Thromb Haemost 1996; 75(03): 460-465
DOI: 10.1055/s-0038-1650297
Original Article
Schattauer GmbH Stuttgart

Technical and Biological Conditions Influencing the Functional APC Resitance Test

G Freyburger
1   The Université de Bordeaux II, Bordeaux, France
2   Hôpital Pellegrin, Bordeaux, France
,
C Bilhou-Nabera
1   The Université de Bordeaux II, Bordeaux, France
,
S Dief
2   Hôpital Pellegrin, Bordeaux, France
,
S Javorschi
1   The Université de Bordeaux II, Bordeaux, France
2   Hôpital Pellegrin, Bordeaux, France
,
S Labrouche
1   The Université de Bordeaux II, Bordeaux, France
2   Hôpital Pellegrin, Bordeaux, France
,
M J Lerebeller
Laboratoire d’Hématologie, Bordeaux, France
,
M R Boisseau
1   The Université de Bordeaux II, Bordeaux, France
› Author Affiliations
Further Information

Publication History

Received 18 September 1995

Accepted after revision 21 November 1995

Publication Date:
26 July 2018 (online)

Summary

Poor anticoagulant response to APC is conveniently screened by a commercially available functional test (Coatest® APC Resistance) allowing identification of APC-resistant patients. These patients may then be genotyped with respect to factor V, the Arg - > Gin mutation being the principle cause of APC resistance. However, determination of phenotype generally precedes that of genotype, and the need for an “abnormality threshold” prompted a study of inter-batch variations and the clinical conditions associated with an altered APC response. The response to APC was assessed twice in plasma from 111 patients using two of four successive kit batches. A modest but significant inter-batch variability was observed. At the same time, we also tested 130 patients with retinal venous occlusion (RVO), 28 patients with glaucoma and 24 normal volunteers. The APCaPTT/aPTT ratio was found to be lower in the presence of elevated thrombin-antithrombin complexes (r = 0.167, p <0.02) and low blood viscosity (at high shear rate: r = 0.305, p <0.0001) independently of any alteration in genotype.

 
  • References

  • 1 Svensson P, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-522
  • 2 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Veiden PJ, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
  • 3 Jorquera JI, Montoro JM, Fernandez MA, Aznar JA, Aznar J. Modified test for activated protein C resistance. Lancet 1994; 344: 1162-1163
  • 4 Rosen S, Johansson K, Lindberg K, Dahlbäck B. (for the APC resistance group). 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
  • 5 Colluci M, Ciavarella N, Giliberti MG, Semeraro N. Resistance to activated protein C (APC): influence of factor V levels. Thromb Haemost 1994; 72: 987-988
  • 6 de Ronde H, Bertina M. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-886
  • 7 Cooper PC, Hampton KK, Makris M, Abuzennadah A, Paul B, Preston FE. Further evidence that activated protein C resistance can be misdiagnosed as inherited functional protein S deficiency. Brit J Haematol 1994; 88: 201-202
  • 8 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a presiously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci 1993; 90: 1004-1008
  • 9 Rao AK, Elliott D, Stadnicki A, De-La-Cadena R, Sherry S. High levels of plasma factor VIIIc impair anticoagulant response to activated protein C. Thromb Haemost 1995; 7: 1126
  • 10 Alhenc-Gelas M, Gandrille S, Aubry ML, Emmerich J, Fiessinger JN, Aiach M. Unexplained thrombosis and factor V Leiden mutation. Lancet 1994; 344: 555-556
  • 11 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 344: 1536-1538
  • 12 Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thromboembolism. Thromb Haemost 1995; 74: 449-453
  • 13 Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci 1994; 91: 1396-1400
  • 14 Griffin JH, Heeb MJ, Kojima Y, Fernandez JA, Kojima K, Hackeng T, Greengard JS. Activated Protein C resistance: molecular mechanisms. Thromb Haemost 1995; 74: 444-448
  • 15 Cumming AM, Tait RC, Fildes IS, Yoong A, Keeney S, Hay CRM. Development of resistance to activated protein C during pregnancy. Brit J Haem 1995; 90: 725-727
  • 16 Ehrenforth S, Radtke KP, Scharrer I. Acquired activated protein C-resis-tance in patients with lupus anticoagulant. Thromb Haemost 1995; 74: 797-798
  • 17 Donner M, Siadat M, Stoltz JF. Erythrocyte aggregation, approach by light scattering determination. Biorheology 1988; 43: 77-89
  • 18 Kluft C, Brachman P, Verdhuyzen-Stolk EC. Screening of fibrinolytic activity in plasma euglobulin fractions on the fibrin plate. In : Davidson JF, Samama MM, Desnoyers PC. eds. Progress in chemical fibrinolysis and thrombolysis. New York: Raven Press; 1976. 2 57-65
  • 19 Trossaërt 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: 1709
  • 20 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
  • 21 Shizuka R, Kanda T, Amagai H, Kobayashi I. False-positive activated protein C (APC) sensitivity ratio caused by freezing and by contamination of plasma by platelets. Thromb Res 1995; 189-190