Robert Terkeltaub, MD


February 08, 2001


A 45-year-old white woman diagnosed with multiple sclerosis (MS) more than 20 years ago had a very strongly positive anticardiolipin IgM (tested at patient's request) in a neurology clinic. Anticardiolipin IgG was negative. She has several white-matter lesions considered consistent with MS by radiograph. Her activated partial thromboplastin time was slightly elevated. Dilute Russell viper venom test (DRVVT) was normal. Antinuclear antibody was negative.

She has a history of miscarriage at about 6 months of pregnancy in the remote past and has one child. There is no history of thrombocytopenia, stroke, or thrombotic events. She does not have livedo reticularis. Aspirin was prescribed because of the very strongly positive anticardiolipin antibody IgM. Protein S was also low. Beta-2 glycoprotein I and repeat testing for anticardiolipin antibodies have been ordered. A lumbar puncture will be repeated because she has numbness in hands, feet, and legs. Cerebral angiography will be performed if felt necessary by a neurologist.

A study published in Medicine[1] in January 2000 (from Lupus Research Institute, St. Thomas Hospital, London) showed that magnetic resonance (MR) images from patients with antiphospholipid syndrome (APS) could not be distinguished from MR images patients with MS and that the response to anticoagulation might be helpful in differential diagnosis. However, it has also been reported that many patients with MS may also have APS, although there appears to be no correlation between these antibodies and any clinical features.

Are there enough data to justify anticoagulation in this patient? Is angiography needed to assess for vasculopathy and thrombotic disease before anticoagulation can be considered? Anticoagulation in APS is indefinite and current criteria require the demonstration of a thrombotic event.

Response from Robert Terkeltaub, MD

This patient has a history of a late pregnancy loss and has carried a diagnosis of chronic MS, associated with active sensory symptoms and recently documented white matter lesions. She carries a high titer IgM anticardiolipin antibody, which along with the late pregnancy loss certainly suggests the diagnosis of an APS syndrome and would meet preliminary criteria for the diagnosis.[1] Despite the recent report in Medicine that you refer to, the association of white matter encephalopathy with primary APS remains controversial.[2,3] In this regard, a significant fraction of patients with true MS may have positive serology for IgG or IgM anticardiolipin antibody.[4,5]

The question concerns whether there is justification for anticoagulation in this case and whether an angiogram should be done to look for CNS vasculopathy and thrombotic disease before anticoagulation is considered. First, in your patient, the lumbar puncture may well be informative regarding MS vs vasculopathy. Second, MR angiography is recommended as a conservative, noninvasive first step to effectively evaluate at least the medium and large vessels before consideration of traditional cerebral angiography. In my view, the low-dose aspirin alone is appropriate in the absence of unequivocally proven cerebral thrombotic vasculopathy in such a patient.


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