Hemostasis - Nomenclature

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 hemostasis2,3,4 (use parenthetical abbreviated terms in accordance with 13.11, Clinical, Technical, and Other Common Terms).

Table 14.7-1. Platelet Hemostasis Terms and Abbreviations

Term

Abbreviation

α-granules


arachidonic acid

AA

ATP P2X1 receptor

P2X1

β-thromboglobulin

βTG or BTG

calcium-calmodulin complex

Ca-CaM or Ca-CM

cyclooxygenase

COX

diacylglycerol

DAG

G proteins (proteins that hydrolyze guanosine triphosphate)

glycoprotein Ia/IIa complex

GpIa-IIa

glycoprotein Ib/IX complex

GpIb-IX

glycoprotein Ib/IX/V complex

GpIb-IX-V

glycoprotein IIb/IIIa complex

GpIIb-IIIa

glycoprotein IV (CD36; see 14.8.7, Lymphocytes)

GpIV

glycoprotein VI

GpVI

inositol triphosphate

IP3

myosin light chain

MLC

myosin light chain kinase

MLCK

myosin light chain, phosphorylated

MLC-PO4

phosphatidylinositol 4,5-biphosphate

PIP2

phosphodiesterase 3A

PDE3A

phospholipase A2

PLA2

phospholipase C

PLC

platelet activating factor

PAF

platelet-derived growth factor

PDGF

platelet factor 3

PF3

platelet factor 4

PF4

platelet ADP P2T adenylate cyclase receptor

P2TAC

platelet ADP P2X1 receptor

P2X1

platelet ADP P2Y1 receptor

P2Y1

prostacyclin, prostaglandin I2

PGI2

prostaglandin D2

PGD2

6-keto prostaglandin F

6-keto PGF

prostaglandin G2

PGG2

prostaglandin H2

PGH2

protein p47

p47

protein p47, phosphorylated

p47phox

protein kinase C

PKC

thromboxane A2

TXA2

thromboxane B2

TXB2

von Willebrand factor (see 14.7.3.6, von Willebrand Factor)

VWF

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:

Glycoprotein

Integrin

GpIa-IIa

α2β1

GpIc-IIa

α6β1

GpIIb-IIIa

αIIBβ3

Table 14.7-2. Endothelium-Associated Terms and Abbreviations

Class and term

Abbreviation

cellular (or cell) adhesion molecules

CAMs

intercellular adhesion molecule 1

ICAM-1

intercellular adhesion molecule 2

ICAM-2

platelet-endothelial cellular adhesion molecule

PECAM

vascular cellular adhesion molecule 1

VCAM-1

cytokines (see 14.8.4, Cytokines)


gro (growth-stimulating factor)

GSF

RANTES (regulated on activation, normal T-expressed, and secreted5(p1638))


integrins


α1β1 integrin


α2β3 integrin


α3β1 integrin


α6β1 integrin


αvβ1 integrin


αvβ3 integrin


miscellaneous


nitric oxide

NO

endothelial (or epithelial) nitric oxide synthase

eNOS (also NOS3)

endothelial cell—associated ADPase (CD39; see 14.8.7, Lymphocytes)


prostacyclin, prostaglandin I2

PGI2

E-selectin


L-selectin


P-selectin


tissue plasminogen activator (see 14.7.4, Inhibition of Coagulation and Fibrinolysis)

tPA

urokinase or urinary-type plasminogen activator (see 14.7.4, Inhibition of Coagulation and Fibrinolysis)

uPA

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:

Term

Synonym

intrinsic pathway

contact system—initiated pathway

extrinsic pathway

tissue factor—mediated or tissue factor—dependent pathway

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

Factor No.

Descriptive name

Synonym(s)

(factor I)a

fibrinogenb


factor II

prothrombinb

prethrombin

(factor III)a

tissue factorb

thromboplastin tissue thromboplastin tissue extract

(factor IV)a

calciumb

calcium ion Ca2+

factor Vb

proaccelerin

(labile factor) (accelerator globulin [AcG])

factor VIIb

proconvertin

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

factor VIIIb

antihemophilic factor (AHF)

antihemophilic globulin (AHG) antihemophilic factor A

factor IXb

plasma thromboplastin component (PTC)

Christmas factor antihemophilic factor B

factor Xb

Stuart factor

Prower factor Stuart-Prower factor

factor XIb

plasma thromboplastin antecedent (PTA)

(antihemophilic factor C)

factor XIIb

Hageman factor

activation factor contact factor (glass factor)

factor XIIIb

fibrin-stabilizing factor (FSF)

(Laki-Lorand factor [LLF]) (fibrinase) (protransglutaminase)


prekallikreinb

Fletcher factor


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

Fitzgerald factor

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:

Image

and action on another factor, with a dashed arrow:

Image

Image

Examples of 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

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:

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) . . .

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

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

VWF:CB



collagen-binding

ristocetin cofactor (RCoF)


VIIIR:RCoF VIII:R:RCo VIIIR:vWF

von Willebrand factor function (ie, platelet aggregation-promoting property of VWF in the presence of the drug ristocetin)

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 disease13,14,15,16 include, but are not limited to, the following:

Type

Sample molecular variants

type 1

VWF Arg854Gln, VWF Cys1149Arg

type 2A

VWF Ile865Thr, VWF Arg834Trp

type 2B type 2M type 2N

VWF Trp550Cys, VWF Arg545Cys has at least 28 variants VWF Thr28Met

type 3

VWF Arg1659ter, VWF Arg2635ter

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:

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

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

Term

Abbreviation

α1-antitrypsin

AAT

α2-macroglobulin

AMG

antithrombin III

ATIII

α-ATIII isoform

α-ATIII

β-ATIII isoform

β-ATIII

ATIII/heparin complex

Do not abbreviate

C1 inhibitor

C1 INH (see 14.8.3, Complement)

heparin cofactor II

Do not abbreviate

lupus coagulation inhibitor (also called lupus anticoagulant)

LCI

protein C

Do not abbreviate

activated protein C

APC

protein S

Do not abbreviate

protein Z

Do not abbreviate

serpin (serine protease inhibitor)

Do not abbreviate

tissue factor pathway inhibitor

TFPI

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

Term

Abbreviation

α2-plasmin inhibitor, α2-antiplasmin

α2PI

aminocaproic acid (Amicar)

ACA

ε-aminocaproic acid

EACA

dimerized plasmin fragment D

D-dimer

fibrin degradation products or fibrin split products

FDP or FSP

Glu-plasminogen (see 14.6.1, Nucleic Acids and Amino Acids)

Do not abbreviate

Lys-plasminogen (see 14.6.1, Nucleic Acids and Amino Acids)

Do not abbreviate

a plasminogen activator inhibitor

PAI-1

protein C inhibitor

PAI-3

thrombin-activated fibrinolytic inhibitor

TAFI

tissue plasminogen activator (when a specific therapeutic formulation of tPA is intended, use the USAN term; see 14.4, Drugs)

tPA

tissue plasminogen activator receptor

tPAR

urokinase or urinary-type plasminogen activator

uPA

urokinase or urinary-type plasminogen activator receptor

uPAR

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 = PTRISI

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.

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