Early Evidence of Bone Marrow Dysfunction in Children with Indeterminate Fulminant Hepatic Failure Who Ultimately Develop Aplastic Anemia

Abstract

In children, aplastic anemia (AA) is a common complication associated with fulminant hepatic failure (FHF). The objective of this study was to determine whether specific pretransplantation clinical and laboratory characteristics can be used to distinguish between patients with FHF who are at higher risk of developing AA. We performed a retrospective casecontrol study to evaluate the clinical and laboratory characteristics of those patients who presented with evidence of FHF and eventually developed aplastic anemia. We identified nine patients with AA, and all had the indeterminate form of FHF and underwent liver transplantation (LTx). The AA patients were compared with a control group of 47 patients with indeterminate FHF that underwent transplantation and did not develop AA. We found that males were over-represented in the group of patients that developed AA (p = 0.01). Furthermore, during the pretransplant period, the AA group had a significantly lower white count (p = 0.005), absolute lymphocyte count (p = 0.004), and platelet count (p = 0.019) when compared with controls. We conclude that evidence of early bone marrow dysfunction is apparent before liver transplantation and the development of AA in a subset of patients with the indeterminate form of FHF.

Evolution in the management of acute liver failure-associated aplastic anaemia in children: A single centre experience

“…Almost four-fifths (78.5%) of our patients are boys, confirming the previously observed male preponderance among adults or children who develop acute hepatitisor ALF-associated AA [7,8]. The cause of this gender difference is unclear and unlikely to be due to hormonal factors given the young, pre-pubertal, age of most of our patients.…”

“…Median time to achieve a partial response to the treatment for the surviving children was 2 months (range 0. [5][6][7][8][9][10][11][12][13][14].…”

“…Up to 28% of patients with acute liver failure (ALF) develop bone marrow failure (BMF), its severity ranging from mild pancytopenia to severe aplastic anaemia (AA) [1][2][3][4][5][6][7][8]. The pathogenesis of acquired BMF has been linked to exposure to viruses, chemicals, including drugs and environmental xenobiotics, but also to immunologically-mediated injury directed to as yet unidentified endogenous antigens associated with haemopoietic stem cells [9].…”

Modern Management of Acute Liver Failure

“…The potent immunosuppressive agents and some antimicrobial drugs used commonly potentially are nephrotoxic and the use of these agents should be modified to optimize the return of renal function. Aplastic anemia can complicate acute liver failure, typically in younger patients who have seronegative hepatitis, and usually persists after transplantation, although bone marrow recovery has been reported after the administration of antithymocyte globulin (ATG) [25,26].…”

Parvovirus Associated Fulminant Hepatic Failure and Aplastic Anemia Treated Successfully With Liver and Bone Marrow Transplantation. A Report of Two Cases

“…More recently, bone marrow transplantation (BMT) has been utilized with excellent outcomes in these patients. An extensive literature search identified only 10 cases that underwent BMT after LT for FHF and AA (5)(6)(7)(8)(9)(10)(11)(12)(13). No causative agent for the FHF or AA has been identified in any of these cases.…”