Cerebral venous thrombosis and the G20210A mutation of factor II.

Cerebral Venous Thrombosis and the G20210A Mutation of Factor II To the Editor: In addition to the article of Longstreth et al1 recently published in Stroke, we describe 2 cases of stroke due to cerebral venous thrombosis with the G20210A mutation as only risk factor. After sequencing of the gene for human prothrombin (factor II) by Degen and Davie2 in 1987, a new mutation of prothrombin (G20210A) was described by Poort et al3 in 1996. It is a common mutation of this factor associated with an increased risk of venous (and possible arterial) thrombosis, as stated by Martinelli et al.4 The mutation can be detected by a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method, as described by Poort.3 Our laboratory uses this method. Recently, we saw 2 patients with a definite diagnosis of cerebral venous thrombosis. No other known risk factor for cerebral venous thrombosis could be found. The finding of the abnormal mutation (G20210A) of factor II gene (both patients had a heterozygous state for the mutation) suggested this as etiology. Patient 1 was a 42-year-old employee and moderate smoker. In his early thirties he had an arterial thrombectomy in a peripheral artery. In his family only his father had suffered a “stroke.” He was admitted to our hospital with a first epileptic seizure, focal in origin. There was a venous infarction in the right frontal lobe. MR angiography (including venous phase) showed a typical stop in the frontal superior sagittal sinus, with loss of draining veins. None of the other tests associated with venous hypercoagulability showed a hypercoagulable state (no activated protein C resistance, proteins C or S deficiency, detectable antinuclear factors, lupus anticoagulants, or antithrombin III). The G20210A mutation was found, showing a heterozygous genotype for this mutation in this patient. Patient 2 was a 63-year-old farmer who was admitted to our hospital 3 days after being missed by his family. He didn’t return home after market day and was disorientated in place, time, and person. A few days earlier, his family had found him to be a little distracted. CT and MRI showed a bithalamic venous infarction. On MR angiography and arteriography there was total obliteration of deep intracerebral venous structures. Anticoagulation was started. He remained with disinhibited frontal behavior. None of the classical risk factors of hypercoagulation were present. He did not smoke. By PCR-RFLP (as described above), he proved to be heterozygous for the G20210A mutation. Besides being a well-known and relatively frequent risk factor for venous thrombosis in general, this mutation must be looked for in the less-frequent cerebral venous thrombosis patients. Testing for this mutation is important because people with this genotype should be strongly advised to avoid other risk factors, such as oral contraceptive use5 and smoking.