Can flow cytometric detection of platelet activation early in pregnancy predict the occurrence of preeclampsia? A prospective study.
OBJECTIVE
An increased platelet activation status is present in patients with preeclampsia. Our purpose was (1) to establish by means of flow cytometry whether platelets circulate in an activated state during the first and second trimesters of pregnancy and (2) to establish whether early platelet activation predicts the onset of preeclampsia.


METHODS
Consecutively, 244 pregnant women were included in a prospective study design. Platelets in whole blood samples from the pregnant women in the first trimester, the second trimester, and after delivery were labeled with the following antibodies associated with platelet activation: anti-CD62P (P-selectin, alpha-granule secretion), anti-CD63 (GP53, lysosomal secretion), anti-CD31 (GPIIa', platelet endothelial cell adhesion molecule-1). The surface antigen exposure was determined by double-label flow cytometry with anti-CD42b (GPIb, a platelet-specific monoclonal glycoprotein) to select platelets and platelet-derived materials. Preeclampsia was defined as a diastolic blood pressure > or = 90 mm Hg and proteinuria > or = 0.3 gm in a 24-hour urine sample (International Society for Study of Hypertension in Pregnancy criteria).


RESULTS
Seventeen of 244 patients had preeclampsia (6.9%). Only first-trimester CD63 expression had an 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 percentage of activated platelets above 2% as a positive test. Likelihood ratios were 1.94 for positive likelihood and 0.69 for negative likelihood. Univariate logistic regression analysis results were odds ratio 2.8 (95% confidence interval 1.0 to 7.6). Multivariate logistic regression analysis results were odds ratio 2.9 (95% confidence interval 0.92 to 8.9). However, the odds ratio of first antenatal diastolic blood pressure was two to four times higher than the odds ratio of first-trimester CD63 expression. The combination of first-trimester CD63 and first antenatal diastolic blood pressure increases the positive likelihood 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 first-trimester CD63 expression is an independent risk factor for development 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 blood pressure. This method of patient selection may enable more efficient intervention studies in patients at risk than do the selection methods used so far.
Konijnenberg
A
A
Department of Gynecology and Obstetrics, Academic Medical Center, Amsterdam, The Netherlands.
van der Post
J A
JA
Mol
B W
BW
Schaap
M C
MC
Lazarov
R
R
Bleker
O P
OP
Boer
K
K
Sturk
A
A
D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000097:blood*; D001792:Blood Platelets / Q000276:immunology; D001794:Blood Pressure; D015815:Cell Adhesion Molecules / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016015:Logistic Models; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D011507:Proteinuria; D060149:Tetraspanin 30
D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30