…to resolve the problems of sickle cell anemia.  The effects of transfusions for sickle cell patients’ hepatobiliary function are poorly understood.  By lowering the level of hemoglobin S and reducing sickling, can this lead to improvement in organs damaged by sinusoidal congestion and infarction?  Well probably not (J Pediatr 2012; 160: 281-85).

Strokes are known to occur in 5-10% of sickle cell patients by 20 years of age and if untreated, >50% have recurrence.  This has led to transfusion programs.  The ‘Stroke with Transfusions Changing to Hydrdoxyurea’ (SWiTCH) study is a multi-center randomized trial trying to determine how current treatment (transfusions and chelation) compares with hydroxyurea/phlebotomy for preventing stroke and managing iron overload.  As part of this study, a baseline assessment with ultrasound showed widespread problems -despite an average of 7 years of transfusions.  In this cohort of 149 patients, the following findings were identified:

• Spleen volumes were increased in more than 1/3rd of patients leading to hypersplenism (low platelet counts). 12 subjects had nonvisible spleens due to autoinfarction.
• Nephromegaly was present.  This finding is known to occur with sickle cell disease and is a marker of glomerular hyperfiltration.
• Hepatobiliary disease was nearly ubiquitous.  37 of 148 had previous cholecytectomy; of the remaining, 46 of 111 (41%) had gallstones and 14% had gallbladder sludge.  Liver lengths were significantly longer as well.

Conclusions: Transfusion therapy was insufficient to reverse or prevent organ damage in children with sickle cell anemia.  An important limitation– the severity of the underlying prevalence of organ dysfunction prior to initiation of transfusion therapy was not known.

Additional references:

• -Blood 2011; 117: 772-9.  Silent cerebral infarcts occur despite regular blood transfusions.
• -Clin Gastro & Hep 2007; 5: 1469.  Reviews types of sickle cell associated liver disease.
• -Pediatric Hematology and Oncology.  2006 Mar;23(2): 95-102(8).  Sickle cell intrahepatic cholestasis (SCIC), which is related to intrahepatic sinusoidal RBC sickling (due to relative hypoxia) and can be associated with progressive hepatomegaly, mild transaminitis, extreme hyperbilirubinemia
• -JPGN 2004; 39: 200.  Review of sickle cell hepatic crisis.  Cholestasis resolves over 3 months.  Acute crisis treated with hyperhydration & transfusion. Cohort of 350; 6 developed hepatic crisis.
• -J Pediatr 2001; 139: 785-789 & 790-796.  Transfusions and hydroxyurea for SS dz.