Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet ’ s Disease

We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet's disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued.

with 91% neutrophils; platelet count: 90,000/mm -3 (NR: 150,000-450,000/mm -3 ); haemoglobin count: 10 g/dL (NR: 13-18 g/dL); C-reactive protein levels: 54 mg/dL (NR: ≤0.8 mg/dL); erythrocyte sedimentation rate: 80 mm/hour (NR: 0-20 mm/hour); blood urea nitrogen levels: 35 mg/dL (NR: 7-25 mg/dL); and creatinine levels: 2.9 mg/dL (NR: 0.6-1.2mg/dL).The thrombocytopaenia was treated with prednisolone and her platelet levels had normalised when a repeat platelet count was performed three weeks later.Urinalysis revealed proteinuria without haematuria.Anti-nuclear, anti-neutrophil cytoplasmic, anti-double strand and anticardiolipin antibodies were negative, as were rheumatoid factor and lupus anticoagulants.Test results for other thrombophilia factors were normal, including hyperhomocysteinemia, antiphospholipid antibodies, protein S, protein C and antithrombin III levels and factor V Leiden.Transthoracic echocardiography (TTE) revealed a mobile thrombus in the right ventricle outflow tract (RVOT) of the subtricuspid apparatus [Figure 3]; this was believed to have been the cause of the patient's respiratory symptoms.Eight days after the neurosurgery and one day after admission to the cardiac surgery ward, open cardiac surgery was performed to remove the clot.Intraoperatively, the thrombus was observed to be located in the RVOT with a single site of attachment to the perimembranous septum and septal tricuspid valve [Figure 4].Surgical exploration of the pulmonary artery and its main branches revealed no other thrombi.A pulmonary thromboembolism was suspected; however, no facilities for lung perfusion scans were available and the patient could not be transferred to another centre due to her general condition.
Postoperatively, the patient suffered from acute renal dysfunction and nephrologists were consulted.heart palpitations and chest pain and was referred to the cardiac surgery ward.In the ward, her medical history revealed classic features of Behcet's disease, including four occurrences of mouth and genital ulcers in the previous year and ophthalmologist-confirmed uveitis.A physical examination revealed signs of the former cranial surgery, multiple aphthous mouth and genital ulcers and left haemiparesis.There were no signs of thrombophlebitis or lower limb oedema.Chest radiography was normal.The results of laboratory tests on admission were as follows: white blood cell count: 19,000/mm -3 (normal range [NR]: 4,300-10,800/mm -3 )   However, the condition resolved spontaneously.A few days later, the patient was treated with immunosuppressive therapy for symptoms of Behcet's disease.Symptoms of oral and genital aphthous ulcers and uveitis were relieved using a combination of oral corticosteroids, prednisolone, azathioprine and cyclophosphamide.Nine days after the cardiac surgery, she was prescribed anticoagulation therapy (heparin and warfarin) to prevent further thrombus formation.The patient discharged on the 13 th postoperative day on warfarin, prednisolone, azathioprine and cyclophosphamide.After three months of treatment, the cyclophosphamide and azathioprine were discontinued due to resolution of the symptoms.At a 10-month follow-up, the patient's general condition was satisfactory and TTE indicated no thrombus recurrence.However, prednisolone was continued indefinitely due to recurrent eye involvement.Warfarin was also continued due to prolonged bedrest caused by haemiparesis which increases the risk of thromboemboli in the extremities.

Discussion
This report presents a patient with Behçet's disease with right ventricle thrombus formation after a previous cerebral artery aneurysm rupture.Cardiac involvement in Behçet's disease is very rare and consists mainly of thrombus formation.While any chamber of the heart may be involved in clot formation, the right atrium, with its unique haemodynamic characteristics, is the most commonly affected chamber. 5All of the layers of the heart are involved in the inflammatory process of Behçet's disease. 6Endothelial inflammation can cause luminal irregularities and thickening which is revealed as thrombi, Loeffler endocarditis and arterial aneurysm formation.Thrombi of the superior and inferior vena cava (IVC) may cause superior vena cava syndrome and Budd-Chiari syndrome.Systemic lupus erythematosus (SLE) can be associated with cardiac thrombosis and cerebral complications; 6 ruling out SLE as a diagnosis was therefore necessary in the current case.
Aneurysms of the large and medium arteriessuch as the aorta, pulmonary and peripheral arteries including the femoral, popliteal, brachial and subclavian arteries-can form part of the vascular involvement in Behçet's disease. 6One important medium-sized artery involved in aneurysm formation is the cerebral artery.Although vascular inflammatory disease is observed in only 25% of patients with Behçet's disease, it is nonetheless the most important predictive factor of Behçet's disease-related mortality. 6he combination of cerebral and cardiac manifestations of Behçet's disease is a very uncommon phenomenon. 7Intracardiac thrombus formation may be caused by cardiac endothelial inflammation or may arise from an extracardiac thrombus that has broken off from the thromboembolism source in a peripheral vein and dislodged into the cardiac chamber.However, emboli that originate from a cardiac chamber are a relatively uncommon occurrence. 7ogulkoç et al. detected 13 cases of pulmonary emboli among 25 subjects with Behçet's disease; in approximately 50% of these cases, thrombosis in the inferior and superior vena cavae and deep lower extremity veins may have been the source of the embolism. 5Most emboli in Behçet's disease patients begin in the cardiac chambers. 8In patients without Behçet's disease, deep vein thrombosis in the lower extremities is usually associated with pulmonary emboli, as thrombi formed in the veins in the absence of inflammation can easily break off and travel to the heart and lungs.Contrary to conventional thromboemboli, the combination of a pulmonary thromboembolism with lower extremity phlebitis is a rare event in patients with Behçet's disease. 8hrombi formed in inflamed vessels are strongly adherent to the endothelium; therefore, these patients have a low risk of thromboembolism. 9,10Houman et al. observed vascular involvement in 43.3% of 113 Behçet's disease cases; of those, 89.8% had deep vein thrombosis. 11Involvement of the deep venous system is more common in men than women. 10Luo et al. evaluated the clinical features of patients with Behçet's disease and cardiac chamber thrombi; they found that intracardiac thrombus formation frequently occurred in young male patients and usually involved the right cardiac chambers. 12n the present case report, the patient was treated with immunosuppressive and antithrombotic drugs following the surgical removal of the cardiac thrombus.Cyclophosphamide, azathioprine and prednisolone were prescribed.Prior to starting treatment with cyclophosphamide and azathioprine, routine baseline assessments were performed, including a complete blood cell count and liver and renal function tests; regular monitoring continued throughout treatment.
To prevent urinary toxicity such as haemorrhagic cystitis, patients need to be adequately hydrated and pass urine frequently.As such, patients should be instructed to increase their fluid intake 24 hours before, during and at least 24 hours after receiving cyclophosphamide. 12

Conclusion
In the present case, a large intracardiac thrombus was detected in a patient with Behçet's disease who had previously undergone neurosurgery for a ruptured cerebral artery aneurysm.The patient underwent openheart surgery for the removal of the thrombus before undergoing immune suppression and antithombotic therapy.At a 10-month follow-up, she was healthy with no evidence of further thrombus formation.

Figure 1 :
Figure 1: Preoperative computed tomography of a 35-year-old female patient with Behçet's disease showing a haemorrhagic mass in the right cranial hemisphere (arrow) indicative of a ruptured cerebral artery aneurysm.

Figure 2 :
Figure 2: Postoperative cerebral angiography of a 35-year-old female patient with Behçet's disease with a ruptured cerebral artery aneurysm in the left middle cerebral artery branch (circle), with aneurysm clip in situ (arrow).

Figure 3 :
Figure 3: Transthoracic echocardiography of a 35-yearold female patient with Behçet's disease showing a large thrombus (arrows) in the right ventricular outflow tract.LA = left atrium; RA = right atrium; LV = left ventricle; RV = right ventricle.

Figure 4 :
Figure 4: Intraoperative photograph of a thrombus in the right ventricular outflow tract of the subtricuspid apparatus (arrow) of a 35-year-old female with Behçet's disease.