title: Multiple platelet defects identified by flow cytometry at diagnosis in acute myeloid leukaemia.
abstract: Summary Previous findings of megakaryocytic hypogranulation and dysmegakaryocytopoietic features in acute myeloid leukaemia (AML) strongly indicate defects in platelet production. The bleeding tendency of these patients may result from dysregulated platelet production, resulting in thrombocytopenia as well as qualitative platelet defects. The present study examined platelet function at diagnosis in 50 AML patients by whole blood flow cytometry. Following in vitro platelet agonist stimulation, platelet activation markers were analysed and compared with 20 healthy individuals. To detect recent in vivo platelet activation, plasma soluble P-selectin (sP-selectin) was measured. Flow cytometric analysis of platelet activation markers demonstrated reduced CD62P [35.6 vs. 118.5 x 10(3) molecules of equivalent soluble fluorochrome (MESF); P < 0.0001], CD63 (11.3 vs. 50.7 x 10(3) MESF; P < 0.0001), and PAC-1 (41.5 vs. 90.5%; P = 0.0001) while reductions in CD42b were abnormal (45.6 vs. 70%; P < 0.0001). sP-selectin levels were similar in patients and healthy controls (0.04 vs. 0.27 fg/platelet; P = 0.84). The presented data indicate that AML pathogenesis may result in multiple platelet defects, involving adhesion, aggregation, and secretion and demonstrate that flow cytometry is a feasible method for platelet function analysis in patients with thrombocytopenia.
authors.affiliation: The Research Laboratory, Department of Haematology, Herlev University Hospital, Copenhagen, Denmark. leinoe@dadlnet.dk
authors.forename: E B
authors.initials: EB
authors.lastname: Leinoe
authors.forename: M H
authors.initials: MH
authors.lastname: Hoffmann
authors.forename: E
authors.initials: E
authors.lastname: Kjaersgaard
authors.forename: H E
authors.initials: HE
authors.lastname: Johnsen
mesh_terms: D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests / Q000379:methods; D018179:Receptors, Thrombin / Q000502:physiology
chemical_list: D019007:P-Selectin; D018179:Receptors, Thrombin; D000244:Adenosine Diphosphate