Acute Hepatic Sequestration in Sickle Cell Disease: Pathogenesis
The causes of hepatic failure in sickle cell disease are numerous. The sickling of red blood cells, multiple blood transfusions, cocaine use, and intravascular hemolysis have been shown to be causes of hepatic failure. The sickling of red blood cells can cause hepatic infarction by vaso-occlusion, resulting in an obstruction in sinusoidal flow. This results in sequestration of red blood cells in the liver. Multiple blood transfusions on a chronic basis can lead to an excessive accumulation of iron in the parenchymal cells of the liver. Iron overload may contribute to organ failure, malignancy, and a higher incidence of painful crises. Cocaine use can cause hypoxic injury from cocaine-induced vasospasm and sickling. Intravascular hemolysis causes excessive production of bilirubin, which exceeds hepatic clearance capacity. The elevated bilirubin levels are caused by hemolysis, ineffective erythropoiesis, and hepatocellular dysfunction. Studies have shown that bone alkaline phosphatase is the major enzyme fraction contributing to the increase in serum alkaline phosphatase.
The acute right upper quadrant syndrome is thought to be the result of sinusoidal stagnation of sickle red blood cells in the liver, resulting in a decrease in circulation through hepatic sinusoids.
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The pathophysiology of intrahepatic cholestasis is a result of sickled red blood cells plugging the hepatic sinusoids, causing vascular stasis and local hypoxia. Kupfer cell hypertrophy develops and the canaliculi become plugged with bile.
Acute hepatic sequestration is believed to be caused by the obstruction of sinusoidal flow by masses of sickled erythrocytes, trapping of red blood cells within the liver, and compression of the biliary tree. This complication may have a similar basis to the splenic sequestration and the sickle lung syndromes.
The diagnosis of hepatic vaso-occlusive syndromes in sickle cell disease is based on clinical, laboratory, and imaging studies. In the past, a liver biopsy was needed to make the diagnosis. However, a recent U.K. study conducted by the Institute of Liver Studies and the Department of Hematological Medicine reported that hepatic disease complicated by sickle cell anemia is a relative contraindication to a percutaneous liver biopsy. They reported serious hemorrhage in 36% and death in 28% of sickle cell patients in hepatic crisis that underwent a percutaneous liver biopsy.
Intravenous hydration and proper analgesia are the initial treatments in sickle cell crisis. Acute hepatic right upper quadrant syndrome is managed conservatively with supportive care. However, it is important to administer a partial red blood cell exchange transfusion early in the treatment of intrahepatic cholestasis or acute hepatic sequestration.
Partial red blood cell transfusions with fresh frozen plasma have shown to help improve hepatic and renal function in intrahepatic cholestasis. Simple red blood cell transfusions may result in hyperviscosity syndrome, which may result in volume overload, heart failure, intracerebral hemorrhage, and death in patients with acute hepatic sequestration. Clinical and biological profiles improve rapidly after exchange transfusions. Red blood cell exchange transfusions decrease the amount of hemoglobin S (HbS) in circulation, resulting in an improvement in oxygen delivery and improvement in the rheologic state. Hydroxyurea may be beneficial in treating sickle cell patients with chronic hepatic sequestration. A patient at St. Jude’s Children’s Hospital in Memphis, TN showed a resolution of his hepatomegaly and normalization of his liver volume demonstrated on serial CT studies after he was treated with hydroxyurea for 60 months. cialis canadian pharmacy
A CT of the abdomen is the preferred diagnostic imaging study for evaluating a sickle cell patient with upper abdominal pain. The CT usually shows diffuse hepatomegaly, which is caused by an expansion of the hepatic reticuloendothelial system. Magnetic resonance imaging (MRI) can provide a qualitative but limited quantitative assessment of hepatic iron overload in patients whose hepatic iron levels are less than 100 ig/mg. The normal values of hepatic iron in men is 200-2,000 ng/g and 200-1,600 [ig/g in women. An abdominal ultrasound may reveal gallstones or may show an increase in the echogenicity of the liver. Tc hepatobiliary imaging using iminodiacetic compounds (HIDA) is reliable in confirming acute cholecystitis if the bilirubin is under 5 g/dl. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography provide the best means for determining the cause, location, and extent of biliary obstruction.