Platelet aggregation in healthy women during normal pregnancy - a longitudinal study

Abstract

Increased platelet activation is involved in obstetric complications such as preeclampsia and intrauterine growth retardation. It is of interest to study platelet aggregation during pregnancy, since increased aggregation theoretically could be a mechanism associated with placenta-mediated complications, which possibly could be prevented by drugs inhibiting platelet aggregation. There are, however, few robust studies describing platelet aggregation during normal pregnancy. The present longitudinal study was performed in order to study platelet aggregation during normal pregnancy resulting in a healthy child, during the puerperium and in nonpregnant, fertile women. Healthy, nonsmoking, pregnant women (n = 104), aged under 39 years and with BMI < 35, were followed during pregnancy and postpartum. Twenty-seven nonpregnant, non-puerperal, fertile women were studied for comparison. Platelet aggregation was determined with multiple electrode impedance aggregometry and analyzed at inclusion, 4 times during pregnancy and after at least 3 months postpartum. Platelet aggregation postpartum was compared with gestational weeks 8-15 and 37-40, respectively, and with nonpregnant, fertile women. Hemoglobin, leucocyte count, platelet count, prothrombin time, and activated partial thromboplastin time were determined at inclusion in order to verify normal hemostasis. Activation of platelets by arachidonic acid, adenosine diphosphate (ADP), and thrombin receptor activating peptide (trap-6) resulted in less aggregation during pregnancy, compared with postpartum (p < 0.03-< 0.001). Platelet aggregation following activation by collagen was unchanged. A minor increase in aggregation as pregnancy continued was found related to ADP (p < 0.021). Positive correlations were found between platelet counts and platelet aggregation. Postpartum platelet aggregation after activation with arachidonic acid, collagen, and trap-6 was lower than in the non-puerperal fertile state. Other hemostatic analyses were normal. In conclusion, there is a minor decrease in platelet aggregation after activation with arachidonic acid, trap-6, and ADP, measured with multiple electrode impedance aggregometry during normal pregnancy resulting in healthy babies, compared with the postpartum period. The small changes in platelet aggregation may be a consequence of a minor decrease in platelet count and probably lack clinical significance under normal conditions. Interindividual variations at certain time-points are substantial, which limits the usefulness of the multiple electrode impedance aggregometry for determining minor changes in platelet function.

L-NAME-induced Preeclampsia: correction of functional disorders of the hemostasis system with Resveratrol and Nicorandil

“…It should be noted that platelet activation can be caused not only by proteins of subendothelial structures, but also by adrenaline, norepinephrine, ADP, immune complexes, peroxide radicals, hypoxia, arterial hypertension, prostaglandins PgG2 and PgH2, arachidonic acid, thromboxane A 2 , platelet activating factor (PAF), phorbol esters, latex, lectins, A23187 ionophore, bacteria and bacterial lipopolysaccharide, tumor cells, increased shear stress, etc. (Blomqvist et al 2018, Kozlovsky et al 2013, Lysenkov et al 2004, Sidorenko et al 2007. It is ischemic placenta that excretes a large number of these humoral factors, which leads to platelet activation.…”

“…Due to the severity of the complications caused by impaired hemostasis in preeclampsia, as well as in connection with the prevailing stereotype, abnormal platelet function has traditionally been considered within the hemostatic system (Blomqvist et al 2018, Burke et al 2013, Burke et al 2016. This is clearly seen even when trying to assess the severity of preeclampsia and other pathological conditions of pregnant women by impairment of their function (Burke et al 2016, Holthe et al 2004, Sidorenko et al 2007.…”

“…But even the available data show contradictions in the results obtained by different authors. However, most authors claim a decrease in the activity of the coagulation system, platelet aggregation ability in early pregnancy, followed by their significant increase in childbirth and in the postnatal period, which looks logical (Blomqvist et al 2018, Burke et al 2013, Freitas et al 2014, Hayashi et al 1999, Hellgren 2003. In the third trimester, the platelet aggregation sensitivity to ADP, adrenaline, ristomycin, collagen and other inducers increases (Blomqvist et al 2018).…”

“…There have only been a small number of scientific publications written recently which discuss a certain independent role of platelets in the development of preeclampsia and the possibility of preventing and treating placental-mediated complications with drugs correcting the function of platelets (Blomqvist et al 2018, Holthe et al 2004, van Vliet et al 2017.…”

Study of the effect of selective inhibitor of Arginase II KUD 975 and of low doses of Acetylsalicylic acid on the functional parameters of the cardiovascular system In experimental preeclampsia

“…Recently, in the literature there has been evidence that disturbances in the hemostatic system can be not only a complication of preeclampsia or develop alongside it, but can also precede its manifestation or, to some extent, contribute to its development. The pathogenetic events that explain the role of activated platelets in the development of endothelial dysfunction in various diseases, including preeclampsia, are described in (Sidorenko et al 2007, Hussien and Emam 2016, Blomqvist et al 2019, Severinova et al 2019.…”