Haematologica 2002; 87:(01)ELT02
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Cerebral venous thrombosis associated to homozygous factor V Leiden mutation in a female of Syrian origin

Yolanda Mira, *Alberto Alfaro, **Amparo Estellés, Amparo Vayá, Fernando Ferrando, Piedad Villa
Thrombosis and Hemostasis Unit. Department of Clinical Pathology. * Department of Neurology. **Thrombosis Research Center. La Fe University Hospital, Valencia. Spain
Correspondence: Dra. Yolanda Mira Fornés, Thrombosis and Hemostasis Unit. Department of Clinical Pathology, La Fe University Hospital, Avda. Campanar 21, 46009 Valencia. España

Inherited coagulation defects are one of the predisposing factors for cerebral venous thrombosis (CVT). An association between factor V Leiden mutation and CVT has been reported in heterozygous patients. In this report, we describe for the first time, to our knowledge, a patient with CVT associated with homozygous Leiden mutation.

CVT is an infrequent condition usually associated with predisposing factors such as hematologic disorders, gynecologic obstetric as well as medical causes.1 In addition, inherited coagulation abnormalities have also been described.2-8 However, in 20%-35% of cases, the etiology remains unknown.1 One of the most prevalent inherited factors recognized as predisposing to venous thrombosis is factor V Leiden mutation.9 The prevalence in Asia minor varies considerably, ranging from 0% to 14%.8 An association between this mutation and CVT has been reported in heterozygous patients.3-5 In this report, we describe, for the first time, to our knowledge, a patient with CVT associated with homozygous Leiden mutation.

A 21-year old female of Syrian origin was admitted to the emergency room because of intensive holocranial headache that began 48h prior to admission. Twelve days before, the patient had suffered a miscarriage in the 6th month of pregnancy. On examination the patient was drowsy, but oriented to person, place and time. She had no focal neurologic deficits. A computed tomography scan (CT) and a magnetic resonance angiography (MRA) was obtained in the first hours and demonstrated a CVT (sagittal, transverse, sigmoid sinus) and thrombus in the left internal jugular vein. Moreover cortical infarctions were identified. She was referred to the ICU presenting hypertension, diplopia, persistent headache and emesis. A bilateral sixth nerve palsy was present. She was treated with heparin, captopril, dexamethasone and mannitol. Routine laboratory tests (including autoimmune disease, lupus anticoagulant and anticardiolipin antibodies ) were unremarkable except a thombocytopenia of 124x103/L. She had no history of thombotic disease, cardiovascular risk factors, or family history of venous thrombotic events.Three days after, a new contrast CT showed no new images . After ten days she was discharged with a normal neurological examination and acenocoumarol treatment . One month later she was pregnant and acenocoumarol stopped because of its teratogenic effect. Treatment with heparin was begun but after 2 months was stopped because of thombocytopenia of 21x103/L. The patient returned to Syria and was treated with AAS (100 mg by day ) until the 6 th month of pregnancy. Since then she returned to our hospital and platelets increased to 75x103/L; treatment with tinzaparin (10,000 IU/day) was begun until four weeks post-partum. Two months later a thrombophilia study revealed homozygous factor V Leiden and MRA no alterations.

From a clinical aspect, we point out that treatment through pregnancy with anticoagulants was successful .In addition in homozygotes patients reported in the literature10 it seems that thrombosis occurred more frequently in the absence of triggering factors. In the present case, CVT had occurred in association with other circumstantial factors such as pregnancy and miscarriage. In agreement with the characteristics of our patient, we suggest that in all young patients with CVT even with triggering risk factors or absence of family history, a study of inherited defects is mandatory. 

References

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