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CASE REPORT
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Cerebral Venous Thromboembolism in Antiphospholipid Syndrome Successfully Treated with the Combined Use of an Anti-Xa Inhibitor and Corticosteroid Masayuki Sugie 1,2, Natsuko Iizuka 1, Yuki Shimizu 1 and Hiroo Ichikawa 1
Abstract We herein report a case presenting with cerebral venous sinus thrombosis (CVST) associated with primary antiphospholipid syndrome (APS). The patient developed recurrent CVST followed by a hemorrhagic ischemic stroke despite the use of warfarin during the appropriate therapeutic window. Thus, we substituted warfarin to rivaroxaban with prednisolone and obtained a good clinical course. In addition to the effect of prednisolone of inhibiting elevated lupus anticoagulants and the recurrence of arterial thrombosis, rivaroxaban may prevent CVST and inhibit hypercoagulability induced by corticosteroids. The combination of an anti-Xa inhibitor and corticosteroid may be an alternative treatment for CVST and arterial thrombus with warfarinresistant APS. Key words: cerebral venous sinus thrombosis, antiphospholipid syndrome, anti-Xa inhibitor, corticosteroid (Intern Med 54: 3051-3056, 2015) (DOI: 10.2169/internalmedicine.54.5045)
Introduction The current mainstay of treatment for venous and/or arterial thromboembolism due to antiphospholipid syndrome (APS) is anticoagulation with oral vitamin K antagonists (VKA) (1, 2). The American Heart Association/America Stroke Association (AHA/ASA) guideline (3) recommends warfarin with a target international normalized ratio (INR) of 2.0-3.0 in cases of APS with venous thromboembolism (VTE). It is also advised that patients with confirmed APS and arterial thrombosis should receive warfarin (INR >3.0) or a combination of aspirin (100 mg daily) and warfarin (INR 2.0-3.0), however, there is a lack of consensus (4). Although corticosteroids are recommended with a low evidence level (Grade C1) for ischemic stroke with APS accompanied by SLE according to the Japanese guidelines for management of stroke (5), no other guidelines for APS refer to treatment with corticosteroids in APS with thromboembolism (1). Recently, new-generation oral anticoagulants have been developed, including dabigatran etexilate (a direct thrombin
inhibitor) and rivaroxaban [the first oral direct factor Xa (FXa) inhibitor]. These anticoagulants are expected to prevent cardioembolism due to non-bulbar atrial fibrillation and are recommended as alternative therapeutic agents for VTE, however, there is no evidence and little experience for their use in APS (2). We herein describe a patient with primary APS who presented with cerebral venous sinus thrombosis (CVST), followed by arterial thromboembolism and hemorrhagic stroke, and was successfully treated with the combined use of an anti-Xa inhibitor and corticosteroid.
Case Report A 41-year-old woman was admitted to our institution with a history of headache, nausea, and impaired vision over the previous 2 months. She had never been diagnosed with hypertension, diabetes mellitus, or an autoimmune disorder. She had no previous history of pregnancy or the use of oral contraceptives. Her severe headache and nausea were initially diagnosed as a migraine by her personal physician, for which she was medicated with non-steroidal anti-
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Department of Neurology, Showa University Fujigaoka Hospital, Japan and ２Department of Neurology, Shin-yurigaoka General Hospital, Japan Received for publication January 27, 2015; Accepted for publication March 16, 2015 Correspondence to Dr. Masayuki Sugie,
[email protected]
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Intern Med 54: 3051-3056, 2015
DOI: 10.2169/internalmedicine.54.5045
Table. The Results of Blood and Cerebral Spainal Fluid Examination. Complete Blood Count WBC 7,600 Hb 14.7 MCV 86 PLT 19.6×104
/μL g/dL fL /μL
Coagulation PT-INR APTT D-dimer CFVIII CFIX CFXI CFXII Protein C Protein S Anti-Cardiolipin A Anti-ȕ2GPI Ab LA PL before PL after AT III
sec μg/mL % % % % % % U/mL U/mL sec sec sec %
0.98 82.7 0.6 135 68 134 73 118 133 7.2 1.2 7.3 58.5 51.2 117
Biochemical examination T-P 6.9 g/dL Alb 4.1 g/dL Glu 116 mg/dL BUN 17 mg/dL Cre 0.61 mg/dL Na 141 mEq/L K 3.8 mEq/L T-Bil 0.4 mg/dL AST 16 U/L ALT 22 U/L LDH 159 U/L Ȗ-GTP 79 U/L CRP 0.75 mg/dL HbA1c 6.4 % ESR-60 22 mm/hr T-cho 207 mg/dL HDL-cho 47 mg/dL TG 198 mg/dL Vitamin A 245 IU/mL Homocystein 13.5 nmol/mL Lp (a) 6.1 mg/dL
PT-INR: prothorombin time-International Normalized Ratio APTT: activated partial thromboplastin time CF: Coagulant factor GPI: glycoprotein I complex antibody LA: lupus anticoagulant PL before: cogulant time before neutralizing with phospholipid PL after : cogulant time after neutralizing with phospholipid AT:III: antithorombin III LP(a): lipoprotein (a)
inflammatory drugs, tryptamine sulfate, and valproic acid. However, her headache and nausea did not improve; rather, they continued to occur every day for 6 weeks and she eventually became unable to ambulate. She noticed the visual impairment 1 week before admission and consulted an ophthalmologist 1 day before admission. An ophthalmologic examination revealed papillary edema without bleeding. She was thus referred and admitted to our department. On admission (2 months after the onset), the patient reported that her spasmodic headache felt as though her bilateral temples were pierced with a lance and accompanied by persistent nausea. During the peak of the headache, she could not move her body at all and she could not tolerate bright light. She was confined to her bed until the following day, when the headache slightly lessened. She described the visual impairment as objects in her visual field being blurry and outlined. She was fully conscious and her vital signs were as follows: blood pressure, 157/102 mmHg; pulse, 97 beats/min; and body temperature, 37.2℃. Her physical examination revealed no skin lesions, including a butterfly rash, or joint swelling or deformation. Her body mass index was 39.8. Neurological examinations revealed bilateral abducens palsy. The peripheral blood examination results are summarized in Table. An elevated erythrocyte sedimentation rate, C-reactive protein level, and HbA1c level were observed. The activated partial thromboplastin time (APTT) was 82.7 seconds (within the normal range: 20-40 sec). Anti-nuclear antibodies including anti-ds DNA and Sm antibody were negative. The levels of serum complement C3, C
Immunity examination ANA ×40 RF 4 Anti-ds DNA Ab
