ALBERT

Description: Introduction Immune thrombocytopenic purpura (ITP) is a common cause of acquired thrombocytopenia in an otherwise asymptomatic adult. It is generally believed to be caused by auto- antibodies against platelet antigens that destroy platelets peripherally and autoreactive cytotoxic T cells, as well as humoral and cellular autoimmunity directed at megakaryocytes, causing impaired platelet production. Cytomegalovirus (CMV) is a known cause of cause of morbidity and mortality in patients with immunosuppressed states, whereas in immunocompetent patients, it commonly manifest as asymptomatic or mononucleosis like syndrome. We are presenting a case of CMV induced thrombocytopenia with severe epistaxis and platelet count of 0 x10 9 in an otherwise healthy immunocompetent male who failed to improve after standard treatments with high dose steroids and intra venous immune globulin (IVIG). Case Description A 36-year-old Caucasian male without any past medical history presented to emergency room (ER) with flu like symptoms for five days associated with subjective fevers, anorexia, nausea, cough and weight loss of 15 lb. in two weeks. He also reported possible tick bite while working in the yard two days prior to admission. No dizziness, vomiting, diarrhea or any bleeding were reported. Denied any smoking, alcohol use or any illicit drug use. No significant family history was reported. On evaluation he was afebrile, normotensive with normal heart rate and respiratory rate. Physical examination was unremarkable. Initial laboratory data revealed hemoglobin of 11.2, platelet count 4 x109, white cell count of 13,100 with 4.5% atypical lymphocytes, aspartate aminotransferase of 41, alanine aminotransferase of 49, and creatinine of 1.4. He tested positive for Influenza A, CMV Immune globulin (Ig)M and IgG antibody. Serological tests for tick panel including anaplasma, babesia, Lyme disease and ehrlichia were negative. Epstein-Barr virus (EBV) antibody, parvo virus antibody, hepatitis screen, HIV screen, auto antibodies including anti-nuclear antibody and anti-double stranded DNA were negative. Coombs test was negative. Further work up includes ADAMTS13 activity was normal. No laboratory evidence of ADAMTS13 deficiency. After excluding all other causes, diagnosis of ITP was made. He was started on Tamiflu for Influenza A and high dose intra venous (IV) methyl prednisone for ITP. After platelet transfusion and two days of IV steroids platelet count improved 43 x 109 and he was discharged home with prolonged prednisone taper. Five days later, he presented to ER with severe epistaxis. Laboratory data revealed platelet count of 0 x109. Serum CMV-DNA was determined by PCR showed viral load of 8,790 copies/ml. Ultrasound abdomen showed mild splenomegaly. He received three doses of IVIG (1g/kg). Platelet count failed to improve after administration of IVIG. Bone marrow biopsy revealed hyper cellular marrow with trilineage hematopoiesis with no increase in CD 34 blasts. Per infectious disease and hematology recommendations, he was started on valganciclovir (900 mg PO BID). One month later, platelet count improved to 150 x 109 and CMV viral load dropped to 413 with subsequent resolution of patient's symptoms. Discussion Secondary ITP is an acquired thrombocytopenia caused by autoantibodies against platelets. Many patients with ITP are asymptomatic. For those who do have symptoms, initial presentations of ITP are petechiae, purpura and epistaxis, with a more severe progression to intracranial hemorrhage or gastrointestinal bleeding leading to a fatal outcome, if treatment is not started on a promptly manner. CMV induced thrombocytopenia in immunocompetent adults seems to be rare. we are presenting a case of CMV induced ITP which failed to improve after standard treatment with high dose steroids and IVIG but responded to anti-viral therapy with valganciclovir. In conclusion, it may be worthwhile to test for CMV infection in patients presenting with ITP. Further research is needed in order to establish treatment guidelines for CMV induced ITP in immunocompetent adults. Disclosures No relevant conflicts of interest to declare.

Description: Adult patients with Sickle Cell Disease (SCD) develop overt proteinuria; microalbuminuria precedes overt proteinuria in Pediatrics. Prior Pediatric cross-sectional studies have evaluated the prevalence and associations of laboratory variables with the presence of microalbuminuria (MiA). This study utilized a prospective SCD nephropathy cohort study to understand the incidence, risk factors, and predictors for the development of MiA. Then, we tested the hypothesis that severe anemia as an infant or toddler, independent of future blood counts, clinical course, or therapies, would be predictive of developing microalbuminuria during adolescence. Methods: We are conducting an IRB approved Pediatric SCD Nephropathy cohort of patients with HbSS or SB0 thalassemia (n=152). We record every standard of care urine albumin/creatinine level obtained since birth (n=595) for each participant in our cohort along with their blood pressure, SCD therapy, complete blood count, and estimated glomerular filtration (cystatin C) from that visit. Patients were classified as having microalbuminuria if their urine albumin/creatinine was ≥ 30 mg/g using a Siemens DCA Vantage Analyzer. T-tests and chi-squared tests were used to compare individual demographic and clinical characteristics for continuous and categorical, respectively, of those patients who developed at least one episode of MiA using SAS 9.4. Next, we used a combination of left, right and interval censored data in a time to development of MiA model. To examine the incidence of MiA and its predictors, we utilized univariate and multivariate parametric survival regression models assuming a logistic distribution. To examine the predictive ability of a single CBC early in life for the development of MiA, we utilized logistic regression and computed the area under the receiving operating characteristics curves (AUC). Based on Baby HUG data, we used a hemoglobin

Description: Introduction: Venetoclax is a highly selective, orally bioavailable BCL2 inhibitor which binds to the BH3 domain of BCL2, displacing proapoptotic proteins such as BIM and BAX that once released facilitate induction of apoptosis. Venetoclax is indicated for the treatment of patients with newly-diagnosed acute myeloid leukemia (AML) who are 75 years or older or have other medical conditions that prevent the use of standard chemotherapy. There are many side effects associated with use of venetoclax. Vitiligo has not been reported as a side effect of Venetoclax. We are presenting a case of vitiligo induced by Venetoclax in a patient with AML. Case description: 71-year-old Caucasian female with ECOG performance status of 2, presented to Hematology/oncology clinic for evaluation for persistent thrombocytopenia. Past medical history is significant for hypothyroidism, essential tremor and chronic fatigue and weakness. Review of systems revealed fatigue, generalized weakness, easy bruising, tremors and weight loss of 10 pounds in 6 months. She denied any fevers, chills, gross bleeding. or any other systemic symptoms. Family history is significant for sarcoma (father). Denied any smoking, alcohol or illicit drug use. Vitals were stable. Physical examination revealed bruising on both arms and legs. Initial laboratory data showed hemoglobin of 10.7, White blood cell count of 3000 with 43% lymphocytes, and platelet count of 15000. Flow cytometry showed 17% blasts and Bone marrow biopsy revealed AML, non-APL type with 30 % blast cells. Karyotype 46, XX. FISH did not reveal any of the common abnormalities observed in MDS. Molecular analysis showed no abnormalities in FLT-3, IDH1/IDH2, NPM1 or CEBPA. Given her performance status, she was not considered a candidate for intense chemotherapy. She was started on low dose cytarabine 20 mg/m2 SQ QD from days 1 to 10 every 28 days with venetoclax 100 mg PO q daily titrated up to 600mg per day. Venetoclax was discontinued on day 10 of treatment due to neutropenia, diarrhea and fatigue. Bone marrow biopsy after one cycle of treatment showed a complete response. Cytarabine was discontinued due to poor tolerability and venetoclax was restarted at 200mg per day. 6 weeks after restarting venetoclax, she developed a mildly painful erythematous macular rash, initially noted in her hands but then extending to neck and chest. The rash then became hypochromic. She was evaluated by dermatology and diagnosed with venetoclax induced Vitiligo. Venetoclax was discontinued secondary to recurrent diarrhea and pancytopenia and then restarted at 100mg per day after recovery from pancytopenia. There was complete resolution of the vitiligo during discontinuation of venetoclax, with recurrence shortly after reinitiating the medicine. She was treated with topical corticosteroids and kept on venetoclax. Discussion: Venetoclax is a selective small-molecule inhibitor of BCL-2, an antiapoptotic protein. It is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and newly diagnosed AML in patients who are not candidates for intense chemotherapy. Adverse events associated with venetoclax include pancytopenia, electrolyte abnormalities, fatigue, edema, tumor lysis syndrome, increases serum AST, diarrhea, upper respiratory infections, fever and rash. To our knowledge, this is the first reported case of vitiligo induced by venetoclax. Skin reactions, including vitiligo should be considered as potential side effects of this medication. Figure Disclosures No relevant conflicts of interest to declare.

Description: Several potential risk factors are being evaluated for their impact on the development of chronic kidney disease (CKD) in patients with Sickle Cell Disease (SCD). Recent studies in animals, children and adults without SCD, have established that acute kidney injury (AKI) can lead to CKD, yet the risk of repeated AKI events during vaso-occlusive crisis (VOC) has not been defined in SCD. During VOC events, patients may be at risk for developing AKI due to the use of nephrotoxic pain medications, dehydration (poor concentrating ability), hemolysis, or inflammatory responses. Multiple gaps in our understanding of AKI in SCD patients need to be addressed. Methods: In order to improve our understanding of the incidence, risk factors, and outcomes associated with AKI, we conducted a two year IRB approved retrospective review of 234 episodes of ICD-10 defined VOC admitted from Children's of Alabama Pediatric Emergency Department (ED). AKI was defined by KDIGO definition of an increase in serum creatinine (SCr) by ≥ 0.3 mg/dl or 50% increase in serum creatinine from baseline. Baseline labs were defined as the most recent outpatient laboratory value and within 12 months from admission. Thirty seven admissions were excluded as their baseline SCr could not be established. Variables analyzed included age, gender, SCD genotype, baseline and admission CBC (hemoglobin (Hb) value, white blood cell count (WBC), absolute neutrophil count (ANC), platelet count, and absolute reticulocyte count (ARC)), length of stay (LOS), and SCD modifying therapy. Generalized mixed effects model for binary outcome with random intercept, to accommodate repeated hospitalizations for the same subject, was fitted to assess the associations between clinical variables and AKI for all patients and severe phenotypes. Similarly, a generalized mixed Poisson effects model with random intercept was fitted to determine if AKI was independently associated with hospital length of stay. Results: Among 197 admissions for VOC, 33 (17%) were identified with AKI. Seventeen (52%) of the thirty three AKI events were first diagnosed in the ED. Compared to children without AKI, patients with AKI had a larger drop in hemoglobin from baseline at admission (0.5 vs. 1.21g/dL, p=0.005). For every 1 unit drop in Hb from baseline to admission, the odds of AKI increased by 49% (OR= 1.49, 95% CI 1.1-2.0). We identified no differences in AKI vs. no AKI by age, gender, SCD genotype, or SCD modifying therapy, change in WBC, ANC, Platelets or absolute reticulocyte count. In multivariate analysis accounting for age, gender, change in blood counts, SCD genotype or therapy, a drop in Hb remained the only significant variable (OR= 1.48, 95% CI 1.05-2.1). Patients with AKI admitted for vaso-occlusive crisis required significantly longer length of stay. The average LOS for those with AKI was 32% longer than the without AKI (OR 1.32, 95% CI 1.10-1.58). Conclusion: Seventeen percent of SCD patients with pain admitted to the hospital can present with or develop AKI. An acute drop in hemoglobin is a major risk factor for developing AKI. Patients that develop AKI require longer hospitalizations for their pain crisis, independent of potential confounders. Research should focus on pathophysiology of kidney injury in patients with SCD, the impact of nephrotoxic medications, and the role by which AKI leads to CKD in this population. Disclosures Askenazi: AKI foundation: Consultancy, Speakers Bureau; BTG: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Baxter: Consultancy, Speakers Bureau. Lebensburger:American Society of Hematology, Scholar Award: Research Funding; National Institutes of Health: Research Funding.