Biological Variation in Tests of Hemostasis

The publisher regrets errors in the above article as originally printed in Seminars in Thrombosis and Hemostasis, Volume 34, Number 7, 2008, pp 635–641.

The following pages contain the entire text of the corrected article.

ABSTRACT

The two components of biological variability are interindividual variability, which is the variability due to the heterogeneity of physiologic influences among subjects, and intraindividual variability, which is due to the variability in the same individual over time. Analysis of biological variation is crucial for estimating the critical difference, which corresponds with a threshold suggestive of a statistically significant difference between two consecutive results of a laboratory parameter in the same subject and is therefore unlikely attributable to casual (random) oscillation of values. Studies on biological variation of tests of hemostasis are outdated, and the published results should be confirmed by using modern, fully automated methods. Biological variation for coagulation screening tests (prothrombin time and activated partial thromboplastin time) is low and comparable with the values registered for hematologic parameters. However, the index of individuality (ratio between intraindividual and interindividual variability) suggests that the usual preoperative screening for coagulation disorders is influenced by the between-subjects variability. Thrombin time is very constant within and between subjects. Proteins such as fibrinogen, clotting factors, and antithrombin show a low biological variability. In contrast, fibrinolytic parameters, such as plasminogen activator inhibitor 1 and fibrinopeptide A, show very high variability, and their interpretation in the clinical setting must take this into consideration.

KEYWORDS

Coagulation tests - biological variation - critical difference - individuality index

REFERENCES

• 1 Fraser C G. Inherent biological variation and reference values.  Clin Chem Lab Med. 2004;  42 758-764
• 2 Fraser C G, Wilkinson S P, Neville R G et al.. Biologic variation of common hematologic quantities in the elderly.  Am J Clin Pathol. 1989;  92 465-470
• 3 Sebastian-Gambaro M A, Lirón-Hernández J, Fuentes-Arderiu X. Intra- and inter-individual biological variability data bank.  Eur J Clin Chem Clin Biochem. 1997;  35 845-852
• 4 Dot D, Mirò J, Fuentes-Arderiu X. Within-subject biological variation of prothrombin time and activated partial thromboplastin time.  Ann Clin Biochem. 1992;  29 422-425
• 5 Costongs G MPJ, Janson P CW, Bas B M, Hermans J, Brombacher P J, van Wersch J WJ. Short-term and long-term intraindividual variations and critical differences of haematological laboratory parameters.  J Clin Chem Clin Biochem. 1985;  23 69-76
• 6 Costongs G MPJ, Bas B M, Janson P CW et al.. Short-term and long-term intraindividual variations and critical differences of coagulation parameters.  J Clin Chem Clin Biochem. 1985;  23 405-410
• 7 Wada Y, Kutihara M, Toyofuku M et al.. Analytical goals for coagulation tests based on biological variation.  Clin Chem Lab Med. 2004;  42 79-83
• 8 Ricos C, Alvarez V, Cava F et al.. Current databases on biological variation: pros, cons and progress.  Scand J Clin Lab Invest. 1999;  59 491-500
• 9 Kouri T, Siloaho M, Pohjavaara S et al.. Pre-analytical factors and measurement uncertainty.  Scand J Clin Lab Invest. 2005;  65 463-475
• 10 Lassen J F, Branslund I, Antonsen S. International normalized ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements.  Clin Chem. 1995;  41 444-447
• 11 Lippi G, Franchini M, Guidi G C. Diagnostic approach to inherited bleeding disorders.  Clin Chem Lab Med. 2007;  45 2-12
• 12 Sakkinen P A, Macy E M, Callas P W et al.. Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology.  Am J Epidemiol. 1999;  149 261-267
• 13 de Maat M P, de Bart A C, Hennis B C et al.. Interindividual and intraindividual variability in plasma fibrinogen, TPA antigen, PAI activity, and CRP in healthy, young volunteers and patients with angina pectoris.  Arterioscler Thromb Vasc Biol. 1996;  16 1156-1162
• 14 Maes M, Scharpé S, Cooreman W et al.. Components of biological, including seasonal, variation in haematological measurements and plasma fibrinogen concentrations in normal humans.  Experientia. 1995;  51 141-149
• 15 Väisänen S, Rauramaa R, Penttilä I et al.. Variation in plasma fibrinogen over one year: relationships with genetic polymorphisms and non-genetic factors.  Thromb Haemost. 1997;  77 884-889
• 16 De Lange M, de Geus E JC, Kluft C et al.. Genetic influences on fibrinogen, tissue plasminogen activator-antigen and von Willebrand factor in males and females.  Thromb Haemost. 2006;  95 414-419
• 17 Chambless L E, McMahon R P, Brown S A, Patsch W, Heiss G, Shen Y. Short-term intraindividuality variability in lipoprotein measurements: the atherosclerosis risk in communities study.  Am J Epidemiol. 1992;  136 1069-1081
• 18 Salomaa V, Rasi V, Stengård J et al.. Intra- and interindividual variability of hemostatic factors and traditional cardiovascular risk factors in a three-year follow-up.  Thromb Haemost. 1998;  79 969-974
• 19 The Fibrinogen Studies Collaboration . Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies.  Am J Epidemiol. 2007;  166 867-879
• 20 Bolon-Larger M, Chamouard V, Bressolle F, Boulieu R. A limited sampling strategy for estimating individual pharmacokinetic parameters of coagulation of coagulation factor VIII in patients with hemophilia A.  Ther Drug Monit. 2007;  29 20-26
• 21 Horne M K, McCloskey D J, Cullinane A M et al.. Parameters of coagulant and fibrinolytic capacity and activity in postmenopausal women: within-subject variability.  Thromb Res. 2002;  107 229-233
• 22 Nguyen N D, Ghaddar H, Stinson V, Chambless L E, Wu K K. ARIC hemostasis study – IV. Intraindividual variability and reliability of hemostatic factors.  Thromb Haemost. 1995;  73 256-260
• 23 Marckmann P, Sandström B, Jespersen J. The variability of and association between measures of blood coagulation, fibrinolysis and blood lipids.  Atherosclerosis. 1992;  96 235-244
• 24 Thompson S G, Martin J C, Meade T W. Sources of variability in coagulation factor assays.  Thromb Haemost. 1987;  58 1073-1077
• 25 Conlan M G, Folsom A R, Finch A et al.. Association of factor VIII and von Willebrand factor with age, sex and risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) study.  Thromb Haemost. 1993;  70 380-385
• 26 Lippi G, Franchini M, Brocco G, Manzato F. Influence of the ABO blood type on the platelet function analyzer PF-100.  Thromb Haemost. 2001;  85 369-370
• 27 Freyburger G, Bilhou-Nabera C, Dief S et al.. Technical and biological conditions influencing the functional APC resistance test.  Thromb Haemost. 1996;  75 460-465
• 28 Favaloro E J, Soltani S, McDonald J, Grezchnik E, Easton L. Laboratory identification of familial thrombophilia: do the pitfalls exceed the benefits? A reassessment of ABO blood group, gender, age, and other laboratory parameters on the potential influence on a diagnosis of protein C, protein S, and antithrombin deficiency and the potential high risk of a false positive diagnosis.  Lab Hematol. 2005;  11 174-184
• 29 Dolan G, Neal K, Cooper P, Brown P, Preston F E. Protein C, antithrombin III and plasminogen: effect of age, sex and blood group.  Br J Haematol. 1994;  86 798-803
• 30 Rodeghiero F, Tosetto A. The VITA project: population-based distributions of protein C, antithrombin III, heparin-cofactor II and plasminogen – relationship with physiological variables and establishment of reference ranger.  Thromb Haemost. 1996;  76 226-233
• 31 Tait R C, Walker I D, Islam S I et al.. Protein C activity in healthy volunteers – influence of age, sex, smoking and oral contraceptives.  Thromb Haemost. 1993;  70 281-285
• 32 Sakkinen P A, Cushman M, Patsy B M et al.. Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.  Thromb Haemost. 1998;  80 134-139
• 33 MacCallum P K, Cooper J A, Howarth D J, Meade T W, Miller G J. Sex differences in the determinants of fibrinolytic activity.  Thromb Haemost. 1998;  79 587-590
• 34 Stegnar M, Pentek M. Fibrinolytic response to venous occlusion in healthy subjects: relationship to age, gender, body weight, blood lipids and insulin.  Thromb Res. 1993;  69 81-92
• 35 Stegnar M, Cuderman T V, Božič M. Evaluation of preanalytical, demographic, behavioural and metabolic variables on fibrinolysis and haemostasis activation markers utilised to assess hypercoagulability.  Clin Chem Lab Med. 2007;  45 40-46
• 36 Hashimoto Y, Kobayashi A, Yamazaki N, Sugawara Y, Takada Y, Takada A. relationship between age and plasma tPA, PA-inhibitor and PA activity.  Thromb Res. 1987;  46 625-633
• 37 Bowles L K, Cooper J A, Howarth D J et al.. Associations of haemostatic variables with body mass index: a community-based study.  Blood Coagul Fibrinolysis. 2003;  14 569-573
• 38 Cushman M, Lemaitre R N, Kuller L H et al.. Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.  Arterioscler Thromb Vasc Biol. 1999;  19 493-498
• 39 Decousus H. Chronobiology of hemostasis. In: Touitou Y, Haus E Biologic Rhythms in Clinical and Laboratory Medicine. Berlin, Germany; Springer 1992: 555-565
• 40 Toulon P, Vitoux J F, Leroy C et al.. Circulating activities during constant infusion of heparin or a low molecular weight derivative (enoxaparine): failure to demonstrate any circadian variations.  Thromb Haemost. 1987;  58 1068-1072
• 41 Kluft C, Jie A FH, Rijken D C, Verheijen J H. Daytime fluctuations in blood of tissue-type plasminogen activator and its fast-acting inhibitor.  Thromb Haemost. 1988;  59 329-332
• 42 Bull G M, Brozonic M, Chakrabarti R et al.. Relationship of air temperature to various chemical, haematological and haemostatic variables.  J Clin Pathol. 1979;  32 16-20