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Thromb Haemost 1999; 81(04): 532-537
DOI: 10.1055/s-0037-1614519
Rapid Communication
Schattauer GmbH

Activated Protein C Resistance (FV:Q506) and Pregnancy

Pelle G. Lindqvist
1   From the Departments of Obstetrics and Gynecology, or Lund, Sweden
,
Peter J. Svensson
2   Department of Medicine, or Lund, Sweden
4   Department of Coagulation Disorders, Lund University, University Hospital, Malmö, or Lund, Sweden
,
Karel Maršál
3   From the Departments of Obstetrics and Gynecology, or Lund, Sweden
,
Lars Grennert
1   From the Departments of Obstetrics and Gynecology, or Lund, Sweden
,
Marie Luterkort
5   Slottsstaden Group Practice. Malmö, Sweden
,
Björn Dahlbäck
4   Department of Coagulation Disorders, Lund University, University Hospital, Malmö, or Lund, Sweden
› Institutsangaben
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Publikationsverlauf

Received 07. August 1998

Accepted after revision 08. Januar 1999

Publikationsdatum:
09. Dezember 2017 (online)

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Summary

Activated protein C (APC) resistance, due to a point mutation in the factor V gene (FV:Q506), is a major risk factor for venous thromboembolism. To determine the prevalence of APC resistance in a large series of pregnant women, and to elucidate its obstetric consequences, we performed a prospective study in Malmö, Sweden, comprising 2,480 women enrolled in early pregnancy. The presence of APC resistance (the FV:Q506 allele) was determined. The women were interviewed about their medical histories including venous thromboembolic events (VTE) in relatives. The outcome variables were the VTE rate, intrapartum blood loss, and the prevalence of selected pregnancy complications such as fetal loss, pre-eclampsia, and intrauterine growth retardation.

The overall prevalence of APC resistance was 11% (270/2480). The APC-resistant subgroup did not differ significantly from the non-APC-resistant subgroup in terms of pregnancy complications, but was characterized by an 8-fold higher risk of VTE (3/270 vs. 3/2210), a lower rate of profuse intrapartum haemorrhage (3.7% vs. 7.9%) (p = 0.02), and less intrapartum blood loss (340 ml vs. 361 ml) (p = 0.04). Despite the high prevalence of APC resistance in this series of gravidae (11%), its presence was unrelated to adverse pregnancy outcome apart from an 8-fold increased risk of VTE.

 

  • References

  • 1 Redman CW. Current topic: pre-eclampsia and the placenta. Placenta 1991; 12: 301-8.
    CrossrefPubMedGoogle Scholar
  • 2 Weiner CP, Brandt J. Plasma antithrombin III activity: an aid in the diagnosis of preeclampsia-eclampsia. Am J Obstet Gynecol 1982; 142: 275-81.
    CrossrefPubMedGoogle Scholar
  • 3 Sanson BJ, Friederich PW, Simioni P, Zanardi S, Hilsman MV, Girolami A, ten Cate JW, Prins MH. The risk of abortion and stillbirth in antithrombin-, protein C-, and protein S-deficient women. Thromb Haemost 1996; 75: 387-8.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 4 Rai R, Regan L, Hadley E, Dave M, Cohen H. Second-trimester pregnancy loss is associated with activated C resistance. Br J Haematol 1996; 92: 489-90.
    PubMedGoogle Scholar
  • 5 Dizon Townson DS, Nelson LM, Easton K, Ward K. The factor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol 1996; 175: 902-5.
    CrossrefPubMedGoogle Scholar
  • 6 Brenner B, Mandel H, Lanir N, Younis J, Rothbart H, Ohel G, Blumenfeld Z. Activated protein C resistance can be associated with recurrent fetal loss. Br J Haematol 1997; 97: 551-4.
    CrossrefPubMedGoogle Scholar
  • 7 Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, Font-cuberta J, Makris M, Mariani G, Noteboom W, Pabinger I, Legnani C, Scharrer I, Schulman S, van der Meer FJ. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348: 913-6.
    CrossrefPubMedGoogle Scholar
  • 8 Grandone E, Margaglione M, Colaizzo D, d’Addedda M, Cappucci G, Vecchione G, Scianname N, Pavone G, Di Minno G. Factor V Leiden is associated with repeated and recurrent unexplained fetal losses. Thromb Haemost 1997; 77: 822-4.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 9 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulantresponse to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
    CrossrefPubMedGoogle Scholar
  • 10 Dahlbäck B. Inherited thrombophilia: resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood 1995; 85: 607-14.
    PubMedGoogle Scholar
  • 11 Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis [see comments]. N Engl J Med 1994; 330: 517-22.
    CrossrefPubMedGoogle Scholar
  • 12 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: 64-7.
    CrossrefPubMedGoogle Scholar
  • 13 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. Br J Haematol 1994; 344: 694-5.
    PubMedGoogle Scholar
  • 14 Emmerich J, Poirier O, Evans A, Marques Vidal P, Arveiler D, Luc G, Aiach M, Cambien F. Myocardial infarction, Arg 506 to Gln factor V mutation, and activated protein C resistance. Lancet 1995; 345: 321
    CrossrefPubMedGoogle Scholar
  • 15 Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-7.
    CrossrefPubMedGoogle Scholar
  • 16 Catto A, Carter A, Ireland H, Bayston TA, Philippou H, Barrett J, Lane DA, Grant PJ. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler Thromb Vasc Biol 1995; 15: 783-5.
    CrossrefPubMedGoogle Scholar
  • 17 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
    CrossrefPubMedGoogle Scholar
  • 18 Holm J, Zöller B, Berntorp E, Erhardt L, Dahlbäck B. Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries. Journal of internal Medicine 1996; 239: 221-26.
    CrossrefPubMedGoogle Scholar
  • 19 Zöller B, Norlund L, Leksell H, Nilsson JE, von Schenck H, Rosen U, Jeps-son JO, Dahlbäck B. High prevalence of the FVR506Q mutation causing APC resistance in a region of southern Sweden with a high incidence of venous thrombosis [letter]. Thromb Res 1996; 83: 475-7.
    CrossrefPubMedGoogle Scholar
  • 20 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: 210-3.
    CrossrefPubMedGoogle Scholar
  • 21 Bokarewa I M, Bremme K, Blombäck M. Arg506-Gln mutation in factor V and risk of thrombosis during pregnancy. Br J Haematol 1996; 92: 473-8.
    CrossrefPubMedGoogle Scholar
  • 22 Lindqvist P, Svensson P, Dahlbäck B, Marsal K. Factor V Q506 Mutation (activated protein C resistance) associated with reduced intrapartum blood loss – a possible evolutionary selection mechanism. Thromb Haemost 1998; 79: 69-73.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 23 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-8.
    CrossrefPubMedGoogle Scholar
  • 24 Svensson PJ, Zöller B, Dahlbäck B. Evaluation of original and modified APC-resistance tests in unselected outpatients with clinically suspected thrombosis and in healthy controls. Thromb Haemost 1997; 77: 332-5.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 25 International classification of diseases, ninth revision (ICD-9). World Health organization Geneva: 1976
    Google Scholar
  • 26 Marsál K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr 1996; 85: 843-8.
    CrossrefPubMedGoogle Scholar
  • 27 Thorp JA, Zucker ML, Plapp FV, Rachael JM, Hinkle C. Factor V Leiden Gene Mutation and Preeclampsia. Matern Fetal Invest 1997; 7: 19-20.
    PubMedGoogle Scholar
  • 28 Bergqvist ÅBergqvist D, Hallbook T. Deep vein thrombosis during pregnancy. A prospective study. Acta Obstet Gynecol Scand 1983; 62: 443-8.
    CrossrefPubMedGoogle Scholar
  • 29 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
    PubMedGoogle Scholar
  • 30 Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) [see comments] . Blood 1995; 85: 1504-8.
    PubMedGoogle Scholar
  • 31 Hirsch DR, Mikkola KM, Marks PW, Fox EA, Dorfman DM, Ewenstein BM, Goldhaber SZ. Pulmonary embolism and deep venous thrombosis during pregnancy or oral contraceptive use: prevalence of factor V Leiden. Am Heart J 1996; 131: 1145-8.
    CrossrefPubMedGoogle Scholar
  • 32 Greer IA. Epidemiology, risk factors and prophylaxis of venous thrombo-embolism in obstetrics and gynaecology. In Thrombo-embolic Disease in Obstetrics and Gynaecology. Greer IA. editor. Baillière Tindall; London: 1997. pp 403-30.
    Google Scholar
  • 33 Walker ID. Congenital thrombophilia. In Thrombo-embolic Disease in Obstetrics and Gynaecology. Greer IA. editor Baillière Tindall; London: 1997. pp 431-45.
    Google Scholar
  • 34 Dahlbäck B. Resistance to activate protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons [see comments]. Thromb Haemost 1995; 73: 739-42.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 35 Faioni EM, Razzari C, Martinelli I, Panzeri D, Franchi F, Mannucci PM. Resistance to activated protein C in unselected patients with arterial and venous thrombosis. Am J Hematol 1997; 55: 59-64.
    CrossrefPubMedGoogle Scholar
  • 36 Altes A, Souto JC, Mateo J, Borrell M, Fontcuberta J. Activated protein C resistance assay when applied in the general population. Am J Obstet Gynecol 1997; 176: 358-9.
    CrossrefPubMedGoogle Scholar
  • 37 Vandenbroucke JP, van der Meer FJ, Helmerhorst FM, Rosendaal FR. Factor V Leiden: should we screen oral contraceptive users and pregnant women?. BMJ 1996; 313: 1127-30.
    CrossrefPubMedGoogle Scholar