Sickle cell intrahepatic cholestasis unresponsive to exchange blood transfusion: a case report

Guimarães, Juliana Albano de; Silva, Luciana Cristina dos Santos

doi:10.1016/j.bjhh.2017.02.006

Cited by 10 publications

(12 citation statements)

References 10 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Severe disease presents with a mean direct bilirubin of 76.8 mg/dL, presence of a coagulation disorder or altered mental status. [8] Based on the above, our patient initially presented with mild disease, however progressed to severe disease. With this progression to severe disease, there is an increased mortality rate as high as 64%, compared to only 4% in mild disease.…”

Section: Discussionmentioning

confidence: 83%

Intrahepatic Cholestasis in a Sickle Cell Patient Unresponsive to Exchange Blood Transfusion

Likhtshteyn

Iqbal

McFarlane

et al. 2020

AJMCR

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 83%

Intrahepatic Cholestasis in a Sickle Cell Patient Unresponsive to Exchange Blood Transfusion

Likhtshteyn

Iqbal

McFarlane

et al. 2020

AJMCR

View full text Add to dashboard Cite

show abstract

“…Intrahepatic cholestasis is believed to be one of the causes of liver failure in patients with SCD. ( 10,18 ) IHC analysis based on staining for cholangiocyte markers cytokeratin 19 (CK‐19) (Fig. 3A,B), epithelial cell adhesion molecule (EpCAM) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Impaired Bile Secretion Promotes Hepatobiliary Injury in Sickle Cell Disease

et al. 2020

View full text Add to dashboard Cite

BaCKgRoUND aND aIMS: Hepatic crisis is an emergent complication affecting patients with sickle cell disease (SCD); however, the molecular mechanism of sickle cell hepatobiliary injury remains poorly understood. Using the knockin humanized mouse model of SCD and SCD patient blood, we sought to mechanistically characterize SCD-associated hepato-pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, and biochemical approaches. appRoaCH aND ReSUltS: SCD mice manifested sinusoidal ischemia, progressive hepatomegaly, liver injury, hyperbilirubinemia, and increased ductular reaction under basal conditions. Nuclear factor kappa B (NF-κB) activation in the liver of SCD mice inhibited farnesoid X receptor (FXR) signaling and its downstream targets, leading to loss of canalicular bile transport and altered bile acid pool. Intravital imaging revealed impaired bile secretion into the bile canaliculi, which was secondary to loss of canalicular bile transport and bile acid metabolism, leading to intrahepatic bile accumulation in SCD mouse liver. Blocking NF-κB activation rescued FXR signaling and partially ameliorated liver injury and sinusoidal ischemia in SCD mice. CoNClUSIoNS: These findings identify that NF-κB/FXRdependent impaired bile secretion promotes intrahepatic bile accumulation, which contributes to hepatobiliary injury of SCD. Improved understanding of these processes could potentially benefit the development of therapies to treat sickle cell hepatic crisis. (Hepatology 2020;72:2165-2181). S ickle cell disease (SCD) is an autosomal-recessive monogenic disorder that affects approximately 100,000 Americans and millions of people worldwide. (1) Sickle cell anemia, the most common form of SCD, is caused by a homozygous mutation in the β-globin gene, leading to hemoglobin polymerization, erythrocyte rigidity, dehydration, vaso-occlusion (tissue ischemia), and premature hemolysis. (2,3) Vaso-occlusion and hemolysis are the predominant pathophysiological events in SCD that contribute to multiorgan damage. (4) Although severely understudied, incidences of acute and chronic liver complications have increased over the last few decades due to the growing life expectancy of

show abstract

“…SCIC is an acute and severe complication with high mortality in patients with SCD, especially in patients with sickle cell anemia and Sβthalassemia [5][6][7][8] ; however, the pathophysiology remains unclear 5,7 . The possible mechanism involves a sequence of events that culminate in liver dysfunction and includes adhesion of deformed erythrocytes to the vascular endothelium, obstruction and congestion of hepatic sinusoids, hypoxemia, ballooning, ischemia, and death of hepatocytes [1][2][3][5][6][7] .…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic interventions for SCIC include hydration, analgesia, oxygen supplementation, antibiotic therapy (when indicated), and blood component transfusion (packed red blood cells, fresh frozen plasma). Exchange transfusion to reduce the proportion of HbS decreases the sickling process, and is the predominant therapeutic intervention despite the absence of studies defining optimal values for HbS [6][7][8] . Fresh frozen plasma transfusion can be used to correct coagulopathy 3 .…”

Section: Discussionmentioning

confidence: 99%

Dengue fever as a potential cause of sickle cell intrahepatic cholestasis: A report of two cases

Oliveira

Costa

Almeida

et al. 2021

Rev. Soc. Bras. Med. Trop.

View full text Add to dashboard Cite

Sickle cell intrahepatic cholestasis is a potentially fatal syndrome characterized by jaundice, painful hepatomegaly, and organ dysfunction. Two cases of sickle cell intrahepatic cholestasis associated with dengue fever were described. Endothelial damage/dysfunction is a mechanism involved in severe hepatobiliary complications related to sickle cell diseases. However, the reasons for the lack of increase in the admission of patients with sickle cell disease having severe acute hepatobiliary complications triggered by endothelial damage/ dysfunction due to dengue fever remain unknown. This study describes the first association between sickle cell intrahepatic cholestasis and dengue fever.

show abstract

Sickle cell intrahepatic cholestasis unresponsive to exchange blood transfusion: a case report

Cited by 10 publications

References 10 publications

Intrahepatic Cholestasis in a Sickle Cell Patient Unresponsive to Exchange Blood Transfusion

Intrahepatic Cholestasis in a Sickle Cell Patient Unresponsive to Exchange Blood Transfusion

Impaired Bile Secretion Promotes Hepatobiliary Injury in Sickle Cell Disease

Dengue fever as a potential cause of sickle cell intrahepatic cholestasis: A report of two cases

Contact Info

Product

Resources

About