5067 Background Protein S deficiency as a risk factor for arterial thrombosis is still debatable. We report a young adult male with known protein S deficiency who presented with stroke. Case report A 39 -year-old African American male with history of Crohn's disease in remission and recurrent deep venous thrombosis (DVT) diagnosed 3 years ago presented with unsteady gait and vertigo. Neurological exam revealed dysmetria, dysdiadochokinesia, and ataxic gait. His International Normalized Ratio (INR) on admission was 1.2 while he was on warfarin. Magnetic Resonance Imaging (MRI) of the brain revealed acute bilateral cerebellar ischemic infarcts. Transthoracic and transesophageal echocardiography did not reveal any septal defects or clots. Carotid doppler studies ruled out possible embolic source. Vasculitic profile revealed normal results. Thrombophilia work up including factor V Leiden mutation, prothrombin G20210A mutation, protein S and protein C level and activity, antithrombin III, homocysteine and the antiphospholipid syndrome was done. The only positive finding was type II protein S deficiency with a solely functional activity deficiency: 37% (Normal range 65%-140%). Three years ago, at the time of initial diagnosis of DVT, thrombophilia work up was done and it revealed similar results. As a result of recurrent DVT and pulmonary embolism, the patient had been on warfarin for 3 years. During this hospitalization, warfarin was continued and the patient attained therapeutic INR upon discharge. Discussion Thrombosis is a common complication of inflammatory bowel disease (IBD) and most commonly present as recurrent DVT with or with out pulmonary embolism. Factor V Leiden mutation, antithrombin deficiency, prothrombin (G20210A) gene mutation, protein C and S deficiency and hyperhomocysteinemia have been documented in IBD. The association between protein S deficiency and IBD has been established mainly based on free protein S level (Saibeni S et al, 2001). However, larger data, other than case reports described in the literature, have failed to prove that such association entails thrombotic events. The incidence of arterial thrombosis is even less in patients with IBD although this has been described in few case reports (Deepak Joshi et al, 2008). In general, existing literature on protein S deficiency and arterial thrombosis exhibits conflicting data. Few cases are reported demonstrating protein S deficiency patients presenting with cerebrovascular accident (Girolami A. et al, 1989; Hector R Martinez et al, 1993). Bilateral cerebellar infarcts in a patient with type II protein S deficiency without history of IBD has been reported in the literature (Verma R, 2007). Our patient with IBD and type II protein S presented with bilateral cerebellar infarcts is an anecdote unprecedented in medical literature. Even if we cannot confirm the causal relationship, the lack of any other risk factors makes protein S deficiency the only possible explanation for the occurrence of cerebrovascular accident in our patient. Conclusion Although the importance of protein S deficiency as stimulus to arterial thrombosis was disregarded in few studies, such cases continue to appear revealing coexistence thus indicating a role. To the best of our knowledge, an arterial thrombosis in a Crohn's disease patient with an exclusive type II protein S deficiency has not been reported before. Our case is unique. The pathogenesis and causality remain challenges necessitating large-scale study addressing young patients to elucidate protein S levels and activity for those who lack any other obvious triggers. Disclosures No relevant conflicts of interest to declare.

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5144 BACKGROUND Bortezomib is widely used to treat multiple myeloma (MM). It is also used in the management of recurrent, relapsed and chemotherapy-refractory other hematological malignancies. Bortezomib is considered to be a safe drug with manageable adverse side effects including peripheral neuropathy, thrombocytopenia and gastrointestinal symptoms. Rare but severe pulmonary complication has been reported in four Japanese and two African-American (AA) patients after bortezomib treatment for multiple myeloma refractory to multiple other regimens. To the best of our knowledge, this is the first case of chemotherapy-naïve AA patient who developed severe pulmonary complication after receiving bortezomib. CASE REPORT A 51-year-old AA female known for hypothyroidism, was diagnosed with IgG kappa MM after she presented with low back pain and was found to have a lytic lesion and compression fracture at the tenth thoracic vertebra. She was started on palliative radiation therapy to T5 to T12 (to a total of 2500 cGY). Four days after starting the radiation therapy, she received bortezomib (1.3 mg / m2) on days 1, 4, 8 and 11 combined with low dose dexamethasone (40 mg IV weekly). On day 12, she developed a dry cough, dyspnea and fever of 101.4 0F. On physical examination, she had coarse crackles in all lung fields. Her white blood cell count remained within normal limit. Computed tomography of the chest with contrast identified new diffuse patchy opacities throughout the lung fields and small bilateral pleural effusions, but no evidence of pulmonary embolism. She became progressively hypoxic and was transferred to the Intensive Care Unit (ICU). Echocardiogram confirmed normal left ventricular function. She was subsequently intubated. Bronchoscopy was done, bronchioalveolar lavage failed to show any infectious organisms or malignancy, whereas transbronchial biopsy showed organizing pneumonia. The patient was treated with intravenous antibiotics and high dose steroid (methylprednisolone 1000mg/24hrs) for 3 days with rapid clinical improvement and was quickly weaned off the ventilator. DISSCUSION The incidence of serious side effects of bortezomib was reported to be less than 5%. Severe pulmonary complications after bortezomib treatment are particularly rare (Richardson PG et al, 2003). In 2006, Miyakoshi S. and colleagues described four Japanese patients who presented with severe pulmonary complication after bortezomib treatment. A genetic predisposition and previous auto peripheral blood stem cell transplant (PBSCT) have been attributed to the adverse effect seen exclusively in Japanese patients. Ohri, Boyer and their colleagues reported similar pulmonary complications in two African-American patients treated with bortezomib (Ohri A et al, 2006; Boyer JE et al, 2006). The clinical symptoms and radiological manifestations of our patient are similar to the previously reported African-American patients. However our case is chemotherapy-naïve whereas previously reported cases were pre-treated with various cytotoxic agents. Our patient had transient fever, no leuckocytosis and negative blood and urine cultures; she also had a negative bronchoalveolar lavage, all argue against the possibility of infection. She had rapid improvement after high dose steroids, which support drug reaction rather than infection. Moreover, organizing pneumonia is a recognized type of drug-induced lung disease (Vahid B et al, 2008) and confirms the adverse event of bortezomib since our patient had no prior chemotherapies and was not on other medication at the time of event. Even if we admit the possibility of spillover effect from the limited field radiation the patient received, the extent of the lung parenchyma injury was far more conspicuous to be explained solely by radiation therapy alone. CONCLUSION This report reinforces the possibility of predictable manifestation of severe pulmonary complication due to bortezomib therapy in chemotherapy-naive African American patients. Clinicians should be aware of this potentially fatal complication and need to cautiously monitor their patients for early signs of respiratory problems. It also highlights the reversible nature of the pulmonary complication with high dose steroids. Patients who get radiation therapy to the chest while receiving bortezomib may need special attention. Disclosures: No relevant conflicts of interest to declare.