Lupus anticoagulant–hypoprothrombinemia syndrome associated with systemic lupus erythematosus: report of 2 cases and review of literature

Abstract

We describe two patients whose initial presentation of systemic lupus erythematosus (SLE) was accompanied by haemorrhagic episodes and significant coagulopathy. Further investigation demonstrated positive lupus anticoagulant and decreased Factor II (prothrombin) activity. Both patients were diagnosed with lupus anticoagulant–hypoprothrombinemia syndrome (LAC–HPS) as a result of non-neutralizing antibodies directed against Factor II. LAC–HPS is a rare clinical entity that can occur in association with SLE, transient viral infections, drug reactions or even in healthy individuals. Mixing studies, which can be affected by other coagulation factor inhibitors, play an important role in the diagnosis of LAC–HPS. Factor VII level was decreased in the second patient, a finding that has not previously been reported in association with SLE. In both patients, bleeding stopped promptly and coagulation studies improved significantly with high dose corticosteroids. We discuss the pathogenesis, diagnosis and management of LAC–HPS in patients with SLE.

Keywords

lupus anticoagulant–hypoprothrombinemia syndrome systemic lupus erythematosus coagulation factor inhibitors

Get full access to this article

View all access options for this article.

References

Sammaritano LR . Update: antiphospholipid antibodies . J Clin Rhuem 1997; 3: 270–278

Peacock NW , Levine SP . A case report: the lupus anticoagulant–hypoprothrombinemia syndrome . Am J Med Sci 1994; 307: 346–349 .

Scott-Timperley LJ , Haire WD . Autoimmune coagulation disorders. In: Dudlick B (ed) Rheum Dis Clin North Am. W.B. Saunders Company: Philadelphia , 1997; 23(2): pp 411–423.

Bernini JC , Buchanan GR , Ashcraft J . Hypoprothrombinemia and severe hemorrhagia associated with lupus anticoagulant . J Pediatr 1993; 123: 937–939 .

Rapaport SI , Ames SB , Duvall BJ . A plasma coagulation defect in systemic lupus erythematosus arising from hypoprothrombinemia combined with antiprothrombinase activity . Blood 1960; 15: 212–227 .

Perkins HA , Acra DJ . The circulating anticoagulant in disseminated lupus erythematosus . Thromb Diath Haemorrh 1961; 5: 250–255 .

Biggs R , Denson KWE . The mode of action of a coagulation inhibitor in the blood of two patients with disseminated lupus erythematosus . Br J Haematol 1964; 10: 198–216 .

Gonyea L , Herdman R , Bridges RA . The coagulation abnormalities in systemic lupus erythematosus . Thromb Diath Haemorrh 1968; 20: 457–464 .

Corrigan JJ , Patterson JH , May NE . Incoagulability of the blood in systemic lupus erythematosus: A case due to hypoprothrombinemia and a circulating anticoagulant . Am J Dis Child. 1970; 119: 365–369 .

10.

Natelson EA , Cyprus GS , Heltig RA . Absent factor II in systemic lupus erythematosus: Immunologic studies and response to corticosteroid therapy . Arthritis Rheum 1976; 19: 79–82 .

11.

Lillquist KB , Dyerberg J , Krogh-Jensen M . The absence of Factor II in a child with systemic lupus erythematosus . Acta Paediatr Scand 1978; 67(4): 533–536 .

12.

Shaulian E , Shoenfeld Y , Berliner S et al. Surgery in patients with circulating lupus anticoagulant . Int Surg 1981; 66(2): 157–159 .

13.

Bajaj SP , Rapaport SI , Fierer DS et al. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome . Blood 1983; 61: 684–692 .

14.

Schwartz S , Esseltine DW . Postextraction haemorrhage in a young male patient with systemic lupus erythematosus . Oral Surg 1984; 57(3): 254–257 .

15.

Small P . Severe hemorrhage in a patient with circulating anticoagulant, acquired hypoprothrombinemia and systemic lupus erythematosus . Arthritis Rheum 1988; 31(9): 1210–1211 (letter).

16.

Hift RJ , Bird AR , Sarembock BD . Acquired hypoprothrombinemia and lupus anticoagulant . Br J Rheum 1991; 30(4): 308–310 .

17.

Eberhard A , Sparling C , Sudbury S et al. Hypoprothrombinemia in childhood systemic lupus erythematosus . Semin Arthrits Rheum 1994; 24: 12–18 .

18.

Grau E , Real E , Pastor E et al. Prothrombin deficiency and haemorrhage with lupus anticoagulant . Am J Hematol 1997; 54(1): 85–85 (letter).

19.

Vivaldi P , Rosetti G , Galli M , Finazzi, G . Severe bleeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome . Case report and review of literature. Haematologica 1997; 82: 345–347 .

20.

Hudson N , Duffy CM , Rauch J et al. Catastrophic haemorrhage in a case of paediatric primary antiphospholipid syndrome and factor II deficiency . Lupus 1997; 6(1): 68–71 .

21.

Tan EM , Cohen AS , Fries JF et al. he 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

22.

Shapiro S , Long M . Hematology: coagulation problems. In: Lahita RG (ed) Systemic Lupus Erythematosus. San Diego: Academic Press , 1999; pp 871–885.

23.

Bajaj SP , Rapaport SI , Barclay S , Herbst K . Acquired hypoprothrombinemia due to nonneutralizing antibodies to prothrombin: Mechanism and management . Blood 1985; 65: 1538–1543 .

24.

Edson JR , Vogt JM , Hasegawa DK . Abnormal prothrombin crossedimmunoelectrophoresis in patients with lupus inhibitors . Blood 1984; 64: 807–816 .

25.

Fleck RA , Rapaport SI , Roa LVM . Anti-prothrombin antibodies and the lupus anticogulant . Blood 1988; 72: 512–519 .

26.

Roubey RA . Mechanisms of autoantibody-mediated thrombosis . Lupus 1998; 7 (Suppl) 2: S114–S119 .

27.

Schleider MA , Nachman RI , Jaffe EA , Coleman A . A clinical study of the lupus anticoagulant . Blood 1976 48: 499–509 .

28.

Horellou MH , Aurousseau MH , Boffa MC et al. Biological and clinical heterogenity of lupus and lupus like anticogulant in fifty-seven patients . J Med 1987; 18: 199–217 .

29.

Simel D, St . Claire EW , Adams J , Greenberg C . Correction of hypothrombinemia by immunosuppressive treatment of lupus antic-oagulant-hypoprothrombinemia syndrome . Am J Med 1987; 83: 563–566 .

30.

Campbell E , Sanal S , Mattson J et al. Factor VII inhibitor . Am J Med 1980; 68: 962–964 .

31.

Gladman DD , Hochberg MC . Epidemiology of systemic lupus erythematosus. In: Lahita RG (ed) Systemic Lupus Erythematosus. San Diego: Academic Press , 1999, pp 537–550.