Nomenclature for sequence variants (mutations and polymorphisms) of the VWF gene is indicated according to 14.6.1.1.1, Sequence Variation, Nucleotides, or as in the following examples¹⁷:

14.7.4 Inhibition of Coagulation and Fibrinolysis

14.7.4.1 Inhibition of Coagulation.

The sample terms listed in Table 14.7-5 are included for reference. Expand at first mention in accordance with 13.11, Clinical, Technical, and Other Common Terms.

Table 14.7-5. Coagulation Terms and Abbreviations

Note: Protein C was named for an investigator’s chromatographic fraction C in which it was discovered. The S in protein S refers to Seattle, where it was discovered. Protein S is not the same as S protein (see 14.8.3, Complement).

14.7.4.2 Fibrinolysis (Fibrin Degradation, Clot Degradation, Thrombolysis).

The sample terms listed in Table 14.7-6 represent entities that are involved in fibrinolysis or its inhibition. Expand at first mention in accordance with 13.11, Clinical, Technical, and Other Common Terms.

Table 14.7-6. Fibrinolysis Terms and Abbreviations

14.7.4.3 Tests of Coagulation.

Two among several tests of coagulation are the prothrombin time (PT) and the partial thromboplastin time (PTT). When the more common activated partial thromboplastin time (aPTT) is used instead of the PTT, this should be specified.

Traditionally, the prothrombin ratio (PTR) had been reported as a ratio of the patient’s PT to the mean laboratory control PT. Reporting the PTR has been refined by use of a modified PTR, the international normalized ratio (INR).^18,19,20 In accordance with a 1985 policy statement of the International Committee on Thrombosis and Haemostasis and the International Committee for Standardization in Haematology,¹⁸ authors are encouraged to report the INR if at all possible. Unlike conversions between conventional and SI units (see 17.1, SI Units), there is no simple conversion factor from the PTR to the INR because the international sensitivity index (ISI) of the thromboplastin used in the actual assay performed must be known. The INR is calculated as shown:

INR = PTR^ISI

Authors should specify the exact method by which their results were initially reported by the laboratory performing the assay and the method of conversion, if any, used on the original results.

Principal Author: Cheryl Iverson, MA

Acknowledgment

Thanks to David Green, MD, PhD, Feinberg School of Medicine of Northwestern University, Chicago, Illinois, for reviewing and providing comments.

References

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13.von Willebrand Factor Variant database. Accessed July 31, 2019. www.vwf.group.shef.ac.uk/variant.html

14.Sadler JE, Budde U, Eikenboom JCJ, et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost. 2006;4(10):2103-2114. doi:10.1111/j.1538-7836.2006.02146.x

15.OMIM: Online Mendelian Inheritance in Man. Updated May 15, 2018. Accessed May 16, 2018. https://www.ncbi.nlm.nih.gov/omim

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17.Goodeve AC, Eikenboom JCJ, Ginsburg D, et al. A standard nomenclature for von Willebrand factor gene mutations and polymorphisms on behalf of the ISIH SSC Subcommittee on von Willebrand Factor. Thromb Haemost. 2001;85(5):929-931.

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