Unexpected Amanita phalloides-Induced Hematotoxicity-Results from a Retrospective Study.

INTRODUCTION: Amanita phalloides poisoning is a serious health problem with a mortality rate of 10-40%. Poisonings are characterized by severe liver and kidney toxicity. The effect of Amanita phalloides poisonings on hematological parameters has not been systematically evaluated thus far. METHODS: Patients with suspected Amanita phalloides poisonings were retrospectively selected from the hospital database of the University Medical Center Groningen (UMCG). Medical data-including demographics; liver, kidney, and blood parameters; treatment; and outcomes-were collected. The severity of the poisoning was scored using the poison severity score. RESULTS: Twenty-eight patients were identified who were admitted to the UMCG with suspected Amanita phalloides poisoning between 1994 and 2022. A time-dependent decrease was observed for hemoglobin and hematocrit concentrations, leukocytes, and platelets. Six out of twenty-eight patients developed acute liver failure (ALF). Patients with ALF showed a higher increase in liver enzymes, international normalized ratios, and PSS compared to patients without ALF. Conversely, hemoglobin and platelet numbers were decreased even further in these patients. Three out of six patients with ALF died and one patient received a liver transplant. CONCLUSION: Our study shows that Amanita phalloides poisonings may be associated with hematotoxicity in patients. The quantification of hematological parameters is of relevance in intoxicated patients, especially in those with ALF.

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.

Amanita phalloides poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of Amanita poisonings. In this study, we investigated the effects of the main toxins of Amanita phalloides, α- and ß-amanitin, on hematopoietic cell viability in vitro. Hematopoietic cell lines were exposed to α-amanitin or ß-amanitin for up to 72 h with or without the pan-caspase inhibitor Z-VAD(OH)-FMK, antidotes N-acetylcysteine, silibinin, and benzylpenicillin, and organic anion-transporting polypeptide 1B3 (OATP1B3) inhibitors rifampicin and cyclosporin. Cell viability was established by trypan blue exclusion, annexin V staining, and a MTS assay. Caspase-3/7 activity was determined with Caspase-Glo assay, and cleaved caspase-3 was quantified by Western analysis. Cell number and colony-forming units were quantified after exposure to α-amanitin in primary CD34+ hematopoietic stem cells. In all cell lines, α-amanitin concentration-dependently decreased viability and mitochondrial activity. ß-Amanitin was less toxic, but still significantly reduced viability. α-Amanitin increased caspase-3/7 activity by 2.8-fold and cleaved caspase-3 by 2.3-fold. Z-VAD(OH)-FMK significantly reduced α-amanitin-induced toxicity. In CD34+ stem cells, α-amanitin decreased the number of colonies and cells. The antidotes and OATP1B3 inhibitors did not reverse α-amanitin-induced toxicity. In conclusion, α-amanitin induces apoptosis in hematopoietic cells via a caspase-dependent mechanism.