Is There an Acute Cardiac or Hepatic Involvement in Hospitalized Sickle Cell Disease Patients with a Vaso-Occlusive Crisis?

Introduction: Sickle cell disease (SCD) is a systemic disease potentially affecting all organs, with acute and chronic damages. Vaso-occlusive crisis (VOC) is the most common acute manifestation of SCD and the first cause of death especially when complicated by acute chest syndrome (ACS). There are very few studies on liver and heart involvement during VOC, whereas these organs are responsible for an increasing proportion of deaths in SCD. The aim of this work is 1/ to estimate the prevalence of acute cardiac and hepatic damage in adult SCD patients hospitalized for VOC and 2/ to study the link between these potential cardiac and/or hepatic failures and the occurrence of an ACS.

Methods: We analyzed the database and the serum library of the PRESEV study (Bartolucci et al., 2016), which was a prospective, monocentric, observational study on VOC in SS/S-β0thalassemia SCD adults at Emergency Department arrival (Henri Mondor University Hospital, Créteil, France). Between July 2006 and September 2012, 250 hospitalizations in 183 patients were recorded in PRESEV. Blood samples were taken on days 1, 2, and 4 of hospitalization and at steady state, at least one month after discharge. The patients were separated into two groups according to their clinical evolution: uncomplicated VOC group and ACS group. Hepatic involvement was defined by cytolysis with ALT > 100 IU/L or by cholestasis with GGT > 120 IU/L and/or conjugated bilirubin > 20 µmol/L. Cardiac involvement was defined by troponin > 14 ng/L and/or NT-proBNP > 300 ng/L (without kidney insufficiency). For each patient, the highest values observed were retained between day 1, 2 and 4. Only the first VOC was retained in patients with multiple hospitalizations.

Results: One hundred and eighty-three patients were included, but cardiac enzymes analysis could only be performed on 174 patients because 9 samples were missing due to difficult venous access. Forty patients (21.9%) developed an ACS during hospitalization. Liver damage was observed for 59 patients (32.2%): biological cholestasis and cytolysis were found for 55 patients (30.1%) and 10 patients (5.5%), respectively. Cardiac involvement was found for 19 patients (10.9%): troponin and NT-proBNP were elevated in six patients (3.4%) and 16 patients (9.2%), respectively. Cholestasis was associated with ACS (40% vs 14.1% ; p < 0.001), blood transfusion requirement (29.1% vs 6.3% ; p < 0.001), and longer hospital stay (7 [5-11] vs 5 [3.7] ; p < 0.001). Hepatic cytolysis and elevated cardiac enzymes were not associated with ACS, transfusion or longer hospital length of stay. NT-pro BNP level was not correlated with the level of GGT (p = 0.526) or conjugated bilirubin (p = 0.136). At steady state, all patients with cholestasis had recovered normal bilirubin levels and 19/55 (34.5%) maintained elevated GGT. Cholestasis and NT-pro BNP level were not correlated, ruling out a hepatic congestion due to a right heart dysfunction.

Conclusion: Biological cholestasis was found for 30% of hospitalized patients during a VOC and was significantly associated with ACS. Cardiac involvement was found in 10% and was not associated with ACS. These results confirm the existence of intrahepatic VOC. Liver monitoring should be considered during VOC, particularly when associated with ACS.

Kassasseya:CSL Behring: Consultancy. Godeau:Amgen: Other: Boards, speaker at educational sessions; Sobi: Other: Boards, speaker at educational sessions; Novartis: Other: Boards, speaker at educational sessions; Grifols: Other: Boards, speaker at educational sessions. Habibi:Novartis: Consultancy; Add-medica: Honoraria; Amgen: Honoraria. Bartolucci:Emmaus: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Hemanext Inc: Consultancy; Innovhem: Other: Co-founder; JazzPharma: Consultancy; Fabre Foundation: Research Funding; Bluebird bio: Consultancy, Research Funding; Roche: Consultancy; Addmedica: Consultancy, Research Funding.