Liver transplantation in a patient with acute liver failure due to sickle cell intrahepatic cholestasis

BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.     

Liver transplantation in children with sickle-cell disease.

Severe liver disease is an unusual but potentially fatal complication of sickle-cell disease (SCD). Liver transplantation has been complicated by ongoing SCD and thrombosis. We reviewed 214 pediatric transplants done at our institution from 1990 to 2005. Three patients were transplanted for complications of SCD, including intrahepatic cholestasis and viral hepatitis. Overall patient and graft survival was 66%. One patient died after 6 years from a subdural hematoma. There were not any incidences of graft loss, primary nonfunction, or thrombosis. All 3 patients required between 1 and 4 postoperative transfusions to keep hemoglobin (Hgb) >9 g/dL with an S fraction of less than 25%. One patient required a preoperative transfusion for a hemoglobin S (HbS) fraction of 30%. Mean follow-up has been 4.2 years (range, 2.6-5.4 years). All 3 children continued to suffer sequelae from their SCD. One child suffered from recurrent sickle-cell hepatopathy and chronic graft failure. In conclusion, children with SCD can in rare instances develop acute and chronic liver failure. These children can be successfully transplanted with good outcomes. Careful attention must be paid to HbS fraction and hemoglobin level to prevent sickling and vascular thrombosis. Unfortunately, liver transplant cannot alter the natural course of the disease.     

Liver transplantation in sickle cell anemia: a case of acute sickle cell intrahepatic cholestasis and a case of sclerosing cholangitis

Very few cases of liver transplantation in patients with sickle cell disease have been reported in peer-reviewed literature. We reviewed the medical records of two patients with sickle cell disease that received liver transplantation at our institution. The first patient was a 27-year-old female who presented with encephalopathy and cholestatic jaundice with a Hemoglobin S (HbS) level of 69.6%. She was diagnosed with acute sickle cell intrahepatic cholestasis. The second patient was a 26-year-old female with sclerosing cholangitis who presented with encephalopathy, bleeding, and cholestatic jaundice. Her HbS level was normal. Both patients underwent liver transplantation successfully but died in the postoperative period from multiorgan failure. We report a rare case of liver transplantation for acute sickle cell intrahepatic cholestasis and a novel case of transplantation in a patient with sickle cell disease and sclerosing cholangitis. Liver transplantation did not lead to a successful outcome in either case.     

Can exchange transfusions treat postoperative intrahepatic colestasis in patients with sickle cell anemia?

BACKGROUND: Although the most common cause of liver failure (LF) in hematologic patients is viral hepatitis, several episodes of sickle cell intrahepatic cholestasis (IHC) have been reported as rare but potentially causative of fulminant LF. Reviewing the literature, we have presented a single case of intrahepatic cholestasis after major liver resection, which was effectively treated by exchange transfusion. METHODS: Serial hemoglobin S, D levels and liver enzymes were monitored postoperatively. RESULTS: Although the patient's intra- and postoperative courses were uneventful, an increased serum bilirubin was identified to be due to intrahepatic sinusoid congestion and subsequent cholestasis. Exchange transfusion was required to maintain HbS below 20% and reverse bilirubin levels to normal values. CONCLUSION: Sickle cell anemia is a rare cause of cholestasis after major hepatic surgery. To our knowledge, this case is the only documented incidence of IHC following major hepatectomy that was effectively treated with exchange transfusion.     

Combined liver and kidney transplantation in a patient with sickle cell disease

Sickle cell intrahepatic cholestasis is a potentially fatal end-organ complication of sickle cell anemia. Renal involvement in sickle cell anemia is common, and in some cases, can present as acute renal failure. Although renal transplants have been performed in patients with sickle cell anemia since the late 1960s and a number of liver transplants have been recently performed for these complications, there has not been experience with dual organ transplantation for sickle cell anemia-related complications. We describe the case of a patient with sickle cell anemia who underwent successful combined liver and kidney transplantation after the development of acute sickle cell intrahepatic cholestasis and renal failure requiring continuous venovenous hemodialysis. The patient underwent a successful combined liver and kidney transplant with limited perioperative complications and preserved allograft function. At 22 months posttransplant, the patient expired as a result of an acute pulmonary embolus in the setting of bilateral hip fractures. Autopsy revealed no evidence of liver or kidney allograft rejection and evidence of chronic sickle cell nephropathy in the native kidney. Combined liver and kidney transplantation is a viable therapeutic option in patients with severe end-organ effects of sickle cell anemia.     

Living related liver transplantation for acute liver failure in children.

The mortality rate among children with acute liver failure (ALF) on the waiting list for liver transplantation is high. We present our experience with living related donor liver transplantation (LRD-LT) in children who required urgent transplantation for ALF. Between December 1995 and July 1997, 6 children underwent LRD-LT for ALF. Cause of liver failure, recipient and donor demographics, clinical and laboratory data, surgical details, complications, and 6-month and 2-year graft and patient survival were recorded. Five boys and 1 girl received left lateral segment grafts from their parents. The mean age was 4 +/- 2.8 years (range, 1 to 9 years). ALF was caused by Wilson's disease in 1 patient and sickle cell intrahepatic cholestasis syndrome in 1 patient; in 4 patients, the cause was unknown. All patients had mental status changes; 2 were on life support. Mean pretransplantation liver function test values were: alanine aminotransferase, 972 +/- 565 U/L (normal, 1 to 53 U/L), total bilirubin, 31.3 +/- 12.4 mg/dL (normal, 0.1 to 1.2 mg/dL), prothrombin time, 34.3 +/- 12.4 seconds (normal, 10.8 to 13.3 seconds), international normalized ratio, 8.46 +/- 5.4 (normal < 2), and fibrinogen, 109 +/- 23.9 mg/dL (normal, 175 to 400 mg/dL). The donors were 5 mothers and 1 father. The mean donor age was 32.5 +/- 7.6 years (range, 19 to 40 years). No donor required blood transfusion, and no donor had any early or late postoperative complications. The donors' mean hospital length of stay was 5 days. In five cases, grafts were blood group-compatible; 1 child received a blood group-incompatible graft. All grafts functioned immediately. No patient had hepatic artery or portal vein thrombosis or biliary complications. The child who received a mismatched graft died of infection of the brain caused by Aspergillus spp at 22 days posttransplantation with a functioning graft. The child with ALF caused by sickle cell intrahepatic cholestasis syndrome developed outflow obstruction 3 months posttransplantation and required retransplantation; he eventually died of vascular complications related to his primary disease. Four children are alive at a mean follow-up of 27 months (range, 14 to 36 months). LRD-LT for children with ALF facilitates timely transplantation without drawing on cadaveric donor resources. The established safety record of LRD-LT made this option appealing to both physicians and parental donors.     

Preoperative Exchange Transfusion for Sickle Cell Disease Patients Undergoing Open‐Heart Surgery: An Exception to the Rule

Abstract Preoperative exchange transfusion is a routine practice in patients with sickle cell disease having elevated sickle cell hemoglobin levels (>40%) undergoing open‐heart surgery on cardiopulmonary bypass. A new approach toward acceptance and management of sickle cell disease patients with high sickle cell hemoglobin levels for open‐heart surgery without preoperative exchange transfusion of blood is presented. (J Card Surg 2010;25:691‐693)     

Sickled erythrocytes, hyphema, and secondary glaucoma: IV. The rate and percentage of sickling of erythrocytes in rabbit aqueous humor, in vitro and in vivo.

The number of erythrocytes adopting the sickled configuration in rabbit aqueous was determined with a masked counting technique in vitro and in vivo. The percentage of cells that became sickled in aqueous humor was greater than that observed in a control salt solution and in the donor blood itself. Aqueous humor, therefore, can be considered a particularly deleterious medium for erythrocytes having a propensity for sickling. Blood samples from six donors with systemically severe hemoglobinopathies (SC, Sthal, and SS) had relatively high levels of hemoglobin S and, in general, showed faster and more frequent sickling than did blood samples from donors with low levels of hemoglobin S (one SS patient, whose chronic blood transfusion regimen had replaced most of his hemoglobin S with normal hemoglobin, and two AS patients). Even erythrocytes from sickle cell trait cases, however, were capable of sickling when immersed in acqueous humor.     

Perioperative management of sickle cell disease in paediatric cardiac surgery

In sickle cell disease, cardiopulmonary bypass may induce red cell sickling. Partial exchange transfusion reduces the circulating haemoglobin S level. We report the management of a child with sickle cell disease who required surgical closure of a ventricular septal defect. Preoperative exchange transfusion of 50% of the total blood volume was performed with fresh packed red cells over three days. Further exchange transfusion was performed as cardiopulmonary bypass commenced. The haemoglobin S level was reduced from 76% to 37%. The blood removed from the patient during the exchanges was processed allowing storage and re-infusion of the patient's plasma and platelets. Combined preoperative and intraoperative exchange transfusions, instead of a single stage 50% volume exchange, was effective and potentially avoids larger haemodynamic effects. Cardiopulmonary bypass was conducted at normothermia and cold cardioplegia was avoided (fibrillatory arrest was used during the surgical repair).     

Management of multiple intracranial aneurysms: neuroanesthetic considerations of sickle cell disease

Intracranial aneurysms are a common complication of sickle cell disease. The management of a patient with multiple intracranial aneurysms and sickle cell disease is described. The English language literature is reviewed. Neuroanesthetic management has traditionally been based on the avoidance of factors said to lead to erythrocyte sickling; however neuropathology typically arises from arterial intimal damage, not from venous sickling. Neuroanesthesia should be based on an appreciation of this pathophysiological model. Consideration of precipitants of vaso-occlusive crises, such as hypothermia, dehydration and possibly altered hemodynamics, should influence management.     

Bilateral lower limb salvage with free flaps in a patient with sickle cell ulcers.

A patient with long-standing bilateral circumferential lower extremity sickle cell ulcerations refractory to conservative management was successfully treated with bilateral free latissimus muscle transfers. This report confirms the value of free tissue transfer in the treatment of these difficult skin ulcerations. Exchange transfusions that brought the SS hemoglobin below 30% were crucial to the prevention of sickling in the microcirculation of the flap during its obligate period of ischemia. Furthermore, they protected the flap during a period of ischemia that exceeded 4 hours following a postoperative arterial thrombosis. In the presence of severe thrombocytosis associated with sickle cell disease, prophylactic treatment with aspirin may be of significant value.     

Liver Transplantation After Hematopoietic Stem Cell Transplant for the Treatment of Sickle Cell Disease: A Case Report

Sickle cell anemia is the most common of the hemoglobinopathies, in which the abnormal hemoglobin formed in deoxygenation states undergoes a polymerization process with consequent erythrocyte deformation and vaso-occlusive events. The need for multiple blood transfusions, prolonged ineffective erythropoiesis, hemolysis, and increased iron absorption can cause iron overload in the liver, leading to liver fibrosis. Hematopoietic stem cell transplantation (HSCT) is currently the only treatment with a curative potential for this disease and can establish normal complete or partial donor-derived erythropoiesis and stabilize or restore function in affected organs, preventing further deterioration of function. However, it does not reverse preexisting liver fibrosis and siderosis. One of the possible complications of patients who undergo HSCT is chronic liver disease, which has a multifactorial cause, with iron overload being an important factor. In the long term, the prevalence of chronic liver disease in HSCT patients, including cirrhosis and its complications, can be significant. Solid organ transplantation after allogeneic hematopoietic cell transplantation for end-organ failure remains a very rare event. It may offer a valuable treatment strategy in selected recipients, although it is associated with significant morbidity and mortality. We report the case of a patient with sickle cell anemia who underwent HSCT and developed severe liver dysfunction requiring liver transplantation 13 years after the procedure. We found no previous report in the literature of orthotopic liver transplant after HCT for the treatment of sickle cell disease.     

Successful liver transplantation in a patient with sickle-cell anaemia

Liver transplantation in the setting of sickle-cell anaemia poses several new challenges to the transplant team. Hypoxaemia, acidosis and a decrease in body temperature are common occurrences that can cause sickling in the peri-operative period, putting the patient at risk of sickle-cell crises or graft dysfunction. We describe a patient with sickle-cell anaemia who successfully underwent transplantation, and we discuss the rationale of various precautions that had to be taken.     

Cardiopulmonary bypass with deep hypothermic circulatory arrest for a patient with sickle cell anemia: a case report.

A 36-year-old sickle cell anemia patient undergoing a pulmonary thromboendarterectomy required the use of cardiopulmonary bypass incorporating deep hypothermic circulatory arrest. Being aware of reported incidences of sickling crises, a team of the surgeon, anesthesiologist, hematologist, and perfusionist met to devise a plan of treatment. Treatment included preoperative and intraoperative exchange transfusion, optimal blood gas management, and increased blood flows during bypass. The surgical procedure was performed and was successful in reducing pulmonary hypertension, incorporating a team approach and utilizing these techniques. No incidence of adverse sickling events was observed during this procedure.     

Rare combination of hematuria due to drepanocytosis (sickle cell) in a white man

A case is presented of a white man with hematuria who was found to have sickle cell trait. When a cause for hematuria cannot be found, before making the diagnosis of “essential hematuria,” sickling of the erythrocytes and hemoglobin electrophoresis should be done, even in a white man. A distant relationship with a black person or persons of certain ethnic groups can be the cause of the disease presenting with this symptom. This case appears to be the second published in the literature and the first in Turkey.     

Perioperative Überwachung der Hämoglobinfraktionen bei homozygoter Sichelzellanämie

This case report presents the perioperative management of double-sided hip arthroplasty in a patient (female, 25 years old) homozygous for sickle cell anemia (SS). The fraction of sickle hemoglobin (Hb S) to total hemoglobin was monitored with an automated cation exchange microcolumn chromatography. The main purpose of ion exchange chromatography is to measure glycated hemoglobin A (HbA1c) in diabetic patients. Furthermore, as a by-product, this test enables the quantitative assessment of aberrant hemoglobin molecules such as sickle cell hemoglobin Hb S with sufficient precision and selectivity. The standard method, hemoglobin-electrophoresis is more complicated and not generally available. For the perioperative estimation of the risk for sickle cell related complications and as a guide for transfusion therapy, knowledge of preoperative Hb S level is essential. In this case report, the clinical use of a rapid laboratory test at low costs with common equipment in a patient with known homozygous sickle cell anemia is demonstrated.     

Cerebrovascular accident in sickle cell disease

Sickle cell disease (SCD) is a common inherited hemoglobin disorder characterized by the presence of sickle shaped erythrocytes in the blood. It can cause stroke in around 10% of children. Repeated blood transfusion are often used in an attempt to dilute blood thus reducing the risk of vaso-occlusion and stroke. We report a case of an 11 years old girl, known patient of sickle cell disease, who did not follow regular blood transfusion protocol and as a result presented with recurrent stroke.     

Two cases of hematuria with hemoglobin C trait

Patients with sickle cell disease commonly experience painless hematuria. Hematuria may be found in patients with sickle cell trait, sickle cell anemia, and sickle cell hemoglobin C disease, but it is believed to be uncommon in patients with other hemoglobinopathies, such as hemoglobin C disease and hemoglobin C trait. We report two cases of children with hemoglobin C trait who presented with persistent painless hematuria. Because it is possible that hematuria in a patient with hemoglobin C trait is purely coincidental, all patients with a hemoglobinopathy and hematuria should undergo a complete evaluation so as not to overlook other causes of hematuria.     

Cholestasis After Pediatric Liver Transplantation–Recurrence of a Progressive Familial Intrahepatic Cholestasis Phenotype as a Rare Differential Diagnosis: A Case Report

Introduction

Nonobstructive cholestasis after pediatric liver transplantation is a common diagnostic and therapeutic dilemma. We describe a girl with neonatal cholestasis because of progressive familial intrahepatic cholestasis 2 (PFIC-2) and presence of a homozygous splice site mutation in the ABCB11 gene. Liver transplantation was performed because of end-stage liver disease at the age of 6. Cholestasis with normal gamma-glutamyl transferase (GGT) developed 8 years after liver transplantation. A liver biopsy showed canalicular cholestasis and giant cell hepatitis without evidence of rejection, mimicking PFIC-2. Immunofluorescence staining of normal human liver sections with patient's serum revealed reactivity toward a canalicular epitope, which could be identified as bile salt export pump (BSEP) using BSEP–yellow fluorescent protein (YFP) transfected cells. Our patient developed a recurrence of a PFIC-2 phenotype due to production of antibodies against BSEP (alloimmune BSEP disease [AIBD]). Intensification of immunosuppressive therapy as well as antibody treatment with plasmapheresis and Rituximab were initiated, leading to stabilization of the clinical condition and depletion of anti-BSEP antibodies in serum. However, after 1 year liver transplantation was necessary again because of end-stage liver insufficiency. Afterward, immunomodulatory treatment consisted of tacrolimus, mycophenolate mofetil, prednisone, immunoadsorption, and high-dose immunoglobulin therapy (1 g/kg/d).

Living-donor liver transplantation for Caroli's disease with intrahepatic adenocarcinoma

A 36-year-old woman who had Caroli's disease with refractory cholangitis and complicated intrahepatic cholangiocarcinoma was successfully treated with living-donor liver transplantation. Preoperative computed tomography and ultrasonography showed a small nodule in the dilated intrahepatic bile duct. In the resected liver specimen, a small papillary tumor was located in the dilated intrahepatic bile duct of the right lobe. The pathological finding revealed a well differentiated papillary adenocarcinoma without invasion to the parenchyma. The patient is currently doing well 2.5 years after transplantation, with no signs of recurrence of the disease. For Caroli's disease, we believe we can achieve good results with liver transplantation, not only for cholangitis but also for the carcinoma when it is localized in the liver and the patient is carefully followed up. Received: December 22, 2000 / Accepted: February 15, 2001