Hepatobiliary laboratory abnormalities among patients with chronic or persistent immune thrombocytopenia (ITP).

Therapies for immune thrombocytopenia (ITP) may be associated with abnormal hepatobiliary laboratory (HBL) values, but the epidemiology of these abnormalities is unknown in the ITP population. The study aim was to provide prevalence and incidence rates, as well as risk factors for abnormal HBL values among a cohort of patients with chronic or persistent primary ITP. Health insurance claims data from 3,244 patients with chronic or persistent ITP was examined to estimate the prevalence of abnormal HBL values: elevated levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total bilirubin, and Alkaline Phosphatase (ALP). Incidence of abnormal HBL values was estimated in a sub cohort of 2557 (79%) patients without evidence of comorbidities related to secondary thrombocytopenia, liver disease, or abnormal HBL values during the 12-month baseline period. The baseline prevalence of ALT and AST > 3x the upper limit of normal (ULN) was 4.6 and 3.7%, respectively. The baseline prevalence of total bilirubin and ALP >1.5x ULN was 4.2 and 3.2%, respectively. The incidence rate of new HBL abnormalities (HBLA) was 1.24/1,000 person-years (95% CI: 0.52-2.56) for ALT>3x ULN and 0.41/1,000 person-years (95% CI: 0.08-1.32) for AST>3x ULN. HBLAs were significantly associated with male gender, liver disease, diabetes, congestive heart failure, lupus, hematological cancers, and HIV infection. In conclusion, the prevalence of HBLA, specifically ALT>3x ULN, among the ITP population is relatively high compared with atrial fibrillation, though within the confidence interval for that estimate. HBLAs were significantly associated with male gender, liver disease, and several other comorbidities, thus, distinguishing drug-induced liver injury in this population is clinically challenging.

Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome.

Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 microg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag neither led to increased 5-bromo-2-deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xenotransplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients with AML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS.