Download PDF
Thromb Haemost 1998; 79(03): 567-570
DOI: 10.1055/s-0037-1614946
Review Articles
Schattauer GmbH

Sensitivity, Specificity and Predictive Value of Modified Assays for Activated Protein C Resistance in Children

Greg Brandt
1   The Division of Hematology/Oncology, S. Illinois University School of Medicine, Springfield, Illinois
,
Ralph Gruppo
2   The Division of Hematology/Oncology, Children’s Hospital Medical Center, Cincinnati, Ohio
,
Charles J. Glueck
3   The Cholesterol Center Jewish Hospital, Cincinnati, Ohio, USA
,
Davis Stroop
2   The Division of Hematology/Oncology, Children’s Hospital Medical Center, Cincinnati, Ohio
,
Ann Becker
2   The Division of Hematology/Oncology, Children’s Hospital Medical Center, Cincinnati, Ohio
,
Ann Pillow
2   The Division of Hematology/Oncology, Children’s Hospital Medical Center, Cincinnati, Ohio
,
Ping Wang
3   The Cholesterol Center Jewish Hospital, Cincinnati, Ohio, USA
› Author Affiliations
Further Information

Publication History

Received 18 April 1997

Accepted after resubmission 31 October 1997

Publication Date:
07 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Very little data is available assessing the clinical utility of coagulation-based APC resistance assays compared to DNA-based analysis for the factor V Leiden mutation in children. Therefore, the clinical utility of four aPTT-based assays for APC resistance was evaluated in 169 children, ages 3 months through 16 years. The prevalence of the Arg506 to Gln mutation was 7/169 (4.1%). Using cutoff points derived from the normal PCR-screened population (n = 162), two assays for APC resistance (APC-SR and n-APC-SR) gave poor concordance with the PCR assay (sensitivity 29% and 57%, respectively). Two modified assays (FDAPC-SR and n-FDAPC-SR), in which patient plasma was prediluted 1:5 in factor V deficient plasma, gave excellent concordance (sensitivity 100%). The predictive value of a positive test was 0.25, 0.44, 1.00 and 0.88 for the APC-SR, n-APC-SR, FDAPC-SR and n-FDAPC-SR, respectively. The FDAPC-SR and n-FDAPC-SR tests gave excellent discrimination using cutoff values derived from the total population (n = 169) without regard to previous PCR screening results.

 

  • 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: 1004-8.
    CrossrefPubMedGoogle Scholar
  • 2 Bertina RM, Koeleman BPC, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
    CrossrefPubMedGoogle Scholar
  • 3 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: 449-53.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Zenz W, Muntean W, Gallistl S, Leschnik B, Beitzke A. Inherited resistance to activated protein C in a boy with multiple thromboses in early infancy. Eur J Pediatr 1995; 154: 285-8.
    CrossrefPubMedGoogle Scholar
  • 5 Kodish E, Potter C, Kirschbaum NE, Foster PA. Activated protein C resistance in a neonate with venous thrombosis. J Pediatr 1995; 127: 645-8.
    CrossrefPubMedGoogle Scholar
  • 6 Zöller B, He X, Dahlbäck B. Homozygous APC-resistance combined with inherited type I protein S deficiency in a young boy with severe thrombotic disease. Thromb Haemost 1995; 73: 743-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Nowak-Gottl U, Koch HG, Aschka I, Kohlhase B, Vielhaber H, Kurle-mann G, Oleszcuk-Raschke K, Kehl HG, Jurgens H, Schneppenheim R. Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism. Br J Haematol 1996; 92: 992-8.
    CrossrefPubMedGoogle Scholar
  • 8 Pipe SW, Schmaier AH, Nichols WC, Ginsburg D, Bozynski ME, Castle VP. Neonatal purpura fulminans in association with factor V R506Q mutation. J Pediatr 1996; 128: 706-9.
    CrossrefPubMedGoogle Scholar
  • 9 Glueck CJ, Brandt G, Gruppo R, Crawford A, Roy D, Tracy T. et al. Resistance to activated protein C and Legg-Perthes disease. Clin Orthop. 1997 in press.
    PubMedGoogle Scholar
  • 10 Rosen S, Johansson K, Lindbery K, Dahlbäck B. (for the APC resistance study group). Multicenter evaluation of a kit for activated protein C resistance on various coagulation instruments using plasma from healthy individuals. Thromb Haemost 1994; 72: 255-60.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 de Ronde H, Bertina RM. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Dahlbäck B. Resistance to activated protein C, the Arg 506 to Gln mutation in the factor V gene, and venous thrombosis: functional tests and DNA-based assays, pros and cons. Thromb Haemost 1995; 73: 739-42.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Ehrenforth S, Radtke KP, Scharrer I. Acquired activated protein C-resistance in patients with lupus anticoagulant. Thromb Haemost 1995; 74: 797-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Jorquera JI, Montoro JM, Fernandez MA, Aznar JA, Aznar J. Modified test for activated protein C resistance. Letters to the Editor. Lancet 1994; 344: 1162-3.
    PubMedGoogle Scholar
  • 15 Dahlbäck B. Modified APC-resistance test offers increased sensitivity and specificity for the FV:Q506 allele. Letter to the Editor. Thromb Haemost 1995; 74: 1380-1.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Engel H, Zwang L, van Vliet HHDM, Michiels JJ, Stibbe J, Lindermans J. Phenotyping and genotyping of coagulation factor V Leiden. Thromb Haemost 1995; 75: 267-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80: 1998-2005.
    PubMedGoogle Scholar
  • 18 Nowak-Göttl U, Kohlhase B, Vielhaber H, Aschka I, Schneppenheim R, Jüngens H. APC resistance in neonates and infants: adjustment of the APTT-based method. Thromb Res 1996; 81: 665-70.
    CrossrefPubMedGoogle Scholar
  • 19 Lindblom B, Holmlund G. Rapid DNA purification for restriction fragment length polymorphism analysis. Gene Anal Tech 1988; 5: 97-101.
    CrossrefPubMedGoogle Scholar
  • 20 Jenny RJ, Pittman DD, Toole JJ, Kriz RW, Aldape RA, Hewick RM. et al. Complete DNA and derived amino acid sequence of human factor V. Proc Nat Acad Sci USA 1987; 84: 4846-50.
    CrossrefPubMedGoogle Scholar
  • 21 Koeleman PC, Reitsma PH, Allart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C deficient families. Blood 1994; 84: 1031-5.
    PubMedGoogle Scholar