Cerebral venous thrombosis remains an important and sometimes an elusive cause of strokes. Oral contraceptives seem to have a strong causative association with this entity. We describe a case that highlights the importance of asking specific questions about oral contraceptive use in patients with strokes due to cerebral venous sinus thrombosis, especially, where the cause remains cryptic

Sheerani, Mughis

Urfy, Mian Zainul Sajadeen

English

eCommons@AKU

eCommons@AKUSection of Neurology Department of MedicineNovember 2006Oral contraceptives and cerebral venousthrombosis: case report and a brief review ofliteratureMughis SheeraniAga Khan UniversityMian Zainul Sajadeen UrfyAga Khan UniversityFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_neurolPart of the Neurology CommonsRecommended CitationSheerani, M., Urfy, M. Z. (2006). Oral contraceptives and cerebral venous thrombosis: case report and a brief review of literature.Journal of Pakistan Medical Association, 56(11), 559-561.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_neurol/163Case ReportOral Contraceptives and Cerebral Venous Thrombosis: case report and a briefreview of literatureMughis Sheerani, Mian Zainul Sajadeen UrfyDepartment of Medicine, The Aga Khan University Hospital, Karachi.AbstractCerebral venous thrombosis remains an importantand sometimes an elusive cause of strokes. Oral contracep-tives seem to have a strong causative association with thisentity. We describe a case that highlights the importance ofasking specific questions about oral contraceptive use inpatients with strokes due to cerebral venous sinus thrombo-sis, especially, where the cause remains cryptic.IntroductionThe role of oral contraceptives in deep vein throm-bosis has been well documented and proven in the contem-porary literature. The risk of deep leg thrombosis in womenwith Factor V leiden mutation who use oral contraceptivescompared with a control has been estimated to be more than30-fold.1 Cerebral Venous sinus thrombosis represents arare disorder usually in middle age group. Independent tri-als and retrospective data analysis in several countries in theworld show markedly increased predisposition in womenwho are taking oral contraceptives especially with genetichypercoagulable disorder.2 A recent Italian case-controlstudy in patients with sinus thrombosis found an odds ratioof 4.2 for oral contraceptive use, after exclusion of pregnantand puerperial women.3 Another study by Cerebral VenousSinus Study Group, Academic Medical Centre Netherlandsreported 30 fold increased risk in women who use oral con-traceptives along with hereditary prothrombotic conditionsas compared to women who have neither.4We present a case of a middle aged lady, who visit-ed The Aga Khan University Hospital emergency depart-ment with acute neurological deficits and was later on foundto have Transverse Sinus Thrombosis. A brief review of lit-erature is added.Case ReportA 42 year old house wife was admitted to the strokeunit with sudden onset of left sided numbness and mildweakness. She was otherwise healthy with no history of anyprevious medical problems.On examination her weight was 64 kg, blood pres-sure was 130/79 mmHg, pulse 80 per minute and she wasafebrile. General examination was unremarkable. Cardiacand respiratory examination was also normal.Neurological examination showed normal cranialnerves except for mild flattening of the left naso-labial fold.There was mild weakness on the left side which was grad-ed as 4 on MRC scale. Left side also showed decreased sen-sation as compared to the right side.Magnetic Resonance Imaging (MRI) of the brainshowed small right parietal stroke. Magnetic ResonanceAngiogram (MRA) was normal.A workup for hypercoagulable state was performedincluding anti-phospholipid  antibodies,  protein C & Sactivity, antithrombin III, Factor V leiden deficiency  andhomocystein levels were within normal range.As no definite cause of stroke was found, the histo-ry was re-assessed. Patient was asked several directed ques-tions about medications. It was revealed by the husband thatshe had been on oral contraceptives for several days prior tothis episode. She took oral contraceptives to cease her men-strual cycle temporarily as she was going for 'Hajj'. Thisinformation was not disclosed by the patient. Magnetic Resonance Venogram (MRV) was per-formed after this information and a thrombus was seen inthe right transverse sinus.Patient was started on anticoagulation and she recov-ered completely.Vol. 56, No. 11, November 2006 559DiscussionCerebral venous sinus thrombosis is a relatively rarecondition which over the past two decades has been diag-nosed more frequently due to greater availability of noninvasive diagnostic methods like MRI and MRV. It presentsusually in a relatively younger age group than other vascu-lar neurological conditions and can result in a significantmorbidity and mortality which ranges from 5 to 30 percent.Though relatively uncommon, CVST is a complex diseasedue to multitude of etiologies that cause it. The etiologiesvary from complex hypercoaguable states to simple physio-logical states like dehydration, pregnancy and peurperium.5Only a few iatrogenic factors can lead to this condition. Theoral contraceptives, androgen therapy and C-Asparaginasetherapy have been implicated as a causative factor forCVST.The role of oral contraceptives in the development ofdeep venous sinus thrombosis is clearly established. CVSTbeing a rare disease, relatively scarce amount of data ispresent in literature as compared to other vascular neurolog-ical abnormalities. But even with the information we have,there is ample evidence to prove that there is a clear causalrelationship between oral contraceptives and the develop-ment of CVST. Increased incidence of CVST in oral contra-ceptive using women was reported for first time in 1970 byBuchanan et al.6 Thereafter, little importance was given tooral contraceptives as being a significant risk factor becauseof lack of biological plausibility until the start of lastdecade, when several retrospective studies showed a strongcausal relationship between the two. A survey from 1993-94on health care cost and utilization in United States revealedoral contraceptive usage as an independent risk factor forintra-cerebral venous thrombosis.7 Since then many studieshave been published particularly from Central Europe,establishing oral contraceptives usage as a risk factor forCVST.8 To our knowledge, no case series or clinical trialhas been published from any center in Pakistan concerningrisk factors for CVST in our population. In our Case Study, a complete hypercoaguableworkup was carried out and was unremarkable. The onlymajor risk was found to be oral contraceptives use prior tothe event. In literature, however, the use of oral contracep-tives seems to be associated with CVST, more strongly inpresence of hereditary hypercoaguable disorders, likeFactor V leiden deficiency, Protein C or S and anti thrombindeficiency and more recently prothrombin gene mutation atposition 20210 (guanine to adenine).9 This mutation was notchecked in our case as it is not available in Pakistan. A case control study by a Dutch group on CVSTrevealed that odds ratio increased from 13 to 34 in womenusing oral contraceptives along with hypercoagulable disor-ders.4 Similar findings have been reported by 3 differentItalian Studies showing oral contraceptives alone as well incombination with hypercoagulable disorders to be a signifi-cant risk factor for the development of CVST.8 This led tothe argument whether women should be screened for hyper-coaguablity before prescribing oral contraceptives. The nextquestion was whether oral contraceptives should be with-held in women with hereditary thrombotic disorders.Considering the prevalence of CVST which is estimated tobe around 1 per 100010, it will not be a cost effective modal-ity and such screening is not recommended any where in theworld. As far as question of withholding oral contraceptivesin carriers of hypercoagulable genes, no clear cut guidelinesare available. It is, however, recommended that other meth-ods of contraception should be used in women with previ-ous episodes of thrombosis.10As far as management of CVST is concerned, it doesnot change with the attributed risk factor and includes anti-coagulation with recommended guidelines. Our patientrecovered completely with anticoagulation using heparinand then switching to warfarin as oral therapy. The preva-lence of oral contraceptives use in Pakistan is relatively lowas compared to western world due to various socio-religiousreasons. Women also tend not to share this information withtheir physicians, as in our case. This case also highlights theimportance of complete documentation of medication histo-ry, which may lead to diagnosis of these rare diseases andprevent unnecessary investigations. ConclusionThough infrequent, CVST remains an importantcause of strokes in young individuals, with oral contracep-tives as one of the iatrogenic causes. Oral contraceptivesshould be prescribed with caution in women with history ofhypercoaguabilty. A detailed medications history might leadto the diagnosis of "cryptogenic strokes" where no obviouscauses are apparent.References1. Kluft C, Lansink M. Effect of oral contraceptives on haemostatic variables.Thromb Haemost 1997:78:315-26.2. Strachan R, Hughes D, Cowie R. Thrombosis of the straight sinus complicat-ing hormone replacement therapy. Br J Neurosurg 1995:9:805-8.3. Mancia D, Buccino G, Scoditti U, Pini M, Taqliqfem AR. Low-oestrogen oralcontraceptives as a major risk factor for cerebral venous and sinus thrombo-sis: evidence from a clinical series. Ital J Neurol Sci 1999 20:231-5.4. De Brujin SF, Stam J, Koopman MM, Vendenbroucke JP. Case-control studyof risk of cerebral sinus thrombosis in oral contraceptive users who are carri-ers of hereditary prothrombotic conditions. BMJ 1998:316:589-92.5. Cantu C, Barinagarrementaria F. Cerebral venous thrombosis associated withpregnancy and peurperium. Review of 67 cases. Stroke 1993: 24: 1880-4.6. Buchanan DS, Brazinsky JH. Dural sinus and cerebral venous thrombosis:incidence in young women receiving oral contraceptives. Arch Neurol1970:22:440-4.7. Lanska DJ, Kryscio RJ. Risk factors for puerperium and postpartum strokeand intracranial venous thrombosis. Stroke 2000:31:1274-82.8. Martinelli I, Battaglioli T, Pedotti P, Cattaneo M, Mannucci PM.Hyperhomocysteinemia in cerebral vein thrombosis. Blood 2003:102:1363-6.9. Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. High risk ofcerebral vein thrombosis in carriers of a prothrombin gene mutation and usersof oral contraceptives. N Engl J Med 1998:338:1793-7.10. Vandenbroucke JP. Cerebral sinus thrombosis and oral contraceptives. BMJ1998:317:483-4.560 J Pak Med Assoc

Oral contraceptives and cerebral venous thrombosis: case report and a brief review of literature

https://ecommons.aku.edu/cgi/viewcontent.cgi?article=1162&amp;context=pakistan_fhs_mc_med_neurol

Oral contraceptives and cerebral venous thrombosis: case report and a brief review of literature

Abstract

Similar works

Full text

Available Versions

eCommons@AKU