Short Communications Cerebral Venous Thrombosis with Lupus Anticoagulants
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Short Communications
Cerebral Venous Thrombosis with Lupus
Anticoagulants
Report of Two Cases
Steven R. Levine, MD, Stuart Kieran, MD, Kevin Puzio, MD, Howard Feit, MD, PhD,
Suresh C. Patel, MD, and K.M.A. Welch, MD
Lupus anticoagulants are circulating autoantibodies, primarily directed against phospholipids, that
prolong the partial thromboplastin time. They have been previously associated with systemic arterial
and venous thrombosis and arterial stroke, but not with cerebral venous thrombosis. We describe 2
young patients with cerebral venous thrombosis documented by intravenous digital subtraction angi-
ography in whom a lupus anticoagulant was demonstrated. Both patients improved with corticoster-
oid and anticoagulant therapy. (Stroke 1987; 18:801-804)
C erebral venous thrombosis (CVT) may result
from a variety of pathologic processes1"3 in-
cluding hypercoagulable states.1"7 Lupus an-
ticoagulants (LAs) are circulating autoantibodies pri-
marily directed against phospholipids.8-10 LAs prolong
ry values included a prolonged partial thromboplastin
time (PTT) of 65 seconds, prothrombin time (PT) of
12.5 seconds, Westergren erythrocyte sedimenta-
tion rate (ESR) of 18 mm/hr, platelet count of
121,000/mm3, and normal serum complement studies.
all phospholipid-dependent coagulation tests and ap- Antinuclear antibody titer was < 1:40, and an IFA-
pear to act by at least several mechanisms.8"15 LAs anti-DNA was < 10. Neurologic consultation diag-
have been associated with an increased incidence of nosed vascular headache with a normal neurologic ex-
systemic arterial and venous thrombotic events 8141617 amination, including funduscopy. Naproxen was
in patients with and without systemic lupus erythema- prescribed. She was discharged and readmitted the
tosus (SLE). 8141618 Ischemic cerebral arterial disease, following week, having just completed a spontaneous
both transient ischemic attacks (TIAs) and stroke, have abortion at 9 weeks.
been recently documented in association with LAs.19"22 The headaches and diplopia persisted and were now
Venous occlusions of the retinal, pulmonary, renal, constant. She began having gait difficulty. There was
hepatic, and lower extremity circulations have also no history of diabetes, hypertension, or heart disease.
been described in patients with LAs. 81317 ' 8 - 23 " 26 TO our She had used oral contraceptives from 1978 through
knowledge, we present the first 2 cases of LA-associat- 1983. There was also a history of recurrent lower ex-
edCVT. tremity deep venous and pulmonary thromboses,
thrombocytopenia, and recurrent herpes labialis.
Report of Two Cases There had been a previous history of monthly mi-
Case J graines preceded by "wavy vision." In December 1984
A 21-year-old white woman was admitted in No- she had a spontaneous abortion at 18 weeks. Patholog-
vember 1985 with a 2-week history of headaches. The ic examination of the fetal placenta revealed macer-
pain was worse on awakening, bitemporal-retroauricu- ation, fibrosis, focal necrosis, placentitis, and chor-
lar in location, and waxed and waned. Coughing or ioamnionitis. The umbilical cord revealed acute
sneezing increased the headache and brought on tran- inflammation in the walls of the arteries and vein.
sient episodes of blurry vision — "like looking through Examination on the second admission revealed nor-
a curtain." She then developed diplopia and photopho- mal optic disks, a left sixth nerve palsy, moderate
bia. At this time she was 2 months pregnant. Laborato- generalized hyperreflexia, and mild dysmetria of the
upper extremities bilaterally. Laboratory investigation
included an ESR of 3 mm/hr, platelet count of
From the Departments of Neurology and Radiology (Neuroradi- 116,OOO/mm3, and a PTT of 54 (normal, 22-36) sec-
ology), Henry Ford Hospital, Detroit. Michigan.
This work was supported in part by National Institutes of Health onds. Her PTT was 52 seconds with 1:1 dilution with
Program Project in Cerebrovascular Disease NS23393 to Henry normal plasma (mixing studies). Platelet neutralization
Ford Hospital. S.L.R. is a research fellow of the American Heart procedures and tissue thromboplastin inhibition con-
Association, Michigan Affiliate. firmed the presence of the LA. PT was 12 (normal,
Address for reprints: Steven R. Levine, MD, Department of
Neurology, K - l l , Henry Ford Hospital, 2799 West Grand Boule- 9.5-11.5) seconds. Antithrombin III level was 99%
vard, Detroit, Ml 48202. (normal, 80-120%). Assays of coagulation factors re-
Received August 30, 1986; accepted January 21, 1987. vealed markedly reduced activity of Factors IX (37%),
Downloaded from http://stroke.ahajournals.org/ by guest on September 16, 20158Q2 Stroke Vol 18, No 4. July-August 1987
XI (19%), and XII (28%) with normal activity of Fac- and mild lid edema. Ophthalmology consultation
tors II and VIII. Head computed tomography (CT) found mild optic disk edema with retinal veins slightly
scan after contrast infusion revealed a partial obstruc- congested and easily collapsed with pressure. A left
tion to filling of the torcular herophili (partial delta fourth nerve palsy was also noted. The neurologic ex-
sign) and was otherwise unremarkable. Cerebrospinal amination was otherwise unremarkable. PTT was pro-
fluid (CSF) examination revealed sterile, clear fluid at longed on 2 occasions, to 39 and 42 (normal, 22-36)
an opening pressure of 420 mm H2O, which contained seconds and failed to correct (41 seconds) with a 1:1
1 white blood cell/mm3, 2 red blood cells/mm3, 17 mg dilution of the patient's serum with normal plasma,
protein/dl, 64 mg glucose/dl, and a nonreactive consistent with the presence of a lupus-like circulating
VDRL. There was no oligoclonal banding. The IgG anticoagulant. The LA was confirmed with platelet
index was 0.8 (normal, 0.4-0.7). She was started on neutralization procedures and tissue fhromboplastin in-
60 mg/day prednisone and 20 mg/day furosemide. The hibition. PT, thrombin clot time, bleeding time, Factor
following day, intravenous digital subtraction cerebral VIII, Antithrombin III, fibrin degradation products,
angiography (IV-DSA) revealed total obstruction to antinuclear antibody, VDRL, and complement studies
filling of the transverse sinus and increased collateral were normal. Platelet count was 74,000/mm3. The
venous drainage around the obstruction (Figure 1). A noncontrast head CT 6 days after admission demon-
diagnosis of cerebral venous sinus thrombosis was strated focal areas of increased density along the
made. She was placed on subcutaneous heparin, war- straight sinus and in the region of the torcular and
farin, and dipyridamole in addition to prednisone and posterior sagittal sinus, consistent with intraluminal
furosemide. Her sixth nerve palsy and headache gradu- thrombi within the dural venous sinus. IV-DSA re-
ally improved, and she has been without further throm- vealed poor filling of the anterior and posterior por-
botic episodes during a 1-year follow-up. Her F I T tions of the superior sagittal sinus. He was treated with
remains slightly prolonged despite therapy. 50 mg/day prednisone and i.v. heparin, and his PTT
decreased to 25 seconds after 5 days. His platelets rose
Case 2 to 340,000/mm3, and his headache and fourth nerve
A 32-year-old white man complained of the insid- palsy gradually resolved. He was maintained on war-
ious onset of increasing left periauricular headache, farin and prednisone. One week later, high-resolution
neck pain, lightheadedness, nausea, vomiting, and un- head CT of the posterior fossa revealed no residual
steady gait. Several days later, he noted diplopia and evidence of CVT.
left ear fullness. One week prior to his headache, he
was evaluated for ankle edema, proteinuria, reduced Discussion
creatine clearance, elevated immune complexes, and Our first patient was pregnant when she developed
thrombocytopenia. Renal biopsy revealed mesangial- her neurologic symptoms, and she subsequently had a
proliferative glomerulonephritis. His mother had a his- spontaneous abortion. Pregnancy alone may increase
tory of idiopathic thrombocytopenic purpura (FTP). the risk of cortical vein thrombosis 126 but usually
Examination revealed no orthostasis, a supple neck, in association with hyperemesis gravidarum and the
resulting dehydration, which were not noted in
our patient. There was also a history of spontane-
ous abortions, deep venous thromboses, and a pulmo-
nary embolus, all documented associations with
LAs.1316"18'2427 The placental pathologic findings from
our patient's miscarriage were characteristic of those
seen in association with LAs. 27 The history of migraine
has not been previously associated with CVT but has
occasionally been noted in association with LAs. 192128
Increased intracranial pressure or pseudotumor cerebri
are well-documented presentations of CVT.1"3 Her CT
and IV-DSA findings, although not specific for CVT,
did not support a diagnosis of idiopathic pseudotumor
cerebri.
Our second patient suffered a sagittal sinus throm-
bosis as well as transverse sinus thromboses in associ-
ation with an LA. He had a mild nephrotic syndrome
secondary to a mesangial-proliferative glomerulone-
phritis. Although nephrotic syndrome may be associat-
* A ed with a "hypercoagulable state,"29 CVT associated
with the nephrotic syndrome is distinctly rare.30 Lau et
FIGURE 1. Intravenous digital subtraction cerebral angio- al30 described a child less than 3 years old with nephrot-
gram: Abrupt, total obstruction to the filling of the transverse ic syndrome and multiple thromboembolic phenom-
sinus (arrow), with resulting increased collateral venous flow ena, including a superior sagittal sinus thrombosis.
(arrowhead). Review of their patient's coagulation data revealed a
Downloaded from http://stroke.ahajournals.org/ by guest on September 16, 2015Levine et al CVT with Lupus Anticoagulant 803
prolonged PTT prior to heparin therapy, suggesting the Our report expands the cerebrovascular manifesta-
possibility of an LA. tions associated with LAs to include CVT and should
One other case in the literature may have had an LA be considered in the differential diagnosis of cerebral
in association with CVT. Averback's31 Case 2, a 29- venous thrombosis.
year-old woman, had a CVT immediately postpartum
with prolonged PTTs, thrombocytopenia, normal PT, Acknowledgments
and "visceral autolysis" of the stillbirth. She complete- The authors wish to express their thanks to Dr. Ma-
ly recovered after treatment with heparin, hydrochlo- ria Sawdyk, MD, Department of Hematology, Henry
rothiazide, and ampicillin. Estanol et al32 reported 20 Ford Hospital, Detroit, for performing and interpreting
women between the ages of 15 and 45 years with the hematologic tests in our patients. We also wish to
intracranial venous thrombosis; 14 of the 20 studied thank Hally Phelps and Nancy Hay for their assistance
were without evidence of circulating anticoagulant. in the preparation of this manuscript.
LA has been associated with venous occlusions of
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32. Estanol B, Rodriguez A, Conte G, Aleman JM, Loyo M, lant
Downloaded from http://stroke.ahajournals.org/ by guest on September 16, 2015Cerebral venous thrombosis with lupus anticoagulants. Report of two cases.
S R Levine, S Kieran, K Puzio, H Feit, S C Patel and K M Welch
Stroke. 1987;18:801-804
doi: 10.1161/01.STR.18.4.801
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