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PREGNANCY OUTCOME IN WOMEN WITH AN ANTIPHOSPHOLIPID
ANTIBODY NEGATIVE ANTIPHOSPHOLIPID-SYNDROME(1)
OBJECTIVE: To characterize the reproductive outcome of women who have clinical features of the antiphospholipid syndrome but lack anticardiolipin antibodies (aCL) and lupus anticoagulant (LA).
STUDY DESIGN: The study group consists of 12 women who had experienced a thrombotic episode and at least one fetal death (Group 1) and 50 with at least two unexplained recurrent midtrimester fetal deaths (Group2). All patients tested negative for IgG and IgM aCL, LA, Protein C, Protein S, and Antithrombin III.
RESULTS: The patients in Group 1 had 19 separate thrombotic episodes including 11 DVTs, 6 pulmonary emboli, 1 CVA, and 1 arterial thrombosis. One woman also had autoimmune thrombocytopenia. Of 56 pregnancies, 16 (29%) were first trimester losses, 19 (34%) ended with fetal death, and 21 (37%) were live births. Those in Group 2 had 322 pregnancies including 77 fetal deaths (40.4%) and 95 (29.5%) live births.
CONCLUSIONS: The rates of pregnancy loss were similar to those in patients with antiphospholipid antibodies (aPL). These data raise the possibility that aPL are markers, not always present, for an as yet undiagnosed condition. The poor pregnancy outcome in these women, as well as their apparently high risk for thrombosis, call for a prospective exclusion of anticoagulant therapy.
COMMENT: A requirement for the diagnosis of the antiphospholipid syndrome is the presence of lupus anticoagulant (LA) or anticardiolipin antibodies (aCL). Our data show that some women have all the clinical features of the syndrome but have no circulating antiphos-pholipid antibodies. This raises the interesting possibility that antiphospholipid antibodies are simply markers, not always present, for an as yet uncharacterized condition associated with thrombosis and fetal death. In fact, the underlying pathology may be the same for both groups.
It is also possible that autoantibodies undetected in conventional LA and aCL assays may be directed against serum phospholipid binding proteins such as beta-2-glycoprotein-1 or prothrombin. Finally, thrombosis and pregnancy losses could be unrelated in patients with antiphospholipid-like syndrome.
It is important for physicians to be aware of the risk of thrombosis and the poor obstetric outcome in these antiphospholipid-like women. However, their management presents a dilemma. Treatment with low-dose aspirin, heparin, or intravenous immune globulin may be rational to prevent devastating recurrent fetal loss. Since there are no data available to either support or refute this approach, a prospective evaluation of these regimens is urgently needed.
1 Scott JR, Silver RM, Branch DW. Dept OB/GYN, Univ Utah, SLC, UT. LUPUS: 5(5): Oct,96, p552.