Baaten 2018 Haematologica

[[Has title::Baaten CCFMJ, Moenen FCJI, Henskens YMC, Swieringa F, Wetzels RJH, van Oerle R, Heijnen HFG, Ten Cate H, Holloway GP, Beckers EAM, Heemskerk JWM, van der Meijden PEJ (2018) Impaired mitochondrial activity explains platelet dysfunction in thrombocytopenic cancer patients undergoing chemotherapy. Haematologica 103:1557-67.]]

» [[Has info::PMID: 29880611 »]]

Was written by::Baaten CCFMJ, Was written by::Moenen FCJI, Was written by::Henskens YMC, Was written by::Swieringa F, Was written by::Wetzels RJH, Was written by::van Oerle R, Was written by::Heijnen HFG, Was written by::Ten Cate H, Was written by::Holloway GP, Was written by::Beckers EAM, Was written by::Heemskerk JWM, Was written by::van der Meijden PEJ (Was published in year::2018) Was published in journal::Haematologica

Abstract: [[has abstract::Severe thrombocytopenia (≤50x10⁹ platelets/L) due to hematological malignancy and intensive chemotherapy is associated with an increased risk of clinically significant bleeding. Since the bleeding risk is not linked to the platelet count only, other hemostatic factors must be involved. In 77 patients with acute leukemia, multiple myeloma or malignant lymphoma, who experienced chemotherapy-induced thrombocytopenia, we studied platelet function. Platelets from all patients - independent of disease or treatment type - were to a variable extent compromised in Ca²⁺ flux, integrin α_IIbβ₃ activation and P-selectin expression, when stimulated with a panel of agonists. The patients' platelets were also impaired in spreading on fibrinogen. Whereas the Ca²⁺store content was unaffected, the patients' platelets showed ongoing phosphatidylserine (PS) exposure, which was not due to apoptotic caspase activity. Interestingly, mitochondrial function was markedly reduced in platelets from a representative subset of patients, as evidenced by a low mitochondrial membrane potential (p<0.001) and low oxygen consumption (p<0.05), while the mitochondrial content was normal. Moreover, the mitochondrial impairments coincided with elevated levels of reactive oxygen species (Spearman's rho=-0.459, p=0.012). Markedly, the impairment of platelet function only appeared after two days of chemotherapy, suggesting origination in the megakaryocytes. In patients with bone marrow recovery, platelet function improved. In conclusion, our findings disclose defective receptor signaling related to impaired mitochondrial bioenergetics, independent of apoptosis, in platelets from cancer patients treated with chemotherapy, explaining the low hemostatic potential of these patients.]] • Keywords: has publicationkeywords::Disorders of platelet function, has publicationkeywords::Hematological malignancies, has publicationkeywords::Platelets, has publicationkeywords::Thrombocytopenia, has publicationkeywords::Transfusion medicine • Bioblast editor: [[has editor::Plangger M]] • O2k-Network Lab: Was published by MiPNetLab::CA Guelph Holloway GP

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Labels: MiParea: MiP area::Respiration, MiP area::mt-Membrane, MiP area::Patients  Pathology: Diseases::Cancer 

Organism: Organism::Human  Tissue;cell: tissue and cell::Blood cells, tissue and cell::Platelet  Preparation: Preparation::Intact cells 

Coupling state: Coupling states::OXPHOS  Pathway: Pathways::N, Pathways::NS  HRR: Instrument and method::Oxygraph-2k 

additional label::Labels, additional label::2018-08, additional label::MitoEAGLE blood cells data, additional label::O2k-brief