Successful treatment of acute sickle cell intrahepatic cholestasis with therapeutic plasma exchange

Acute sickle cell intrahepatic cholestasis (SCIC) is a potentially life-threatening complication of sickle cell disease (SCD) characterised by extreme hyperbilirubinaemia in the absence of significant obstruc-tion by gallstones, and is caused by extensive sickling within the hepatic sinusoids leading to ischaemia and damage of hepatocytes with ballooning and intracanalicular stenosis and cholestasis. Left untreated, it can cause progressive liver damage and ultimately overt liver failure [1]. Even though there is no robust evidence on the benefit of any therapeutic intervention [2], red cell exchange (RCE) is widely acceptedasthemainstayoftreatmentasitcangreatlyimproveclinical outcomes [3]. We have treated a 30-year-old man with sickle cell anaemia (haemoglobin [Hb] SS) and a background of recurrent vaso-occlusive crises


Acute sickle cell intrahepatic cholestasis (SCIC) is a potentially life-
threatening complication of sickle cell disease (SCD) characterised by extreme hyperbilirubinaemia in the absence of significant obstruction by gallstones, and is caused by extensive sickling within the hepatic sinusoids leading to ischaemia and damage of hepatocytes with ballooning and intracanalicular stenosis and cholestasis. Left untreated, it can cause progressive liver damage and ultimately overt liver failure [1]. Even though there is no robust evidence on the benefit of any therapeutic intervention [2], red cell exchange (RCE) is widely accepted as the mainstay of treatment as it can greatly improve clinical outcomes [3].
We have treated a 30-year-old man with sickle cell anaemia  dropped by 48% after the first procedure, and after the second, there was no significant increment between procedures hence we reduced to 1 plasma volume for the last 2. By the fifth procedure, it had stabilised to values less than 100 umol/L, corresponding to the patient's steady state. Ferritin dropped by 65% after the first TPE and continued to drop subsequently with no increments between procedures (Figure 1). ALT and AST normalised after the first and second procedures respectively and remained within normal levels thereafter. His clotting screen, platelet count and renal function remained normal throughout.
His Hb that had dropped from 102 g/L on admission to 82 g/L before commencing TPE dropped further to 59 g/L after the third proce- a situation accentuated during crises [4]. Furthermore, such cytokines are considered to play an important role in the pathogenesis of the acute chest syndrome and cause tissue damage leading to chronic sickle lung disease [5,6]. TPE has the potential to remove a whole host of harmful substances such as free Hb, inflammatory cytokines and prothrombotic proteins from the circulation [7], and it has been used successfully as an adjunct to RCE for treatment of multiorgan failure [8] and ACS [9] while we have advocated its use in the acute management of fat embolism syndrome in SCD after adequate RCE [10].
This is the first reported case of TPE used as monotherapy without the use of red cell transfusion for acute SCIC or indeed any other acute sickle-related complication, and the dramatic biochemical, radiological and sustained clinical improvement we observed shows that TPE can lead to rapid improvement of the systemic inflammation during a sickle crisis and that its role as an adjunct to RCE or as an alternative when the latter is contraindicated needs to be further explored as a potentially important intervention to be added to our armamentarium in managing complications of SCD.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

AUTHOR CONTRIBUTIONS
Dimitris A. Tsitsikas designed the project and wrote the paper; Rhys Hall and John Meenan coauthored the paper; Funmilayo Orebayo, Oloruntoyin Bello-Sanyaolu and Saket Badle collected data and critically reviewed the manuscript; and Manisha Sharma, Susan Jain and Jun Liong Chin co-designed the project and critically reviewed the manuscript.