Extensive platelet activation in preeclampsia compared with normal pregnancy: enhanced expression of cell adhesion molecules.
OBJECTIVE
Platelets play an important role in the pathophysiologic mechanisms of preeclampsia. Our purpose was to investigate by means of flow cytometry to what extent platelets circulate in an activated state during normal pregnancy and whether this activation is more extensive in preeclampsia.


METHODS
Platelets in whole blood from 10 preeclamptic third-trimester pregnant women (highest diastolic blood pressure range 100 to 130 mm Hg, proteinuria range 0.59 to 11.5 gm/24 hr) and from 10 normotensive third-trimester pregnant controls were analyzed with the following activation markers: anti-P-selectin (alpha-granule secretion), anti-CD63 (lysosomal secretion), PAC-1 (monoclonal antibody against fibrinogen receptor conformation of the glycoprotein IIb/IIIa complex), anti-platelet endothelial cell adhesion molecule-1, and annexin-V (a placental protein that binds to negatively charged phospholipids, present on the outside of the platelet plasma membrane after activation). The differences in surface antigen exposure between the two groups were determined by double-label flow cytometry. Flow cytometric data were analyzed in two ways: first, the percentages of activated platelets above a certain threshold compared with a nonpregnant control sample were determined, indicative for activation of a subpopulation of cells, and, second, the mean fluorescence intensities were determined, indicative of the mean surface antigen expression of the total platelet population.


RESULTS
Analysis of the percentage of activated platelets proved most informative. With this analysis an enhanced platelet activation status was present in 4 of 10 normotensive patients and a more extensive platelet activation status in all 10 preeclamptic patients, as indicated by P-selectin (p = 0.008) and CD63 (p = 0.03) expression. Increased platelet endothelial cell adhesion molecule-1 (p = 0.005) expression was also observed in preeclampsia.


CONCLUSIONS
Flow cytometric analysis clearly indicated that platelets circulate in a more extensively activated state during preeclampsia than during normal pregnancy. The increased platelet endothelial cell adhesion molecule-1 expression in preeclamptic patients demonstrates that, besides alpha-granular and lysosomal release, other hitherto unknown mechanisms are involved. Platelet endothelial cell adhesion molecule-1 appears to be the best marker to distinguish preeclamptic patients from normotensive pregnant women. Only a subpopulation of the platelets appears to be activated.
Konijnenberg
A
A
Department of Gynecology and Obstetrics, Academic Medical Center, Amsterdam, The Netherlands.
Stokkers
E W
EW
van der Post
J A
JA
Schaap
M C
MC
Boer
K
K
Bleker
O P
OP
Sturk
A
A
D000328:Adult; D017304:Annexin A5 / Q000097:blood; D015703:Antigens, CD / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000097:blood*; D054641:Dual Specificity Phosphatase 2; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000097:blood; D012044:Regression Analysis; D060149:Tetraspanin 30
D017304:Annexin A5; D015703:Antigens, CD; C554586:CD63 protein, human; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases