Reliability of a Modified Tissue Factor-Dependent Factor V Assay for Activated Protein C Resistant Factor Va Using a Calcium-Containing Thromboplastin

Dzung The Le; Kathleen J Donnelly; Ning Wu; Barbara K Sevilla; Samuel I Rapaport

doi:10.1055/s-0038-1655993

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1997; 77(03): 481-485
DOI: 10.1055/s-0038-1655993

Coagulation

Schattauer GmbH Stuttgart

Reliability of a Modified Tissue Factor-Dependent Factor V Assay for Activated Protein C Resistant Factor Va Using a Calcium-Containing Thromboplastin

Authors

Dzung The Le

The Department of Pathology, University of California, San Diego, California, USA
Kathleen J Donnelly

The Department of Pathology, University of California, San Diego, California, USA
Ning Wu

The Department of Pathology, University of California, San Diego, California, USA
Barbara K Sevilla

The Department of Pathology, University of California, San Diego, California, USA
Samuel I Rapaport

¹The Department of Medicine and Pathology, University of California, San Diego, California, USA

Abstract

als PDF herunterladen

Summary

The original tissue factor-dependent factor V assay for activated protein C resistant factor Va (Blood 1995; 85: 1704-1711) has been modified to use a calcium containing thromboplastin and to express results as an observed to expected ratio (Obs./Exp.). The latter permits establishing a normal range independent of variations due to differences in reagents. Comparing Obs/Exp ratios with DNA analysis in 72 persons revealed that an Obs/Exp ratio of 0.6 distinguished without overlap normals from heterozygotes for FV R506Q. Three homozygotes had a ratio of <0.1. Application of this Obs/Exp cut-off ratio of 0.6 to a total of 226 plasma samples tested to date discriminated without overlap between normals and heterozygotes. We conclude that this assay – readily adaptable to any dedicated coagulation laboratory and capable of yielding reliable results in all clinical circumstances in which testing is indicated – can distinguish between normals and heterozygotes for the FV R506Q mutation without the need for confirmatory DNA analysis.

PDF (1598 kb)

Referenzen

References
1 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C:prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-1008
2 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
3 Greengard JS, Sun X, Xu X, Fernandez JA, Griffin JH, Evatt B. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 1994; 343: 1361-1362
4 Voorberg J, Roelse J, Koopman R, Büller H, Berends F, ten Cate JW, Mertens K, van Mourik JA. Association of idiopathic venous thromboembolism with single point-mutation at Arg⁵⁰⁶of factor V. Lancet 1994; 343: 1535-1536
5 Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521-2524
6 Sun X, Evatt B, Griffin JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83: 3120-3125
7 Griffin JH, Evatt B, Wideman C, Fernandez JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 1993; 82: 1989-1993
8 Koster T, Rosendaal FR, de Ronde H, Briet E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C:Leiden Thrombophilia Study. Lancet 1993; 342: 1503-1506
9 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-522
10 Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb Haemost 1995; 74: 449-453
11 Braun A, Muller B, Rosche AA. Population study of the G1691A mutation (R506Q, FV Leiden) in the human factor V gene that is associated with resistance to activated protein C. Hum Genet 1996; 97: 263-264
12 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-1134
13 Arruda VR, Annichino-Bizzacchi JM, Costa FF, Reitsma PH. Factor V Leiden (FVQ 506) is common in a Brazilian population. Am J Hematol 1995; 49: 242-243
14 Beauchamp NJ, Daly ME, Hampton KK, Cooper PC, Preston FE, Peake IR. High prevalence of a mutation in the factor V gene within the U.K. population:relationship to activated protein C resistance and familial thrombosis. BrJ Haematol 1994; 88: 219-222
15 Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation [see comments]. Lancet 1994; 344: 1453-1457
16 Hellgren M, Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995; 173: 210-213
17 Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995; 346: 1593-1596
18 Cooper PC, Abuzenada A, Preston FE. APC Resistance test, a New Phenomenon – The Role of Platelets. British Society for Haematology 1994; 33
19 Girolami A, Simioni P, Scarano L. Evaluation of activated protein C resistance in stored plasma. Lancet 1994; 343: 1288-1290
20 Jones DW, Winter M. Activated Protein C Resistance is Affected by Freezing and Thawing. British Society for Haematology 1994; 32
21 Bokarewa MI, Blombäck M, Egberg N, Rosén S. A new variant of interaction between phospholipid antibodies and the protein C system. Blood Coagul Fibrinolysis 1994; 5: 37-41
22 Halbmayer WM, Haushofer A, Schon R, Fischer M. Influence of lupus anticoagulant on a commercially available kit for APC-resistance. Thromb Haemost 1994; 72: 645-646
23 de RondeH, Bertina RM. Laboratory diagnosis of APC-resistance:a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-886
24 Vasse M, Leduc O, Borg JY, Chretien MH, Monconduit M. Resistance to activated protein C:evaluation of three functional assays. Thromb Res 1994; 76: 47-59
25 Hampton KK, Preston FE, Greaves M. Resistance to activated protein C. N Engl J Med 1994; 331: 130
26 Rosen S, Johansson K, Lindberg K, Dahlback B. Multicenter Evaluation of a Kit for Activated Protein C Resistance on Various Coagulation Instruments Using Plasmas from Healthy Individuals. Thromb Haemost 1994; 72: 255-260
27 Shizuka R, Kanda T, Amagai H, Kobayashi I. False-positive activated protein C (APC) sensitivity ratio caused by freezing and by contamination of plasma with platelets. Thromb Res 1995; 78: 189-190
28 Sidelmann J, Gram J, Pedersen OD, Jespersen J. Influence of plasma platelets on activated protein C resistance assay. Thromb Haemost 1995; 74: 993-994
29 Denson KW, Reed SV, Haddon ME. The modified APC resistance test. Thromb Haemost 1995; 74: 74
30 Aillaud MF, Succo E, Alessi MC, Gandois JM, Gallian P, Morange P, Juhan-Vague I. Resistance to activated protein C – diagnostic strategy in a laboratory of haemostasis. Thromb Haemost 1995; 74: 1197-1198
31 Henkens CM, Bom VJ, van der Meer J. Lowered APC-sensitivity ratio related to increased factor VUI-clotting activity. Thromb Haemost 1995; 74: 1198-1199
32 Leroy-Matheron C, Levent M, Pignon J, Mendonca C, Gouault-Heilmann M. The 1691 G-A mutation in the factor V Gene:relationship to activated protein C (APC) resistance and thrombosis in 65 patients. Thromb Haemost 1996; 75: 4-10
33 Jorquera JI, Montoro JM, Fernandez MA, Aznar JA, Aznar J. Modified test for activated protein C resistance. Lancet 1994; 344: 1162-1163
34 Trossaert M, Conard J, Horellou MH, Samama MM, Ireland H, Bayston TA, Lane DA. Modified APC resistance assay for patients on oral anticoagulants. Lancet 1994; 344: 344
35 Sakata T, Kario K, Katayama Y, Matsuyama T, Kato H, Miyata T. Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state. Thromb Res 1996; 82: 235-244
36 Fisher M, Fernandez JA, Ameriso SF, Xie D, Gruber A, Paganini-Hill A, Griffin JH. Activated protein C resistance in ischemic stroke not due to factor V Arginine-506 – Glutamine mutation. Stroke 1996; 27: 1163-1166
37 van der BomJG, Bots ML, Haverkate F, Slagboom E, Meijer P, de Jong PTVM, Hofman A, Grobbee DE, Kluft C. Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med 1996; 125: 265-269
38 Le DT, Griffin JH, Greengard JS, Mujumdar V, Rapaport SI. Use of a generally applicable tissue factor-dependent factor V assay to detect activated protein C-resistant factor Va in patients receiving warfarin and in patients with a lupus anticoagulant. Blood 1995; 85: 1704-1711
39 Wu N, Le DT. Rapid identification of APC resistant (APC-R) FVa gene by PCR amplification with sequence-specific primers. Blood 1995; 86 (Suppl. 01) 927a (abstract)