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Baaten 2018 Haematologica
Additional label Labels  + , 2018-08  +
Coupling states OXPHOS  +
Diseases Cancer  +
Has abstract Severe thrombocytopenia (≤50x10<sup>
Severe thrombocytopenia (≤50x10<sup>9</sup> 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 Ca<sup>2+</sup> flux, integrin α<sub>IIb</sub>β<sub>3</sub> activation and P-selectin expression, when stimulated with a panel of agonists. The patients' platelets were also impaired in spreading on fibrinogen. Whereas the Ca<sup>2+</sup>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.
ow hemostatic potential of these patients.  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/29880611 PMID: 29880611] »[[File:O2k-brief.png|36px|link=http://wiki.oroboros.at/images/4/4d/Baaten_2018_Haematologica_O2k-brief.pdf |O2k-brief]]  +
Has publicationkeywords Disorders of platelet function  + , Thrombocytopenia  + , Transfusion medicine  + , Hematological malignancies  + , Platelets  +
Has title Baaten CCFMJ, Moenen FCJI, Henskens YMC, S
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.
g chemotherapy. Haematologica 103:1557-67.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Respiration  + , mt-Membrane  + , Patients  +
Pathways N  + , NS  +
Preparation Intact cells  +
Tissue and cell Blood cells  + , Platelet  +
Was published by MiPNetLab CA Guelph Holloway GP +
Was published in journal Haematologica +
Was published in year 2018  +
Was written by 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 +
Categories Publications
Modification date
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11:03:37, 17 April 2019  +
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