Resistance to activated protein C (APC) caused by the R506Q mutation in factor V is the most common inherited risk factor for venous thrombosis. To elucidate whether APC-resistance is a risk factor for venous thrombosis after elective total hip replacement, the association between APC-resistance (presence of FV:Q506 allele) and postoperative thrombosis was investigated in patients (n = 198) randomised to received short (during hospitalisation, n = 100) or prolonged prophylaxis (three weeks after hospitalisation, n = 98) with low molecular weight heparin (LMWH). Among APC-resistant individuals receiving short prophylaxis, 7/10 developed thrombosis as compared to 2/12 receiving long prophylaxis (p <0.0179). Odds ratio for association between APC-resistance and thrombosis in the short prophylaxis group was 4.2 (CI 95% 1.02-17.5) (p <0.0465). Among those receiving prolonged, prophylaxis, there was no increased incidence of thrombosis associated with APC-resistance. Two unexpected observations were made. One was that APC-resistance was much more common in women (19/109) than in men (3/89) (p <0.001). The other was that even women without APC-resistance were much more thrombosis-prone than men. Thus, 24/48 of women with normal FV genotype and short prophylaxis developed thrombosis vs 8/42 among men, p = 0.002. The increased risk of thrombosis associated with female gender and APC-resistance was neutralised by the prolonged treatment. In conclusion, among patients receiving short prophylaxis, female gender was found to be a strong risk factor for venous thrombosis. Even though APC-resistance appeared to be a risk factor for postoperative thrombosis, the uneven distribution of APC-resistance between men and women, taken together with the increased risk of thrombosis among women, precluded valid conclusions to be drawn about the association between APC-resistance and an increased risk of thrombosis. Our results suggest that prolonged prophylaxis with LMWH after hip surgery is more important for women than for men.
References
1
Bergqvist D.
Postoperative thromboembolism. Frequency, etiology, prophylaxis. Berlin, Heidelberg, New York: Springer-Verlag; 1983
4
Zimlich RH,
Fulbright BM,
Friedman RJ.
Current status of anticoagulation therapy after total hip and total knee arthroplasty. J Am Acad Orthop Surg 1996; 04: 54-62
5
Green D,
Hirsh J,
Heit J,
Prins M,
Davidson B,
Lensing AW A.
Low molecular weight heparin: A critical analysis of clinical trials. Pharmacol Rev 1994; 46: 089-109
6
Bergqvist D,
Benoni G,
Bjӧrgell O,
Fredin H,
Hedlundh U,
Nicolas S,
Nilsson P,
Nylander G.
Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696-700
7
Dahlbäck B,
Carlsson M,
Svensson PJ.
Familial thrombofilia 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
9
Koster T,
Rosendaal FR,
de RondeF,
Briët E,
Vandenbroucke JP,
Bertina RM.
Venous thrombosis due to poor response to activated protein C: Leiden thrombofilia study. Lancet 1993; 342: 1503-1506
11
Dahlback B,
Hillarp A,
Rosen S,
Zoller B.
Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis. Ann Hematol 1996; 72: 166-176
12
Bertina RM,
Koeleman BPC,
Koster T,
Rosendaal FR,
Dirven RJ,
de RondeH,
van der VeldenPA,
Reitsma PH.
Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
13
Zӧller B,
Svensson PJ,
He X,
Dahlbäck B.
Identification of the same factor V mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521-2524
14
Planes A,
Vochelle N,
Darmon JY,
Fagola M,
Bellaud M,
Huet Y.
Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348: 224-228
15
Crowther MA,
Hayward CPM,
Hamid C,
Johnston M,
Gent M,
Levine M,
Hirsh J,
Ginsberg J.
Activated protein C resistance is not associated with postoperative deep vein thrombosis in patients undergoing hip or knee surgery. Blood. 1995 616. abstract.
16
Faunø P,
Ravn HB,
Lassen JF,
Lund ED,
Jensen J.
Association between activated protein C resistance and postoperative deep vein thrombosis. Thromb Haemost 1995; 73, 1370 abstract.