SESSION TYPE: Physiology/PFTs/ Rehabilitation PostersPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PM

PURPOSE:

Cardiopulmonary complications such as acute chest syndrome (ACS) and vasoocclusion induced pulmonary infarction are prevalent in SCD. These result in pulmonary fibrosis, pulmonary hypertension, and high output cardiac failure. Abnormal PFTs have been reported in adults (upto 90%) with SCD. These include Restriction (fibrosis from repeated ACS), obstruction or mixed obstructive-restrictive physiology and isolated reduction in DLCO. It is important for the clinicians to recognize SCD related PFT abnormalities to avoid errors in diagnosis and misguided therapy. The aim of the study is to report prevalence and patterns of abnormal PFT finding in children and adolescents.

METHODS:

30 patients were included with median of 14 years (range: 10-19). 15 were males and 15 were females. Patients were subclassified into five groups: obstructive, restrictive, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. ATS/ERS 2005 interpretation strategy was used to diagnose restriction obstruction based on NHANES-II reference values. The DLCO were not corrected for Hg or alveolar volume.

RESULTS:

Normal PFTs were present in 22/30 (73%). Obstructive physiology was noted in 3, Restrictive physiology in 4 (all with reduced VC but normal TLC). DLCO was normal in all except one though all were anemic with a median Hb of 9 (4.9-11.1 mg/dl). Chest X-Ray was available in 17 patients; normal in 3 and abnormal in 14 (82%); Cardiomegaly was noted in 8 (57%); Prominent Pulmonary Artery (Pulmonary Hypertension) in 6 (43%); 2 patient had both cardiomegaly and prominent vascular marking.

CONCLUSIONS:

Unlike adult patients, most children with SCD had normal PFT including normal DLCO despite severe anemia. The low incidence of PFT is abnormality is attributed to fewer episode of sickle cell crises, vasoocclusive or ACS. The normal DLCO is explained by high blood volume from high cardiac output in chronic anemia.

CLINICAL IMPLICATIONS:

Majority of Children and Adolescents have normal PFT's. DLCO could be normal even in the presence of severe anemia due to high cardiac output state. Longitudinal PFT's in children are helpful in monitoring the progression of SCD.DISCLOSURE: The following authors have nothing to disclose: Ameer Rasheed, Viswanath Vasudevan, Farhad ArjomandNo Product/Research Disclosure InformationThe Brooklyn Hospital Center, Brooklyn, NY.

SESSION TYPE: Miscellaneous Global Case Report PostersPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM

INTRODUCTION:

Sickle cell disease (HbS) is an inherited disorder due to homozygosity for the abnormal hemoglobin S. Although it is rare in Caucasians , it is a prevalent disease in Saudi Arabia.(1) Vaso-occlusive phenomena and hemolysis are the clinical hallmarks of sickle cell disease which can lead to extramedullary hemopoises and reactive lymphadenopathy .However, rare cases of hematological malignancies have been reported in patients with sickle cell disease but are often underdiagnosed(2). We report a case of non hodgkin lymphoma in an adult patient with sickle cell anaemia that was associated with ahypercoaguble state.

CASE PRESENTATION:

We report a 23-years old lady, who is a case of sickle cell disease and rheumatic heart disease. She presented with recurrent pulmonary emboli despite anticoagulation and left lower lobe pneumonia for which she required mechanical ventilation. CT chest showed hilar and mediastinal lymphadenpathy. Transbronchial fine needle aspiration were consistent with reactive lymphadenopathy. However , in view of atypical presentation and unresolving left lower lobe pneumonia leading to failure to wean off mechanical ventilation, true cut lung biopsy and transesophageal lymph node biopsy were performed and unmasked the diagnosis of non Hodgkin lymphoma( B cell type) for which she was started on chemotherapy.

DISCUSSION:

In this case we report a rare association between sickle cell disease and non hodgkins lymphoma . Although extramedullary hematopoesis is a recognized cause of reactive lymphadenopathy in sickle cell disease, but when the lymph nodes are persistent and associated with other manifestation like fever ,weight loss and hypercoagulable state, other differential diagnosis needs to be entertained. These include infections especially tuberculosis, malignancy, lymphoproliferative and immunologic disorders. The association of tuberculosis with sickle has been suggested by Lionnet et al who reported higher incidence of lymph node tuberculosis in sickle cell disease than epidemiologically comparable population (3). In our community, tuberculosis is endemic especially in black and low socioeconomic class , therefore it was highly considered in our patient but seemed most unlikely due to repeatedly negative AFB stains in the cytology specimens and the negative culture .In adult SCD, only few cases of hematological malignancies have been reported in literature(2) These included acute leukemia, multiple myeloma ,Hodgkins disease and malignant histiocytosis. Up to our knowledge, our patient is the first case of non Hodgkin lymphoma reported in adult SCD. Although the relationship between these malignancies and sickle cell disease is not yet defined,the possibility of a common chromosomal alteration has been suggested,however ,further cytogenetic studies are still needed. The presentation of this case with recurrent PE involving main pulmonary arteries despite therapeutic anticoagulation was unusual.The association between hematological malignancies and hypercoagulable state is well known and is thought to to be related to factor V Leiden and prothrombin mutation,in addition to acquired antiphospholipid antibodies . However in diffuse large B-cell lymphoma the risk of thrombosis is much higher ( 35.7%).This is thought to result from local Compression of mediastinal vessels causing narrowing of the lumen and venous stasis

CONCLUSIONS:

This case report highlights the importance of thoroughly investigating lymphadenopathy in sickle cell patients before accepting extramedullary hemopoeisis as the underlying cause, especially in presence of hypercoagulable state and unresolving pneumonia in order not to miss the possibility of lymphoma.1) El-Hazmi MA, Warsy AS. On the nature of sickle cell disease in the south-western province of Saudi Arabia .Acta Haematol. 1986;76(4):212-6.2) Paydas S: Sickle cell anemia and hematological neoplasias Leuk Lymphoma 2001 Jul;43(7):1431-43) Lionnet F., Bachmeyer C, Sloma I, Rossier A, Thioliere B, Maier M, Grateau G, Girot R: Tuberculosis in adult patients with Sickle cell disease J Infec 2007 Nov; 55(5): 439-44DISCLOSURE: The following authors have nothing to disclose: Hadil AlOtairNo Product/Research Disclosure InformationKing Khalid University Hospital, Riyadh, Saudi Arabia.

SESSION TYPE: Critical Care Case Report PostersPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM

INTRODUCTION:

Acute chest syndrome (ACS) is a complication of patients with sickling syndromes (SS). Diffuse Alveolar Hemorrhage (DAH) is not a common presentation of ACS.

CASE PRESENTATION:

19-year-old male with hemoglobin SC disease (SCD) without sickle sequelae presented with diffuse mild body pain associated to fevers, chills and mild nonproductive cough. There was neither pertinent social history nor sick contacts. A CT chest revealed bilateral lower lobe consolidations. The patient was found to have a CBC with 16300 WBC, Hb of 9.7 and 37000 platelets. His HgbS and C were 45% and 39% respectively. A nasopharyngeal swab was negative. Sputum culture was negative. Given his stable oxygen saturation and clinical condition, the patient received ceftriaxone and azithromycin for community-acquired pneumonia. Subsequently his respiratory status and clinical condition deteriorated requiring intubation. Given the persistent fever and increased oxygen requirement, a bronchoscopy was performed finding DAH. IV steroids were started and a red cell exchange transfusion was performed. His post-exchange Hgb S and C values decreased to 16% and 14% respectively. An autoimmune workup and cultures of bronchial specimens were negative. Following these interventions the patient improved and was successfully extubated one day after and weaned to room air.

DISCUSSION:

ACS is defined as a new pulmonary infiltrate associated with chest pain, fever, tachypnea, or cough(1). The pathogenesis is complex, and the establishment of a cause is difficult. Multiple factors may be associated including: infection, fat embolus or hypoventilation(2). It's often impossible to distinguish ACS from pneumonia/pneumonitis or pulmonary infarction on clinical grounds and a definite etiology is usually established only in 38% of cases after an extensive evaluation. SCD is a SS usually with lower anemia due to the compound heterozygosity of Hgb C providing some anti-sickling benefit that prolongs red cell survival and. However, individuals with SCD are at risk for the same complications including ACS but at a decreased frequency(3). To our knowledge, DAH is not a common complication in ACS in SS. Our patient's development of DAH might have been from tissue ischemia from development of ACS, his underlying thrombocytopenia, or directly from the pneumonitis.

CONCLUSIONS:

Recognizing the possibility of DAH in patients presenting with a clinical picture of ACS and initiating therapy is important given the high morbidity and mortality of this condition.1) Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. 2000;342(25):18552) Graham LM, Sickle cell disease: pulmonary management options. Pediatr Pulmonol Suppl. 2004;26:1913) Ballas SK, Lewis CN, Noone AM, et al. Clinical, hematological, and biochemical features of Hb SC disease. Am J Hematol. 1982;13(1):37DISCLOSURE: The following authors have nothing to disclose: Ricardo Restrepo, MIchael Baram, Jay Herman, Vipul Kumar, Omar IbrahimNo Product/Research Disclosure InformationThomas Jefferson University, Philadelphia, PA.

BACKGROUND:

Hyperhemolysis syndrome is a serious transfusion reaction mostly reported in association with sickle cell disease, characterized by destruction of both donor and host red blood cells (RBCs) by an unknown mechanism.

CASE REPORT:

A 21-year-old man with sickle cell disease and multiple prior transfusions received two phenotype-matched, compatible RBC units during a brief admission for pain crisis. He developed rapid-onset progressive anemia and hemoglobinuria. Methylprednisolone, erythropoietin, and rituximab were administered. Fifteen days posttransfusion the hemoglobin (Hb) concentration decreased to 3.1 g/dL, with evidence of severe congestive heart failure. No new antibodies were identified. It was felt that his heart failure would not improve without increasing oxygen-carrying capacity. A combination of volume overload, anemia, and hemolysis prompted a novel isovolemic procedure to increase Hb level without removing his own RBCs or causing fluid overload. A cell separator was used operating on the plasma-exchange program, with three cross-match-compatible, washed RBC units as the replacement fluid. After the procedure, there was no evidence of hemolysis. Over the following 6 days, the congestive heart failure resolved, the Hb concentration increased to 7.5 g/dL, and the patient fully recovered. He had a similar event 3 years previously.

CONCLUSIONS:

Plasma-to-RBC replacement may be beneficial for selected patients with life-threatening anemia. This intervention provides immediate improvement in oxygen-carrying capacity, conserving the patient's own RBCs, while avoiding fluid overload. Although blood transfusion may precipitate further hemolysis, this case report describes successful plasma-to-RBC exchange transfusion with concurrent supportive care to offset hemolysis, including corticosteroid, intravenous immunoglobulin, and rituximab.

Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94-99%) in SCA (N = 458), lower (P < 0.0001) than non-SCA (median 99%, IQ range 98-100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (P < 0.001, Adj r (2) = 0.09). In non-SCA only age correlated with SpO2. α-thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient -0.60, P < 0.0001). In multivariable models, lower SpO2 correlated with higher MCH (β-coefficient -0.32, P < 0.001) or with decreased copies of α-thalassemia 3.7 deletion (β-coefficient 1.1, P < 0.001), and independently in both models with lower HbF% (β-coefficient 0.15, P < 0.001) and Glucose-6-Phosphate Dehydrogenase genotype (β-coefficient -1.12, P = 0.012). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.

Hematopoietic stem cell transplantation (HSCT) is a new window to therapy of many diseases. From March 1991 through April 2011, a total of 3237 HSCT were performed in the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. Here we report 20 years experience of HSCT.Our strategy and aim include the protraction of cytogenetic and molecular biological diagnostic tests, the expansion of the first Iranian Cord Blood Bank (ICBB) and development of the first Iranian Stem Cell Donor Program (ISCDP), and improvement the researches in new therapeutic fields.Totally, 3237 patients were undergone HSCT. Of these transplants, 2205 were allogeneic stem cell transplantation, 1016 autologous and 16 syngeneic. Among 2205 patients who were undergone allogenic-HSCT, 34 received cord blood stem cells as stem cell source for transplantation. It is important to point out that cord blood bank at our center provides reliable storage of cord blood stem cells for our patients. Stem cell transplantation was performed for treatment of various diseases such as acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, beta-thalassemia major, sickle- cell thalassemia, sickle- cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combined immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. Also, we had 220 cellular therapies for post-myocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, Diabetes Mellitus and GvHD treatment. 45 patients were undergone retransplantation in this center.About 78.2% of the patients (2530 of 3237) remained alive between one to 211 months after stem cell transplantation. Nearly, 21.8% (707) of our patients died after stem cell transplantation. The main causes of death were relapse, infection, hemorrhagic cystitis, graft-versus- host disease and etc.In Iran, HSCT has been successfully adapted in routine clinical care. Recently, new methods such as double cord blood and haploidentical transplantation have been used to treat many life-threatening diseases.

ABSTRACT

BACKGROUND:

The contribution of environmental tobacco smoke exposure (ETS) to pulmonary morbidity in children with sickle cell anemia (SCA) is poorly understood. We tested the hypothesis that children with SCA and ETS would have an increased prevalence of obstructive lung disease and respiratory symptoms compared to children with SCA but without ETS.

METHODS:

Parent-report of ETS and respiratory symptom frequency were obtained for 245 children with SCA as part of a multi-center prospective cohort study. 196 children completed pulmonary function testing. Multivariable regression models evaluated the associations between ETS exposures at different time points [prenatal, infant (birth-2 years), preschool (2 years -first grade) and current], and lung function and respiratory symptoms.

RESULTS:

Among 245 participants, a high prevalence of prior (44%) and current (29%) ETS was reported. Of the 196 children who completed pulmonary function testing, those with parent-reported infant and current ETS were more likely to have airway obstruction (defined as Forced Expiratory Volume in 1 second /Forced Vital Capacity ratio (FEV1/FVC) below the lower limit normal) compared to unexposed children (22.0% vs. 3.1%, p&lt;0.001). Those with ETS also had a lower FEF25-75/FVC ratio (0.82 vs. 0.97, p=0.001) and were more likely to have evidence of bronchodilator responsiveness(23% vs. 11%, p=0.03). Current and prior ETS and in utero exposure were associated with increased frequency of respiratory symptoms.

CONCLUSIONS:

ETS exposure is associated with evidence of lower airway obstruction and increased respiratory symptoms in SCA.

The ameliorating effect of high fetal hemoglobin (HbF) levels on the incidence of pain episodes in sickle cell anemia (SCA) is well-known; however, in children this relationship is less clearly established. We hypothesized that higher HbF levels in children with SCA are associated with fewer severe pain episodes. A meta-analysis of data from the Silent Infarct Transfusion Trial (n = 456) and the Cooperative Study of Sickle Cell Disease (n = 764), demonstrated that baseline HbF levels were associated with the incidence of severe pain, commonly defined across studies as an event requiring hospitalization (P-value = 0.02). Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Recurrent/persistent pneumonia in children continues to be a major challenge for the pediatricians. The aim of our study was to establish the prevalence and underlying causes of recurrent/persistent pneumonia in children in Upper Egypt.Assiut University Children Hospital, Assiut, Egypt.Patients, admitted for pneumonia to the hospital during 2 years, were investigated with microbiological, biochemical, immunological and radiological tests in order to establish the prevalence of recurrent/persistent pneumonia and to find out its underlying causes.113 out of 1228 patients (9.2%) met the diagnosis of recurrent/persistent pneumonia. Identified causes were; aspiration syndrome (17.7%), pulmonary TB (14.0%), congenital heart disease (11.5%), bronchial asthma (9.7%), immune deficiency disorders (8.8%) and vitamin D deficiency rickets (7.0%). Other causes included; congenital anomalies of the respiratory tract, interstitial lung diseases, bronchiectasis, and sickle cell anemia. No predisposing factors could be identified in 15% of cases.Approximately 1 out of 10 children with diagnosis of pneumonia in Assiut University Children Hospital had recurrent/persistent pneumonia. The most frequent underlying cause for recurrent/persistent pneumonia was aspiration syndrome, followed by pulmonary TB.

We sought to evaluate whether patients with sickle cell anemia (SCA) have left ventricular (LV) systolic dysfunction.We conducted a Medline, Embase, Ebscohost, and Google scholar literature search articles published before April 2010. All studies that compared any measure of LV function (eg, ejection fraction [EF], fractional shortening [FS], or cardiac index [CI]) between normal control subjects and SCA (hemoglobin SS) patients were included. Among 57 studies that qualified for review, 19 studies including 841 SCA patients and 554 control subjects met the inclusion criteria. There were no significant differences in either LVEF (Hedge g = 0.15; 95% confidence interval -0.84 to 1.14; P = .76) or FS (P = .28) between SCA patients and control subjects. CI was significantly higher (P < .001) and LV end-systolic stress-volume index (load independent) was significantly lower (P < .001) in SCA patients. All LV systolic measures inversely correlated with age (all P < .001). LV end-systolic and -diastolic dimensions were significantly higher in SCA patients and increased with age.SCA patients have similar load-dependent but lower load-independent measures of LV systolic function than control subjects. SCA is associated with LV dilation. LV structural and functional abnormalities appear to be age dependent with progressive LV dilation and impairment over time.