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Al-Abdwani R, Al Farsi A, Zachariah M, Adawi BA, Al-Rashdi A, Dhande NR, Elsidig N, Alhinai Z. Septic shock and fulminant hepatic failure secondary to Q fever in a child with sickle cell disease: First case report. Int J Infect Dis 2024; 148:107243. [PMID: 39278400 DOI: 10.1016/j.ijid.2024.107243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 08/21/2024] [Accepted: 09/11/2024] [Indexed: 09/18/2024] Open
Abstract
Q fever is a zoonosis with a worldwide distribution that is caused by the intracellular bacterium Coxiella burnetii. Although most infections in children are asymptomatic and self-limiting, some experience severe or chronic manifestations. Its manifestations in patients with sickle cell disease are unknown, as there are no reports currently. We report the case of a 4-year-old child with sickle cell disease who was admitted to the intensive care unit with fever, septic shock and fulminant hepatic failure secondary to hepatic sequestration crisis and intrahepatic cholestasis. Coxiella burnetii infection was confirmed by molecular and serologic assays. Empiric therapy with doxycycline had a significant impact on his course, and he made an excellent recovery despite requiring extensive life-supportive measures initially. This is the first report of Q fever in a patient with sickle cell disease, demonstrating its capability to manifest as acute sickle hepatopathy with critical illness.
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Affiliation(s)
- Raghad Al-Abdwani
- Department of Child Health, Sultan Qaboos University Hospital, University Medical City, Muscat, Sultanate of Oman
| | - Ahmed Al Farsi
- Sur Hospital, Ministry of Health, Muscat, Sultanate of Oman
| | - Matthew Zachariah
- Department of Child Health, Sultan Qaboos University Hospital, University Medical City, Muscat, Sultanate of Oman
| | - Badriya Al Adawi
- Department of Microbiology and Immunology, Sultan Qaboos University Hospital, University Medical City, Muscat, Sultanate of Oman
| | - Azza Al-Rashdi
- Central Public Health Laboratory, Ministry of Health, Muscat, Sultanate of Oman
| | - Naga Ram Dhande
- Department of Child Health, Sultan Qaboos University Hospital, University Medical City, Muscat, Sultanate of Oman
| | - Nagi Elsidig
- Department of Child Health, Sultan Qaboos University Hospital, University Medical City, Muscat, Sultanate of Oman
| | - Zaid Alhinai
- Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
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2
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Denoon RB, Soares Ferreira Junior A, Tuttle B, Onwuemene OA. Therapeutic plasma exchange for sickle cell disease acute complications: A systematic review. Transfusion 2024; 64:1570-1587. [PMID: 38934252 DOI: 10.1111/trf.17932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 04/25/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024]
Affiliation(s)
| | | | - Brandi Tuttle
- Duke University Medical Center Library, Duke University Medical Center, Durham, North Carolina, USA
| | - Oluwatoyosi A Onwuemene
- Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
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3
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Rizvi I, Solipuram D, Kaur N, Komel A, Batool S, Wang J. The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy. Br J Haematol 2024. [PMID: 38978231 DOI: 10.1111/bjh.19620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 06/19/2024] [Indexed: 07/10/2024]
Abstract
Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all-inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l-glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed.
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Affiliation(s)
- Insia Rizvi
- Division of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Divya Solipuram
- Internal Medicine, Nassau University Medical Center, East Meadow, New York, USA
| | - Navneet Kaur
- Internal Medicine, North Alabama Medical Center, Florence, Alabama, USA
| | - Aqsa Komel
- Internal Medicine, Nishtar Medical College and Hospital, Multan, Punjab, Pakistan
| | - Saba Batool
- Internal Medicine, Carle Health Methodist Hospital, Peoria, Illinois, USA
| | - Jennifer Wang
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
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4
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Dasiah YSP, Saeid M, Ahmed F. Intrahepatic Cholestasis in a Pregnant Patient With Sickle Cell Disease: A Case Report. Cureus 2024; 16:e60611. [PMID: 38894784 PMCID: PMC11185666 DOI: 10.7759/cureus.60611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/19/2024] [Indexed: 06/21/2024] Open
Abstract
Sickle cell intrahepatic cholestasis (SCIC) is a potentially fatal complication of sickle cell disease (SCD) with a high mortality rate, observed mainly in patients with homozygous SCD. Intrahepatic cholestasis of pregnancy is a known complication in pregnancy and usually presents in the late second or third trimester with itching, elevated bile acids, and elevated liver enzymes. Intrahepatic cholestasis in a pregnant patient with homozygous SCD is a rare occurrence. We present the case of a patient who was diagnosed with homozygous SCD during her second pregnancy and developed cholestasis with abnormal levels of liver enzymes at 25 weeks gestation, requiring delivery at 30 weeks gestation due to very high bile acid and liver enzyme levels. The patient was successfully managed.
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Affiliation(s)
| | - Martina Saeid
- Internal Medicine, New Medical Center (NMC) Royal Women's Hospital, Abu Dhabi, ARE
| | - Fatmaelzahraa Ahmed
- Obstetrics and Gynaecology, New Medical Center (NMC) Royal Women's Hospital, Abu Dhabi, ARE
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Hassanzadeh M, Sanat ZM, Khayatian S, Sotoudeheian M, Shahbazian A, Hoseini S. Acute sickle cell hepatopathy: A case report and literature review. J Natl Med Assoc 2024; 116:119-125. [PMID: 38383222 DOI: 10.1016/j.jnma.2023.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 09/01/2023] [Accepted: 09/30/2023] [Indexed: 02/23/2024]
Abstract
Sickle cell disease (SCD) is an inherited hemoglobinopathy with protean clinical manifestations. The liver could be affected by various SCD-associated complications of an overlapping nature. The clinical presentations of "sickle cell hepatopathy" range from clinically asymptomatic patients to those with life-threatening complications. Herein we report an SCD patient who presented with right upper quadrant abdominal pain and jaundice, eventually diagnosed as a self-limited form of acute sickle cell hepatopathy with overlapping features of acute hepatic crisis and benign intrahepatic cholestasis. Using this patient as an illustration, we will review the spectrum of hepatobiliary presentations in the SCD population.
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Affiliation(s)
- Morteza Hassanzadeh
- Department of Internal Medicine, School of Medicine, Colorectal Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
| | - Zahra Momayez Sanat
- Department of Internal Medicine, School of Medicine, Digestive Diseases Research Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Somayeh Khayatian
- Department of Internal Medicine, School of Medicine, Digestive Diseases Research Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | | | - Amirmasoud Shahbazian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Wadhavkar N, Nsubuga JP, Ibrahim N, Kumar P, Hsu A, Simmons S. Acute Liver Failure With Liver Enzymes >5,000 in Sickle Cell Disease. ACG Case Rep J 2024; 11:e01303. [PMID: 38511165 PMCID: PMC10954052 DOI: 10.14309/crj.0000000000001303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 02/12/2024] [Indexed: 03/22/2024] Open
Abstract
Sickle cell disease is a hemoglobinopathy often complicated by painful vaso-occlusive episodes, acute chest syndrome, stroke, and myocardial infarction. Sickle cell intrahepatic cholestasis (SCIC) is a rare and potentially fatal complication of sickle cell disease. SCIC is thought to involve progressive hepatic injury due to sickling within sinusoids. We present the case of a young patient with SCIC and acute liver failure, requiring prompt treatment with exchange transfusion. Our case describes features that should raise suspicion for hepatic failure in SCIC and highlights exchange transfusion as a successful management approach in similar patients with an otherwise high risk of mortality.
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Affiliation(s)
- Neha Wadhavkar
- Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI
| | - John Paul Nsubuga
- Division of Gastroenterology, The Warren Alpert Medical School of Brown University, Providence, RI
| | - Nouran Ibrahim
- The Warren Alpert Medical School of Brown University, Providence, RI
| | - Prasanna Kumar
- Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, RI
| | - Andrew Hsu
- Division of Hematology Oncology, The Warren Alpert Medical School of Brown University, Providence, RI
| | - Shannon Simmons
- Division of Gastroenterology, The Warren Alpert Medical School of Brown University, Providence, RI
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Vadlapudi SS, Srivastava A, Rai P, Singh RK, Sarma MS, Poddar U, Yadav RR. Jaundice in a Child with Sickle Cell Anemia: A Case Based Approach. Indian J Pediatr 2024; 91:73-80. [PMID: 37556033 DOI: 10.1007/s12098-023-04747-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/21/2023] [Indexed: 08/10/2023]
Abstract
Sickle cell anemia (SCA) is an autosomal recessive disorder caused by a mutation in beta globin gene. Hepatobiliary system is affected in 10-40% of patients with SCA and has a multifactorial etiology. The authors present a child with SCA and conjugated hyperbilirubinemia due to biliary obstruction. He underwent endoscopic retrograde cholangiopancreatography (ERCP) and biliary stenting, had complications of post sphincterotomy bleed, retroperitoneal hematoma and post laparoscopic cholecystectomy sepsis with acute sickle hepatic crisis. He was managed successfully and is doing well on follow-up. Here authors discuss a stepwise approach in management of jaundice in a patient with SCA. Patients with SCA are prone to develop vaso-occlusive crisis (VOC) during periods of stress. VOC affects the liver as acute sickle hepatic crisis, acute hepatic sequestration or sickle cell intrahepatic cholestasis and is collectively termed as sickle cell hepatopathy. Hemolysis due to sickling results in cholelithiasis with its associated complications. These patients are vulnerable to viral hepatitis and hemochromatosis due to multiple blood transfusions. There may be a concomitant acute viral hepatitis, drug induced liver injury, Budd-Chiari syndrome or other chronic liver diseases. These conditions have considerable clinical overlap and may coexist, making the evaluation more challenging. Detailed history, examination and investigations are required for differentiation of etiology. Periods of stress must be tackled with proper hydration, oxygen supplementation, maintaining hemoglobin >10 g/dL, and a low hemoglobin S fraction. Patients with SCA and conjugated hyperbilirubinemia are "high-risk" and best managed by a multidisciplinary team. Preventive strategies like timely vaccinations, chelation, etc. must be practised.
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Affiliation(s)
- Srinivas Srinidhi Vadlapudi
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Praveer Rai
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rajneesh K Singh
- Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rajanikant R Yadav
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
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Manganas K, Delicou S, Xydaki A, Kourakli A, Evliati L, Vlachaki E, Klironomos E, Diamantidis M, Lafiatis I, Kattamis A, Koskinas J. Predisposing factors for advanced liver fibrosis in patients with sickle cell disease. Br J Haematol 2023; 202:1192-1198. [PMID: 37438880 DOI: 10.1111/bjh.18970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 06/26/2023] [Accepted: 06/27/2023] [Indexed: 07/14/2023]
Abstract
Sickle cell disease (SCD) is one of the most common monogenic disorders worldwide and liver complications are common in this group of patients. Our study aims to highlight the prevalence of chronic liver complications and the main predisposing factors for advanced liver fibrosis in SCD patients. For this purpose, 219 patients from eight Thalassemia and Sickle Cell Units across Greece enrolled in our study and history of liver related disease complications was recorded, as well as a full laboratory and imaging analysis concerning their liver function. 13.6% of the patients had advanced liver fibrosis. The presence of liver fibrosis was significantly correlated with advanced age, male gender, cholelithiasis and higher LDH, γ-GT, INR, direct and indirect bilirubin levels. These patients had exhibited significantly more episodes of liver crises and acute intrahepatic cholestasis. No correlation was observed with right heart failure or previous viral hepatitis. Patients with advanced liver fibrosis were receiving a more intensive transfusion therapy for a longer period of time and had higher Liver Iron Concentration levels. Our study shows that liver complications and cirrhosis is a significant cause of morbidity in patients with SCD and it is primarily associated with intravascular hemolysis and vaso-occlusive phenomena and secondarily with iron overload.
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Affiliation(s)
| | - Sophia Delicou
- Thalassemia and Sickle Cell Unit, Hippokration General Hospital, Athens, Greece
| | - Aikaterini Xydaki
- Thalassemia and Sickle Cell Unit, Hippokration General Hospital, Athens, Greece
| | - Alexandra Kourakli
- Thalassemia & Hemoglobinopathies Unit, Hematology Division, Department of Internal Medicine, University of Patras Medical School, University Hospital, Patras, Greece
| | - Loukia Evliati
- Thalassemia and Sickle Cell Unit, General Hospital of Athens "Evaggelismos", Athens, Greece
| | - Efthymia Vlachaki
- Thalassemia and Sickle Cell Unit, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Evangelos Klironomos
- Thalassemia and Sickle Cell Unit, "Venizelion" General Hospital, Heraklion, Greece
| | - Michail Diamantidis
- Thalassemia and Sickle Cell Unit, General Hospital of Larissa, Larissa, Greece
| | - Ioannis Lafiatis
- Thalassemia and Sickle Cell Unit, "Vostanio" General Hospital of Mytilene, Mytilene, Greece
| | - Antonios Kattamis
- "Agia Sophia" Children Hospital, First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
| | - John Koskinas
- Department of Internal Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece
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9
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Ettinger NA, Guffey D, Anum SJ, Fasipe T, Katkin J, Bhar S, Airewele G, Saini A, Tubman VN. Multi-center retrospective study of children with sickle cell disease admitted to pediatric intensive care units in the United States. Sci Rep 2023; 13:6758. [PMID: 37185357 PMCID: PMC10130031 DOI: 10.1038/s41598-023-32651-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 03/30/2023] [Indexed: 05/17/2023] Open
Abstract
Data on outcomes and interventions for children with sickle cell disease (SCD) admitted to a pediatric intensive care units (PICU) are unknown. We provide the first comprehensive multi-center report on PICU interventions associated with death, the need for invasive respiratory support or stroke among critically ill children with SCD. We collected retrospective multi-center cohort data from January 1, 2012 to December 31, 2019 utilizing the Virtual Pediatric Systems, LLC database. We identified 3388 unique children with SCD, accounting for a total of 5264 PICU admissions from 138 PICUs. The overall mortality rate for the PICU admissions cohort was 1.8% (95/5264 PICU admissions, 95/3388 [2.8%] of all unique patients), the rate of needing of needing Invasive Respiratory Support (IRS, a composite category of exposure) was 21.3% (872/4093 PICU admissions with complete data) and the overall rate of stroke (ischemic or hemorrhagic) was 12.5% (657/5264 PICU admissions). In multivariable analysis adjusting for admission age category, sex, race/ethnicity, PRISM-3 score at admission, exposure to IRS, quartile of unit volume of patients with SCD, and patient origin, admitted children who needed invasive respiratory support (IRS) had higher adjusted odds ratios for mortality (adjusted odds ratio [aOR], 19.72; 95% confidence interval [CI] 8.98-43.29; p < 0.001), although admitted children > 2 years old had decreased aOR for needing IRS (aOR 0.25-0.62; 95% CI 0.16-0.94; p < 0.001-0.025). By contrast, admitted children > 2 years old had a strikingly increased aOR for stroke (aOR 7.57-16.32; 95% CI 2.25-52.15; p < 0.001). These groups may represent PICU-specific subsets of patients with SCD who are at higher risk for more serious illness and should deserve early consideration for referral to a pediatric institution providing comprehensive care for patients with SCD.
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Affiliation(s)
- Nicholas A Ettinger
- Division of Pediatric Critical Care, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, 6651 Main Street, MC: E1420, Houston, TX, 77030, USA.
| | - Danielle Guffey
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
| | - Shaniqua J Anum
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Titilope Fasipe
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Julie Katkin
- Division of Pulmonology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Saleh Bhar
- Division of Pediatric Critical Care, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, 6651 Main Street, MC: E1420, Houston, TX, 77030, USA
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Gladstone Airewele
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Arun Saini
- Division of Pediatric Critical Care, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, 6651 Main Street, MC: E1420, Houston, TX, 77030, USA
| | - Venée N Tubman
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
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Edwards CL, Scott S, Boggan M, Meek J, Alston K, Pearson A, McDougald A, Broadnax M, Wood M, Barker CS, Miller J, Whitworth E, James O, Sollers Iii JJ, Bryson WJ, Thorpe R, Byrd G, Whitfield KE, Sudhakar S, Parker DO, Livingston J, Shah N, Railey K. Intrahepatic cholestasis in sickle cell disease: A review of diagnostic criteria, treatments, and case reports. J Natl Med Assoc 2023; 115:26-37. [PMID: 36599744 DOI: 10.1016/j.jnma.2022.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 09/15/2022] [Accepted: 12/07/2022] [Indexed: 01/04/2023]
Abstract
Objective To delineate the etiology, symptomatology, and treatment of sickle cell intrahepatic cholestasis (SCIC). Sickle cell disease (SCD) is the most frequently inherited hematologic disease, and SCIC is one rare and often fatal complication and comorbid disease. The literature contains only a small number of case reports involving SCIC and hence limited guidance can be obtained. Methods We reviewed the scientific literature to evaluate the science of SCIC to determine if there were consistencies in presentation, evaluation, treatment, and clinical outcomes. Results We reviewed 6 case reports and a limited number of clinical papers on SCIC. We reported consistencies in clinical presentation and treatment outcomes among cases as well as serological and hematological finding. Conclusions While there is some consistency in the symptom presentation of individuals with SCIC, reliable evaluation and clinical procedures were not demonstrated in what we reviewed. Further research is needed to delineate the attributes of this complicated disease that occurs within SCD.
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Affiliation(s)
- Christopher L Edwards
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States.
| | - Sharena Scott
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | - Michaela Boggan
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | - Jordan Meek
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | - Kiera Alston
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | - Aiden Pearson
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | | | | | - Mary Wood
- Duke University Medical Center, United States
| | | | | | | | - Osaffo James
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States
| | - John J Sollers Iii
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | | | | | | | | | - Shiv Sudhakar
- Internal Medicine and Infectious Disease, College of Medicine, California Northstate University, 9700 W. Taron Dr. Elk Grove, CA 95757, United States
| | - Debra O Parker
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
| | - Jonathan Livingston
- North Carolina Central University, 1801 Fayetteville St., Durham, NC 27707, United States; NCCU Debra O. Parker Research Incubator, United States
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11
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Lad H, Naskar S, Punyasri Pasupuleti SKDB, Nahrel R, Sihare P, Chandak GR, Patra PK. Evaluation of pharmacological efficacy and safety of hydroxyurea in sickle cell disease: Study of a pediatric cohort from Chhattisgarh, India. Pediatr Hematol Oncol 2022; 40:395-406. [PMID: 36226857 DOI: 10.1080/08880018.2022.2126042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Sickle cell disease (SCD) is a disease of abnormal hemoglobin associated with severe clinical phenotype and recurrent complications. Hydroxyurea (HU) is one of the US-FDA approved and commonly used drug for the treatment of adult SCD patients with clinical -severity. However, its use in the pediatric groups remains atypical. Despite a high prevalence of the disease in the state Chhattisgarh, there is a lack of evidence supporting its use in pediatric patients. This study aimed to evaluate the pharmacological and clinical efficacy and safety of HU in a large pediatric cohort with SCD from Central India. The study cohort consisted of 164 SCD (138 Hb SS and 26 Hb S beta-thalassemia) children (≤14 years of age) on HU therapy, who were monitored for toxicity, hematological and clinical efficacy at baseline (Pre-HU) and after 24 months (Post-HU). The results highlight the beneficial effects of HU at a mean dose of 18.7 ± 7.0 mg/kg/day. A significant improvement was observed, not only in physical and clinical parameters but also in hematological parameters which include fetal hemoglobin (Hb F), total hemoglobin, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, when evaluated against the baseline. We did not observe any significant adverse effects during the treatment period. Similar results were obtained on independent analysis of Hb SS and Hb Sβ patients. These findings strengthen the beneficial effect of hydroxyurea in pediatric population also without any serious adverse effects and builds up ground for expanding its use under regular monitoring.
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Affiliation(s)
- Harsha Lad
- Chhattisgarh Institute of Medical Sciences (CIMS), Bilaspur, Chhattisgarh, India
| | - Shoma Naskar
- Genomic Research on Complex diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, Telangana, India
| | - S K D B Punyasri Pasupuleti
- Genomic Research on Complex diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, Telangana, India
| | - Rakesh Nahrel
- Chhattisgarh Institute of Medical Sciences (CIMS), Bilaspur, Chhattisgarh, India
| | - Pradeep Sihare
- Sihare Children's Hospital, Bilaspur, Chhattisgarh, India
| | - Giriraj R Chandak
- Genomic Research on Complex diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, Telangana, India
| | - Pradeep K Patra
- Chhattisgarh Institute of Medical Sciences (CIMS), Bilaspur, Chhattisgarh, India
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12
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Trivedi K, Abbas A, Kazmi R, Shaaban H, Miller R. Hyperhemolytic Crisis Following Transfusion in Sickle Cell Disease With Acute Hepatic Crisis: A Case Report. Cureus 2022; 14:e27844. [PMID: 36110470 PMCID: PMC9461243 DOI: 10.7759/cureus.27844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2022] [Indexed: 11/05/2022] Open
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13
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Khan A, Nashed B, Issa M, Khan MZ. Sickle Cell Intrahepatic Cholestasis: Extremely Rare but Fatal Complication of Sickle Cell Disease. Cureus 2022; 14:e22050. [PMID: 35295370 PMCID: PMC8916923 DOI: 10.7759/cureus.22050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2022] [Indexed: 11/09/2022] Open
Abstract
Sickle cell intrahepatic cholestasis (SCIC) is a rare but potentially fatal complication of sickle cell disease (SCD), with high mortality, observed mainly in patients with homozygous sickle cell anemia. Herein, we have reported a case of severe SCIC with a poor outcome despite aggressive measures including exchange transfusion and use of vasopressors. The patient was admitted with generalized weakness, confusion, rigors, chills, and signs of hepatic failure, such as hyperbilirubinemia, hypoalbuminemia, and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. The patient received two exchange transfusions, but he continued to deteriorate clinically despite exchange transfusion and developed hemorrhagic shock and multiorgan failure. The patient was made comfort care as per family wishes. This case emphasizes the importance of early diagnosis of sickle cell intrahepatic cholestasis and poor prognosis despite aggressive measures.
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14
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Barbetta A, Goldbeck C, Lim A, Martin SP, Kahn JA, Sheikh MR, Emamaullee J. Treatment and outcomes of hepatocellular carcinoma in patients with Sickle cell disease: a population-based study in the U.S. HPB (Oxford) 2022; 24:234-243. [PMID: 34294525 PMCID: PMC8733051 DOI: 10.1016/j.hpb.2021.06.420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/27/2021] [Accepted: 06/21/2021] [Indexed: 01/09/2023]
Abstract
BACKGROUND Sickle cell disease (SCD) is a rare hemoglobinopathy which can result in chronic liver disease and cirrhosis. Patients with SCD have an increased risk of hematologic malignancy, but the prevalence of hepatocellular carcinoma (HCC) in this population is unknown. Herein, the association of SCD with HCC was examined using registry data. METHODS The SEER-Medicare database was queried to identify patients diagnosed with HCC between 2000 and 2015, and further stratified by SCD status. Propensity matching was performed to examine cancer-related survival and treatment outcomes. RESULTS Overall 56,934 patients with HCC were identified, including 81 patients with SCD. Patients with SCD more frequently had cirrhosis [48.1% (39/81) vs 23.5% (13,377/56,853), p < 0.01] yet presented with smaller tumors [<5 cm: 51.9% (42/81) vs 38.5% (21,898/56,853), p = 0.01]. After propensity matching, SCD was not associated with attenuated survival (aHR 0.73 95%CI 0.52-1.01). When stratified by treatment, patients with SCD had equivalent outcomes to chemotherapy (p = 0.65), TACE/TARE (p = 0.35), resection (p = 0.15) and transplantation (p = 0.67) when compared to non-SCD patients. CONCLUSION This study confirms that a subset of patients with SCD will develop HCC. Importantly, therapeutic options for HCC should not be limited by pre-existing SCD, and similar survival should be expected when compared to non-SCD patients.
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Affiliation(s)
- Arianna Barbetta
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, 1510 San Pablo St, Los Angeles, 90033, CA, USA
| | - Cameron Goldbeck
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, 1510 San Pablo St, Los Angeles, 90033, CA, USA
| | - Angelina Lim
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, 1510 San Pablo St, Los Angeles, 90033, CA, USA
| | - Sean P Martin
- Deparment of Surgery, UPMC Pinnacle, 111 S Front St, Harrisburg, 17101, PA, USA
| | - Jeffrey A Kahn
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, 1510 San Pablo St, Los Angeles, 90033, CA, USA
| | - M Raashid Sheikh
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, 1510 San Pablo St, Los Angeles, 90033, CA, USA
| | - Juliet Emamaullee
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, 1510 San Pablo St, Los Angeles, 90033, CA, USA.
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15
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Saeed O, Panarelli N, Umrau K, Lee H, Westerhoff M, Cheng J, Lin J. The Histopathologic Features of Sickle Cell Hepatopathy: A Multi-Institutional Study. Am J Clin Pathol 2022; 157:73-81. [PMID: 34463318 DOI: 10.1093/ajcp/aqab096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/04/2021] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVES Recent data on hepatic histopathology in patients with sickle cell disease (SCD) are lacking. METHODS A total of 39 liver biopsies from SCD patients from 4 medical institutes were systematically evaluated. RESULTS The average age of patients was 27 years; 23 were female. The majority of the patients had hemoglobin SS (33), 3 had hemoglobin SC, and 3 sickle cell trait. Elevated liver functional tests and evaluation for cirrhosis were the main indications for biopsy. At the time of biopsy, most had elevated liver transaminases or hepatomegaly. The most common histopathologic abnormalities were Kupffer cell erythrophagocytosis (76.9%), hemosiderosis (74.4%), sinusoidal dilatation (71.8%), and intrasinusoidal sickled red cells (69.3%). Portal inflammation, lobular inflammation, and bile duct injury were mild to minimal and present in a minority of cases. Advanced fibrosis was present in 28.2% of the cases. CONCLUSIONS The typical histopathologic features seen in patients with SCD include Kupffer cell erythrophagocytosis, hemosiderosis, sinusoidal dilatation, and intrasinusoidal sickled red cells in a pauci-inflammatory or uninflamed background. Necrosis is less common than reported in older literature. Pathologists should be aware that significant portal and lobular inflammation, interface activity, and bile duct injury are unusual and may be suggestive of other etiologies.
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Affiliation(s)
- Omer Saeed
- Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA
| | - Nicole Panarelli
- Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Kavita Umrau
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
| | - Hwajeong Lee
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
| | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Jerome Cheng
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Jingmei Lin
- Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA
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Safhi MA, Baghdadi RM, Al-Marzouki AF, Al-Sayes F. Response to Hydroxyurea in a Patient With Sickle Cell Hepatopathy: A Case Report. Cureus 2021; 13:e20649. [PMID: 34976545 PMCID: PMC8712197 DOI: 10.7759/cureus.20649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2021] [Indexed: 11/17/2022] Open
Abstract
Sickle cell hepatopathy is an underreported entity lacking clear management guidelines. This case highlights the potential role of hydroxyurea (HU) in improving the hepatic dysfunction seen among patients with sickle cell disease (SCD). We herein present the clinical course of a patient prior to and after the initiation of hydroxyurea with an emphasis on long-term outcomes and the patterns of liver injury over a 15-year time course.
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17
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Towerman AS, Wilson DB, Hulbert ML. Epstein-Barr virus-induced sickle hepatopathy. Pediatr Blood Cancer 2021; 68:e29196. [PMID: 34180131 DOI: 10.1002/pbc.29196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/26/2021] [Accepted: 06/12/2021] [Indexed: 11/05/2022]
Abstract
Sickle hepatopathy comprises a spectrum of disorders that vary in severity. Intravascular sickling and sinusoidal occlusion are the principal drivers of sickle hepatopathy, but infection or autoimmunity can act as triggers. We describe two cases of acute sickle hepatopathy initiated by primary Epstein-Barr virus (EBV) infection, a previously unreported association. The first case entailed a 14-year-old girl with hemoglobin SC (HbSC) disease who developed hepatic sequestration crisis that responded to a simple transfusion of erythrocytes. The second case was that of a 16-year-old boy with HbSC disease who experienced life-threatening intrahepatic cholestasis with multiorgan failure.
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Affiliation(s)
- Alison S Towerman
- Departments of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.,School of Nursing, St. Louis University, St. Louis, Missouri, USA
| | - David B Wilson
- Departments of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.,Department of Developmental Biology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA
| | - Monica L Hulbert
- Departments of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA
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18
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Response to: Acute Liver Failure in a Sickle Cell Patient. J Pediatr Gastroenterol Nutr 2021; 73:e27-e28. [PMID: 33797447 DOI: 10.1097/mpg.0000000000003142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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19
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Acute Liver Failure in a Sickle Cell Patient. J Pediatr Gastroenterol Nutr 2021; 73:e27. [PMID: 33797446 DOI: 10.1097/mpg.0000000000003141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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20
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Felli E, Felli E, Muttillo EM, Memeo R, Giannelli V, Colasanti M, Pellicelli A, Diana M, Ettorre GM. Liver transplantation for sickle cell disease: a systematic review. HPB (Oxford) 2021; 23:994-999. [PMID: 33431265 DOI: 10.1016/j.hpb.2020.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 12/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Sickle cell disease is a group of autosomal recessive disorders characterised by haemolytic anaemia. Liver is one of the most affected organs, ranging from liver tests alterations to acute liver failure for which liver transplantation is the only life-saving treatment. METHODS This study aims to make a systematic review of the current literature to evaluate indications, timing, and results of liver transplantation for patients affected by SCD. RESULTS Twenty-nine patients in total were reported worldwide until 2018, the average patient age is 28.7 (0.42-56), all patients have a pre-transplant diagnosis of SCD. Cirrhosis at transplantation was present in six-teen (n = 16, 55.1%) patients. In ten patients (n = 10, 34.5%), acute liver failure arises from healthy liver and presented sickle cell intrahepatic cholestasis. Eleven patients (n = 11, 39.2%) died, three (n = 3, 10.7%) in the first postoperative month, and seven (n = 7, 25%) in the first year. Mean follow-up was 27 months (range: 7-96), one-year overall survival was 48.7%. DISCUSSION Liver transplantation for SCD has been increasingly reported with encouraging results. Indications are presently reserved for acute liver failure arising both in healthy liver and end-stage liver disease.
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Affiliation(s)
- Emanuele Felli
- Department of General, Digestive, and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France; IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France; Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France; Institute of Viral and Liver Disease, Inserm U1110, Strasbourg, France.
| | - Eric Felli
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France; Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France
| | - Edoardo M Muttillo
- Department of General, Digestive, and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France; Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Riccardo Memeo
- Division of Hepato-Pancreato-Biliary Surgery, "F. Miulli" General Hospital, Acquaviva Delle Fonti, Bari, Italy; Liver Transplant Unit, Policlinico di Bari, Bari, Italy
| | - Valerio Giannelli
- San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
| | - Marco Colasanti
- San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
| | - Adriano Pellicelli
- San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
| | - Michele Diana
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France; Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France; ICUBE Laboratory, Photonics Instrumentation for Health, University of Strasbourg, Strasbourg, France
| | - Giuseppe M Ettorre
- San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
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21
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Burley NB, Miller KD. Acute Liver Failure in Sickle Cell Disease: A Perfect Storm. Cureus 2021; 13:e15680. [PMID: 34159039 PMCID: PMC8212850 DOI: 10.7759/cureus.15680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Sickle cell hepatopathy is a well-described but uncommonly seen complication of sickle cell disease and is usually caused by multiple overlapping processes. A more acute liver complication is hepatic sequestration which is important to recognize in order to initiate life-saving treatment. A 33-year-old woman with sickle cell disease complicated by painful crises, splenic infarction and significant alcohol abuse presented with gastrointestinal distress, pain crisis, acute-on-chronic anemia, and hyperbilirubinemia in the setting of greater than baseline alcohol consumption. She was found to have hepatomegaly, encephalopathy, severe jaundice, and severe hyperbilirubinemia. She was treated with red cell exchange and supportive care which resulted in an improvement in her symptoms as well as hyperbilirubinemia. She was discharged with plans for monthly red cell exchange, iron chelation therapy, and close monitoring of liver disease was planned upon discharge. This case illustrates that chronic liver disease can occur in sickle cell disease (Hgb SS) especially in the setting of acquired iron overload. More acutely, sequestration is a serious and life-threatening complication of sickle cell disease that can culminate in acute liver failure. Primary treatment for hepatic sequestration is red cell exchange along with management of contributing comorbidities, and symptomatic management of encephalopathy. In end-stage liver disease, transplantation may be considered in the context of the patient’s clinical status.
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22
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Rodrigues L, Almeida S, Salgado C, Gonçalves C. Pediatric Acute Liver Failure in Sickle Cell Disease. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 29:192-196. [DOI: 10.1159/000515469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 02/20/2021] [Indexed: 11/19/2022]
Abstract
<b><i>Introduction:</i></b> Sickle cell intrahepatic cholestasis (SCIC) is one of the rarest and the most severe acute hepatic manifestations of sickle cell disease (SCD) and it can rapidly progress to acute liver failure. It is associated with a high mortality rate, demanding prompt recognition and management. <b><i>Case Presentation:</i></b> We report a case of a 7-year-old boy with a history of homozygous HbS SCD who presented to the emergency department with fever, increasing abdominal pain, and jaundice. His course was complicated by acute liver injury (AST 9,472 IU/L, ALT 2,683 IU/L, total bilirubin 15.4 mg/dL; conjugated bilirubin 8.69 mg/dL, hypoalbuminemia 2.6 g/dL, and persistent hypoglycemia), with acute liver failure (coagulopathy not corrected by vitamin K administration with INR 3.26, decreased factors V 10% and VII 28%, and West Haven grade I hepatic encephalopathy associated with mild hyperammonemia of 71 µmol/L). After excluding other causes of acute liver failure, the patient was diagnosed as having SCIC and was successfully treated with manual exchange transfusion. <b><i>Conclusion:</i></b> This case reinforces that exchange transfusion is an effective treatment for SCIC and that it should be introduced promptly to prevent fulminant and potentially fatal liver failure.
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24
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Abstract
Sickle hepatopathy is an umbrella term describing various pattern of liver injury seen in patients with sickle cell disease. The disease is not uncommon in India; in terms of prevalence, India is second only to Sub-Saharan Africa where sickle cell disease is most prevalent. Hepatic involvement in sickle cell disease is not uncommon. Liver disease may result from viral hepatitis and iron overload due to multiple transfusions of blood products or due to disease activity causing varying changes in vasculature. The clinical spectrum of disease ranges from ischemic injury due to sickling of red blood cells in hepatic sinusoids, pigment gall stones, and acute/chronic sequestration syndromes. The sequestration syndromes are usually episodic and self-limiting requiring conservative management such as antibiotics and intravenous fluids or packed red cell transfusions. However, rarely these episodes may present with coagulopathy and encephalopathy like acute liver failure, which are life-threatening, requiring exchange transfusions or even liver transplantation. However, evidence for their benefits, optimal indications, and threshold to start exchange transfusion is limited. Similarly, there is paucity of the literature regarding the end point of exchange transfusion in this scenario. Liver transplantation may also be beneficial in end-stage liver disease. Hydroxyurea, the antitumor agent, which is popularly used to prevent life-threatening complications such as acute chest syndrome or stroke in these patients, has been used only sparingly in hepatic sequestrations. The purpose of this review is to provide insights into epidemiology of sickle cell disease in India and pathogenesis and classification of hepatobiliary involvement in sickle cell disease. Finally, various management options including exchange transfusion, liver transplantation, and hydroxyurea in hepatic sequestration syndromes will be discussed in brief.
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Key Words
- AASLD, American Association for the Study of Liver Diseases
- ACLF, Acute on chronic liver failure
- ALF, Acute liver failure
- ALT, Alanine transaminase
- AST, Aspartate transaminase
- FFP, Fresh frozen plasma
- GIT, Gastrointestinal tract
- HAV, Hepatitis A virus
- HBV, Hepatitis B virus
- HCV, Hepatitis C virus
- HEV, Hepatitis E virus
- HIC, Hepatic iron content
- HbS, Sickle hemoglobin
- HbSS, Sickle cell disease homozygous
- INR, International normalized ratio
- PT, Prothrombin time
- RUQ, Right upper quadrant
- SC, Scheduled caste
- SCD, Sickle cell disease
- SCIC, Sickle cell intrahepatic cholestasis
- ST, Scheduled tribe
- TJLB, Transjugular liver biopsy
- UDCA, Ursodeoxycholic acid
- cholelithiasis
- intrahepatic cholestasis
- sickle cell hepatopathy
- sickle cholangiopathy
- sickle hepatic crisis
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Affiliation(s)
| | - Anil C. Anand
- Address for correspondence. Anil C Anand, Professor and Head, Department of Gastroenterology & Hepatology, Kalinga Institute of Medical Sciences, Bhubneshwar, India.
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Abstract
Liver involvement is found in nearly 40% of children with sickle cell disease. The most frequent complication is cholelithiasis. The most severe complication is acute hepatic crisis, with symptoms ranging from increasing jaundice to multiple organ failure and death. The emergency and mostly efficient treatment is exchange transfusion. Chronic cholangiopathy is increasingly recognized, with autoimmune features in most cases, worsened by chronic ischemia. Transfusion-related iron overload is not yet a concern in children, and hepatotoxicity of iron chelators is rare. We propose recommendations to prevent, explore, and treat these complications. We emphasize the close collaboration required between hepatologists and specialists of sickle cell disease.
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Hequet O, Fort R, Driss F. Red blood cell exchange in an emergency in sickle cell disease. Transfus Apher Sci 2020; 59:102996. [PMID: 33189570 DOI: 10.1016/j.transci.2020.102996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Red blood cell exchange (RBCEx) has become a standard therapy to remove abnormal red blood cells (RBCs) in patients with sickle cell disease (SCD). In the last few decades, numerous RBCEx procedures have been performed chronically during regular programs, while numerous procedures have also been performed in an emergency for several indications, this therapeutic option being very efficient in vital and emergency situations. In both groups of indications, large amounts of sickle RBCs have to be removed, which requires great precision and the setting of specific hematological targets. The aim of this review is to discuss the aims, clinical and biological targets, and the requirements and precautions when performing RBCEx in an emergency. Moreover, we analyze how improvement of the techniques as well as the clinical and biological targets has led to optimization of the procedures in emergency settings. We also consider the outstanding issues that require additional investigation.
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Affiliation(s)
- O Hequet
- Apheresis Unit, Etablissement Français du Sang Auvergne Rhône-Alpes, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
| | - R Fort
- Department of Internal Medicine, CHU Edouard Herriot, Lyon, France; Laboratoire LIBM EA7424, Equipe "Biologie Vasculaire et du Globule Rouge", Université Claude Bernard, Lyon, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne, Paris, France
| | - F Driss
- Biological Hematological Unit, Centre Hospitalier universitaire Bicêtre, le Kremlin-Bicêtre, France
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Kinger NP, Moreno CC, Miller FH, Mittal PK. Abdominal Manifestations of Sickle Cell Disease. Curr Probl Diagn Radiol 2020; 50:241-251. [PMID: 32564896 DOI: 10.1067/j.cpradiol.2020.05.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 04/24/2020] [Accepted: 05/26/2020] [Indexed: 12/24/2022]
Abstract
Sickle cell disease is a debilitating hematologic process that affects the entire body. Disease manifestations in the abdomen most commonly result from vaso-occlusion, hemolysis, or infection due to functional asplenia. Organ specific manifestations include those involving the liver (eg, hepatopathy, iron deposition), gallbladder (eg, stone formation), spleen (eg, infarction, abscess formation, sequestration), kidneys (eg, papillary necrosis, infarction), pancreas (eg, pancreatitis), gastrointestinal tract (eg, infarction), reproductive organs (eg, priapism, testicular atrophy), bone (eg, marrow changes, avascular necrosis), vasculature (eg, vasculopathy), and lung bases (eg, acute chest syndrome, infarction). Imaging provides an important clinical tool for evaluation of acute and chronic disease manifestations and complications. In summary, there are multifold abdominal manifestations of sickle cell disease. Recognition of these sequela helps guide management and improves outcomes. The purpose of this article is to review abdominal manifestations of sickle cell disease and discuss common and rare complications of the disease within the abdomen.
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Affiliation(s)
- Nikhar P Kinger
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA.
| | - Courtney C Moreno
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA
| | - Frank H Miller
- Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Pardeep K Mittal
- Department of Radiology and Imaging, Medical College of Georgia, Augusta, GA
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Hogen R, Kim M, Lee Y, Lo M, Kaur N, Kahn J, Chopra S, Qazi Y, Sedra A, Kim J, O'Brien L, Genyk Y, Sher L, Emamaullee J. Liver Transplantation in Patients with Sickle Cell Disease in the United States. J Surg Res 2020; 255:23-32. [PMID: 32540577 DOI: 10.1016/j.jss.2020.05.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/26/2020] [Accepted: 05/06/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Up to 30% of patients with sickle cell disease (SCD) develop chronic liver disease via etiologies including sickle cell hepatopathy, acquired viral hepatitis, or secondary hemochromatosis. It is unclear how many patients with SCD ultimately undergo liver transplantation (LT) and what factors are associated with survival after LT. In this study, we examined LT outcomes in these patients by reviewing the Scientific Registry of Transplant Recipients (SRTR) and our institutional experience. METHODS Analysis of the SRTR identified 23 LT recipients and five simultaneous liver and kidney transplantation (SLKT) recipients with SCD. Patient demographics and graft and patient survival were analyzed. Two patients with SCD at our institution underwent SLKT. RESULTS Review of the SRTR revealed that recipients with SCD had significantly higher model for end-stage liver disease scores (33 versus 21, P = 0.004), preoperative intensive care unit admission (43.5% versus 19.1%, P = 0.007), preoperative dialysis (17.4% versus 4.9%, P = 0.009), and were more likely to be status 1 (26.1% versus 12.1%, P = 0.041) when compared with the reference population of African American LT recipients. Despite being higher risk at the time of LT, patients with SCD had equivalent posttransplant graft and patient survival when compared with the reference population (P = 0.5 and P = 0.2, respectively) and a 2:1 propensity score-matched group (P = 0.5 and P = 0.2, respectively). Two recent SLKT recipients with SCD from our institution have performed well with stable allograft function. CONCLUSIONS Data from the SRTR demonstrate that patients with SCD can expect equivalent graft and patient survival after LT despite exhibiting more comorbidities at the time of LT. The low number of patients with SCD who underwent LT in the SRTR in comparison with the rate of chronic liver disease in this population raises the question as to whether a disparity in access to LT exists for this complex population.
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Affiliation(s)
- Rachel Hogen
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Michelle Kim
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Yelim Lee
- California Institute of Technology, Pasadena, California
| | - Mary Lo
- Department of Preventive Medicine, University of Southern California, Los Angeles, California
| | - Navpreet Kaur
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Jeff Kahn
- Department of Laboratory Medicine and Pathology, University of Southern California, Los Angeles, California
| | - Shefali Chopra
- Department of Laboratory Medicine and Pathology, University of Southern California, Los Angeles, California
| | - Yasir Qazi
- Department of Medicine, University of Southern California, Los Angeles, California
| | - Ashraf Sedra
- Department of Anesthesiology, University of Southern California, Los Angeles, California
| | - Jim Kim
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Lauren O'Brien
- Department of Laboratory Medicine and Pathology, University of Southern California, Los Angeles, California
| | - Yuri Genyk
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Linda Sher
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Juliet Emamaullee
- Division of Hepatobiliary and Abdominal Organ Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California.
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Maji P, Malik R, Lodha R, Bagga A. Sickle Cell Intrahepatic Cholestasis with Acute Liver Failure and Acute Kidney Injury: Favourable Outcome with Exchange Transfusion. Indian J Pediatr 2020; 87:83. [PMID: 31520310 DOI: 10.1007/s12098-019-03071-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 08/22/2019] [Indexed: 11/26/2022]
Affiliation(s)
- Prabir Maji
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Department of Pediatrics, AIIMS, New Delhi, India
| | - Rohan Malik
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Department of Pediatrics, AIIMS, New Delhi, India.
| | - Rakesh Lodha
- Division of Pulmonology and Intensive Care, Department of Pediatrics, AIIMS, New Delhi, India
| | - Arvind Bagga
- Division of Nephrology, Department of Pediatrics, AIIMS, New Delhi, India
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Suddle AR. Management of liver complications in sickle cell disease. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2019; 2019:345-350. [PMID: 31808845 PMCID: PMC6913458 DOI: 10.1182/hematology.2019000037] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Liver disease is an important cause of morbidity and mortality in patients with sickle cell disease (SCD). Despite this, the natural history of liver disease is not well characterized and the evidence basis for specific therapeutic intervention is not robust. The spectrum of clinical liver disease encountered includes asymptomatic abnormalities of liver function; acute deteriorations in liver function, sometimes with a dramatic clinical phenotype; and decompensated chronic liver disease. In this paper, the pathophysiology and clinical presentation of patients with acute and chronic liver disease will be outlined. Advice will be given regarding initial assessment and investigation. The evidence for specific medical and surgical interventions will be reviewed, and management recommendations made for each specific clinical presentation. The potential role for liver transplantation will be considered in detail.
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Affiliation(s)
- Abid R Suddle
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
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Adkins BD, Savani BN, Booth GS. Management of Sickle Cell Intrahepatic Cholestasis: An Argument in Favor of Automated Exchange Transfusion. Clin Hematol Int 2019; 1:127-133. [PMID: 34595422 PMCID: PMC8432363 DOI: 10.2991/chi.d.190630.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 06/23/2019] [Indexed: 11/17/2022] Open
Abstract
Sickle cell disease patients are commonly treated at transfusion medicine services, and understanding of the hepatic manifestations of the disease is key for optimal management, specifically, in individuals presenting with sickle cell intrahepatic cholestasis (SCIC). SCIC represents a rare, severe hepatic crisis wherein sinusoidal red cell sickling leads to massive hepatocyte dysfunction and cholestatic laboratory findings. Acute SCIC is defined by abdominal pain with progressive hepatic injury associated with hyperbilirubinemia, renal failure, encephalopathy, and coagulopathy. Patients are generally managed with red blood cell exchange transfusion (RBCEx), when available, as this is a potentially fatal condition. Simple transfusion may be utilized in resource-poor environment or when patients refuse RBCEx. As less than 50 adult cases have been described in the literature, many of them with limited follow-up, randomized clinical trials comparing RBCEx with other treatments are currently unfeasible. Likewise, a chronic form exists, but is less well characterized, and is associated with persistent bilirubinemia and a variable course in terms of progressive hepatic disease. We undertake a brief review of the literature and discuss two cases of SCIC managed with RBCEx at our institution.
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Affiliation(s)
- Brian D Adkins
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Bipin N Savani
- Department of Internal Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Garrett S Booth
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
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Ben Yakov G, Sharma D, Alao H, Surana P, Kapuria D, Etzion O, Hsieh MM, Tisdale JF, Fitzhugh CD, Kleiner DE, Levy EB, Chang R, Rivera E, Huang A, Koh C, Heller T. Vibration Controlled Transient Elastography (Fibroscan®) in sickle cell liver disease - could we strike while the liver is hard? Br J Haematol 2019; 187:117-123. [PMID: 31218662 DOI: 10.1111/bjh.16047] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 04/23/2019] [Indexed: 01/22/2023]
Abstract
Vibration controlled transient elastography (VCTE) is validated for the evaluation of hepatic fibrosis in different liver diseases. Sickle cell liver disease (SCLD) results from a cumulative hepatic injury and its lifelong and progressive nature raises the need for a non-invasive tool for fibrosis evaluation. Fifty patients, aged between 23 and 59 years with sickle cell disease and suspected SCLD underwent a VCTE followed by a liver biopsy. Biopsies were evaluated for various scores of liver disease that were then correlated to VCTE score. 90% of our patients had an Ishak Fibrosis (IF) score between 0-2 (Group A-minimal to no fibrosis) and 10% of the patients had IF score between 3-6 (Group B-advanced fibrosis). The median Transient Elastography (TE) for patients in Groups A and B was 4·8 kilopascals (kPa) and 17·6 kPa, respectively. A positive correlation was shown between TE and IF score, R = 0·0·68 (P = <0·0001); a positive correlation was also shown with Histology Activity Index fibrosis score, R = 0·64 (P = <0·0001). This study emphasises the need for further studies of non-invasive tools and their utility in liver fibrosis evaluation of patients with SCLD.
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Affiliation(s)
- Gil Ben Yakov
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Disha Sharma
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Hawwa Alao
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | | | | | - Ohad Etzion
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Matthew M Hsieh
- Molecular and Clinical Hematology Branch, NHLBI, NIH, Bethesda, MD, USA
| | - John F Tisdale
- Molecular and Clinical Hematology Branch, NHLBI, NIH, Bethesda, MD, USA
| | | | | | - Elliot B Levy
- Interventional Radiology, Department of Diagnostic Radiology, NIH, Bethesda, MD, USA
| | - Richard Chang
- Interventional Radiology, Department of Diagnostic Radiology, NIH, Bethesda, MD, USA
| | | | - Amy Huang
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | | | - Theo Heller
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
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Houwing ME, de Pagter PJ, van Beers EJ, Biemond BJ, Rettenbacher E, Rijneveld AW, Schols EM, Philipsen JNJ, Tamminga RYJ, van Draat KF, Nur E, Cnossen MH. Sickle cell disease: Clinical presentation and management of a global health challenge. Blood Rev 2019; 37:100580. [PMID: 31128863 DOI: 10.1016/j.blre.2019.05.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 05/17/2019] [Accepted: 05/17/2019] [Indexed: 01/12/2023]
Abstract
Sickle cell disease is an autosomal recessive, multisystem disorder, characterised by chronic haemolytic anaemia, painful episodes of vaso-occlusion, progressive organ failure and a reduced life expectancy. Sickle cell disease is the most common monogenetic disease, with millions affected worldwide. In well-resourced countries, comprehensive care programs have increased life expectancy of sickle cell disease patients, with almost all infants surviving into adulthood. Therapeutic options for sickle cell disease patients are however, still scarce. Predictors of sickle cell disease severity and a better understanding of pathophysiology and (epi)genetic modifiers are warranted and could lead to more precise management and treatment. This review provides an extensive summary of the pathophysiology and management of sickle cell disease and encompasses the characteristics, complications and current and future treatment options of the disease.
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Affiliation(s)
- M E Houwing
- Department of Paediatric Haematology, Erasmus University Medical Center - Sophia Children's Hospital, Wytemaweg 80, 3015, CN, Rotterdam, the Netherlands.
| | - P J de Pagter
- Department of Paediatric Haematology, Erasmus University Medical Center - Sophia Children's Hospital, Wytemaweg 80, 3015, CN, Rotterdam, the Netherlands.
| | - E J van Beers
- Department of Internal Medicine and Dermatology, Van Creveldkliniek, University Medical Center Utrecht, Internal mail no C.01.412, 3508, GA, Utrecht, the Netherlands.
| | - B J Biemond
- Department of Internal Medicine and Clinical Haematology, Amsterdam University Medical Centers, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands.
| | - E Rettenbacher
- Department of Paediatric Haematology, Radboud University Medical Center - Amalia Children's Hospital, Geert Grooteplein Zuid 10, 6500, HB, Nijmegen, the Netherlands.
| | - A W Rijneveld
- Department of Haematology, Erasmus University Medical Center, Wytemaweg 80, 3015, CN, Rotterdam, the Netherlands.
| | - E M Schols
- Department of Haematology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, the Netherlands.
| | - J N J Philipsen
- Department of Cell Biology, Erasmus University Medical Center, Wytemaweg 80, 3015, CN, Rotterdam, the Netherlands.
| | - R Y J Tamminga
- Department of Paediatric Oncology and Haematology, University Medical Center Groningen - Beatrix Children's Hospital, Postbus 30001, 9700, RB, Groningen, the Netherlands..
| | - K Fijn van Draat
- Department of Paediatric Haematology, Amsterdam University Medical Centers - Emma Children's Hospital, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Department of Plasma Proteins, Sanquin Research, the Netherlands.
| | - E Nur
- Department of Internal Medicine and Clinical Haematology, Amsterdam University Medical Centers, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands.
| | - M H Cnossen
- Department of Paediatric Haematology, Erasmus University Medical Center - Sophia Children's Hospital, Wytemaweg 80, 3015, CN, Rotterdam, the Netherlands.
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Abstract
Patients with sickle cell disease can develop liver disease as a result of intrahepatic sickling of erythrocytes, viral hepatitis and iron overload secondary to multiple blood transfusions, and gallstone disease as a result of chronic hemolysis. The spectrum of clinical liver disease is wide and often multifactorial. Some patients develop cirrhosis that may progress to end-stage liver failure. Limited evidence exists for medical treatments. Exchange blood transfusions may improve outcomes in the acute liver syndromes. Liver transplantation may be an option for chronic liver disease. The role for prophylactic cholecystectomy in preventing complications of gallstone disease is controversial.
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Affiliation(s)
- Eleni Theocharidou
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
| | - Abid R Suddle
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK.
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Haydek JP, Taborda C, Shah R, Reshamwala PA, McLemore ML, Rassi FE, Chawla S. Extreme hyperbilirubinemia: An indicator of morbidity and mortality in sickle cell disease. World J Hepatol 2019; 11:287-293. [PMID: 30967906 PMCID: PMC6447425 DOI: 10.4254/wjh.v11.i3.287] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 01/16/2019] [Accepted: 01/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sickle cell disease (SCD) is a disorder that results in increased hospitalizations and higher mortality. Advances in management have resulted in increases in life expectancy and led to increasing awareness of sickle cell hepatopathy (SCH). However, its impact in patients on the natural history and outcomes of SCD is not known. Our study aims to describe the prevalence of extreme hyperbilirubinemia (EH), one form of SCH, its effect on morbidity and mortality, and correlations between sickle cell genotype and SCH type. We hypothesize that EH is associated with higher morbidity and mortality. AIM To investigate the effects of EH on morbidity and mortality among patients with SCD. METHODS This retrospective cohort study was performed using a database of patients with SCD treated at Grady Memorial Hospital between May 2004 and January 2017. Patients with EH (defined as total bilirubin above 13.0 mg/dL) were identified. A control group was identified from the same database with patients with total serum bilirubin ≤ 5.0 mg/dL. Electronic medical records were used to extract demographic information, laboratory values, radiology results, current medications, need for transfusions and mortality data. Two samples T-test, chi-squared test and Fisher's exact test were then used to compare the parameters between the two groups. RESULTS Out of the database, fifty-seven charts were found of patients with bilirubin > 13 mg/dL. Prevalence of severe SCH as defined by EH was 4.8% (57/1172). There were no demographic differences between patients with and without EH. Significant genotypic differences existed between the two groups, with hemoglobin SS SCD being much higher in the EH group (P < 0.001). Patients with severe EH had a significant elevations in alanine aminotransferase (157.0 ± 266.2 IU/L vs 19.8 ± 21.3 IU/L, P < 0.001), aspartate aminotransferase (256.5 ± 485.9 U/L vs 28.2 ± 14.7 U/L, P < 0.001) and alkaline phosphatase (218.0 ± 176.2 IU/L vs 85.9 ± 68.4 IU/L, P < 0.001). Patients with EH had significantly higher degree of end organ failure measured with quick Sequential Organ Failure Assessment scores (0.42 ± 0.68 vs 0.01 ± 0.12, P < 0.001), increased need for blood products (63% vs 5%, P < 0.001), and exchange transfusions (10.5% vs 1.3%, P = 0.022). CONCLUSION Among patients with SCD, elevated levels of total bilirubin are rare, but indicative of elevated morbidity, mortality, and need for blood transfusions. Large differences in sickle cell genotype also exist, but the significance of this is unknown.
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Affiliation(s)
- John Paul Haydek
- Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States
| | - Cesar Taborda
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, United States
| | - Rushikesh Shah
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, United States
| | - Preeti A Reshamwala
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, United States
| | - Morgan L McLemore
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30329, United States
| | - Fuad El Rassi
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30329, United States
| | - Saurabh Chawla
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, United States.
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Fort R. Recommendations for the use of red blood cell exchange in sickle cell disease. Transfus Apher Sci 2019; 58:128-131. [PMID: 30879904 DOI: 10.1016/j.transci.2019.03.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Sickle cell disease (SCD) is a genetic disorder characterised by a single mutation of the beta globin gene, causing the production of an abnormal haemoglobin called sickle haemoglobin (HbS). In its deoxygenated form, HbS polymerises, causing major rheological disorders, which presents clinically as periodic vaso-occlusive crises, chronic haemolysis and chronic vascular dysfunction. Patients often resort to a background treatment, and transfusion remains the cornerstone in the management of the disease, significantly reducing morbidity and mortality. The aim of red blood cell exchange (RBCX) is to improve tissue oxygenation by increasing haemoglobin levels while lowering HbS levels. RBCX can be performed by manual or automated exchange, and each technique has its own set of advantages and disadvantages. This article will outline the transfusion indications for the main complications of SCD, as well as the most appropriate strategy to use.
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Affiliation(s)
- Romain Fort
- Department of Internal Medicine, CHU Edouard Herriot, Lyon, France; Laboratoire LIBM EA7424, Equipe "Biologie Vasculaire et du Globule Rouge", Université Claude Bernard, Lyon, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne, Paris, France.
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Schranz M, Lucà MG, D’Antiga L, Fagiuoli S. The Liver in Systemic Illness. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019:361-396. [DOI: 10.1007/978-3-319-96400-3_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Intrahepatic Cholestasis in a Sickle Cell Patient Unresponsive to Exchange Blood Transfusion. AMERICAN JOURNAL OF MEDICAL CASE REPORTS 2019; 7:67-70. [PMID: 31535002 PMCID: PMC6750246 DOI: 10.12691/ajmcr-7-4-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
With the advent of hydroxyurea, the sickle cell population has been enjoying a prolonged life span as compared to the pre-hydroxyurea era. Traditionally, acute complications of sickle cell disease includes acute chest syndrome, MI and stroke. In this report we present a case of an elderly man with sickle cell disease who presented with intrahepatic cholestasis (SCIC); a rather rare and fatal complication of sickle cell hemoglobinopathy. The patient presented with jaundice and elevated bilirubin up to 53, his hospital course was complicated by coagulopathy and encephalopathy, and expired on day 43 of presentation after failing multiple therapeutic interventions including exchange transfusion. In this report, we will provide literature review and discuss the underlying pathophysiologic mechanisms of intrahepatic cholestasis in the sickle cell population highlighting the need for immediate recognition and institution of therapy for this fatal complication of sickle cell disease, particularly in elderly populations with low metabolic reserve.
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Duncan CN, Talano JAM, McArthur JA. Care of the Critically Ill Pediatric Sickle Cell Patient. CRITICAL CARE OF THE PEDIATRIC IMMUNOCOMPROMISED HEMATOLOGY/ONCOLOGY PATIENT 2019. [PMCID: PMC7122989 DOI: 10.1007/978-3-030-01322-6_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Sickle cell disease is the most common inherited disease in the United States. Through the effects of hemolysis and vaso-occlusion, it has the potential to incite critical illness involving multiple organ systems. Children with sickle cell disease are at risk of multiple types of shock resulting in a need for ICU care. Our youngest patients with sickle cell disease are at highest risk of infection due to lack of splenic function, and this can present with septic shock. Hypovolemic shock can occur secondary to severe acute anemia as seen with splenic sequestration or a delayed transfusion reaction. As one ages, the risk of cardiac dysfunction – diastolic and systolic dysfunction as well as pulmonary hypertension – can result in cardiogenic shock. In addition to shock, patients with sickle cell disease are at risk for respiratory failure from acute chest syndrome as well as acute neurologic deterioration from stroke. For these reasons, critical care physicians must be familiar with the unique management of sickle cell complications in order to provide the best possible care for this vulnerable population.
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Affiliation(s)
| | - Julie-An M. Talano
- Children’s Hospital of Wisconsin-Milwaukee, Medical College of Wisconsin, Milwaukee, WI USA
| | - Jennifer A. McArthur
- Department of Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN USA
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40
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Kwun Lui S, Krasinskas A, Shah R, Tracht JM. Orthotropic Liver Transplantation for Acute Intrahepatic Cholestasis in Sickle Cell Disease: Clinical and Histopathologic Features of a Rare Case. Int J Surg Pathol 2018; 27:411-417. [PMID: 30198363 DOI: 10.1177/1066896918798467] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Sickle cell disease has a wide range of hepatic manifestations, with acute intrahepatic cholestasis being one of the rarest and most fatal, often resulting in acute fulminant hepatic failure. Liver transplantation is an emerging but rarely utilized treatment for hepatic failure in the setting of sickle cell disease. Few such cases have been reported in the literature, with little emphasis on histopathologic correlation. We report a case of acute intrahepatic cholestasis in a patient with sickle cell disease who underwent orthotropic liver transplantation and describe novel correlating histopathologic features. The patient is a 29-year-old man who presented with hyperbilirubinemia, acute kidney injury, and coagulopathy. He was diagnosed clinically with acute intrahepatic cholestasis and received an orthotropic liver transplant. The explanted liver demonstrated marked sinusoidal expansion by sickled erythrocytes, hyperplastic Kupffer cells, and extramedullary hematopoiesis. There was extensive sinusoidal and centrizonal fibrosis with occlusion of central veins reminiscent of chronic sinusoidal obstructive syndrome, a previously undescribed pattern of injury. This case represents one of the few reported cases of sickle cell intrahepatic cholestasis treated by transplantation and demonstrates the rarely reported histopathologic features and gives insight to a potentially new mechanism of injury in these patients. Familiarity with the morphologic features of sickle cell hepatopathy and its clinical manifestations is important as transplantation in sickle cell-related liver injury increases in frequency.
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Pecker LH, Patel N, Creary S, Darbari A, Meier ER, Darbari DS, Fasano RM. Diverse manifestations of acute sickle cell hepatopathy in pediatric patients with sickle cell disease: A case series. Pediatr Blood Cancer 2018; 65:e27060. [PMID: 29667721 DOI: 10.1002/pbc.27060] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 02/09/2018] [Accepted: 03/01/2018] [Indexed: 12/15/2022]
Abstract
The hepatic complications of sickle cell disease (SCD) are associated with increased morbidity and mortality in adults; children usually survive but may suffer significant sequelae. Few diagnostic tools differentiate the various hepatic manifestations of SCD. Why patients exhibit one hepatic pathology versus another is unclear. We report four pediatric patients with hemoglobin SS disease with diverse manifestations of acute hepatic involvement including acute sickle hepatic crisis, hepatic sequestration, sickle cell intrahepatic cholestasis, and a non-SCD cause of hepatopathy in a patient with viral hepatitis. These complications require a systematic approach to extensive evaluation and coordinated multidisciplinary care.
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Affiliation(s)
- Lydia H Pecker
- Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nidhi Patel
- Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California
| | - Susan Creary
- Center for Innovation in Pediatric Practice, Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, Ohio
| | - Anil Darbari
- Division of Gastroenterology, Hepatology, and Nutrition, Children's National Health System, Washington, District of Columbia
| | | | - Deepika S Darbari
- Division of Hematology, Children's National, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
| | - Ross M Fasano
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia
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43
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Gehrie EA, Ness PM, Bloch EM, Kacker S, Tobian AAR. Medical and economic implications of strategies to prevent alloimmunization in sickle cell disease. Transfusion 2017; 57:2267-2276. [PMID: 28653325 PMCID: PMC5695925 DOI: 10.1111/trf.14212] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/13/2017] [Accepted: 05/15/2017] [Indexed: 01/03/2023]
Abstract
BACKGROUND The pathogenesis of alloimmunization is not well understood, and initiatives that aim to reduce the incidence of alloimmunization are generally expensive and either ineffective or unproven. In this review, we summarize the current medical literature regarding alloimmunization in the sickle cell disease (SCD) population, with a special focus on the financial implications of different approaches to prevent alloimmunization. STUDY DESIGN AND METHODS A review of EMBASE and MEDLINE data from January 2006 through January 2016 was conducted to identify articles relating to complications of SCD. The search was specifically designed to capture articles that evaluated the costs of various strategies to prevent alloimmunization and its sequelae. RESULTS Currently, there is no proven, inexpensive way to prevent alloimmunization among individuals with SCD. Serologic matching programs are not uniformly successful in preventing alloimmunization, particularly to Rh antigens, because of the high frequency of variant Rh alleles in the SCD population. A genotypic matching program could offer some cost savings compared to a serologic matching program, but the efficacy of gene matching for the prevention of alloimmunization is largely unproven, and large-scale implementation could be expensive. CONCLUSIONS Future reductions in the costs associated with genotype matching could make a large-scale program economically feasible. Novel techniques to identify patients at highest risk for alloimmunization could improve the cost effectiveness of antigen matching programs. A clinical trial comparing the efficacy of serologic matching to genotype matching would be informative.
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Affiliation(s)
- Eric A Gehrie
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
| | - Paul M Ness
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
| | - Evan M Bloch
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
| | - Seema Kacker
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
| | - Aaron A R Tobian
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
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D’Ambrosio R, Maggioni M, Donato MF, Lampertico P, Cappellini MD, Graziadei G. Decompensated Cirrhosis and Sickle Cell Disease: Case Reports and Review of the Literature. Hemoglobin 2017; 41:131-133. [DOI: 10.1080/03630269.2017.1341420] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Roberta D’Ambrosio
- Divisione di Gastroenterologia ed Epatologia, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italia
| | - Marco Maggioni
- Divisione di Anatomia Patologica, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italia
| | - Maria F. Donato
- Divisione di Gastroenterologia ed Epatologia, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italia
| | - Pietro Lampertico
- Divisione di Gastroenterologia ed Epatologia, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italia
| | - Maria D. Cappellini
- Centro per le Malattie Rare, Divisione di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italia
| | - Giovanna Graziadei
- Centro per le Malattie Rare, Divisione di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italia
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Ipe TS, Pham HP, Williams LA. Critical updates in the 7thedition of the American Society for Apheresis guidelines. J Clin Apher 2017; 33:78-94. [DOI: 10.1002/jca.21562] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 05/17/2017] [Accepted: 05/29/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Tina S. Ipe
- Department of Pathology and Genomic Medicine; Houston Methodist Hospital; Houston Texas
| | - Huy P. Pham
- Department of Pathology, Division of Laboratory Medicine; University of Alabama, Birmingham, Alabama
| | - Lance A. Williams
- Department of Pathology, Division of Laboratory Medicine; University of Alabama, Birmingham, Alabama
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Nutan F, Gollahalli NS. Coexisting Sickle Cell Anemia and Sarcoidosis: A Management Conundrum! Clin Med Insights Blood Disord 2017; 10:1179545X16685314. [PMID: 28579850 PMCID: PMC5428084 DOI: 10.1177/1179545x16685314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/17/2016] [Indexed: 12/02/2022]
Abstract
Sickle cell disease and Sarcoidosis are conditions that are more common in the African American population. In this report we share an unfortunate patient who had hepatic sarcoidosis but could not receive steroids since that precipitated acute liver failure. We have discussed potential therapy options but we need more options that improve mortality.
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Affiliation(s)
- Fnu Nutan
- Virginia Commonwealth University (VCU), Richmond, VA, USA
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Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher 2017; 31:149-62. [PMID: 27322218 DOI: 10.1002/jca.21470] [Citation(s) in RCA: 276] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Joseph Schwartz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
| | - Anand Padmanabhan
- Blood Center of Wisconsin, Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Nicole Aqui
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rasheed A Balogun
- Division of Nephrology, University of Virginia, Charlottesville, Virginia
| | - Laura Connelly-Smith
- Department of Medicine, Seattle Cancer Care Alliance and University of Washington, Seattle, Washington
| | - Meghan Delaney
- Bloodworks Northwest, Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Nancy M Dunbar
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Volker Witt
- Department for Pediatrics, St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Yanyun Wu
- Bloodworks Northwest, Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Beth H Shaz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.,New York Blood Center, Department of Pathology.,Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia
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Guimarães JAD, Silva LCDS. Sickle cell intrahepatic cholestasis unresponsive to exchange blood transfusion: a case report. Rev Bras Hematol Hemoter 2017; 39:163-166. [PMID: 28577654 PMCID: PMC5457482 DOI: 10.1016/j.bjhh.2017.02.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 02/13/2017] [Accepted: 02/15/2017] [Indexed: 12/20/2022] Open
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D'Ambrosio R, Maggioni M, Graziadei G. Chronic cholestasis in a patient with sickle-cell anemia: Histological findings. Dig Liver Dis 2016; 48:1402. [PMID: 27666963 DOI: 10.1016/j.dld.2016.08.130] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 08/20/2016] [Accepted: 08/31/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
| | - Marco Maggioni
- Division of Pathology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Giovanna Graziadei
- Centro Anemie Congenite, Division of Internal Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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50
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Acute Disseminated Encephalomyelitis. J Clin Apher 2016; 31:163-202. [PMID: 27322219 DOI: 10.1002/jca.21474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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