ALBERT

Description: Introduction: Unfractionated heparin (UFH), or low-molecular-weight heparin (LMWH), is commonly used with mechanical prophylaxis as an anticoagulant to reduce the risk for venous thromboembolism (VTE). However, overuse of these prophylaxes can increase the risk of bleeding, heparin-induced thrombocytopenia (HIT) and associated medical cost. PURPOSE: The aim of this study is to determine the incidence of DVT prophylaxis among hospitalized nonsurgical patients in a community medical center. To evaluate the use of the prophylaxes as described above, the investigators collected data on medical inpatients and addressed how to avoid overuse. Method: A retrospective inpatient chart review of 100 general internal medicine patients analyzed data using Padua Prediction Score as the risk estimate for deep venous thrombosis (DVT). High risk for VTE was defined by a cumulative score 〉=4 and low risk was a score = 4 were treated with DVT prophylaxis of which 10 patients were only treated with heparin and 36 patients were given both mechanical and chemical prophylaxis. Collectively, 53.7% of the patients received treatment with DVT prophylaxis (p 〈 0.001, Chi-Square test). Discussion: In hospital settings, physicians want to avoid DVT or PE so they tend to consider patients as being at moderate risk for DVT without using any method of DVT risk assessment. This leads to unnecessary overuse of DVT prophylaxis on patients and may increase the risk of bleeding and injury. Conclusion: Our data suggests that there DVT prophylaxis including UFH and LMWH was over prescribed among patients with who had marginal risk for DVT in hospitalized nonsurgical patients in a community medical center. Clinical implications: To avoid the overuse of DVT prophylaxis, physicians need to follow guidelines. Education and inclusion of the guidelines in EHRs of information on VTE risk assessment for hospitalized medical patients upon admission may reduce unneeded DVT prophylaxis and the risk of bleeding and costs associated with additional care needs. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4665 Introduction: Multiple sclerosis (MS) is an autoimmune inflammatory and chronic demyelinating disease. Occurrence of hypercoagulable states and breast cancer in patients with multiple sclerosis (MS) has not been extensively reported. We report a case of a female MS patient with recurrent DVTs, elevated factor VIII levels, and advanced breast cancer with aggressive biologic phenotypes. Case report: A 45-year-old Caucasian female with a history of MS had a breast mass diagnosed on a screening mammogram. She was diagnosed with right breast carcinoma (2.5 × 2.5 × 1.6 cm), T2 N3 M0, which correlated to stage IIIC. She underwent a right modified radical mastectomy with 16/25 lymph nodes involved, ER/PR status was positive, HER-2/neu 0 with high Ki67. Her post-surgery treatment plan included 4 cycles of Cyclophosphamide and Taxotere chemotherapy. She also received chest wall radiation as well as tamoxifen and aromatase inhibitor (Femara) therapy. The patient had never been on hormone replacement therapy or oral contraceptives. She had bilateral salpingo-oophorectomy and hysterectomy and pathology was unremarkable. Patient was diagnosed with Multiple Sclerosis at age 27. She was treated with intermittent courses of steroids, Interferon b-1b, Interferon b-1a, and Mitoxantrone (MTX) for relapsing/remitting MS for several years until she developed left hemiparesis, hypoesthesias, and residual visual dysfunction that prompted her to start IVIG therapy and plasmapheresis. Past medical history presents recurrent DVT (in 2006) and elevations of coagulation factor VIII (355%). The patient also developed superior vena cava thrombosis in the presence of Lovenox and coumadin therapy. Discussion: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system, frequently complicated by devastating neurologic symptoms and progressive disability. Risks of DVT in bedridden or wheelchair-bound MS patients have been suggested. Previous studies show that the frequency of DVT in late-stage MS may be over 40%. Additionally, in MS patients without risk factors, it has been suggested with an autoimmune inflammatory disease that the inflammatory infiltration in MS plaques located close to small or medium-sized veins could have a role as well. The lumbar puncture could also be one of other thrombophilic factor in MS, since after dural puncture the decrease of cerebrospinal fluid pressure induces a rostrocaudal sagging effect with traumatic damage to the fragile venous endothelial wall and may trigger a venous vasodilatation with resultant stasis. Elevated factor VIII levels are a risk factor for venous thrombosis and may also be associated with the risk of arterial thrombosis in coronary heart disease. Studies show that factor VIII levels may be increased by chronic inflammation. However, elevated factor VIII levels in patients with MS have never been reported. There is no cure for MS, though there are several drugs such as immunomodulatory agents that can slow or stop its progress. However, current data show a small increased risk of breast cancer in women with MS. The size of the breast tumor was also larger for woman with MS. More specifically, the proportions of biologically aggressive phenotypes that can worsen the prognosis of breast cancer incrementally despite the biologic phenotype at diagnosis also were investigated in this group of patients. One hypothesis linking breast cancer and MS involves long-term use of immunomodulatory agents including IFNs and glatiramer. Immunomodulatory therapy may impart immune system alterations that promote enhancement of cancer cells’ ability to evade immune recognition and cancer metastasis by altering the body’s ability to conduce immunosurveillance. However, consistent with previous observations, this remains unexplained and warrants further attention. Conclusion: The Female patient with MS described in this article presents an example of recurrent DVT, Superior Vena Cava thrombosis, elevated factor VIII levels, and breast cancer with stage IIIC and biologically aggressive phenotypes. The authors concern is that there is an increased risk of hypercoagulation states and breast cancer development in patients with MS. The systematic application of long-term preventive DVT may be considered for this group of patients. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Immunoglobulin M-producing multiple myeloma (IgM MM) accounts for less than 1% of all myeloma cases. Because the disorder is rare,its clinical characteristics and long-term prognosis remain unknown. Hyperviscosity occurs from pathologic changes of either cellular or protein fractions of the blood such as are found in MM (particularly IgA and IgG3) and other diseases. Case Presentation A 65-year-old male smoker presented to emergency room (ER) with headache, dizziness, shortness of breath, symmetrical finger pain, nose bleeds, and blood in stool. On lab work hemoglobin was 7.9 gm/dl. Review of the peripheral blood smear showed atypical lymphocytes. CT chest showed left axillary and supraclavicular lymphdenopathy. Serum protein was 13 gm/dl, Serum protein electrophoresis showed a monoclonal IgM kappa gammopathy with UIEP confirming the bence jones proteinuria. A bone marrow biopsy showed about 80% cellularity with diffuse and solid neoplastic plasma cell infiltrates that were CD138+, CD20- and CD3-. Flow cytometric analysis of the bone marrow aspirate demonstrated a small fraction of clonal plasma cell population that were CD38+, CD138+, CD45-, and CD56-, Fluorescent in Situ Hybridization confirmed neoplastic plasma cells with kappa light chain restriction, and cyclinD1-. On examination, the patient had a erythematous skin changes and edematous bilateral symmetrical finger findings. Discussion: MM with IgM gammaglobulin is a rather distinct subtype of MM displaying clinical and pathologic features of both MM and WM. The clinical presentation of WM is similar to that of MM except that organomegaly is common in WM but is uncommon in MM and lytic bone disease and renal disease are uncommon in WM but are common in MM. The criteria for diagnosis of IgM myeloma (and its differentiation from WM) requires the presence of either lytic bone lesions and/or evidence of the t(11;14) translocation. It is also characterized by negative CD20, D56 and CD117 phenotype. All the reported cases of IgM myeloma had been treated with melphalan and prednisolone with suboptimal results. Some patients were treated with VAD (vincristine, adriamycin and dexamethasone) regimen, others with CTD protocol. The results were similar to the MP regimen. Radiotherapy was mainly used as palliative measure. Conclusion: Our case suggests that IgM multiple myeloma can presents as hyperviscosity syndrome with isolated skin manifestation and may have unique clinical characteristics. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: B-cell chronic lymphocytic leukemia is one of the common lymphoproliferative disorders in the adult patient population. It is very uncommon to find bi-nucleated lymphocytes as a morphological feature in this disorder. Our patient was diagnosed with CLL and was found to have bi-nucleated lymphocytes in the peripheral smear. The mechanism behind this type of morphological feature of lymphocytes is unknown in CLL, and whether it has prognostic value on disease outcome is undetermined. Case Description: 62 y/o man was referred to hematology oncology after diagnosis of small cell lymphocytic leukemia was made s/p a right inguinal lymph node biopsy. His CBC revealed a wbc count of 14,000, Rbc count of 4,360, Absolute lymphocyte count of 11,500 and Platelet count of 125,000. The patient did not have any B-symptoms. On physical exam, a pertinent finding was palpable right axillary adenopathy. The CT of abdomen /pelvic to evaluate these findings. This revealed extensive axillary, abdominal/pelvic lymphadenopathy, hepatosplenomegaly and cardio phrenic lymphadenopathy. The patient had a biopsy of the right inguinal lymph node as well as bone marrow biopsy. Biopsy results showed small lymphocytic cells, some of which show occasional large nucleoli were consistent with small lymphocytic lymphoma/chronic lymphocytic leukemia, and morphologic characteristics of the lymphocytes showed bi-nucleated lymphocytes in peripheral blood smear (figure A). Flow cytometric analysis confirmed a lymphocytic population with lambda light chain restriction, expressing CD5, CD19, CD20, and CD23 consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. Bone marrow biopsy showed a hypercellular marrow with 75 % cellularity mainly composed of mature lymphocytes with scattered macrophages and eosinophils, Flow cytometric analysis (Clarient FI11-041053) of the bone marrow is interpreted as chronic lymphocytic leukemia/small cell lymphoma with the abnormal B cells representing 56% of the viable white cells. FISH study showed deletion of the ATM gene (11q22-23), D13S319 (13q14) and TP53 (p53) were observed in 29%, 71% and 35.5% of the cells analyzed, respectively. A subset of cells with the 13q deletion (20.5% of the total cells) showed homozygous deletion of D13S319 (13q14). ATM deletion is associated with progressive disease and poor prognosis in cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).He did not have any other previous history of malignancy or hematologic disorder. Discussion: B-cell chronic lymphocytic leukemia is one of the common lymphoproliferative disorders in the adult patient population. To make a diagnosis requires absolute lymphocyte count 〉4x10 9 and lymphoid cell morphology. In CLL, leukemic cells are small and mature appearing lymphocytes, which have regular nuclear and cytoplasmic outlines and scant weakly basophilic cytoplasm. Surface markers that define a CLL cell are proteins such as antibody light chains (kappa or lambda) and CD proteins (CD5, CD19, CD20, and CD23). In our patient absolute lymphocyte count was 11.5x109 and lymphocytic population showed surface marker lambda light chain and CD proteins CD5, CD19, CD20 and CD23 which was consistent with CLL/SLL on inguinal lymph node biopsy, but morphology of lymphocytes was small and mature bi-nucleated lymphocytes, which is very uncommon. Although bi-nucleated lymphocytes are described in a disorder "Polyclonal chronic B-cell lymphocytosis with bi-nucleated lymphocytes". Detection of an extra chromosome for the long arm of chromosome 3 +i(3)(q10) has been considered a specific marker of Polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL),which was not present in our case. One case study by Amouroux et al, included four patients with B-cell CLL who were found to have bi-nucleated lymphocytes. Disease course was stable in one patient, one patient had an indolent course and only one required treatment due to rapid doubling time of lymphocytes. Our patient initiated chemotherapy with Rituxan and Fludara, as he had progressive disease with hepatosplenomegaly, lymph nodes and bone marrow involvement. Conclusion: Bi -nucleated lymphocytes in B-cell CLL are very rare. Explanations as to the etiology of this morphological feature in B-cell CLL is unknown. There is no sufficient evidence that bi-nucleated lymphocytes in CLL has any impact on disease progression. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4663 Background Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. The incidence of cerebrovascular accident (CVA) in young adults has been increasing. Since the etiology of CVA in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report 2 cases of ischemic stoke in young adults with multiple risk factors. Case Report No. 1. A 46-year-old male presented to the ER with loss of consciousness. Past medical history was unremarkable. MRA confirmed occlusion of the left posterior cerebral artery. Transesophageal Echocardiogram (TEE) revealed a patent foramen ovale (PFO) and atrial septal aneurysm (ASA). Hypercoagulable evaluation confirmed increased IgM anticardiolipin antibody, a lupus anticoagulant, and heterozygous MTHFR (Methylenetetrahydrofolate reductase) C677T mutation. Anticoagulation therapy was started with Heparin and then switched to Coumadin. Aspirin was also initiated along with folic acid, Vitamin B6 and B12, and smoking cessation therapy. Unfortunately, the patient developed hemiparesis and dementia after stroke. No. 2. A 50-year-old female presented to the ER with headache and blurred vision for one hour. Patient had cerebrovascular accident (CVA) 7 years prior to that event. She has been taking aspirin. MRI confirmed encephalomalacia in the left cerebellar hemisphere. TEE revealed a PFO. During the PFO closure procedure, an atrioseptal defect and a myxomatous were diagnosed. Patient was directed to use clopidogrel for at least six months after procedure, and aspirin indefinitely. Discussion The differential diagnosis for potential etiology in young people (under 55 years of age) of CVA is broader than that for older adults. Ischemic strokes are much more common than hemorrhagic in this group of patients. The atypical causes are more prevalent in the younger population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease needs to be considered. Cardiogenic cerebral embolus is the most common cause of stroke in young adults. Stroke can be associated with abnormalities of the atrial septum, specifically PFO, atrial septal defect (ASD), aneurysm, and cardiac myxomas. Studies show that the prevalence of PFO in patients who have stroke of unknown cause (cryptogenic stroke) may be about 40 percent. More specifically, PFO increases the rate of paradoxical thromboembolic stroke that occurs by allowing blood clots from the venous system to enter the arterial system. This is particularly true in patients who have had a stroke at an age less than 55 years. PFO closure procedures may help to identify underlying causes of CVA, as was discussed in case 2. Some studies have described an association between atrial septal aneurysm (ASA) and embolic strokes. The embolus might originate in an ASA or from a clot around the edges of a PFO. The mechanism of cerebrovascular events with ASA may be platelet/thrombus formation at the site of the aneurysm. Aspirin may be effective therapy for preventing CVA. Emboli from cardiac myxomas also can lead to cerebral ischemia, infarction, and aneurysm formation. Up to half of cardiac myxomas produce systemic emboli. Consequently, studies show that inherited thrombophilic disorders in the pathogenesis of stroke might relate to congenital heart diseases. The data suggests that Factor V Leiden G1691A mutation or Prothrombin G20210A variant may be associated with PFO. An increased prevalence of right-to-left shunts in patients with cerebrovascular accident CVA and activated protein C resistance has also been documented. Antiphospholipid Antibody Syndromes (APS) are recognized as independent risks for Cerebrovascular Accident (CVA). APS are associated with a heterogeneous group of disorders that result in hypercoagulable states involving arterial and venous thrombosis. Cerebral circulation is particularly affected in APS. Conclusion Based on these observations, the authors conclude that hypercoagulable testing should be performed in young patients with CVA. In addition, PFO closure procedures may be an important diagnostic tool that helps to identify a subset of patients in whom the etiology of CVA was not apparent. Disclosures: No relevant conflicts of interest to declare.