PMID- 10930987 OWN - NLM STAT- MEDLINE DCOM- 20000913 LR - 20190705 IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 110 IP - 1 DP - 2000 Jul TI - Increased platelet activation and abnormal membrane glycoprotein content and redistribution in myeloproliferative disorders. PG - 116-24 AB - Chronic myeloproliferative disorders (MPDs) are characterized by a high incidence of thrombohaemorrhagic complications, possibly caused by platelet dysfunction. In an attempt to define platelet functional abnormalities, we assessed the expression of activation-dependent membrane proteins in unstimulated and agonist [ADP and thrombin receptor-activating peptide (TRAP)]-stimulated platelets using quantitative whole blood flow cytometry in samples from 50 MPD patients and 30 controls. The receptor densities of activation markers and glycoproteins (GPs) were quantified using standardized fluorescent beads. Compared with controls, the mean percentage of P-selectin-positive (15.3% vs. 7.2%; P < 0.001) and thrombospondin (TSP)-positive (6.6% vs. 3.7%; P = 0.003) platelets was increased in unstimulated platelets from patients. Patients having experienced a thrombotic event had a higher mean percentage of TSP-positive non-stimulated platelets than patients without a history of thrombosis (9.0% vs. 4.6%; P = 0.02) and a higher GPIV molecules of equivalent fluorochrome (MEF) value (33113 vs. 24471 MEF; P = 0.02). Mean MEF values of monoclonal antibodies (mAbs) against GPIb (34055 vs. 38945 MEF; P < 0.001) and GPIIb/IIIa (1416 vs. 1648 MEF; P < 0. 001) were significantly reduced among patients, whereas surface expression of GPIV was increased in patients (28273 vs. 16258 MEF; P < 0.001). In TRAP (10 micromol/l) stimulated whole blood, the MEF of P-selectin (9611 vs. 13293 MEF; P = 0.004) and CD63 (2385 vs. 5177 MEF; P < 0.001) and the ratio of PAC-1/GPIIb/IIIa MEF (0.98 vs. 2. 00; P < 0.001) was reduced in patients, indicating either a reduced granule GP content or an intrinsic cellular defect in receptor-mediated granule secretion and activation of the GPIIb/IIIa complex. Expressed as the relative change of MEF compared with unstimulated platelets, TRAP induced decrease of GPIb (7.8% vs. 45%; P < 0.001) and increase of GPIIb/IIIa (49.1% vs. 95.7%; P < 0.001) and GPIV expression (17.8% vs. 55.2%; P < 0.001) was attenuated in patients. FAU - Jensen, M K AU - Jensen MK AD - Department of Haematology, Rigshospitalet, University Hospital of Copenhagen, Denmark. mkj@rh.dk FAU - de Nully Brown, P AU - de Nully Brown P FAU - Lund, B V AU - Lund BV FAU - Nielsen, O J AU - Nielsen OJ FAU - Hasselbalch, H C AU - Hasselbalch HC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Bacterial Proteins) RN - 0 (Biomarkers) RN - 0 (Membrane Glycoproteins) RN - 0 (MtrB protein, Bacteria) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factors) RN - 61D2G4IYVH (Adenosine Diphosphate) SB - IM CIN - Br J Haematol. 2001 Jan;112(1):253. PMID: 11225605 MH - Adenosine Diphosphate MH - Adult MH - Aged MH - Aged, 80 and over MH - *Bacterial Proteins MH - Biomarkers/analysis MH - Blood Platelets/*metabolism MH - Case-Control Studies MH - Female MH - Flow Cytometry MH - Humans MH - Male MH - Membrane Glycoproteins/*metabolism MH - Middle Aged MH - Myeloproliferative Disorders/blood/*metabolism MH - *Platelet Activation MH - RNA-Binding Proteins MH - Transcription Factors EDAT- 2000/08/10 11:00 MHDA- 2000/09/19 11:01 CRDT- 2000/08/10 11:00 PHST- 2000/08/10 11:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/08/10 11:00 [entrez] AID - bjh2030 [pii] AID - 10.1046/j.1365-2141.2000.02030.x [doi] PST - ppublish SO - Br J Haematol. 2000 Jul;110(1):116-24. doi: 10.1046/j.1365-2141.2000.02030.x.