CAN FLOW CYTOMETRIC DETECTION OF PLATELET ACTIVATION EARLY IN PREGNANCY PREDICT THE OCCURRENCE OF PREECLAMPSIA - A PROSPECTIVE-STUDY

OBJECTIVES: An increased platelet activation status is present in pati ents with preeclampsia. Our purpose was (1) to establish by means of f low cytometry whether platelets circulate in an activated state during the first and second trimesters of pregnancy and (2) to establish whe ther early platelet activation predicts the onset of preeclampsia. STU DY DESIGN: Consecutively: 244 pregnant women were included in a prospe ctive study design. Platelets in whole blood samples from;he pregnant women in the first trimester, the second trimester, and after delivery were labeled with the following antibodies associated with platelet a ctivation: anti-CD62P (P-selectin, alpha-granule secretion), anti-CD63 (GP53, lysosomal secretion), anti-CD31 (GPlla', platelet endothelial cell adhesion molecule-1). The surface antigen exposure was determined by double-label flow cytometry with anti-CD42b (GPlb, a platelet-spec ific monoclonal glycoprotein) to select platelets and platelet-derived materials. Preeclampsia was defined as a diastolic blood pressure gre ater than or equal to 90 mm Hg and proteinuria greater than or equal t o 0.3 gm in a 24-hour urine sample (International Society for Study of Hypertension in Pregnancy criteria). RESULTS: Seventeen of 244 patien ts had preeclampsia (6.9%). Only first-trimester CD63 expression had a n area under the curve >0.5 by receiver-operator characteristic curve analysis and was selected as a possible predictor of preeclampsia. We found a sensitivity of 47% and a specificity of 76% with use of a perc entage of activated platelets above 2% as a positive test. Likelihood ratios were 1.94 for positive likelihood and 0.69 for negative likelih ood, Univariate logistic regression analysis results were odds ratio 2 .8 (95% confidence interval 1.0 to 7.6). Multivariate logistic regress ion analysis results were odds ratio 2.9 (95% confidence interval 0.92 to 8.9). However, the adds ratio of first antenatal diastolic blood p ressure was two to four times higher than the odds ratio of first-trim ester CD63 expression. The combination of first-trimester CD63 and fir st antenatal diastolic blood pressure increases the positive likelihoo d ratio from 1.94 to 9.4, with a sensitivity of 41%, a specificity of 96%, and a negative likelihood ratio of 0.62. CONCLUSIONS: Increased f irst-trimester CD63 expression is an independent risk factor for devel opment of preeclampsia. CD63 expression might be useful to identify a subgroup of patients with a high risk for development of preeclampsia, especially in combination with first-trimester antenatal diastolic bl ood pressure. This method of patient selection may enable more efficie nt intervention studies in patients at risk than do the selection meth ods used so far.