Preeclampsia is defined as a new onset of hypertension associated with proteinuria and fluid retention detected for the first time after the 20th week of gestation. Preeclamsia, or “toxemia of pregnancy” complicates 2–8% of all pregnacies Citation[1]. Although the causes of pregnancy-induced hypertension are not completely clear, one of the responsible mechanisms is thought to be a disorder of consumptive coagulopathy with predominant involvement of platelets Citation[2]. However, there is an ongoing debate about whether platelet hyperactivity indeed exists during preeclampsia, and if available data are sufficient for justification of broad antiplatelet strategies. We compared whole blood platelet aggregation in patients preeclampsia with matched normal pregnant women and evaluated whether there is an association of preeclampsia severity with platelet activity.
Normal pregnant women without preeclampsia (n = 30) and those with preeclampsia (n = 30) were enrolled in the study. Mild preeclampsia was defined as a systolic blood pressure over 140 mmHg but less than 160 mmHg and/or diastolic pressure of more than 90 mmHg but less than 110 mmHg, recorded on at least two occasions 6 hours apart, and proteinuria levels producing a 2+ reaction on a standart urine dipstick (>300 mg/dl) on two occasions 4–24 hours apart, but for no more than 1 g/daily loss. Severe preeclampsia was diagnosed when sustained systolic blood pressure exceeds 160 mmHg and/or diastolic blood pressure was higher than 110 mmHg for at least 6 hours, in combination with proteinuria levels producing a 2+ reaction on a standart urine dipstick (>300 mg/dl) on two occasions 4–24 hours apart or over 5 g of proteinuria during a 24-hour-period. In addition, symptoms of pulmonary edema, seizures, oliguria (<50 mL/24 h), elevated liver enzymes, thrombocytopenia (<1,000,000/mm3), or cerebral manifestations such as headache or blurry vision, were also cosidered as a severe disease according to standard criteria of Committee on Terminology, of the American College of Obstetricians and Gynecologists Citation[3]. We excluded subjects receiving any antiplatelet agent, nonsteroid anti-inflammatory drugs and those multiple pregnancies, ruptured membranes, chronic hypertension and diabetes mellitus. Collagen-induced platelet aggregation was assessed with Multiplate® Electrical Impedance Aggegometer (MEA, Dynabyte, Munich, Germany) amd expressed in aggregation units (AU).
Clinical and demographic characteristics of our study population are presented in .
Table I. Baseline characteristics of pregnant women with preeclampsia and controls.
There were no statistically significant differences between patients with preeclampsia and normal pregnancy with regard to the maternal age and gestation at delivery; however, patients with preeclampsia exhibited significantly higher blood pressure, proteinuria levels and parity.
The characteristics of patients with mild versus severe preeclampsia are outlined in .
Table II. Baseline characteristics of pregnant women with severe and mild preeclampsia.
Of the women with preeclampsia (n = 30), half were diagnosed with severe disease. Platelet aggregation induced by collagen (617 ± 314 vs 810 ± 407, p = 0.1) were comparable between preeclampsia and normal pregnancies. Moreover, in subgroup analysis, patients with severe preeclampsia had similar platelet activity (798 ± 498 vs. 821 ± 313, p = 0.6) compared to women with mild preeclampsia.
In contrast to the majority of reports, we found that neither preeclampsia per se, nor its severity was associated with significant changes of whole blood platelet aggregation when compared to matched normal pregnancies. Since we found no differencies in platelet aggregation between preeclamptic and normal pregnancies, and no remarkable changes in the subgroup analysis, the index data challenge uniform use of antiplatelet therapy in such patients. Although, the large meta-analysis of individual patient data from 32,217 women, and their 32,819 babies, recruited to 31 randomized trials of preeclampsia primary prevention suggests small but consistent reductions in the relative risk of preeclampsia, premature birth or having a pregnancy with a serious adverse outcome with antiplatelet agents Citation[4]. However, the same study suggests that antiplatelet therapy has no impact on the risk of death of the fetus or baby, having a small for gestational age infant, or bleeding events for either the women or their babies. Not surprisingly, an excellent Cochrane Database systematic review Citation[4] concludes that antiplatelet agents, largely low-dose aspirin, may have moderate benefits when used for prevention of preeclampsia and its consequences, but it is entirely unknown which women are most likely to benefit, when treatment is best started, which agent, and at what dose. Our findings should be confirmed in larger, better randomized studies with more comprehensive assessment of platelet activity indices focusing on clinical outcomes.
Disclosures and conflicts
The authors reports no conflicts of interest.
References
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- ACCOG Committee on Obstetric Practice. Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol 2000;99:159–167.
- Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: A meta-analysis of individual patient data. Lancet 2007; 369: 1791–1798