Splenic and Liver Involvement in Sickle Cell Disease

Sickle Cell Disease (SCD) is one of the most common severe monogenic inherited disorder worldwide characterized by the presence of hemoglobin S (HbS). HbS causes Hb polimerization leading to hemolytic anemia and vaso-occlusion due to erythrocyte rigidity, and is responsible of clinical acute events and chronic progressive multiorgan damage, which becomes evident with increasing age. The term SCD is used to refer to all the different genotypes: Sickle Cell Anemia (SCA) referring to homozygosis for β^S allele; HbS/β-thalassemia, compound of β-thal and β^S allele (T-SCD); and HbSC disease, owing to the coinheritance of β^S and β^calleles. In Italy T-SCD is more frequent than SCA (70% vs 30% of SCD patients).

This retrospective study involved 63 adult SCD patients of the Hereditary Anemia Centre of the Foundation IRCCS “Ca' Granda” Ospedale Maggiore Policlinico, in Milan, Italy. The aim was to assess and compare splenic and liver involvement in SCA and T-SCD patients.

Mutation analysis of the b globin gene was performed by direct DNA sequencing by the ABI Prism 310 genetic analyzer. Clinical and hematological parameters were evaluated by routine tests and physical examination according to guidelines for SCD follow-up.

Sixty-three adult SCD patients, 19 SCA and 44 T-SCD patients, were evaluated. The b mutations detected in T-SCD were severe (b°) in 69.8%, and moderate or mild (b⁺-b⁺⁺) in 30.2% of patients. The mean age of SCA patients was 36±8 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years and the mean age at the presentation to our Centre was 32±8 years.

Five out of 19 (26.3%) of SCA group and 17/44 (38.6%) of T-SCD group were male. HbF mean levels were 7.7±4.9% and 10.7±7.5% respectively in SCA and T-SCD; Hb total mean levels were lower in SCA (9.2±1.2 g/dl) than in T-SCD (10.3±3.2 g/dl) patients. Comparing SCA and T-SCD patients, there was not statistically significant difference in the prevalence of clinical manifestations, except for splenic features. Splenectomy was performed in 3/19 (15.8%) SCA patients vs 23/44 (52.3%) T-SCD patients (p-value < 0.001). For the remaining patients, splenomegaly was absent in SCA, while was detected in 11/21 (52.4%) T-SCD. All SCA patients (100%) had functional asplenia, which was absent in T-SCD patients. Splenic infarctions were present in 2/16 (12.5%) SCA patients and in 6/21 (28.6%) T-SCD patients, of whom 5 had splenomegaly and one normal spleen size (pvalue <0.001). Liver damage is a clinical characteristic complication of adult life and plays an important role in the outcome of adult SCD patients. In our two groups 1/19 (5.3%) SCA and 3/44 (6.8%) T-SCD patients showed a severe alteration in cholestatic liver indices, and all of them showed high values of liver stiffness (KPa) detected by transient elastography suggesting cirrhosis in the SCA patient and fibrosis in the other ones. We underline a more severe increase of cholestatic indices if compared with the alterations of necrotic and stasis liver indices. Signs of liver failure were present in the SCA patient and in one of T-SCD patients. Both patients underwent to liver trans-jugular biopsy in order to evaluate the degree of liver damage. Trans-jugular approach was chosen because of high risk of bleeding with percutaneous procedure. Liver histology of the SCA patient showed signs of necrotic-inflammatory activity with packed sickle cells in the liver sinusoids, suggestive for “sickle liver cirrhosis”, while the biopsy of the T-SCD patient showed only liver fibrosis. They underwent to exchange transfusion in order to reduce the amount of sickling and were candidate to liver transplant.

These data suggest that T-SCD patients, particularly those with severe b mutations, have similar clinical course than SCA patients. Splenomegaly is present only in T-SCD patients and seems to induce splenic infarctions. Only SCA patients experience functional asplenia. Liver involvement, a severe complication of the adult life, is characterized in both groups by sickle cholestatic liver involvement, that can lead to liver failure and, in some cases, to liver transplantation. Exchange transfusion, if started early at the diagnosis of liver disease, can avoid liver transplantation in some selected cases.

Cappellini:Novartis Pharmaceuticals: Honoraria, Research Funding.