Acute liver failure at 26 weeks' gestation in a patient with sickle cell disease

Introduction: Sickle cell intrahepatic cholestasis (SCIC) is one of the rarest and the most severe acute hepatic manifestations of sickle cell disease (SCD) and it can rapidly progress to acute liver failure. It is associated with a high mortality rate, demanding prompt recognition and management. Case Presentation: We report a case of a 7-year-old boy with a history of homozygous HbS SCD who presented to the emergency department with fever, increasing abdominal pain, and jaundice. His course was complicated by acute liver injury (AST 9,472 IU/L, ALT 2,683 IU/L, total bilirubin 15.4 mg/dL; conjugated bilirubin 8.69 mg/dL, hypoalbuminemia 2.6 g/dL, and persistent hypoglycemia), with acute liver failure (coagulopathy not corrected by vitamin K administration with INR 3.26, decreased factors V 10% and VII 28%, and West Haven grade I hepatic encephalopathy associated with mild hyperammonemia of 71 µmol/L). After excluding other causes of acute liver failure, the patient was diagnosed as having SCIC and was successfully treated with manual exchange transfusion. Conclusion: This case reinforces that exchange transfusion is an effective treatment for SCIC and that it should be introduced promptly to prevent fulminant and potentially fatal liver failure.

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Splenic and Liver Involvement in Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.4763.4763 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4763-4763

Author(s):

Giovanna Graziadei ◽

Alessia Marcon ◽

Ilaria Gandolfi ◽

Martina Soldarini ◽

Erika Poggiali ◽

...

Keyword(s):

Liver Transplantation ◽

Sickle Cell Disease ◽

Liver Failure ◽

Sickle Cell ◽

Exchange Transfusion ◽

Adult Life ◽

Liver Involvement ◽

Cell Disease ◽

The Mean

Abstract Abstract 4763 Background. 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 βS allele; HbS/β-thalassemia, compound of β-thal and βS allele (T-SCD); and HbSC disease, owing to the coinheritance of βS and βcalleles. In Italy T-SCD is more frequent than SCA (70% vs 30% of SCD patients). Aims. 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. Methods. 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. Results. 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. Conclusions. 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. Disclosures: Cappellini: Novartis Pharmaceuticals: Honoraria, Research Funding.

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Hyperferritinemia and Hemophagocytic Lymphohistiocytosis. Single Institution Experience in Adult and Pediatric Patients.

Blood ◽

10.1182/blood.v120.21.2135.2135 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2135-2135 ◽

Cited By ~ 5

Author(s):

Alice D. Ma ◽

Yuri D. Fedoriw ◽

Philip Roehrs

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Liver Failure ◽

Sickle Cell ◽

Hemophagocytic Lymphohistiocytosis ◽

Pediatric Patients ◽

Adult Patients ◽

Cell Disease ◽

Clinical Criteria ◽

Shock Liver

Abstract Abstract 2135 Hemophagocytic lymphohistiocytosis (HLH) is a multisystem disorder characterized by immune dysregulation and hypercytokinemia. Diagnostic criteria include a genetic mutation consistent with familial HLH or the presence of 5 of 8 defined clinical criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low/absent NK cell function, hyperferritinemia, and elevated soluble CD25). In pediatrics, a ferritin value of >10,000 mχγ/L has been reported to have 90% sensitivity and 96% specificity in defining the presence of HLH (Allen, C. E., Yu, X., Kozinetz, C. A. and McClain, K. L. (2008). Pediatr. Blood Cancer). We examined if hyperferritinemia (all patients with ferritin level >10,000 mχγ/L between 2007 and 2012) correlated with diagnosis of HLH in 94 patients (73 adult; 21 pediatric) at our institution. Chart reviews were performed to evaluate the presence or absence of HLH criteria, additional clinical features that may be indicative of HLH, and diagnosis. These data resulted in our classification of patients into four groups (Table 1): (1) “clinically defined HLH” when predetermined criteria were met; (2) “potential HLH” when clinical criteria was suggestive of HLH, but not all criteria were met; (3) “possible HLH” when rheumatologic syndromes, liver disease, or fever/DIC was present of unknown etiology; or (4) “Non-HLH” when the elevated ferritin was a result of a known etiology (Table 2). As expected, 18 (86 %) of pediatric patients with a ferritin > 10,000 mχγ/L had clinically defined or potential/possible HLH. Notably, 44 (60 %) of adult patients with a ferritin > 10,000 mg/L had clinically defined or potential/possible HLH. Such an incidence of HLH in the adult population with elevated ferritin raises caution for appropriate diagnosis of this population and clearly warrants further study. If patients with sickle cell disease, GVH, or known causes for liver failure are excluded, then HLH should be suspected in 83% of adult patients with ferritins >10,000 mcg/L. Table 1: HLH classifications of 94 patients with ferritin > 10,000 mχγ/L Adult, n = 73 n (%) Pediatric, n = 21 n (%) Clinically defined HLH 18 (25) 12 (57) Potential HLH 9 (12) 5 (24) Possible HLH 17 (23) 1 (5) Non-HLH 29 (40) 3 (14) Table 2: Diagnoses of non-HLH patients with ferritin > 10,000 mcg/L (some diagnoses overlap) Liver failure of clear etiology (10) APAP toxicity (4) Shock liver (4), EtOH, Other Sickle cell disease (9) 7 adult, 2 peds, all with probable iron overload Other tumors (9) CMML+VT+shock liver, prostate ca with bone mets, CMML to AML, MDS/MPD with infection, AML, T lymphoblastic lymphoma with cholestasis, allo txp for AML with iron overload, ALL+ abd wall hematoma Iron overload (11) 9 sickle cell, 1 Castlemans, 1 allo txp for AML Other Pancreatitis, GVH (3) Table 3: Clinical suspicion for HLH Potential HLH (%) Possible HLH (%) Total Adult 9 17 Peds 5 1 HLH suspected? Adult 1 (11) 2 (12) Peds 4 (80) 1 (100) All criteria sent? Adult 1 (11) 1 (6) Peds 2 (40) 1 (100) Hematology involved? Adult 6 (67) 11 (64) Peds 5 (100) 1 (100) Did hematologist note ferritin? Adult 1 (17) 3 (27) Peds 5 (100) 0 Disclosures: Ma: Novo Nordisk Inc.: Consultancy, Speakers Bureau.

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