CASE DISCUSSION:
Approach to SLE Patient with Sagittal Sinus Thrombosis
A l3 year
old African-American female previously diagnosed with SLE is brought to the
pediatric hospital in a comatose state. She had been well until 2 days
before admission when she developed a runny nose, low grade fever, and a
headache. She worsened 8 hours before admission when her headache became
severe and she became lethargic 2 hours before admission. Upon admission,
she was noted to respond to pain but not to commands. She had decreased
strength and movement of the left arm and leg.
Her
past history is noteworthy for the diagnosis of SLE at age 12 based upon finger
arthritis, palatal ulcers, + ANA 1:640, + anti-DS DNA, C3 45 and C4 7, and
hematuria and proteinuria. Her anticardiolipin IgG was 4 times normal and
her lupus anticoagulant was positive. A renal biopsy revealed WHO Class
III nephritis with an activity index of 6/24 and chronicity index of
0/12. She was begun on prednisone after 3 Solumedrol pulses,
hydroxychloroquine, and a baby aspirin. After 8 months, mycophenolate was
added as a steroid-sparing drug. Her medication compliance became
erratic.
Physical
exam also revealed a B/P of 150/90, HR 110, RR 20. She is noted to have a
2+ malar rash, swollen PIP joints, and enlarged axillary lymph nodes. No
other abnormal physical findings were present other than the neurologic
findings noted above. A brain CT scan revealed a large right sagittal sinus
thrombosis. MRI with contrast detected increased right cerebral
signal. Preliminary laboratory testing
revealed a WBC of 7,000/mm3 with 75% segs, Hgb. 10.6 g%, platelets 70,000/mm3,
ESR 55 mm/hr, CRP 3.0 (<0.8), C3 65, C4 8, and a urinalysis with 1+ protein,
1+ blood, 6-10 RBC/hpf.
The
ICU attending consults neurology and rheumatology and initiates steroid
therapy, but no anti-coagulation due to the risk of conversion to a
bleed. What are your recommendations and justifications for your plan?
DISCUSSANT
Robin
Brey, MD
Pediatric
Neurologist
The patient is a 13 year-old African American girl
with the diagnosis of SLE since age 12, who is brought to the hospital in a
comatose state, with the focal findings of left sided weakness. Symptoms began
2 days prior to admission with the symptoms of headache, runny nose and
low-grade fever. Her past history is significant for renal involvement related
to SLE, arthritis and palatal ulcers. She also has high positive levels of
anticardiolipin IgG and a positive lupus anticoagulant.
This young woman has symptoms and laboratory findings
of an SLE flare. In addition she has a right sagittal sinus thrombosis. This
could be related to a prothrombotic state associated with antiphospholipid
antibodies, but could also be related to SLE disease activity. We are not told
whether the “increased signal on the right” seen on brain MRI is related to
clot in the sagittal sinus, or brain infarction. This information is important
for prognostic reasons, as children with sinus thrombosis who also have brain
infarction (either ischemic or hemorrhagic) may have a worse outcome (with or
without treatment) (1). Other further work-up that may be helpful in this
patient includes the search for other prothrombotic states such as Factor V
Leiden, sickle cell disease and deficiencies of proteins C, S and Antithrombin
III, although a study of 160 consecutive children with sinovenous thrombosis
found that the most frequent prothrombotic abnormality seen was anticardiolipin
antibody of the IgG isotype (1). This study also found that another important
risk factor for the development of sinovenous thrombosis in children is chronic
systemic disease of a variety of types.
Regardless of what we consider the cause of the
sagittal sinus thrombosis to be, I would treat this patient with IV heparin
acutely, and continue her on oral anticoagulants for 3-6 months thereafter.
Although we do not have results from large, randomized controlled trials,
empiric treatment for this condition for the past decade has been to use
anticoagulation. A recent small study of 17 children with venous sinus
thrombosis showed that anticoagulation in 15 of them did not result in bleeding
complications or worsening of their neurological condition (2). Only 2 of the
17 children did not undergo anticoagulation, and all children improved
clinically. While the results from this study seem to suggest that cerebral
venous sinus thrombosis has a good prognosis in children, in fact, death or
significant neurologic deficits are seen in about 50% of children with cerebral
sinus thrombosis (2). In studies in adults with cerebral venous thrombosis
anticoagulation, even in the presence of
hemorrhagic strokes, did not lead to bleeding complications and lead to
improved outcomes (3). A recent Cochrane Database of Systematic Reviews
concluded that based on the limited evidence available, anticoagulant treatment
for cerebral sinus thrombosis appeared safe and was associated with potentially
important reductions in death and dependency that did not reach statistical
significance (4).
Perhaps a more difficult question is related to how
long the warfarin treatment should be continued if we attribute the thrombosis
to anticardiolipin antibodies. There are no studies in children or adults to
help guide us in answering this question. Observational studies in adults with
deep venous thrombosis associated with antiphospholipid antibodies suggest that
longer term anticoagulation may be needed. It is not at all clear that these
results can be generalized to children with deep venous thrombosis or anyone
with cerebral venous sinus thrombosis. Given 1) the difficulty and morbidity
associated with warfarin treatment in children and 2) the fact that we cannot
say that the sagittal sinus thrombosis in this patient was not due, at least in
part, to a SLE flare, I would treat her with warfarin for six months and then
resume her baby aspirin treatment.
I would treat this patient with three
methylprednisolone pulses followed by oral prednisone for her non-nervous
system SLE manifestations. We are told that she has been erratic in her
medication compliance of late. This may be the trigger for her current disease flare.
For this reason, I would resume the rest of her prior medications
(hydroxychloroquine and mycophenolate) as well, except for the baby aspirin
until she is taken off warfarin. When she recovers neurologically, I would also
discuss the reasons for the noncompliance with the patient and her family. This
would help me identify issues that to be addressed in order to increase
compliance, e.g. psychological counseling, changing medications to reduce
side-effects.
References