To assess retrospectively three antithrombotic treatments in the secondary prevention of thrombosis in the antiphospholipid syndrome (APS), 23 patients (six systemic lupus erythematosus, seven lupus-like disease and 10 primary antiphospholipid syndrome) were included in this study. Treatments assessed were: (1) aspirin 75 mg daily, (2) warfarin (international normalised ratios (INRs) 2.0-2.9) ± aspirin 75 mg daily, and (3) warfarin (INRs > 2.9) ± aspirin 75 mg daily. Where patients had received two or three of these treatments successively, the periods of time on each treatment were added and the number of patients with recurrence(s) on each treatment were compared by Fisher's exact probability test.
'High' anticoagulation (INRs > 2.9) ± aspirin 75 mg daily was more effective than aspirin 75 mg daily in preventing further thromboembolic events (P = 0.0053). In addition, when comparing 'high' anticoagulation ± aspirin 75 mg daily versus 'low' anticoagulation (INRs 2.0-2.9) ± aspirin 75 mg daily, there was a trend in favour of 'high' anticoagulation (P = 0.066). No statistically significant difference could be demonstrated when comparing 'low' anticoagulation ± aspirin 75 mg daily with aspirin 75 mg daily (P = 0.092).
These results suggest that aggressive anticoagulation with or without low-dose aspirin is effective in preventing further thromboembolic events in APS.
Hughes Grv.The antiphospholipid syndrome: ten years on. Lancet1993; 342: 341-4.
2.
Harris EN, Baguley E., Asherson RA, Hughes Grv.Clinical and serological features of the antiphospholipid syndrome (APS). Br J Rheumatol1987; 26(Suppl. 2): 19 (abstract).
3.
Asherson RA, Khamashta MA, Ordi-Ros J. et al. The 'primary' antiphospholipid syndrome: major clinical and serological features. Medicine1989; 89: 366-74.
Mackworth-Young CG, Loizou S., Walport MJPrimary antiphospholipid syndrome: features of patients with raised anticardiolipin antibodies and no other disorder. Ann Rheum Dis1989; 48: 362-7.
6.
Love PE, Santoro SAAntiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders: prevalence and clinical significance. Ann Intern Med1990 ; 112: 682-98.
7.
Alarcon-Segovia D., Delezé M., Oria CV et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine1989 ; 68: 353-65.
8.
Asherson RA, Khamashta MA, Gil A. et al. Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease and the primary antiphospholipid syndrome . Am. J. Med1989; 86: 391-9.
9.
Briley DP, Coull BM, Goodnight SHNeurological disease associated with antiphospholipid antibodies. Ann Neurol1989; 25: 221-7.
10.
Levine SR, Brey RL, Joseph Clm, Havstad S., APASS Group. Risk of recurrent thromboembolic events in patients with focal cerebral ischemia and antiphospholipid antibodies. Stroke1992; 23(Suppl. I): I-29-I-32.
11.
Levine SR, Syhnggwon K., Deegan MJ, Welch Kma.Ischemic stroke associated with anticardiolipin antibodies. Stroke1987; 18: 1101-6.
12.
Levine RL, Deegan MJ, Futrell N., Welch Kma.Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases. Neurology1990; 40: 1181-9.
13.
Ford PM, Brunet D., Lillicarp DP, Ford SEPremature stroke in a family with lupus anticoagulatn and antiphospholipid antibodies. Stroke1990; 21: 66-71.
14.
The APASS Group. Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia. Stroke1990; 21: 1268-73.
15.
Kushner MJProspective study of anticardiolipin antibodies in stroke. Stroke1990; 21: 295-8.
16.
Coull BM, Goodnight SHAntiphospholipid antibodies, prethrombotic states and stroke. Stroke1990; 25: 13-18.
17.
Harris EN, Gharavi AE, Asherson RA, Boey ML, Hughes Grv.Cerebral infarction in systemic lupus: association with anticardiolipin antibodies . Clin Exp Rheumatol1984; 2: 47-51.
18.
Montalban J. , Codina A., Ordi J. et al. Antiphospholipid antibodies in cerebral ischemia. Stroke1991 ; 22: 750-3.
19.
Williams RCCerebral infarction in systemic lupus: association with anticardiolipin antibodies. Clin Exp Rheumatol1984; 2: 3-4.
20.
Piette JC, Wechsler B., Blétry O., Frances C.Approche clinique du syndrome des antiphospholipides: des faits aux interrogations . La Presse Médicale1992; 21: 2081-4.
21.
Lockshin MDWhich patients with antiphospholipid antibody should be treated and how?Rheum Dis North Am1993; 19: 235-47.
22.
Khamashta MA , Wallington T.Management of the antiphospholipid syndrome . Ann Rheum Dis1991; 50: 959-62.
23.
Babikian VL , Levine SRTherapeutic considerations for stroke patients with antiphospholipid antibodies. Stroke1992 ; 23(Suppl. I): I-33-I-37.
24.
Exner T., Rickard KA, Kronenberg H.Studies on phospholipids in the action of a lupus coagulation inhibitor . Pathology1975; 7: 319-28.
25.
Gharavi AE, Harris EN, Asherson RA et al. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis1987; 46: 1-6.
26.
Harris EN, Gharavi AE, Patel SP et al. Evaluation of the anticardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol1987; 68: 2115-22.
27.
Whisnant JPSpecial report from the National Institute of Neurologic Disorder and Stroke. Classification of cerebrovascular diseases. III. Stroke1990; 21: 637-76.
28.
McNeil HP, Chesterman CN, Krilis SAImmunology and clinical importance of antiphospholipid antibodies . Adv Immunol1991; 49: 193-279.
29.
Alarcon-Segovia D., Perez-Vazquez ME, Villa AR, Drenkard C., Cabiedes J.Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum1992; 21: 275-86.
30.
Kittner SJ, Gorelick PBAntiphospholipid antibodies and stroke: an epidemiologic perspective . Stroke1992; 23(Suppl. I): I-19-I-22.
31.
Hess DCStroke associated with antiphospholipid antibodies. Stroke1992; 23(Suppl. I): I-23-I-28.
32.
Brey RL, Hart RG, Sherman DG, Tegeler CHAntiphospholipid antibodies and cerebral ischemia in young people . Neurology1990; 40: 1190-6.
33.
Levine SR, Welch Kma.The spectrum of neurologic disease associated with antiphospholipid antibodies. Lupus anticoagulatns and anticardiolipin antibodies. Arch Neurol1987; 44: 876-83.
34.
Ginsburg KS , Liang MH, Newcomer L. et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med1992; 117: 997-1002.
35.
Bakimner R. , Fishman P., Blank M. et al. Induction of antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3) . J Clin Invest1992; 89: 1558-63.
Ingram SB, Goodnight SH, Benett RMAn unusual syndrome of a devastating noninflammatory vasculopathy associated with anticardiolipin antibodies: report of two cases. Arthritis Rheum1987; 30: 1167-72.
38.
Smith KJ, Skelton HG, James WD et al. Cutaneous histopathologic findings in 'antiphospholipid syndrome'. Correlation with disease, including human immunodeficiency virus disease. Arch Dermatol1990; 126: 1176-83.
39.
Reyes E., Alarcon-Segovia D.Leg ulcers in the primary antiphaspholipid syndrome. Report of a case with a peculiar proliferative small vessel vasculopathy. Clin Exp Rheumatol1991; 9: 63-6.
40.
Bowles CAVasculopathy associated with the antiphospholipid antibody syndrome . Rheum Dis North Am1990; 16: 471-89.
41.
Lie JTVasculopathy in the antiphospholipid syndrome: thrombosis or vasculitis, or both?J Rheumatol1989; 16: 713-15.
42.
Harris ENAn acute disseminated coagulopathy-vasculapathy associated with the antiphospholipid syndrome. Arch Intern Med1991 ; 151: 231-3.
Barbut D., Borer JS, Wallerson D. et al. Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events. Cardiology1991; 79: 99-109.
45.
Nardone Soscia P, Romain PLAntiphospholipid antibodies: is there a role in cardiac valvular disease and its thromboembolic complications?Cardiology1992; 80: 1-6.
46.
Eber B.Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events. Cardiology1992; 80: 156.
47.
Rosove MH, Brewer Pmc.Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med1992; 117: 303-8.
48.
Landi G., Calloni MV, Sabbadini MG et al. Recurrent ischemic attacks in two young adults with lupus anticoagulant . Stroke1983; 14: 377-9.
49.
Fischer M., McGehee W.Cerebral infarct, TIA and lupus inhibitor. Neurology1986; 36: 1234-7.
50.
Young SM, Fischer M., Sigsbee A., Erichetti A.Cardiogenic brain embolism and lupus anticoagulant. Ann Neurol1989; 26: 390-2.
51.
Pope JM, Canny Clb, Bell DACerebral ischemic events associated with endocarditis, retinal vascular disease and lupus anticoagulant. Am J Med1991; 90: 299-309.
52.
Asherson RA , Baguley E., Pal C., Hughes Grv.Antiphospholipid syndrome: five year follow-up . Ann Rheum Dis1991; 50: 805-10.
53.
Asherson RA , Chan Jkh, Harris EN et al. Anticardiolipin antibody, recurrent thrombosis and warfarin withdrawal. Ann Rheum Dis1985; 44: 823-5.
54.
DerksenRHWM, de Groot PG, Kater L, Nieuwenhuis HK. Patients with antiphospholipid antibodies and venous thrombosis should receive long-term anticoagulant treatment . Ann Rheum Dis1993; 52: 689-92.
Hull R., Hirsh J., Jay R. et al. Different intensities of oral anticoagulant therapy in the treatment of proximal vein thrombosis. New Engl J Med1982; 307: 1676-81.
57.
Gerstmann BB , Piper JM, Tomita DK et al. Oral contraceptive estrogen dose and the risk of deep vein thromboembolic disease. Am J Epidemiol1991; 133: 32-7.
