Increased circulating platelet-leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count.
Platelet-leukocyte adhesion may occur as a consequence of platelet activation and possibly plays a key role in the deposition of activated platelets and fibrin in the thrombotic plug. The aim of the present study was to assess by whole blood flow cytometry the presence of circulating platelet-leukocyte aggregates (PLA) and the platelet-leukocyte response to platelet agonist stimulation (ADP and TRAP) in 50 patients with chronic myeloproliferative disorders (MPD) and 30 controls. PLA were identified as platelet-granulocyte/monocyte aggregates (PGMA), platelet-monocyte aggregates (PMA) and defined as the percentage of leukocytes coexpressing the platelet-specific marker glycoprotein Ib. Compared to controls the mean percentage of PGMA and PMA was increased in unstimulated whole blood from patients with MPD (7.98 vs. 1.76%; p<0.001 and 12.34 vs. 3.2%; p<0.001, respectively). The percentage of PGMA was correlated to the platelet count (r=0.46; p<0.001), percentage of P-selectin (r=0.69; p<0.001) and thrombospondin (r=0.58; p<0.001) positive platelets and platelet expression of GPIV (r=0.33; p=0.02). The mean percentage of PGMA and PMA was significantly increased in ADP-stimulated whole blood of patients (57.14 vs. 47.92%; p=0.009 and 54.91 vs. 45.89%; p<0.001, respectively). Compared to patients without a history of thrombosis, patients having experienced microvascular disturbances or a thrombotic event had a higher mean percentage of PGMA and PMA in non-stimulated whole blood (10.07 vs. 6.34%; p=0.025 and 14.81 vs. 10.48%; p=0.021, respectively) and a higher percentage of PGMA in ADP stimulated whole blood (64.32 vs. 51.50%; p<0.01). These data document an increased frequency of PLA in non-stimulated whole blood in MPD associated with a previous history of thrombosis or microvascular disturbances.
Jensen
M K
MK
Department of Haematology L, 4041, Rigshospitalet, University Hospital of Copenhagen, 2100 Copenhagen Ø, Denmark. mkj@dadlnet.dk
de Nully Brown
P
P
Lund
B V
BV
Nielsen
O J
OJ
Hasselbalch
H C
HC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood; D002449:Cell Aggregation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D011506:Proteins / Q000494:pharmacology; D018179:Receptors, Thrombin; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology; D013927:Thrombosis / Q000453:epidemiology* / Q000209:etiology
D015815:Cell Adhesion Molecules; D011506:Proteins; D018179:Receptors, Thrombin; D000244:Adenosine Diphosphate