INTRODUCTION

Sickle cell disease (SCD) is a red blood cells (RBC) genetic disorder characterized by the production of abnormal hemoglobin (Hb) – hemoglobin S (HbS). When deoxygenated, HbS tends to polymerize leading to decreased pliability of the RBC and inducing hemolysis and vaso-occlusive events.¹

In SCD the liver can be injured by different mechanisms: hepatic sinusoidal vaso-occlusion, choledocholithiasis from chronic haemolysis, hemosiderosis from chronic transfusions, and viral hepatitis.² Sickle cell intrahepatic cholestasis (SCIC) is an unusual severe form of hepatic crisis, characterized by jaundice, fever and severely impaired hepatocellular function with coagulopathy.³ SCIC can evolve to acute liver failure with a high mortality despite supportive care and exchange blood transfusions (EBT).² When all therapeutic fails, liver transplantation (LT) can be the last and only option.

The role of LT for SCD is still not well defined as there are few cases reported in literature.⁴ Most patients experience postoperative complications due to infections related to immunosuppression, thrombosis caused by the SCD or death from other organ failure complications.

Blood management for LT in SCD patients is also a challenge, as a substantial amout of RBC units may be needed due to the contraindication for intraoperative use of cell-saver by the risk of sickling of the RBC. The RBC units need to be HbS negative and phenotypically identical to the patient to prevent alloimmunization or to respect previous RBC alloimmunization from earlier transfusions.^{1, 5, 6}

CASE REPORT

A 42 year-old caucasian male, with a combination of sickle cell and beta thalassemia mutation (HbS/β Thalassemia), presented for LT.

At the age of 3 he was diagnosed with a compound heterozygous condition in which the inheritance of HbS mutated allele from one parent and a beta-zero thalassemic mutated allele (β⁰Thal) from the other (HBB:c.118C>T), resulted in a total abolishment of Hb A production. He presented basal Hb values of 8 g/dL with HbS>80%.

His medical history revealed about two painful vaso-occlusive crises per year and frequent respiratory infections. At the age of 7 years a splenectomy was performed and at 33 years, a laparoscopic cholecystectomy. He tested negative for HBV, HCV and HIV.

His RBC phenotype was A Rh+ CCDee K- and he was regularly transfused with identical RBC. In 2010, antibody screening, using a DiaClon test IgG gel card (Bio-Rad Laboratories, DiaMed GmbH), revealed RBC alloantibodies that were identified as anti-Jka and anti-Kpa. The patient phenotype was Jka and Kpa negative.

An iron chelation program was initiated after 20 RBC units transfusion, with irregular adherence. In 2016 magnetic resonance imaging showed a liver iron concentration of 250 µmol Fe/g; he also presented a mildly dilated myocardiopathy with normal ventricular function.

In July 2016, SCIC was diagnosed with jaundice and anorexia and total bilirubin of 40.39 mg/dl, evolving to “acute on chronic liver failure” (ACLF). He was placed on waiting list for LT (MELD score: 27; Child-Pugh:C).

The peritransplant management included regular partial manual EBT to maintain HbS<30% and Hb around 8-10 g/dl. LT from an ABO type identical adult cadaveric donor was performed 31 days after admission. In Table I, we present a summary of laboratory values at the time of LT.

The graft liver was transplanted using the piggy-back technique after 6 hours of cold ischemia. LT duration was 5h30m with a warm ischemia of 25 minutes. Immunosuppression was initiated with Basiliximab intraoperative, in the anhepatic phase, and a second dose was administered at day 4 after LT.

During surgery, as the use of cell salvage was contraindicated, the patient was transfused with 21 RBC units, 24 units of fresh frozen plasma, 1 unit of platelet concentrate pool. All RBCs transfused were HbS and Jka negative. Due to the non-elective nature of the surgery, it was not possible to obtain an entirely phenotypically matched blood stock for this patient. Therefore, he was transfused with 3 RBC units positive for antigen “c” and one for “E”; 10 days after LT, anti-c and anti-E alloantibodies were detected.

During the postoperative period his HbS remained between 3% and 16.2%. Immunosuppressive regimen post-LT included Tacrolimus and Prednisolone. Biopsy of the explanted liver showed cirrhosis with abundant iron deposits. Early postoperative course was complicated by acute renal failure. Enterococcus Faecium was isolated from bile fluid and Klebsiella pneumoniae from biliary drainage insertion site, successfully treated with vancomycin and meropenem, respectively.

The patient was discharged 23 days after surgery and remained well 14 months after LT, despite two hospitalizations for respiratory infections and one for intensive IV quelation therapy. He remains under surveillance by the Haematology and Hepatology Departments, to evaluate the need for EBT and to manage side effects of immunosuppression, respectively.

DISCUSSION

LT in SCD patients presents several challenges.⁷ LT itself has high morbidity and mortality risk, being a major surgery that can be complicated with massive hemorrhage.

A recent study, with one of the largest series of LT in SCD (includes 21 patients with SCD who underwent LT over a period of 28 years), suggests that LT remains a life-saving procedure with high postoperative mortality and morbidity rates, particularly in those patients undergoing urgent LT comparatively to elective ones. Elective LT presents better outcomes, similar to those obtained in general population, particularly with regard to patient and post-transplant graft survival.⁹

MELD score is predictor of short-term mortality and values are significantly higher in patients with indication for urgent LT. ^9,10 Patients with indication for LT and associated organ failure, like our patient with ACLF, have poor prognosis. However is important to refer that the prognosis of these patients without LT is also limited and very poor.⁹

For the Transfusion Service it is challenging to provide an adequate blood stock, considering the non-elective nature of the surgery, the contraindication for cell salvage use and the need for HbS negative and phenotypically identical RBC units. The patient´s RBC alloimmunization presented a further obstacle to blood management. Despite the immunosuppression therapy initiated intraoperatively, the patient developed two additional RBC alloantibodies, 10 days after LT, most probably a secondary immune response.⁶

LT planning in SCD patients must take into account not only the surgery itself but also the postoperative management by a multidisciplinary team, in order to avoid vaso-occlusive crisis, graft rejection, infectious complications and iron deposition. Hb and HbS levels should be carefully controlled with regular RBC transfusions or EBT, although the intensity and regularity of the transfusion therapy is not well established.^3,7,8 We aimed to keep Hb around 9 g/dL and HbS ≤ 45% after LT. Patient compliance with chelation therapy is essential. Neurological complications are particularly frequents after LT, with prior reports describing them in 66% of these patients.^9,10 In this case, no neurological changes were observed in the patient.

There still have been few reports of LT in SCD patients. The poor results previously reported have improved presumably due to better patient selection and perioperative management. Good organ function, is essential to achieve a successful outcome and it is important to provide a long-term multidisciplinary team follow-up to ensure patient care after LT.

Quadro I

Laboratory values at the time of LT.

PT – Protrombin time; INR – International Normalized Ratio; aPTT (r)– Activated partial thromboplastin time ratio; FV – Factor V; AST – Aspartase aminotransferase; ALT – Alanine aminotransferase; GGT – Gamma-glutamyl transferase; ALP – alkaline phosphatase; LDH – Lactate dehydrogenase; CRP – C-Reactive protein.

  BIBLIOGRAFIA  

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