ALBERT

Description: Background: PMBCL is a recognized separate entity within the group of diffuse large B-cell lymphoma (DLBCL) (Harris et al, Blood, 1994) with clinical, pathological and recently described molecular distinctiveness. It typically presents as a bulky mediastinal mass with the SVC syndrome, early stage disease, occurring predominantly in young females. The therapeutic approach has paralleled that of DLBCL consisting of anthracycline based regimens with or without the addition of radiation therapy (RT). In recent years, the use of rituximab has become part of the treatment of DLBCL, with outcome improvement demonstrated in patients 〉60 years of age (Coiffier et al, NEJM 2002) and recently 10 cm or 〉 1/3 of the thoracic diameter) was present in 7 patients; SVC syndrome was seen in 3. None of the patients had marrow involvement. Median follow up was 13 months (range 9–47). All patients received 4–6 cycles of R-CHOP. Two patients received maintenance rituximab (one received 4 weekly treatments at 6 months and the other received 4 weekly treatments at 3 and 6 months). RT was given to 6 patients. Eight patients had a complete remission (CR) following R-CHOP and two patients had near CR (〉 90% reduction); they subsequently achieved CR after the RT. Conclusions: Great variations of CR rates in the treatment of PMBCL, ranging from 10 to 95% for anthracycline containing regimens have been reported in the literature. Reported CR rates for CHOP alone range from 45–80% and optimal anthracycline based therapies are still being debated. Regardless of the initial regimen, failure patterns most commonly described in PMBCL were either no response to initial treatment or early progression, typically seen within 6 to 12 months. All of our patients achieved and remain in CR with a median follow up of 13 months. We recognize the limitations of our study (i.e. short median follow up, absence of control group, heterogeneous therapeutic approaches). However, this retrospective analysis demonstrates that the addition of rituximab could potentially contribute to the initial response to CHOP in comparison to traditionally reported CR rates found in the literature. Long term follow up in a larger series is necessary for the assessment of outcome improvement with the addition of rituximab in PMBCL patients. Charcteristics of 10 PMBCL patients treated with R-CHOP Median age (yrs) (range) 30 (22–56) Female/Male 7/3 Low IPI Score (total) (%) 8 (80%) High LDH (total) (%) 9 (90%) B Symptoms (total) (%) 2 (20%) Stage I and II (total) (%) 8 (80%) Bulky Disease (total) (%) 7 (70%) SVC Syndrome (total) (%) 3 (30%) High Beta2 microglobulin (total) (%) 0 (0%) Bone Marrow Involvement (total) (%) 0 (0%) RT (total) (%) 6 (60%) CR (total) (%) 10 (100%) Median Follow up (mts) (range) 13 (9–47)

Description: Abstract 4402 Background: Professional, evidence-based guidelines are developed to help physicians implement best practice care. Unfortunately, guidelines are not followed. Platelet transfusion guidelines have recently changed to a prophylactic transfusion threshold of 10, 000/μ L from the older threshold of 20,000/μ L. We conducted a retrospective analysis at a metropolitan teaching hospital to assess how well physicians comply with the new professional guidelines as well as the older, less stringent criteria to administer platelet transfusions. Methods: All patients admitted to the medical service who received platelet transfusions over a two month period in 2010 were reviewed. These patients represented the following services: ICU, general medicine, medical step down, interventional cardiology, CCU, and the cardiac step down unit. The indication selected in the computerized physician order entry (CPOE) system was compared to the clinical indication found in the patients’ medical record. The medical record clinical indication was then evaluated against the American Society of Hematology (ASH) 2007 “Evidence-Based Platelet Transfusion Guidelines” (Slichter SJ. Hematology 2007): bleeding and platelets ≤50, 000/μ L, pre-invasive procedure and platelets ≤50, 000/μ L, prophylactic transfusion for platelets ≤10, 000/μ L and WHO bleeding grade ≥ 2. We also assessed how the patients’ clinical indication met the older less stringent prophylactic threshold for platelet transfusion of ≤20, 000/μ L laid forth by the landmark study by Gaydos LA. et. al. (The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J Med 1962). Results: A total of 108 patients received platelet transfusions; 29 were medicine patients to tally 95 platelet transfusions. The most common patient clinical indication was “platelets ≤ 20, 000/μ L without bleeding” (27%), while the clinical indication was not specified in 16% of cases. The CPOE documented indication coincided with the patient's clinical indication from the medical record in 23% of cases. Sixty five percent of the time the patient's clinical indication failed to meet the currently accepted 2007 ASH guidelines and 36% of cases failed to meet the older less stringent guidelines. Conclusions: A majority of platelet transfusions did not meet the current professional guidelines for indication. Our pilot study suggests the need for more physician education regarding evidence-based guidelines for platelet transfusions, and in a larger context, initiatives to enhance compliance. We are currently developing an educational intervention and plan to reassess compliance with indications pre and post intervention. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: A restrictive approach to blood transfusion was shown to be safe and effective over a decade ago, but liberal transfusion practices prevail in many institutions. In 2012, the American Association of Blood Banks published its guidelines encouraging a restrictive approach to transfusions (Carson, B J. et al. Ann Intern Med. 2012;157(1):49-58). In 2013, the American Society of Hematology, along with the American Board of Internal Medicine began a "Choosing Wisely" campaign to educate physicians to limit unnecessary blood transfusions (L K Hicks, et al. Blood. 2013 Dec 5;122(24):3879-83). These guidelines were based on over a decade of published research demonstrating the non-inferiority (and occasionally superiority) of the restrictive approach. Hemodynamically stable patients do not benefit from transfusions to a Hb 〉9 g/dl. (Bush, R et al. Am J Surg. 1997; 174: 143-148; Hebert, P et al. N Engl J Med 1999; 340:409-417; Barkun A N et al. Ann Intern Med. 2010; 152: 101-113; Carson, J L N Engl J Med 2011; Carson JL et al. Am Heart J. 2013; 165: 365: 2453-2462; Holst, L et al. N Engl J Med 2014;371:1381-91;). Our hospital started an active patient blood management (PBM) program in January 2013 with intensive educational lectures for all departments, addressing physician trainees as well as senior physicians. This led to a modest drop in blood utilization, but many patients continued to receive liberal transfusions. In July 2013, our institution hired a transfusion safety officer (TSO) to review all orders for blood transfusion that fell outside of the medical board approved guidelines (a restrictive policy). This report details the results of our activities and highlights the importance of one-on-one education to change practices that are ingrained over time. Methods: In January 2013, educational lectures along with pocket cards containing restrictive indications were given to the Internal Medicine, ICU, Surgical, and Ob/Gyn house staff to promote a restrictive transfusion approach. In July 2013, a TSO was hired to supplement educational efforts regarding PBM. The TSO underwent training and then trained the blood bank staff. By January 2014, the entire technical staff was trained to screen all packed red blood cell (pRBC) requests prospectively for compliance with the medical board guidelines (transfuse for Hb

Description: Background Immunoglobulin (IVIG) is used to treat autoimmune conditions, but there are reports of brisk hemolysis within 48 hours (hrs) of treatment due to anti-A isohemogglutinins(1). Despite these reports, hemolysis remains an unrecognized side effect of IVIG. Methods We presented a series of 3 cases of IVIG-induced hemolysis in patients with autoimmune neurological disorders. In the investigative phase, we traced the cases to a common IVIG lot number. The sample was tested to determine the anti-A titer levels. Case Studies (See Table 1) Case 1 75-year-old man presented with SOB and dysarthria from myasthenia gravis (MG). He received IVIG for 4 days. He developed a hemolytic anemia with 3 g drop in hemoglobin (Hb) 48 hours later. He needed a pRBC transfusion and folic acid. Case 2 59-year-old female with history of MG treated with IVIG at another hospital until 3 months earlier in crisis, with SOB and dysphagia. She received IVIG for 5 days and rituximab. She improved and was discharged, but returned to the ER 7 days later with SOB. Her Hb fell to 8.0 g/dL from 13 g/dL on last admission. She required a pRBC transfusion, folic acid, and vitamin B12 with improvement of SOB. Case 3 20-year-old female admitted for lower extremity weakness, diagnosed with presumed syndrome (GBS). She received IVIG for 4 days. On the 5th day, her Hb fell from 15 g/dL to 9 g/dL. She began prednisone, folic acid, and vitamin B12 with improvement in her Hb. Conclusions Although acute hemolysis is well described in the literature, it is under recognized, as exemplified by the first two cases. Their initial SOB was due to MG, so when SOB recurred, they were misdiagnosed with recurrent MG. A hemolytic anemia was later suspected, and a work up revealed a positive DAT. The initial eluate was negative against type O panel cells, suggesting a drug related hemolysis. It was only when the eluate was tested against type A cells that the etiology became clear. The third patient's hemolytic reaction was then rapidly identified. These cases remind us to consider IVIG induced anti-A hemolysis in patients who are blood type A and AB, and to evaluate the eluate against the appropriate reagent cells. These patients should receive specific IVIG that is low in anti-A isohemagglutinins. Since the second patient did not hemolyze from earlier exposure to IVIG, she likely received a low titer product. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4386 Background: Progressive multifocal leukoencephalopathy (PML) associated with natalizumab in multiple sclerosis (MS) treatment is a complication for which therapeutic plasma exchange (TPE) has been used. We describe such a case treated with TPE. Case Report: A 54 year old woman with a past medical history of relapsing-remitting MS presented with recent onset ataxia and bilateral upper and lower extremity weakness and right hand dysmetria. Two weeks prior to presentation, she completed 57 treatments with natalizumab, a monoclonal antibody against cellular adhesion molecule α4-integrin that blocks lymphocytes from crossing the blood-brain barrier. Brain MRI showed new non-enhancing lesions in the right cerebellum and anterior left temporal lobe. Natalizumab was discontinued and investigation revealed high serum and CSF titers of JC virus DNA indicative of PML. The patient underwent a total of 3 TPE's (1 every other day) with 3L of 5% albumin solution (1.4 plasma volume [PV]) used as replacement each TPE. After TPE, the patient initially showed improvement of neurological function and was transferred to inpatient acute rehabilitation. However, 4 days later she suffered a seizure and developed slurred speech. MRI showed that the cerebellar lesion had extended into the pons. The patient also developed dysphagia requiring nasogastric tube feeding and poorly-localized pain requiring pain management. She was treated with steroids for possible Immune Reconstitution Inflammatory Syndrome (IRIS) and discharged to hospice care for rehabilitation and pain management. The patient's condition continued to deteriorate and she died shortly after being arriving at hospice. Conclusion: Natalizumab selectively immune suppresses the CNS putting patients at risk for PML and TPE with or without immunadsorption, can rapidly reverse the immune suppression by clearing natalizumab. Although we did not measure natalizumab concentrations in our patient, 1 report showed that a series of 3 TPE's (1.5 PV) significantly decreased natalizumab levels while another showed that 3–5 TPE's (1–1.5 PV) was effective. The effect of reducing natalizumab is to exchange the problem of a typically fatal opportunistic infection for the problem of an aggressive potentially injurious immune response to that virus. IRIS itself requires intense management to prevent brain injury or death and while there is no set standard of care, steroids are typically used. According to the manufacturer's global monitoring system, the majority of natalizumab induced PML cases are treated with TPE which typically induces IRIS within days to weeks. The most recent mortality rate for all PML cases related to this drug is 22%, significantly lower than that seen with AIDS or in the oncology setting. Although our patient initially improved after TPE, the proximity of the PML to her brainstem, with or without IRIS, made her particularly vulnerable. Whether TPE may lead to more severe IRIS, as suggested by one report, requires further study. Nevertheless, given the severe consequences of PML itself, we would recommend TPE for natalizumab -induced PML. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4708 Background: Treatment of CNS hemorrhage in patients on anti-platelets usually includes transfusion of platelets. Management of bleeding in other sites has not been thoroughly studied. Objective: To identify practice patterns of treatment of hemorrhage in patients on anti-platelets (aspirin and clopidogrel) at a tertiary care hospital within a 3 month period. Methods: This is a retrospective chart review. The Emergency Department provided a list of admitted patients. Target population was identified using the Emergency Department computer system. The patients chart was used in order to extract the following data: age, gender, co-mobridities, medications, baseline and lowest hemoglobin, platelet count, international normalized ratio, partial thromboplastin time and thrombin time, source and type (spontaneous vs trauma) of bleeding, use of packed red blood cells transfused within the first 24 hours, transfusion of platelets; prothrombin complex concentrate; fresh frozen plasma; factor VII; use of desmopressin, surgery or endoscopy within 48 hours from admission. Bleeding was categorized as life threatening, major or minor according to the International Society on Thrombosis and Hemostasis criteria. Statistical analysis was performed with the use of Excel (Microsoft). Results: 31 patients with bleeding on anti-platelets were admitted from April 2012 to June 2012. Baseline characteristics and treatment practices are summarized in Table 1. The majority of the bleeds were due to aspirin alone, and anti-platelet agents were discontinued 93% of the time. Most bleeds requiring admission were classified as either life threatening or major. Frequency of packed red cell transfusion in life threatening bleeds was 5/6 (83%), 11/17 (65%) in major bleeds and 2/8 (25%) in minor bleeds. 4 patients were transfused with platelets (one had a CNS bleed), all had the anti-platelets discontinued and they had lower platelet counts compared to non transfused patients [93.2(84) vs 217(80.3), p=0.02]. No patient required desmopressin. All patients who had their anti-platelets continued had minor bleeds. All the bleedings stopped within 48 hours from admission and no deaths secondary to hemorrhagic shock were recorded. Discussion: This is a quality assurance project to assess current physician practices for the management of bleeding in patients on anti-platelet agents. Except for the actual platelet counts, there is no obvious difference between patients transfused with platelets vs non-transfused. At our institutions, anti-platelet related major bleeds are not routinely managed with platelet transfusions. There is a need for additional research to better clarify management. Our study is limited by the fact that it is a retrospective, single institution study. Furthermore, bleeding in inpatients on anti-platelets was not assessed. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4331 Intro: Evidence-based guidelines are developed and promoted to help physicians implement best practice care. The American Society of Hematology (ASH) platelet transfusion guidelines changed in 2007 to a prophylactic transfusion threshold of 10, 000/μL from the previous 20,000/μL. We conducted a retrospective analysis at a metropolitan teaching hospital to assess how well physicians are complying with the new professional guidelines as well as the older, less stringent criteria to administer platelet transfusions. We then assessed the effect of an educational intervention on transfusion practices. Methods: All patients receiving platelet transfusions over a five-month period from Jan-Feb, and April-June 2010, admitted to the medical, critical care and cardiac services were reviewed. The medical record clinical indication was then evaluated against the ASH 2007 “Evidence-Based Platelet Transfusion Guidelines” (Slichter SJ. Hematology 2007): bleeding and platelets ≤50, 000/μL, pre-invasive procedure and platelets ≤50, 000/μL, prophylactic transfusion for platelets ≤10, 000/μL and WHO bleeding grade ≥ 2. We also assessed how the patients’ clinical indication met the previous prophylactic threshold for platelet transfusion of ≤20, 000/μL laid forth by the landmark study by Gaydos LA. et. al. (The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J Med 1962). Following initial data collection, we implemented an educational intervention by giving a lecture, reviewing all indications for platelet transfusions, and distributing a pocket card to the house-staff on the medical wards in August, 2010. We subsequently gathered post-intervention data following the methods described above for four consecutive months from Sept-December, 2011. Results: Eighty-six patients on the selected units received a total of 241 platelet transfusions. Fifty nine percent of the time the patient's clinical indication failed to meet the currently accepted 2007 ASH guidelines and 37% of cases failed to meet even the older guideline. Eighty-one patients received a total of 237 platelet transfusions post-intervention. Forty-seven percent of the time the patient's clinical indication failed to meet the currently accepted 2007 ASH guidelines and 19% of cases failed to meet the older guideline. Conclusions: Based on the significant difference observed between the pre- and post-educational intervention groups, our initial study shows that updating physicians on current evidence-based guidelines for platelet transfusions is a simple and effective means to improve transfusion practices. Periodic educational interventions may prove to even further enhance physician compliance with up-to-date guidelines and we plan to implement additional educational interventions throughout the upcoming academic year. Disclosures: No relevant conflicts of interest to declare.

Description: Background: The characteristics of post-surgical thrombocytopenia have not been well described. Interpretation of the reported data was potentially confounded by the fact that many of the patients were receiving heparin.1,2 We aimed to evaluate the post-operative thrombocytopenia in orthopedic surgery patients who were not exposed to heparin in order to better define the characteristics of this phenomenon. Methods: A retrospective chart review was conducted on patients who underwent a knee or hip replacement from 2012 to 2015. Exclusion criteria were: age 65 years, compared to patients aged ≤65 years (p=0.004) as shown in Figure 2. Specifically, the average drop in PLT at nadir (day 2) relative to baseline was significantly larger in patients aged 〉65 years (mean PLTday2 - mean PLTday0 = -72.3x10^9/L) compared to patients aged ≤65 years (mean PLTday2 - mean PLTday0 = -47.5x10^9/L. Discussion: Our data demonstrate that reduction in PLT occurs frequently after orthopedic surgery in a non-heparinized population. This drop was seen in the majority of patients (92.7%) with the nadir occurring on day 2, as previously published.1,2 However, only 28% of patients were actually thrombocytopenic. In addition, five patients had an increase in PLT by day 1 without any significant drop below baseline thereafter. There was no significant association with regards to age, gender, or type of surgery to explain this rise in PLT. This study also highlighted several other points which have not previously been published in the literature. There was a significant difference in PLT reductions in patients 〉65 years compared to ≤65 years (24.8x10^9/L), suggesting that advanced age increases the risk of thrombocytopenia which requires closer monitoring. The etiology for the decreased PLT cannot be bone marrow suppression, since there was no concordant decrease in WBC count. The rise in WBC count suggests an inflammatory response that should have been reflected in a secondary thrombocytosis. This discrepancy is unexplained. Although 28% of patients experienced thrombocytopenia by day 2, the nadir remained 〉100x10^9, and only one patient had PLT below that level. Therefore, alternative causes should be considered in patients that experience severe thrombocytopenia post-operatively, as this was a rare finding in our study. Conclusion: Reduction in PLT is a frequent post-operative finding in orthopedic surgery patients, even after removing confounding factors such as heparin exposure, but clinical thrombocytopenia is uncommon. Nadirs typically occur by day 2. Alternative etiologies should be considered when PLT is 65 was associated with a more significant drop in PLT post-operatively. References: 1. Warkentin TE. Thrombocytopenia Caused by Platelet Destruction, Hypersplenism, or Hemodilution. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, editors. Hematology: Basic Principles and Practice, ed 6. Elsevier Inc.; 2013. p. 1895-912. 2. Greinacher A, Selleng K. Thrombocytopenia in the intensive care unit patient. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program 2010;2010:135-43. Figure 1 Trend of post-operative platelet counts. Figure 1. Trend of post-operative platelet counts. Figure 2 Post-operative platelet count profiles in patients aged 65 years. Figure 2. Post-operative platelet count profiles in patients aged 65 years. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2420 Poster Board II-397 Introduction: Pseudohyperkalemia represents an artificial elevation in serum potassium concentration. It is well described that patients with thrombocytosis may have elevated serum but normal plasma potassium. The difference between serum and plasma potassium is felt to be due to potassium release from platelets during clotting. We propose that a similar mechanism will lead to “pseudonormokalemia,” where serum potassium appears to be in the normal range (3.5-5.0 MEq/L) despite below-normal levels in the plasma(500,000/uL) to 68 control patients (platelets