Q J Med 2001; 94: 114-115
© 2001 Association of Physicians
Correspondence |
Migraine in Hughes syndrome—heparin as a therapeutic trial?
Lupus Research Unit, Rayne Institute, St Thomas' Hospital, London
Sir,
One of the most prominent features of the procoagulant antiphospholipid (Hughes) syndrome (APS) is headache.1 These vary from classical intermittent migraine to almost continuous incapacitating headache. Over and above the considerable fear of stroke in these patients, the headaches are, themselves, often incapacitating.
We have anecdotally noted that in patients with, for example, DVT commencing anticoagulation with warfarin (coumadin), there has been a dramatic improvement—sometimes a total disappearance—of this symptom.2 Furthermore, we have observed the same phenomenon in some of our APS patients starting heparin therapy. The decision whether to commence anticoagulant therapy, especially in a patient without previous overt thrombosis or with no thrombotic lesions on brain MRI, is difficult. Starting warfarin (coumadin) implies a medium- to long-term therapeutic commitment.3
In an attempt to facilitate this decision, we sought to assess the use of a 7-day ‘therapeutic trial’ of low-molecular-weight (LMW) heparin in such patients.
We treated five patients with APS and intractable headaches with a 7-day course of daily LMW heparin (Dalteparin, 5000 IU subcutaneously twice daily). None had significant brain MRI lesions, but all had features of APS, notably previous venous thrombosis (2), livedo (3), previous recurrent pregnancy loss (4), and thrombocytopenia (3). All 5 had moderate- or high-titre antiphospholipid antibodies. In three patients, the use of aspirin had, in the patients’ opinion, resulted in partial improvement in headache; in two, there had been no effect.
In all five patients, there was a marked improvement (with a total disappearance in three) of the headache, in the majority within 48 h of starting heparin. The headaches returned in all five patients on cessation of heparin. All five patients are being considered for long-term warfarin treatment.
There is no doubt that in some patients with APS, the headaches are relieved when anticoagulation is started. For those patients without major previous thrombosis, treatment with low-dose aspirin is commonly used and, occasionally, there is improvement in the headache. The decision to try warfarin for an essentially ‘non-thrombotic’ clinical feature is extremely difficult. One future approach in antibody-positive patients without major thrombosis, would be to consider a low-dose warfarin (low INR) regimen. A national trial prospectively comparing aspirin with low-dose warfarin is currently being run by the Arthritis Research Campaign, under the co-ordination of the Lupus Research Unit in St Thomas' Hospital, London.4
An alternative, more pragmatic approach in the shorter term, might be to consider a ‘therapeutic trial’ of self-administered LMW heparin for one week in APS patients with intractable headache. Such a short, and safe ‘therapeutic trial’ might help predict those patients in whom more substantive anticoagulant therapy could be considered for this distressing complaint.
References
1. Hughes GRV. Off the beaten track: a clinician's view. In: Hughes Syndrome. MA Khamashta, ed. London, Springer 2000: 105–10.
2.
Cuadrado MJ, Khamashta MA, Hughes GRV. Migraine and stroke in young women. Q J Med2000; 93:317–9.
3.
Khamashta MA, Cuadrado MJ, Mujic F, Taub N, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid antibody syndrome. N Engl J Med1995; 332:993–7.
4. Khamashta MA. Primary prevention of thrombosis in subjects with positive antiphospholipid antibodies. J Autoimmun2000; 15: in press.
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