title: Stimulus-specific defect in platelet aggregation in polycythemia vera.
abstract: We have previously reported that polymorphonuclear granulocyte (PMN) and monocyte oxidative metabolism is reduced in polycythemia vera (PV) patients compared to healthy control subjects, after stimulation with cell surface receptor-dependent stimuli such as n-formyl-methionyl-leucyl-phenylalanine, leukotriene B4 and platelet-activating factor (PAF). In contrast, the oxidative response to phorbol myristate acetate (PMA) is normal. We now show that, in PV patients exhibiting significantly reduced PMN chemiluminescence after PAF stimulation, PAF induced platelet aggregation was also reduced--40 +/- 3% compared to 50 +/- 2% in controls (p < 0.01). The defective aggregatory response to PAF in PV remained over a wide range of stimuli concentrations. Platelet aggregation induced by PMA and ADP, however, was similar in PV and controls. In contrast, platelet aggregation induced by PAF (or by ADP and PMA) was not significantly reduced in patients with chronic myeloid leukemia, essential thrombocythemia and multiple myeloma. Furthermore, the release of beta-thromboglobulin was slightly but not significantly higher after PAF stimulation in PV and this argues against an abnormal PAF receptor as the cause of the defective function. Thus, not only PV neutrophils, but also PV platelets show a discrete defect of the stimulus response coupling for PAF, indicating a disease-specific abnormality that appears to be of clonal origin.
authors.affiliation: Department of Clinical Chemistry, Stockholm Söder Hospital, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Le Blanc
authors.forename: A
authors.initials: A
authors.lastname: Berg
authors.forename: J
authors.initials: J
authors.lastname: Palmblad
authors.forename: J
authors.initials: J
authors.lastname: Samuelsson
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood; D008163:Luminescent Measurements; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011087:Polycythemia Vera / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010972:Platelet Activating Factor; D000244:Adenosine Diphosphate; D013755:Tetradecanoylphorbol Acetate