Thromb Haemost 2005; 93(04): 694-699
DOI: 10.1160/TH04-11-0723
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation

An 8-year longitudinal comparison with mitral valve replacement and inherited thrombophilia
Paul R. J. Ames
1   Leeds University Teaching Hospitals, Rheumatology, Leeds, United Kingdom
,
Antonio Ciampa
2   Haemostasis Unit, G. Moscati Hospital, Avellino, Italy
,
Maurizio Margaglione
3   Genetics Unit, University of Foggia, Foggia, Italy
,
Giovanna Scenna
4   Haemostasis Unit, A. Cardarelli Hospital, Naples, Italy
,
Luigi Iannaccone
4   Haemostasis Unit, A. Cardarelli Hospital, Naples, Italy
,
Vincenzo Brancaccio
4   Haemostasis Unit, A. Cardarelli Hospital, Naples, Italy
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 07. November 2004

Accepted after revision 10. Januar 2005

Publikationsdatum:
14. Dezember 2017 (online)

Summary

The aimof this studay was to compare bleeding and re-thrombosis in primary antiphospholipid syndrome (PAPS), mitral valve replacement (MVR) and inherited thrombophilia (IT) at different oral anticoagulation intensities. It entailed a prospective 8-year follow-up on 67 patients with PAPS, 89 with IT and 24 with MVR. Anticardiolipin (aCL) antibodies detected by Elisa and lupus anticoagulant by clotting assays. At INR 2–3 minor bleeding rate was higher in MVR (33.3) than PAPS (10.9) and IT (4.2)(p<0.0001). At INR 3–4 minor bleeding rate was higher in PAPS (142) than IT (33.3) and MVR (5.8)(p<0.0001). At either INR major bleeding rate were not significantly different across the three groups, but in PAPS major and minor bleeding rates were superior at INR 3–4 than INR 2–3 (p=0.02 and p<0.0001). Re-thrombosis rate was higher in PAPS than IT at INR 2–3 (4.0 vs 0.35) (p=0.01) and at INR 3–4 (10.5 vs. nil). The hazard ratio for re-thrombosis between PAPS and IT was 13 (95% IC 1.6–102.2, p=0.015). By regression analysis, baseline IgG aCL titre (>80 GPL) (p=0.001) and male sex (p=0.03) independently predicted re-thrombosis. In conclusion, in PAPS, high intensity oral anticoagulation was not superior to conventional intensity in preventing re-thrombosis but was offset by greater bleeding rates. Male sex and elevated baseline IgG aCL predicted re-thrombosis in PAPS that is 13-fold more re-thrombogenic than IT.

 
  • References

  • 1 Rosove MH, Brewer PMC. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992; 117: 303-8.
  • 2 Khamashta MA, Cuadrado MJ, Mujic F. et al. The management of thrombosis in the antiphospholipid syndrome. N Engl J Med 1995; 332: 993-7
  • 3 Ruiz-Irastorza Guillermo, Khamashta MA, Hunt BJ. et al. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome. Analysis of a series of 66 patients treated with oral anticoagulation to a target international normalised ratio of 3.5. Arch Intern Med 2002; 162: 1164-9.
  • 4 Schulman S, Svenungsson E, Grandqvist S. and the Duration of Anticoagulation Study Group. Anticardiolipin antibodies predict early recurrence in thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med 1998; 104: 332-8.
  • 5 Ginsberg JS, Wells PS, Brill-Edwards P. et al. Antiphospholipid antibodies and venous thromboembolism. Blood 1995; 86: 3685-91.
  • 6 Crowther MA, Ginsberg JS, Julian J. et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349: 1133-8.
  • 7 Wilson WA, Gharavi AE, Koike T. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-11.
  • 8 Greaves M, Cohen H, MacHin SJ. et al. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol 2000; 109: 704-15.
  • 9 Brancaccio V, Ames PRJ, Glynn J. et al. A rapid screen for lupus anticoagulant (LA) by comparing a sensitive and insensitive aPTT reagent provides also good discrimination from oral anticoagulants, congenital factor deficiency and heparin. Blood Coagul Fibrinolysis 1997; 8: 155-60.
  • 10 Ames PRJ, Pyke S, Iannaccone L. et al. Antiphospholipid antibodies, haemostatic variables and thrombosis – A survey of 144 patients. Thromb Haemost 1995; 73: 768-73.
  • 11 Meroni PL, Moia M, Derksen RHWM. et al. Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis. Lupus 2003; 12: 504-7.
  • 12 Alarcon-Segovia D, Boffa MC, Branch W. et al. Prophylaxis of the antiphospholipid syndrome: a consensus report. Lupus 2003; 12: 499-503.
  • 13 Ames PRJ, Iannaccone L, Tommasino C. et al. Coagulation activation and fibrinolytic imbalance in subjects with idiopathic antiphospholipid antibodies. A crucial role for acquired free protein S deficiency. Thromb Haemost 1996; 76: 190-4.
  • 14 Cervera R, Piette JC, Font J. et al. Euro Phospholipid Project Group. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019-27.
  • 15 Orlando E, Cortelazzo S, Marchetti M. et al. Prolonged bleeding time in patients with lupus anticoagulant. Thromb Haemost 1992; 68: 495-9.
  • 16 Erkan D, Leibowitz E, Berman J. et al. Perioperative management of antiphospholipid syndrome: hospital for special surgery experience, review of the literature and recommendations. J Rheumatol 2002; 29: 843-9.
  • 17 Madan R, Khoursheed M, Kukla R. et al. The anaesthetist and the antiphospholipid syndrome. Anaesthesia 1997; 52: 72-6.