Thromb Haemost 1999; 81(01): 18-21
DOI: 10.1055/s-0037-1614410
Review Article
Schattauer GmbH

APC-resistance Is a Risk Factor for Postoperative Thromboembolism in Elective Replacement of the Hip or Knee – A Prospective Study

Tomas L. Lindahl
1   From the Departments of Clinical Chemistry, University Hospital, Linköping
,
Tom H. Lundahl
2   Västervik Hospital, Västervik, University Hospital, Linköping, Sweden
,
Lennart Nilsson
3   Northern Älvsborg Hospital, Trollhättan, University Hospital, Linköping, Sweden
,
Christer A. Andersson
4   Department of Orthopaedic Surgery, University Hospital, Linköping, Sweden
› Author Affiliations
Further Information

Correspondence to:

Tomas L. Lindahl, MD PhD
Department of Clinical Chemistry
University Hospital
S-58185 Linköping
Sweden
Phone: +46 13 22 32 27   
Fax: +46 13 22 32 40   

Publication History

Received01 April 1998

Accepted after revision08 October 1998

Publication Date:
08 December 2017 (online)

 

Summary

Postoperative venous thromboembolic complications are commonly seen after total replacement of the hip or knee. Recently, an inherited defect with resistance to the anticoagulant activity of activated protein C (APC-resistance) has been detected. APC-resistance seems to be a common risk factor, especially in Sweden, and it increases the propensity for venous thrombosis. This study assesses the prevalence of APC-resistance in a general population and its clinical significance for patients undergoing surgery associated with a high risk of thromboembolic complications. In a prospective cohort study, we analysed for APC-resistance in 645 consecutive patients before elective replacement of the hip or knee at 3 hospitals in southern Sweden. Thromboprophylaxis with LMWH-heparin was given to all patients throughout the hospitalisation period. We recorded events of clinical thromboembolism for 3 months postoperatively. Venography, ultrasonography or pulmonary scintigraphy was requested by the clinicians according to the existing routines, i.e. only patients with symptoms of thromboembolism were examined. A thromboembolic complication was registered in 20 (3.1%) patients. Fifty per cent of the venous thrombi had a proximal location. Only 0.3% of the patients had verified pulmonary embolism. APC-resistance was found in 14.1% of the patients, of whom 9.9% had experienced postoperative thromboembolism compared with 2.0% of the patients without APC-resistance (p <0.0007). We conclude that APC-resistance is a frequent risk factor for symptomatic postoperative deep venous thrombosis with an estimated relative risk of 5.0 (95% confidence interval: from 1.9 to 12.9) in elective replacement of the hip or knee.


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  • References

  • 1 Turpie AGG, Levine MN, Hirsch J. et al A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986; 315: 925-9.
  • 2 Bergqvist D. Review of clinical trials of low molecular weight heparins. Clinical review. Eur J Surg 1992; 158: 67-8.
  • 3 Bergqvist B, Benoni G, Björgell O. et al Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696-700.
  • 4 Dahl O E, Andreassen G, Aspelin T. et al Prolonged thromboprophylaxis following hip replacement surgery – results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin®). Thromb Haemost 1997; 77: 26-31.
  • 5 Planes A, Vochelle N, Darmon JY, Fagola M, Huet Y. Risk of deep venous thrombosis after hospital discharge in patients undergoing total hip replacement. Double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348: 224-8.
  • 6 Lassen MR, Borris LC. on behalf of the Danish Prolonged Thromboprophylaxis Study Group. Prolonged thromboprophylaxis with low molecular weight heparin (Fragmin) after total hip arthroplasty- a placebo-controlled study. Thromb Haemost 1995; 73: 1104.
  • 7 Bergqvist D, Jendteg S, Johansen L, Persson U, Ödegaard K. Cost of long-term complications of the deep venous thrombosis of the lower extremities: An analysis of a defined patient population in Sweden. Ann Inter Med 1997; 126: 454-7.
  • 8 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterized by a poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Nat Acad Sci 1993; 90: 1004-8.
  • 9 Svensson P J, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
  • 10 Bertina RM, Koeleman BPC, 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.
  • 11 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
  • 12 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. J Int Med 1996; 239: 221-6.
  • 13 Svensson PJ, Benoni G, Fredin H, Björgell O, Nilsson P, Hedlund U, Nylander G, Bergqvist D, Dahlbäck B. Female gender and resistance to activated protein C (FV:Q506) as potential risk factors for thrombosis after elective hip arthroplasty. Thromb Haemost 1997; 78: 993-6.
  • 14 Bloemenkamp KWM, Rosendaal FR, Helmerhorst FM, Büller 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: 1593-6.
  • 15 Ridker PM, Hennekens CH, Lindpainter K. et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. New Engl J Med 1995; 332: 912-7.
  • 16 Dahlbäck B, Hillarp A, Rosen S, Zöller B. Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis. Am Hematol 1996; 72: 166-76.
  • 17 Svensson P J, Zöller B, Dahlbäck B. Evaluation of original and modified APC-resistance test in unselected outpatients with clinically suspected thrombosis and in healthy controls. Thromb Haemost 1997; 77: 332-5.
  • 18 In: Altman DG. ed. Practical statistics for medical research, 1st edn. London, UK: Chapman & Hall; 1996: 229-72.
  • 19 Ryan DH, Mark AC, Ginsberg JS, Francis CW. Relation of Factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery. Ann Intern Med 1998; 128: 270-6.

Correspondence to:

Tomas L. Lindahl, MD PhD
Department of Clinical Chemistry
University Hospital
S-58185 Linköping
Sweden
Phone: +46 13 22 32 27   
Fax: +46 13 22 32 40   

  • References

  • 1 Turpie AGG, Levine MN, Hirsch J. et al A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986; 315: 925-9.
  • 2 Bergqvist D. Review of clinical trials of low molecular weight heparins. Clinical review. Eur J Surg 1992; 158: 67-8.
  • 3 Bergqvist B, Benoni G, Björgell O. et al Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696-700.
  • 4 Dahl O E, Andreassen G, Aspelin T. et al Prolonged thromboprophylaxis following hip replacement surgery – results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin®). Thromb Haemost 1997; 77: 26-31.
  • 5 Planes A, Vochelle N, Darmon JY, Fagola M, Huet Y. Risk of deep venous thrombosis after hospital discharge in patients undergoing total hip replacement. Double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348: 224-8.
  • 6 Lassen MR, Borris LC. on behalf of the Danish Prolonged Thromboprophylaxis Study Group. Prolonged thromboprophylaxis with low molecular weight heparin (Fragmin) after total hip arthroplasty- a placebo-controlled study. Thromb Haemost 1995; 73: 1104.
  • 7 Bergqvist D, Jendteg S, Johansen L, Persson U, Ödegaard K. Cost of long-term complications of the deep venous thrombosis of the lower extremities: An analysis of a defined patient population in Sweden. Ann Inter Med 1997; 126: 454-7.
  • 8 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterized by a poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Nat Acad Sci 1993; 90: 1004-8.
  • 9 Svensson P J, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
  • 10 Bertina RM, Koeleman BPC, 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.
  • 11 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
  • 12 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. J Int Med 1996; 239: 221-6.
  • 13 Svensson PJ, Benoni G, Fredin H, Björgell O, Nilsson P, Hedlund U, Nylander G, Bergqvist D, Dahlbäck B. Female gender and resistance to activated protein C (FV:Q506) as potential risk factors for thrombosis after elective hip arthroplasty. Thromb Haemost 1997; 78: 993-6.
  • 14 Bloemenkamp KWM, Rosendaal FR, Helmerhorst FM, Büller 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: 1593-6.
  • 15 Ridker PM, Hennekens CH, Lindpainter K. et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. New Engl J Med 1995; 332: 912-7.
  • 16 Dahlbäck B, Hillarp A, Rosen S, Zöller B. Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis. Am Hematol 1996; 72: 166-76.
  • 17 Svensson P J, Zöller B, Dahlbäck B. Evaluation of original and modified APC-resistance test in unselected outpatients with clinically suspected thrombosis and in healthy controls. Thromb Haemost 1997; 77: 332-5.
  • 18 In: Altman DG. ed. Practical statistics for medical research, 1st edn. London, UK: Chapman & Hall; 1996: 229-72.
  • 19 Ryan DH, Mark AC, Ginsberg JS, Francis CW. Relation of Factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery. Ann Intern Med 1998; 128: 270-6.