EXTENSIVE PLATELET ACTIVATION IN PREECLAMPSIA COMPARED WITH NORMAL-PREGNANCY - ENHANCED EXPRESSION OF CELL-ADHESION MOLECULES

OBJECTIVES: Platelets play an important role in the pathophysiologic m echanisms of preeclampsia. Our purpose was to investigate by means of flow cytometry to what extent platelets circulate in an activated stat e during normal pregnancy and whether this activation is more extensiv e in preeclampsia. STUDY DESIGN: Platelets in whole blood from 10 pree clamptic third-trimester pregnant women (highest diastolic blood press ure range 100 to 130 mm Hg, proteinuria range 0.59 to 11.5 gm/24 hr) a nd from 10 normotensive third-trimester pregnant controls were analyze d with the following activation markers: anti-P-selectin (alpha-granul e secretion), anti-CD63 (lysosomal secretion), PAC-1 (monoclonal antib ody against fibrinogen receptor conformation of the glycoprotein Ilb/l lla complex), anti-platelet endothelial cell adhesion molecule-1, and annexin-V (a placental protein that binds to negatively charged phosph olipids, present on the outside of the platelet plasma membrane after activation). The differences in surface antigen exposure between the t wo groups were determined by double-label flow cytometry. Flow cytomet ric data were analyzed in two ways: first, the percentages of activate d platelets above a certain threshold compared with a nonpregnant cont rol sample were determined, indicative for activation of a subpopulati on of cells, and, second, the mean fluorescence intensities were deter mined, 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 plat elet activation status was present in 4 of 10 normotensive patients an d a more extensive platelet activation status in all 10 preeclamptic p atients, as indicated by P-selectin (p = 0.008) and CD63 (p = 0.03) ex pression. Increased platelet endothelial cell adhesion molecule-1 (p = 0.005) expression was also observed in preeclampsia. CONCLUSIONS: Flo w cytometric analysis clearly indicated that platelets circulate in a more extensively activated state during preeclampsia than during norma l pregnancy. The increased platelet endothelial cell adhesion molecule -1 expression in preeclamptic patients demonstrates that, besides a-gr anular and lysosomal release, other hitherto unknown mechanisms are in volved. Platelet endothelial cell adhesion molecule-1 appears to be th e best marker to distinguish preeclamptic patients from normotensive p regnant women. Only a subpopulation of the platelets appears to be act ivated.