Danazol-induced life-threatening cerebral venous thrombosis in a patient with aplastic anemia

Sir, Cerebral venous thrombosis (CVT) is common in women and mostly reported during puerperium.[] Exogenous androgens, used either to increase muscle mass in various sports or in various clinical situations, can occasionally predispose to CVT.[,,] A 40-year-old male presented with acute onset headache and altered sensorium. Six months before this admission, he was evaluated for pancytopenia and was diagnosed to have aplastic anemia on bone marrow biopsy. Since then, he was on danazol therapy, 200 mg per day. Neurological examination revealed drowsy patient opening eyes and localizing to pain with bilateral papilledema, aphasia, and right hemiparesis (motor power grade 3/5). Investigations showed hemoglobin - 8.9 g% and platelet count - 90 000/cu.mm. Cranial computerized tomography (CT) scan showed left frontal hemorrhagic infarct with surrounding edema, 8 mm midline shift, and subfalcine herniation [Figure 1]. An emergency left frontal craniotomy was done. Peroperatively, the superficial cortical veins draining the left frontal lobe were thrombosed. Frontal lobe was significantly bulging out of the dural opening. Following decompression of the hemorrhagic infarct, frontal lobe became lax and pulsatile. Postoperatively, he was electively ventilated and managed with cerebral decongestants. Histopathological examination of the material confirmed the diagnosis of CVT; H and E stained sections showed thrombi in almost all cortical veins and extensive venous stasis in the surrounding brain parenchyma [Figures 2 and 3]. A repeat CT brain done 48 hours later showed adequate decompression of the infarct with resolving edema and midline shift [Figure 4]. Subsequently low molecular weight heparin was administered for 10 days. Laboratory evaluation for antithrombin III activity, protein C, S factor V Leiden, plasma homocysteine, and anticardiolipin antibodies were within normal limits. He improved neurologically over the next few weeks. At discharge, he was conscious, alert, and oriented. His aphasia and right hemiparesis improved completely. As he had aplastic anemia, further oral anticoagulation was not considered and the offending drug danazol was discontinued. At 4-month follow-up, the patient is leading an independent life. Exogenous androgen administration causing CVT has been reported only in a few instances earlier.[,,] Most often, androgens were either administered as an anabolic hormone for body building or as a therapeutic intervention for aplastic anemia. Danazol (a synthetic androgenic steroid) has been found to induce a procoagulant state by decreasing cyclooxygenase activity, thereby enhancing platelet function. This predisposes to arterial and venous thrombosis.[] There has been a few case reports of danazol-induced intracranial hypertension (IH).[,] The most probable cause of IH in these patients was underlying dural sinus thrombosis. In this patient, other risk factors that predispose to CVT have been excluded. Anemia can also predispose to CVT; however, in this patient, the hemoglobin was not too low. The only risk possible factor for CVT in this patient was danazol therapy. Treatment of CVT includes anticoagulation and cerebral decongestants. There is place for decompressive hemicraniectomy in patients with space-occupying venous infarct with or without hemorrhage.[] Our patient had decompressive craniotomy as he had space-occupying infarct and evidence of impending herniation. Our patient is probably the first case report of danazol-induced life-threatening CVT warranting surgical decompression. If the patient while on androgen therapy develops CVT, then the drug needs to be discontinued and alternative therapy may be considered for aplastic anemia.[] In patients with CVT, anticoagulation therapy should be initiated at the earliest to prevent extension of the thrombosis.[] However, there are no prospective studies about the timing of anticoagulation in the postoperative period in these patients. In aplastic anemia with CVT, the place of anticoagulation therapy is controversial. In this patient, anticoagulation was administered in the immediate postoperative period and continued for a short period since the inciting factor, danazol, was withdrawn. REFERENCES - 1. Kalita J, Bansal V, Misra UK, Phadke RV. Cerebral venous sinus thrombosis in a tertiary care setting in India QJM. 2006;99:491–2 - 2. Sahraian MA, Mottamedi M, Azimi AR, Moghimi B. Androgen-induced cerebral venous sinus thrombosis in a young body builder: Case report BMC Neurol. 2004;4:22 - 3. 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