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Cerebral venous thrombosis (CVT) is a rare disorder, with an incidence of approximately 4/1 000 000 per year, occurring more frequently in women than in men (ratio of 1.29:1).1 CVT is a multifactorial condition, known predisposing factors include venous stasis, hypercoagulability, vasculitis, systemic lupus erythematosus, and trauma. Mortality after CVT ranges from 5% to 30%.1 The optimal treatment consists of anticoagulation for six months and should only be maintained beyond this time if known risk factors for CVT persist. Treatment should not be discontinued in case of an asymptomatic haemorrhagic transformation of the associated venous infarct.2
In recent years, a few thyrotoxic patients with CVT have been reported. An association between hyperthyroidism and increase of FVIII has also been described,3 and recent data suggest an increased incidence of venous thrombosis in patients with hyperthyroidism and high FVIII levels.4 Here we report a patient with increased FVIII levels and an autoimmune hyperthyroidism, who developed a CVT complicated by venous infarction.
A 39 year old woman was admitted to the emergency room after a brief episode of convulsions, preceded by a short period of perseveration, verbal aggressiveness, and disorientation. Four days before admission, she had developed a sudden, pulsatile left sided headache, which was unresponsive to paracetamol and ibuprofen. Personal and family medical histories were unremarkable. She had been taking oral contraceptive medication for several years and smoked two cigarettes a day. Neurological examination was normal, except for a temporary confusional state that lasted less than 24 hours. Electroencephalography demonstrated a slow arrhythmia in the left temporal region, without epileptic activity. Brain computed tomography revealed a left temporal hypodense lesion, with moderate contrast enhancement. Magnetic resonance imaging of the brain performed 24 hours later, showed a non-specific hyperintense lesion on the T1 weighted images. The magnetic resonance venography (fig 1) revealed an extensive thrombosis of the left lateral sinus with involvement of the distal part of the jugular vein. The diagnosis of a temporal venous infarct was made. Treatment with unfractionated heparin was started promptly and maintained for one week, followed by oral anticoagulation with an INR between 2 and 3. Oral contraceptive treatment was discontinued and the patient was advised to stop smoking. Extensive screening for coagulopathies including antiphospholipid syndrome, dysfibroginaemia, deficiencies in antithrombin, protein C and S, hyperhomocysteinaemia, and activated protein C resistance revealed no abnormalities. The G20210A prothrombin gene mutation was absent. Autoimmune tests including ANF, ANCA, complement and rheumatoid factors were negative. Further analysis revealed a state of hyperthyroidism with a TSH value below 0.015 mIU/l (normal: 0.27–4.2), free triiodothyronin of 12.1 ng/l (normal: 9.3–18.0 ng/l), and an increased free thyroxin of 28.8 ng/l (normal: 9.3–18.0 ng/l). Anti-TSH receptor antibodies were found consistent with Graves-Basedow’s disease. The patient was treated with thiamazole (3×10 mg/day), followed by the administration of radioactive iodine (9 mCi). One month after discontinuation of oral contraceptives, thyroid tests remained increased. FVIII procoagulant protein showed a marked increase: 1680 IU/l (normal levels: 500–1500 IU/l) and remained slightly raised five weeks later. Meanwhile the patient developed a hypothyroidism, necessitating a substitution treatment with LT4. After a further six months both thyroid tests and FVIII levels normalised and anticoagulants were stopped.
Increase of clotting FVIII occurs in several conditions such as strenuous exercise, fever, pregnancy, renal failure, adrenaline (epinephrine) infusion, prednisone treatment, and intravascular haemolysis.3 Hyperthyroidism, whatever its origin, also induces a significant increase in FVIII levels, with a comparatively short activated partial thromboplastin time, while other clotting factors remain within normal limits.3 Moreover, correction of thyroid function results in a normalisation of FVIII levels. In patients with recurrent hyperthyroidism, levels of FVIII are known to fluctuate with thyroid function. The physiopathological mechanism involved remains unclear. Excessive adrenergic activity occurring in hyperthyroid patients could have a direct effect on the production of FVIII. The fact that administration of propanolol inhibits the increase of FVIII in patients with hyperthyroidism supports this theory.
In 1995 a large study was performed on 301 case-control pairs, younger than 70 with a first episode of deep vein thrombosis.4 Patients with malignant disorders were excluded. The authors showed that high levels of FVIII contribute to the development of venous thrombosis in a dose dependent manner. In multivariate analysis FVIII concentrations above 1500 IU/l result in a 4.8-fold higher risk of developing venous thrombosis. It was also shown that this is not an acute phase reaction, and that high levels of FVIII persist for months after the thrombotic event. Recently, it was calculated that the reported incidence of CVT and hyperthyroidism is significantly higher than expected by chance alone.5 A small number of case reports mention the concomitant occurrence of thyrotoxicosis and CVT. To our knowledge, this is the first reported case of CVT of the left lateral sinus associated with clinically silent hyperthyroidism and increased FVIII levels. Correction of thyroid function resulted in normalisation of FVIII levels. This report emphasises the need for thyroid evaluation in every patient with CVT and other venous thromboembolic events, even in the absence of clinical signs of hyperthyroidism. Every patient with hyperthyroidism, especially if immobilised, has a significantly higher risk of developing venous thromboembolism and should benefit from maximal preventive measures.
Competing interests: none declared
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