Normal Complete Blood Count Research Articles

Lysinuric protein intolerance: an overlooked diagnosis

BackgroundLysinuric protein intolerance (LPI) is an autosomal recessively inherited inborn error of metabolism (IEM) caused by the defect in the dibasic cationic amino acid transporter found on the basolateral membrane of the lung, small intestine, and kidney due to mutations in the SLC7A7 gene, which encodes the y+LAT1 protein. LPI may present as an acute hyperammonemic episode or as chronic symptoms. Major clinical symptoms are feeding problems, vomiting and diarrhea, failure to thrive, hepatosplenomegaly, and cytopenia. We present a delayed diagnosis of symptomatic LPI with a homozygous mutation in the SLC7A7 gene.Case presentationA 15-year-old girl was referred to our clinic due to growth retardation and diarrhea. Physical examination showed short stature, retarded puberty, and hepatosplenomegaly. Laboratory tests showed normal complete blood count and biochemical analyses except elevated aspartate aminotransferase, triglyceride, total cholesterol, and ferritin. Peripheral blood smear and hemoglobin electrophoresis were within normal limits. Bone marrow analysis showed hemophagocytic cells. Postprandial ammonium level was found elevated. Low lysine, arginine, and ornithine and elevated glycine and alanine in plasma amino acid analysis and high amount of lysine and slightly elevated arginine and ornithine excretion in urine were detected. Molecular genetic analysis of the SLC7A7 gene showed a previously reported homozygous mutation. Low protein diet, sodium benzoate, l-carnitine, low-dose l-citrulline, and calcium replacement were initiated. The patient is now in good condition still being followed up in our department.ConclusionsLPI is a metabolic disorder with multi-systemic involvement that may have severe consequences if left untreated. Initiation of early treatment is essential for the prevention of severe chronic complications. Also, confirmation of the genetic defect may provide the parents to have healthy offsprings in the future with the help of genetic counselling and preimplantation genetics.

ACUTE DYSPNEA ASSOCIATED WITH CRAZY PAVING APPEARANCE

SESSION TITLE: Global Case Report Posters SESSION TYPE: Global Case Reports PRESENTED ON: October 18-21, 2020 INTRODUCTION: A ‘crazy-paving’ appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. We report a case 43 yrs old middle aged lady admitted with Acute onset of breathlessness with crazy paving appearance on chest Computed tomography of chest, secondary to heart failure. CASE PRESENTATION: Middle age lady with no other comorbidities admitted with complaints of sudden onset of breathlessness since today evening. At the time of presentation to emergency room she was dyspneic, Tachypneic, Tachycardia. Her vitals were HR 102/mt, RR 36/mt,spo2 86% on Room air, Bp 180/100mmhg. She was started on high flow oxygen and nebulized medications.Cardiac examination revealed a normal S1 and diminished S2, with no murmurs or extra sounds. Auscultation of the chest revealed inspiratory crackles bilaterally. His abdominal examination was unremarkable without organomegaly. Laboratory findings revealed a normal complete blood count and differential blood count. Serum electrolytes, liver and renal function tests were all normal.A chest radiograph (figure1) demonstrated diffuse airspace opacities on both sides of lung. A CT scan of the chest (figure2) was obtained showed diffuse, multifocal, patchy, ground-glass opacities with superimposed reticulations resulting in a crazy-paving appearance.Routine 2 D echo was done, revealed Rheumatic Heart disease with Severe mitral stenosis, Tricuspid stenosis and Moderate Tricuspid regurgitation,and diagnosed as acute decompensated heart failure. NT-pro BNP was 3450pg/ml. She was started on diuretics along with other medications. Repeated x ray (figure 3)showed complete clearance of airspace opacities. DISCUSSION: A ‘crazy-paving’ appearance of the lungs on a high-resolution computed tomography (CT) scan of the chest, defined as scattered or diffuse ground-glass attenuation superimposed on a network of interlobular septal thickening and intralobular lines. Initially, this radiographic pattern was thought to be specific for alveolar proteinosis, (1) but has subsequently been reported in a variety of interstitial and airspace pulmonary disorders (2,3) Although common, congestive heart failure and cardiogenic pulmonary edema have been reported previously as a cause for crazy-paving appearance in only in few cases. (3) CONCLUSIONS: Crazy-paving pattern on CT scan, once considered to be specific for pulmonary alveolar proteinosis, is now known to be nonspecific and may be seen in association with a wide spectrum of pulmonary diseases. Reference #1: Godwin JD, Muller NL, Takasugi JE. Pulmonary alveolar proteinosis: CT findings. Radiology. 1988;169:609–13. Reference #2: Johkoh T, Itoh H, Muller NL, et al. Crazy-paving appearance at thin-section CT: Spectrum of disease and pathologic findings. Radiology. 1999;211:155–60. Reference #3: Murayama S, Murakami J, Yabuuchi H, Soeda H, Masuda K. “Crazy paving appearance” on high resolution CT in various diseases. J Comput Assist Tomogr. 1999;23:749–52. DISCLOSURES: No relevant relationships by Nagarajan Appusamy, source=Web Response

Kinetics of pre-myelodysplastic syndromes blood values correlate with disease risk and survival.

We reviewed pre-diagnosis clinical data of 420 patients with pathologically confirmed myelodysplastic syndromes (MDSs) presenting with anemia. In 232 patients with yearly pre-diagnosis complete blood counts (CBCs), we also analyzed CBC kinetics in respects to a standardized timepoint in which all patients had similar levels of hemoglobin (Hgb). At the standardized timepoint (last documented 12 > Hgb ≥ 11 g/dL), occurring months-years before diagnosis, median CBC values were Hgb 11.4 g/dL, absolute neutrophil count (ANC) 2.7 × 103 (k)/mcl, and platelets (PLTs) 181 k/mcl. Gradual changes in CBC could be observed years prior to this timepoint, for the most part while within normal/near-normal limits. During this time, most patients had a coexisting alternative etiology for anemia. Patients with high-risk cytogenetic/blast features had a rapid and steeper decrease in counts in the last year before developing a concerning anemia (decrease in: Hgb 0.75 g/dL vs 0.55 g/dL; PLT 29.5 vs 4.5 k/mcl; ANC 0.86 vs 0.4 k/mcl, P = .03). Low-risk patients had a high rate of longstanding mild anemia (31% vs 16%, P = .05). Rate of development of cytopenia and number of involved hematopoietic lines were prognostic. In 65% of patients, with near normal CBC at the standardized timepoint, but in whom there was a decrease in multiple hematopoietic lines over the preceding year, the 5-year overall survival (5yOS) was 53% compared to 71% in patients with isolated slowly progressing anemia (20% of patients). In 15% of patients with mild cytopenia developing after both a rapid decrease and multiple involved lines, prognosis was dismal (5yOS 34%). In conclusion, kinetics of pre-MDS CBC values correlate with disease risk and survival.

Multiple Autoimmune Syndrome: An Unusual Combination of Autoimmune Disorders

Autoimmune diseases are multifactorial with environmental and heritable factors. Autoimmunity reflects an altered immune status, therefore the presence of more than one disorder is not uncommon. The coexistence of three or more autoimmune diseases in a patient constitutes multiple autoimmune syndrome (MAS). This is an interesting case of a middle-aged female who had celiac disease, primary biliary cholangitis, autoimmune hepatitis and evolving CREST (Calcinosis, Rhaynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasia) syndrome. Fifty years old female patient presented with generalized fatigue, fever, weight loss, vertigo and constipation. She was a diagnosed case of celiac disease, and responded well to glutenfree diet. Family history was unremarkable for any autoimmune disorder. Laboratory workup showed normal complete blood counts, markedly elevated transaminases and alkaline phosphates. Her antinuclear antibodies (ANA) test was strongly positive (>1:320) and showed an anti-centromere pattern. Anti-extractable nuclear antibody(ENA) assay showed anti-mitochondrial and anti- CENP B antibodies. Liver biopsy revealed overlap syndrome (primary biliary cholangitis and autoimmune hepatitis). This patient had celiac disease, primary biliary cholangitis and autoimmune hepatitis. Extensive immunological workup unexpectedly revealed the presence of anti-centromere protein B (anti-CENP B) antibodies which are strongly associated with CREST syndrome. Clinical re-evaluation of the patient gave clues of the evolving CREST syndrome. This case report highlights the importance of adequate immunological investigations in conjunction with clinical information for adequate patient management to achieve favorable consequences in the future. Patients suffering from an autoimmune disease need special attention as multiple immune- mediated disorders may be present simultaneously or sequentially during the course of the disease process. MAS patients are at a higher risk of acquiring infections and tumor development due to prolonged use of immunosuppressants. These patients need close surveillance for the development of another autoimmune disease, so as to control the current disease and to prevent future complications. This case report emphasizes the importance of a multidisciplinary team approach including an immunologist who may facilitate a better understanding of disorders related to the breakdown of immune tolerance.

Pancreaticoduodenectomy in a patient with intestinal malrotation and distal cholangiocarcinoma: a case report and review of the literature

BackgroundA combination of intestinal malrotation and distal cholangiocarcinoma is considered a rare condition and poses some difficulties in surgical management. We present a case of a patient with asymptomatic nonrotation of the midgut with a concomitant distal cholangiocarcinoma who underwent successful pancreaticoduodenectomy.Case presentationA 52-year-old Sudanese man presented to our hospital with progressive painless jaundice associated with dark urine, pale stool, and itching for the last 2 months. He had no other complaint or significant previous medical history apart from being an ex-smoker. His clinical examination revealed a palpable gallbladder and scratch mark. His other systems were unremarkable. His blood test results showed a normal complete blood count, elevated total bilirubin (mainly direct bilirubin), elevated alkaline phosphatase, and normal cancer antigen 19-9 and carcinoembryonic antigen. Ultrasound, computed tomography of the abdomen, and magnetic resonance cholangiopancreatography showed a dilated intrahepatic and extrahepatic biliary system down to the distal part, where the lumen was obstructed by a periampullary mass measuring 2.4 by 2.1 cm. The patient’s gallbladder was distended. He had no liver metastases or ascites and few lymph nodes. Inversion of the superior mesenteric artery and superior mesenteric vein but no invasion was seen, and malrotation of the bowel was observed with the large bowel on the left side and the small bowel to the right of the abdomen. Endoscopic retrograde cholangiopancreatography showed a fleshy ampulla that was stented. Laparotomy showed malrotation, with the duodenum straight on the right side of the midline, and Ladd’s band crossed the second portion of the duodenum. The vessels were approached from the lateral side meticulously after kocherization of the duodenum and pancreas, dissection along an extended portion of the superior mesenteric artery to assure preservation of the superior mesenteric artery and branches going to the jejunum, Ladd’s procedure, division of the jejunum 10 cm below the uncinate process of pancreas, and modified pancreaticoduodenectomy were performed, and anastomoses were performed in the standard fashion. The patient had an uneventful postoperative course, started oral feeding after 5 days, and discharged to home on day 10 for regular follow-up. Histopathology confirmed distal cholangiocarcinoma, and the patient was referred for further oncological management.ConclusionsPancreaticoduodenectomy can be safely performed in patients with intestinal malrotation with some modifications of the standard approach. Meticulous dissection after preoperative identification of vascular anomaly and a lateral approach are of great help to reduce morbidity.

ABCL-311: The Burden of Non-Hodgkin Lymphoma Developed in an Ataxia Telangiectasia Child

Context: Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by progressive neurologic impairment, cerebellar ataxia, immunodeficiency, ocular and cutaneous telangiectasia, and predisposition to malignancy. AT patients have a 100-fold increased risk for the development of lymphoid malignancies, particularly non-Hodgkin lymphomas (NHL). In these patients, severe pulmonary infections are the most frequent cause of death, followed by the combination of pulmonary infection and malignancy. Objective: Evaluation of a clinical case of hematologic malignancy in a child diagnosed with primary immunodeficiency (PID) AT. Methods: We analyzed clinical records, biopsy of lymph node, evaluation of serum immunoglobulins by ELISA, and neurologic involvement by MRI. Results: A 13-year-old boy diagnosed as AT was referred to the Oncologic hospital due to multiple lymphadenopathy. He was born to non-consanguineous healthy parents. Previous medical history revealed waddling gait when he started walking. He was consulted by a neuropediatrician as being suspected of cerebral palsy. Brain MRI revealed cerebellar vermis hypoplasia with enlargement of cisterna magna. The patient also experienced recurrent respiratory infections. At the age of 12 years, the patient had fever of unknown origin for several months, which was unresponsive to antibiotics, and the patient's cervical and submandibular lymph nodes began to enlarge, which progressed. A biopsy was performed, and the patient was diagnosed with NHL, DLBCL type. On presentation, the patient had multiple enlarged cervical, submandibular, axillary, and inguinal lymph nodes and telangiectasia of the bulbar conjunctiva. Neurologic examination revealed decreased tendon reflexes, ataxia, and dysarthria. Laboratory investigations identified a normal complete blood count and biochemistry tests, but the alpha-fetoprotein level was high. There were decreased levels of IgA and IgG and a high level of IgM. Computed tomography showed involvement of cervical, submandibular, axillary, upper mediastinum, and hilum lymph nodes. The patient received CHOP chemotherapy with a reduced dose. The treatment was well-tolerated, despite neutropenia, grade 3 mucositis, and neutropenic fever. Unfortunately, at the last interruption after chemotherapy, the patient had chickenpox and died due to multiple organ failure. Conclusions: Patients with PID have a high risk of developing cancer. It is important to consider AT in a child with pre-existing ataxia or hematologic malignancy that was diagnosed at a younger age than expected.

3154 – RHESUS MACAQUES AS NATURAL MODELS FOR AGE-RELATED CLONAL HEMATOPOIESIS

Clonal hematopoiesis (CH) describes the clonal expansion of blood cells derived from hematopoietic stem/progenitor cell (HSPC) sharing the same somatic mutations. Recent large deep sequencing studies revealed that CH somatic mutations are prevalent in peripheral blood cells of individuals without overt hematological abnormalities and become increasingly common and larger in clone size with age. While the risk of eventual progression to hematologic abnormalities or leukemia appears to be higher in individuals with CH, the parameters impacting on progression are unclear. In addition, CH confers a greater risk for cardiovascular disease (CVD) and possibly other systemic diseases. However, commonly used experimental animals such as mice do not develop CH and there is a lack of natural in vivo model organisms to investigate the mechanisms underlying CH development and malignant progression. We addressed this unmet need via the investigation of the rhesus macaque (RM) as a potential model organism for CH given the close phylogenetic relationship to humans and the associated comparable HSPC frequencies, replication times, telomere lengths and bone marrow environments. We assessed the incidence and variant allele frequency (VAF) of CH somatic mutations in 35 aged RM (median age 27) by error-corrected targeted ultra-deep sequencing of the exons from the top 56 human CH genes. We identified 7 animals (median age 30) carrying at least one somatic mutation in CH genes on this panel with a VAF between 0.5% to 11.4%. Furthermore, in one animal where longitudinal samples were available, we observed a gradual expansion of a one-base pair deletion in DNMT3A across multiple cell-lineage as a function of age. All animals showed normal complete blood counts and were without overt hematological malignancies. While we continue to expand our study cohort, data so far suggest that RM is a natural model for CH.

Secondary adrenal insufficiency: an insidious consequence of the opioid epidemic?

A 22-year-old woman was admitted to the medicine service with generalised abdominal pain and nausea. Medical history included a recent motor vehicle accident resulting in multiple orthopaedic injuries and development...

Vitamin B12 deficiency without anemia in the middle- and old-aged population in Sulaymaniyah City

Background: In our laboratory, we received many cases of Vitamin B12 deficiency without anemia, and we observed that the deficiency is more prominent in females than males. It is well known that Vitamin B12 deficiency is usually associated with macrocytic anemia. However, the clinical importance of Vitamin B12 insufficiency without any hematological abnormality is underestimated in the Sulaymaniyah city population. Thus, the aim of this study is to assess the frequency of Vitamin B12 deficiency with normal complete blood counts (CBCs), especially in the middle- and old-aged population. Materials and Methods: Within the period from April 2018 to April 2019, the patients came to the Dr. Hisham Alrawi Private Laboratory for Vitamin B12 level estimation; the CBCs for all patients with Vitamin B12 deficiency have been collected. We selected patients with low-level Vitamin B12, which were 149 patients, aged 30 years and above. Normal serum Vitamin B12 value in our laboratory is 191–633 pg/ml according to the e411 Roche competitive-binding luminescence immunoassay system. CBC has been collected were done for all patients with Vitamin B12 deficiency by Orphee Mythic 18 Hematology Analyzer. Results: The mean of their age is 64 years, and the mean of hemoglobin (Hb) level is 12.1 g/dL, whereas the mean of Vitamin B12 level is 131.3 pg/ml. About 74 (49.6%) of them have anemia, and 75 (51.4%) are with the normal CBC parameters. The mean of the Hb in females is with the normal range (12.1 g/dL), whereas the mean of the Hb in the males is lower than the normal range (12 g/dL). Conclusions: Vitamin B12 deficiency is common in middle and old age in Sulaymaniyah city, especially in females. Thus, screening programs for B12 levels estimation for this age group are recommended to avoid expected complications.

P1493 Univentricular heart diagnosed by echocardiography in a patient with good functional capacity

Abstract A 32 years old male without a history of cardiac disease or surgery was referred to our hospital due to abnormal findings on electrocardiography (ECG). He was a healthy active young man applying for private health insurance and did not have any symptoms. On physical examination he had normal vital signs and a systolic ejection murmur was present in the pulmonic area. His Oxygen saturation was 93% and had a functional capacity of 11 METs. On electrocardiography which is shown in part A and B of the figure, he had right axis deviation and poor R progression. On chest x-ray (part C of the figure) he had top normal cardiothoracic ratio and prominent main pulmonary artery (PA). On laboratory data he had normal complete blood count and normal electrolytes. Because of the murmur found in physical examination and the right axis deviation in ECG, transthoracic echocardiography was done for the patient which revealed single ventricle with left ventricle morphology and mild systolic dysfunction (part D of the figure). Abdominal and atrial situs were solitus. There was normal inferior vena cava continuity into the right atrium. Transesophageal echocardiography was also done for the patient which revealed thickening of the pulmonary valve and presence of a subvalvular web which resulted in severe subvalvular PS (part E and F of the figure). There were dilated main PA and its branches. The left sided atrioventricular valve had mild regurgitation while the right sided one had mild to moderate regurgitation. There was dilated coronary sinus due to persistent left superior vena cava. The case describes the role of echocardiography in diagnosing rare congenital heart disease in a patient without symptoms of cardiac disease. Abstract P1493 Figure

Study of some factors associated with prolonged neonatal jaundice

Objective The aim was to study some factors associated with prolonged neonatal jaundice and to find out the important investigations that should be performed to such cases. Background Prolonged neonatal jaundice represents a dilemma for many doctors. Many factors are responsible for its occurrence. Patients and methods This is a cross-sectional study on 55 cases of prolonged neonatal jaundice, conducted from Menoufia and Benha university hospitals from November 2017 to July 2018. All cases were subjected to history taking, clinical assessment, and investigations including complete blood count, c-reactive protein, total and direct serum bilirubin, blood group and RH factor for the cases and their mothers and urine analysis. We investigated cases with prolonged direct hyperbilirubinemia for alanine aminotransferase, aspartate aminotransferase and abdominal ultrasonography. Results Cases aged ranged from 14 to 49 days of life, with mean age '19.3 ± 5.3' that included nine preterm and 46 full term. Prolonged indirect neonatal hyperbilirubinemia was found in 85% of cases, while 15% had direct hyperbilirubinemia. All cases showed normal complete blood count. C-reactive protein is negative in all cases. Breast-milk jaundice was found in 32.7%, ABO incompatibility in 22%, while RH incompatibility in only 3.6% of cases. Pyuria greater than or equal to 6 pus cells/ High power field (HPF) was found in 20% of cases and they had higher serum bilirubin than the other cases without pyuria. Conclusion The most common associated factor was breast-milk jaundice, then ABO incompatibility and then pyuria. Blood group identification to the mother and their neonates and urine analysis have a great diagnostic value in these cases. Larger studies are needed to confirm these findings.

Acute Coronary Syndrome and Myocardial Ischemia in Hypertrophic Cardiomyopathy

47 years old male smoker with no co morbidities, presented with history of chest pain in the retrosternal area for the 3 days. The Pain was described as sharp, non-exertional and intermittent. Patient did not have any family history of known cardiac disease or sudden cardiac death. A Clinical examination failed to reveal any abnormalities. An ECG revealed deep T wave inversion in the anterolateral chest leads with left ventricular hypertrophy (LVH). Bloods analysis showed normal Complete blood count, liver function and mildly increased cardiac troponins. The Patient was admitted to the CoronaryCare Unit with a diagnosis of acute coronary syndrome. Patient was initiated dual antiplatelets, fondaparinux and high intensity atorvastatin. Following this, an echocardiogram revealed severe Left ventricular hypertrophy and reduced LV (left ventricular) cavity dimensions. Good LV systolic function with grade 3 diastolic dysfunction was noted. Coronary angiogram showed a normal right and left coronary system. Patient was diagnosed with hypertrophic cardiomyopathy. Cardiac MRI Showed severe Left ventricular hypertrophy with interventricular septum thickness 3.7 cm with rest of the walls hypertrophied. There was evidence of severe fibrosis of the septum, anterior and lateral wall. On the basis of severe left ventricular hypertrophy (especially septal thickness >3.5 cm) and myocardial fibrosis, Patient was started on beta blockers and ICD was inserted for primary prevention of arrhythmias.

A Patient with ACHOO – The Autosomal Dominant Compelling Helio-Ophthalmic Outburst syndrome

Case report: The patient is a 36-year-old woman who was referred to our allergy-immunology clinic by her primary care physician to be assessed for a possible allergic disorder. The patient states that since early teenage she has had frequent bouts of sneezing generally preceded by nasal itching and often occurring when she first goes outdoors. She denies having a chronic cough or wheezing and has no symptoms suggestive of allergic conjunctivitis or sinusitis. She has not had urticaria or anaphylactoid reactions. Her mother and 29-year-old sister have similar complaints but have never been assessed for possible allergies. The patient’s medical history is otherwise unremarkable. On physical examination her vital signs were within normal limits. Her conjunctivae were not inflamed or edematous and she had no edema or pallor of her nasal mucosa and no tenderness of her paranasal sinuses. Her lungs were clear to auscultation and free of wheezes on deep breathing. The remainder of her exam was unremarkable. Laboratory assessment revealed a normal complete blood count and metabolic panel. Skin testing to 66 regional allergens was negative, and her serum IgG, IgA, IgM, IgD, and IgE levels were within normal limits. Because she was suspected as having ACHOO, she was dark adapted and then exposed to a bright light which instantaneously precipitated her nasal itching and sneezing, confirming the diagnosis.

Caplacizumab As Step-up Therapy in Refractory TTP Utilizing Adamts-13 Activity and Evidence of End-Organ Damage

Background: Thrombotic Thrombocytopenic Purpura (TTP) is a form of microangiopathic hemolytic anemia that is classically characterized by the clinical pentad of fever, hemolytic anemia, thrombocytopenia, renal dysfunction, and neurologic dysfunction. The pathophysiology of acquired TTP is marked by autoantibody formation against ADAMSTS13, an enzyme responsible for breaking down von Willebrand Factor (vWF) multimers. Standard therapy for TTP includes both replenishing functional ADAMTS-13 and immune-modulation with plasma-exchange and steroids/rituximab, respectively. A novel therapy addresses the microvascular thrombosis hallmark of end-organ damage in TTP. Caplacizumab, a humanized immune globulin that inhibits vWF interaction with platelets, achieved its primary endpoint of faster time to platelet normalization than placebo in the Stage 3 HERCULES trial when given up-front with additional standard therapies. Case Summary: A previously health 26-year-old G3P2 female presented to the ED at 38 weeks gestation with fatigue and confusion. She was found to have a platelet count of 5,000 per microliter, hematocrit of 18.6%, lactate dehydrogenase (LDH) of 1,750 IU/L, and haptoglobin of 11mg/dL. Peripheral blood smear was remarkable for evidence of microangiopathic hemolytic anemia. She had a normal serum creatinine. She was diagnosed clinically with TTP and subsequently underwent emergent caesarian section. She was started on plasma exchange given her ADAMTS13 activity of 6% and features of severe TTP. Her neurological status and platelets initially responded well to plasmapheresis (PE) at 1x volume alone; however, on Day 6 her platelets decreased from 97,000 to 15,000 per microliter. This prompted initiation of both steroids, weekly rituximab and increasing PE to 1.5 x. She continued to be refractory and acutely declined on Day 7, during which she developed worsening headaches followed by seizure, renal failure with proteinuria, uncontrolled hypertension and increasing hemolysis. She required ICU admission and one session of hemodialysis. Despite increasing PE, steroids and rituxan, the patient's inhibitor peaked to 142 U/ml with an ADAMTS-13 activity of 0% on Day 9. PE was increased to 1.5 x volume twice daily. Caplacizumab was obtained and initiated on Day 10. Her platelets on Day 11 were at their nadir of 4,000 per microliter, with an inhibitor of 93.9 and an ADAMTS-13 activity of 0%. She remained in the ICU, where her mental status, renal function improved gradually. She was found with a reticulocyte index of 1.29, for which she was treated with Vitamin B-12 for a methylmalonic acid level of 798 nmol/L (range 87-318 nmol/L) and a low normal level of vitamin B-12. PE was stopped on Day 22 after confirming her platelet level remained >150,000 per microliter for more than three days. Her course was further complicated by aspiration, parainfluenza 3, MSSA bacteremia, and E Coli UTI, for which she received antibiotics and supportive treatment. She completed four cycles of rituximab on Day 27, and was discharged to home with a steroid taper and an additional 21 days of caplacizumab. She was readmitted three times during those 21 days for hemiplegic migraines. She achieved remission with normal complete blood count and ADAMTS13 >109% with an inhibitor 3 on Day 54, after which she was administered her last dose of caplacizumab on Day 56. Discussion: We detail the clinical and treatment course in our patient with severe, acquired TTP from pregnancy. Our timing of caplacizumab administration differed from that in the HERCULES Trial. Rather than administering caplacizumab at the onset of diagnosis, we utilized markers of end-organ damage, ADAMTS13 activity and inhibitor level to gauge the trajectory of the disease process before administering additional therapies. This may represent an alternative approach to treating aTTP in a post-caesarian patient given concern for risk of bleeding and lack of trial data that adequately captures the bleeding risk of this sub-population. Lastly, we describe reticulocytopenia and Vitamin B12 deficiency in this patient complicating her recovery from TTP. The etiology of her B12 deficiency is still unclear ( anti-parietal antibody titer <1:120). Figure Disclosures No relevant conflicts of interest to declare.

Clinical Spectrum, Long-Term Outcomes and Predictors of Relapse after Imatinib Discontinuation in FIP1L1-Pdgfra-Associated Chronic Eosinophilic Leukemia: Data from 150 Patients

Introduction. Cases series of patients with FIP1L1-PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P+ CEL) are scarce and of small sample-size. Low-dose imatinib mesylate (IM) is highly effective in this setting. Although successful treatment discontinuation has been reported, approximately 40% of the patients subsequently relapse. To date, no predictor of relapse after IM discontinuation has yet been evidenced. Methods. We conducted a French multicentric retrospective of patients diagnosed with F/P+ CEL between 2003-2019. Weight loss was defined as a 10% weight loss over the course of the disease's history. Complete (CHR) and partial (PHR) hematological responses were defined as a normalization of the absolute eosinophil count (AEC) and as a reduction in peripheral blood eosinophilia by at least 50% from baseline, respectively. Relapses were defined as the recurrence of eosinophilia, with or without evidence of F/P-gene transcript, but without any other explanation. Complete molecular response (CMR) was defined as a negative RT-PCR and/or RQ-PCR assay for F/P rearrangement. A backward stepwise logistic regression model was used to identify factors associated with relapse after IM discontinuation. Results. One hundred and fifty F/P+ CEL patients (145 males; mean (SD) age at diagnosis: 49 (+/-12 years) were included, among which 26 (17%) did not report any symptom. The main involved organs were the spleen (n=65, 43%), skin (n=47, 31%), heart (n=27, 18%), lungs (n=36, 24%), central nervous system (n=14, 9%), and bones/joints (n=8, 5%). Four (2,6%) patients showed features of vasculitis, involving the skin (n=2) and the CNS (n=2). The mean peak AEC was 10.3 G/L (+/-6 G/l). Besides eosinophilia, the most frequent associated complete blood count (CBC) abnormalities were thrombocytopenia (n=43, 28%), anemia (n=37, 24%), hyperleukocytosis (n=33, 22%) and monocytosis (n=25, 16%). Forty-seven (31%) patients had normal CBC besides eosinophilia. Bone marrow karyotype was normal in 91% (when tested, n=94). Serum vitamin B12 and tryptase (mean: 2386 (+/-1435) pmol/L and 34 (+/-20) µg/L) levels were elevated in 74 (94%) and 44 (79%) of patients respectively, whereas CRP and IgE levels were elevated in 31 (26%) and 12 (14%) each. None of the 37 (25%) patients that received first-line glucocorticoid therapy achieved CHR. All but 3 patients received IM (daily starting dose: 100 (n= 102; 72%), 200 (n=13; 9%) or 400 mg (n=20; 14%)), of whom 100% and 99% achieved CHR and CMR (when tested: n=84), respectively. The mean follow-up (FU) was 80 (+/- 56) months, with overall survival at 1, 5 and 10 years of 99%, 95% and 84% (reaching 100%, 98% and 89% in the 147 IMB-treated patients) respectively. Overall, 8 (5%) patients died during FU, including untreated patients with acute myeloblastic leukemia transformation (n=2) and a single patient with massive cerebral infarction. Eight patients relapsed during IM tapering, all of which were successfully treated when higher doses of IM were resumed. After a median [IQR] of 44 [27-72] months of IM treatment, 46 (32%) patients eventually discontinued IM, amongst whom 19 (41%) relapsed after a median of 10[4-23] months (42% of relapses defined by PCR). In multivariate analysis, weight loss (HR: 5,02 95%CI[1,9 - 28,04]; p =0,004), the time between onset of eosinophilia and IM initiation (HR 1,02 [1,00 - 1,03]; 0,01) and duration of IM treatment prior to discontinuation (HR: 0,97 [0,95-0,99]; p=0,01) were independent factors of relapse (Table 1). Conclusion. This large cohort further confirms that F/P+ CEL almost exclusively affects male patients, with spleen, skin, heart and lung involvements being the most frequent. While glucocorticoids never lead to the normalization of CBC parameters, IM is highly effective and treated patients carry an excellent prognosis. After IM discontinuation, although 60% of patients maintain CHR overtime, 40% subsequently relapse, with weight loss, time between onset of eosinophilia and IM initiation and duration of IM treatment prior to discontinuation being significant but moderate independent factors of relapse. Disclosures Nicolini: Incyte Biosciences: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Sun Pharma Ltd: Consultancy. Tavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte Biosciences: Honoraria; Amgen: Honoraria; Servier: Honoraria; Jazz Pharmaceuticals: Honoraria. Jardin:Servier: Honoraria; janssen: Honoraria; celgene: Honoraria; roche: Honoraria; amgen: Honoraria.

1465 A Rare Cause of Infective Ileocolitis: Brucella Abortus

INTRODUCTION: Brucellosis is the world's most widespread zoonotic disease. It is a systemic infection that can involve many organs. The gastrointestinal manifestations of human brucellosis are relatively uncommon and nonspecific such as diarrhea and abdominal pain. Reports of documented specific gastrointestinal lesions caused by Brucella species are rare. CASE DESCRIPTION/METHODS: A 31-year-old male presented with complaints of intermittent fever, chills, and night sweats of 11-month duration. His symptoms were associated with lower abdominal pain and intermittent bleeding per rectum. On physical examination, the patient had mild tenderness to palpation at the lower abdomen. Laboratory tests revealed normal liver enzymes and normal complete blood count. Stool testing for ova or parasites, Clostridium difficile toxins, and stool cultures for pathogenic microorganisms were all negative. Serology testing for Brucella agglutinin titer was positive for Brucella abortus at 1:160; blood culture for Brucella were negative. A pan CT scan revealed hepatomegaly and few sclerotic bony lesions involving thoracic vertebrae. A colonoscopy was performed which showed multiple aphthous ulcers at the terminal ileum (TI) with normal intervening mucosa. There were multiple aphthous ulcers in the cecum, ascending colon and transverse colon. The descending colon, sigmoid colon and rectum appeared normal. Microscopic examination of biopsies from the TI showed focal active ileitis with focal ulceration including infiltration of the lamina propria by mixed acute and chronic inflammatory cells including many eosinophils. Biopsies from the right colon showed focal active colitis with focal ulceration including focal cryptitis and preserved crypt architecture. The patient was diagnosed with brucellosis with ileocolonic involvement, and treated with trimethoprim/sulfamethoxazole and rifampicin given orally for 6 weeks. Four weeks after starting treatment, the patient reported resolution of his fever, abdominal pain and bleeding per rectum. The patient is scheduled to undergo a repeat colonoscopy to evaluate for resolution of ileocolitis endoscopically. DISCUSSION: We report an extremely rare cause of infective ileocolitis due to brucellosis. This appears to be only the fifth well-documented case of brucella colitis; and the first case describing ileocolitis due to brucellosis. Although rare, ileocolitis should be considered in the work-up of patients with brucellosis who have abdominal pain, diarrhea or bleeding per rectum.

2752 Nivolumab-Induced Hemorrhagic Gastroduodenitis

INTRODUCTION: Immune Checkpoint Inhibitors are a growing class of cancer immunotherapy agents used to treat a range of malignancies including melanoma, lung cancer, & Hodgkin’s lymphoma. With their increased use, a number of gastrointestinal side effects have been recognized with the most common being colitis and pancreatitis. Few previous case reports have characterized gastroduodenitis as a complication of checkpoint inhibitors. We describe a case of severe hemorrhagic gastroduodenitis secondary to nivolumab, a PD-1 checkpoint inhibitor. CASE DESCRIPTION/METHODS: A 66-year-old female with history of Stage IV non-small cell lung cancer having recently received her fourth dose of nivolumab presented with one week of nausea, vomiting, and abdominal pain. The pain was sharp, 8 out of 10 in intensity, epigastric, non-radiating, and episodic. It was associated with nausea and non-bloody, non-bilious vomiting. There was no history of NSAID or alcohol use. Upon arrival to emergency department her blood pressure was 104/62 mmHg, heart rate 88 bpm, and temperature 36.7 degrees Celsius. She had epigastric tenderness without rebound or guarding. Laboratory workup revealed a normal complete metabolic profile and complete blood count. Her lipase was elevated at 394 IU/L (78 IU/L upper limit of normal.) A CT abdomen/pelvis demonstrated moderate diffuse gastric wall thickening with mucosal hyperenhancement, and mild peripancreatic edema. Patient was initially treated for pancreatitis with intravenous fluids and pain control. She continued to have severe epigastric pain on Day 4 of admission, thus upper endoscopy was pursued. Upper endoscopy showed diffuse severe inflammation with hemorrhage characterized by congestion, erythema, and friability in the entire examined stomach, and moderately diffuse erythema without hemorrhage in the duodenal bulb. Biopsies showed severe chronic active gastritis and were negative for H. pylori. She was started on prednisone 1 mg/kg daily, and symptoms improved. She was discharged to home with close oncology follow up. DISCUSSION: The increasing use of immune checkpoint inhibitors has led to a rising rate of immune-related adverse events affecting the gut. While gastroduodenitis is an uncommon side effect in comparison to colitis or pancreatitis, more cases are being reported in the literature. Early recognition of symptoms in relation to immunotherapy is important in providing timely removal of offending agent and treating appropriately.

1900 Crushing the Star: Esophageal Foreign Body Extraction Using Dormia Basket

INTRODUCTION: Sharp objects impacted in the esophagus require prompt endoscopic removal. Removal of sharp foreign bodies can be technically challenging and care should be taken to avoid inducing esophageal trauma during retrieval. CASE DESCRIPTION/METHODS: A 69-year-old female presented with sudden onset dysphagia and sharp chest pain for 1 day. While eating cake one day prior to arrival, she reported sudden, sharp, central chest pain followed by a sensation of food being stuck in her esophagus. Her physical examination was unremarkable with no abdominal tenderness. Her laboratory tests revealed normal complete blood count and chemistry. Chest x-ray revealed no acute abnormality. Upper endoscopy showed a sharp star-shaped foreign body (FB) approximately 2 cm in diameter (Figure 1). The FB was lodged in the distal esophagus, causing mucosal trauma. Due to the large size of the FB, insertion of an overtube was not considered to facilitate removal. An attempt was first made to extract the FB with rat-tooth forceps, but it could not be retrieved through the upper esophageal sphincter. Mucosal trauma was seen in the mid and proximal esophagus following this attempt. The FB was then advanced to the gastric antrum using a Roth net. Attempts to break the FB using argon plasma coagulation (APC) and a snare were unsuccessful due to the rigid nature of the FB. Subsequently, a 2T dual channel therapeutic gastroscope was inserted, and a Dormia stone retrieval basket was used to grasp the foreign body. Using the crushing power of the basket, the FB was successfully crushed and pulled inside the large therapeutic channel of the scope. The scope was withdrawn without additional mucosal trauma. The FB consisted of a star-shaped cake decoration with sharp edges (Figure 2). Following the procedure, the patient reported immediate improvement in her chest pain. DISCUSSION: This is a unique case wherein after the failure of conventional foreign body extraction devices, a Dormia stone retrieval basket was used to crush the object within the stomach allowing for safe retrieval. Gastroenterologists should consider this approach when retrieving irregularly-shaped, sharp, but pliable FBs. For the general public, care should be taken when eating food with non-edible decorations and toppers to avoid inadvertently swallowing or aspirating these objects.

2367 A Rare Case of Primary Glomus Tumor of Liver

INTRODUCTION: Glomus tumors are very rare mesenchymal perivascular tumors arising in glomus body. They are mainly found in skin of extremities but rarely arise in visceral organs like gastrointestinal tract, mediastinum, bladder, and kidney. However, glomus tumors occurring in liver is extremely rare. We found only seven case reports in English literature so far. Our case is incidentally found after imaging was obtained to evaluate significantly elevated inflammatory markers. CASE DESCRIPTION/METHODS: A 60-Yr-old African American female with medical history of atrial fibrillation, hypertension, rheumatoid arthritis, anxiety, depression, adenomatous polyps was referred for evaluation of an abnormal PET-CT scan. She was seen by her rheumatologist with a complaint of worsening pain in her hips and lower back and 5lbs weight loss over past 3months. Laboratory evaluation showed normal complete blood counts and liver function tests but CRP 14.8mg/L, sedimentation rate 100mm/hr. A PET-CT scan showed an intensely hyper metabolic, peripherally enhancing, 2 cm × 1.8 cm, left hepatic lobe lesion concerning for malignancy. Moderately increased uptake was noted in cecal area suspicious for a primary site. No FDG avid nodal metastases, or vasculitis noted. A colonoscopy showed 1cm adenomatous polyp in cecum but no malignancy seen. A CT guided biopsy of the liver mass was performed which showed sheets of small bland cells with scant to moderate eosinophilic cytoplasm with centrally placed small nuclei.There is prominent vascular network throughout the tumor and the cells are positive for CD34 stain, smooth muscle actin, collagen IV, but negative for glycipan-3, arginase, AE1/3, pCEA, synaptophysin, chromogranin, KIT and DOG1. A diagnosis of glomus tumor was made. She was discussed in hepatobiliary conference and a recommendation was made for a surgical excision. She was seen by a surgeon but she denied surgery. DISCUSSION: Glomus tumor in liver is very rare and we report eighth case. Our patient is asymptomatic and immunohistochemical stains confirmed glomus tumor. It is vascular surrounded by epithelioid cells with round to oval nuclei, and eosinophilic cytoplasm. Tumor cells are positive for for markers like SMA, desmin , vimentin; may be positive for CD34/31, but negative for cytokeratins, CD117, neuroendocrine markers like synaptophysin, chromogranin, or protein S-100. The natural course and management options are not clear though surgical resection is recommended. The tumor is benign and has favorable prognosis.

Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia.

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow disorder with mutations in ribosomal protein genes. Several animal models have been developed to study the pathological mechanism of DBA. Previously, we reported that the complete knock-out of both Rpl5 and Rps24 alleles were lethal, while heterozygous Rpl5+/- and Rps24+/- mice showed normal phenotype. To establish a more efficient mouse model for mimicking DBA symptoms, we have taken advantage of RNAi technology to generate an inducible mouse model utilizing tetracycline-induced down-regulation of Rpl5. After two weeks of treatment with doxycycline in drinking water, a subset of treated shRNA Rpl5+/- adult mice developed mild anemia while control mice had normal complete blood counts. Similarly, treated shRNA Rpl5+/- mice developed reticulocytopenia and bone marrow erythroblastopenia. Detection of DBA symptoms in these mice make them a valuable DBA model for studying the pathological mechanism underlying DBA and for further assessment of the disease and drug testing for novel therapies.