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 F1α |
6-keto PGF1α |
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:
and action on another factor, with a dashed arrow:
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.
References
1.Monroe DM, Hoffman M. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol. 2006;26(1):41-48. doi:10.1161/01.ATV.0000193624.28251.83
2.Marder VJ, Aird WC, Bennett JS, Schulman S, White GC II, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 6th ed. Lippincott Williams & Wilkins; 2013.
3.Dorland’s Illustrated Medical Dictionary. 32nd ed. WB Saunders; 2012.
4.Konkle B. Bleeding and thrombosis. In: Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. McGraw-Hill; 2012:457-464.
5.Stedman’s Medical Dictionary. 28th ed. Lippincott Williams & Wilkins; 2006.
6.Owen CA Jr. A History of Blood Coagulation. Mayo Foundation for Education and Research; 2001.
7.Giangrande PL. Six characters in search of an author: the history of the nomenclature of coagulation factors. Br J Haematol. 2003;121(5):703-712. doi:10.1046/j.1365-2141.2003.04333.x
8.Blomback M, Abildgaard U, van den Besselaar AM, et al. Nomenclature of quantities and units in thrombosis and haemostasis (recommendation 1993): a collaborative project of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH/SSC) and the Commission/Committee on Quantities and Units (in Clinical Chemistry) of the International Union of Pure and Applied Chemistry—International Federation of Clinical Chemistry (IUPAC-IFCC/CQU[CC]). Thromb Haemost. 1994;71(3):375-394.
9.The International Society on Thrombosis and Haemostasis website. Accessed July 31, 2019. https://www.isth.org
10.Peake I, Tuddenham E. A standard nomenclature for factor VIII and factor IX gene mutations and associated amino acid alterations: on behalf of the ISTH SSC Subcommittee on Factor VIII and Factor IX. Thromb Haemost. 1994;72(3):475-476.
11.Marder VJ, Mannucci PM, Firkin BG, Hoyer LW, Meyer D. Standard nomenclature for factor VIII and von Willebrand factor: a recommendation by the International Committee on Thrombosis and Haemostasis. Thromb Haemost. 1985;54(4):871-872.
12.Marder VJ, Roberts HR. Proposed symbols for factor VIII and von Willebrand factor. Ann Intern Med. 1986;105(4):627. doi:10.7326/0003-4819-105-4-627_1
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
16.Hampshire DJ, Goodeve AC. The International Society on Thrombosis and Haemostasis von Willebrand Disease database: an update. Semin Thromb Hemost. 2011;37(5):470-479. doi:10.1055/s-0031-1281031
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.
18.International Committee for Standardization in Haematology, International Committee on Thrombosis and Haemostasis: ICSH/ICTH recommendations for reporting prothrombin time in oral anticoagulant control. Thromb Haemost. 1985;53(1):155-156.
19.Hirsh J, Dalen JE, Deykin D, Poller L. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 1992;102(suppl 4):312S-326S.
20.Hirsh J, Poller L. The international normalized ratio: a guide to understanding and correcting its problems. Arch Intern Med. 1994;154(3):282-288. doi:10.1001/archinte.1994.00420030084008