Mechanisms involved in agonist-induced hyperaggregability of platelets from normal pregnancy

Abstract

There is substantial evidence of increased platelet reactivity in vivo and in vitro during pregnancy. Platelet activation occurs in pregnancy with a risk of the development of preeclampsia. In this study, platelet behavior was studied during 28-40 weeks of gestation in a group of women who remained normotensive and a group of nonpregnant female controls. Platelet aggregation and ATP release stimulated by agonists (i.e. collagen and adenosine 5'-diphosphate) were markedly enhanced in washed platelets from pregnant subjects. Furthermore, the collagen-evoked increase in intracellular Ca(2+) ([Ca(2+)](i)) mobilization in fura-2-AM-loaded platelets was also enhanced in pregnant subjects. Moreover, the binding activity of fluorescein isothiocyanate-triflavin toward the platelet glycoprotein IIb/IIIa complex did not significantly differ between the nonpregnant and pregnant groups. In addition, the amount of thromboxane A(2) (TxA(2)) formation from pregnant subjects was significantly greater than that from nonpregnant subjects in both resting and collagen-activated platelets. On the other hand, prostaglandin E(2) formation in the presence of imidazole in either resting or arachidonic acid (100 microM)-treated platelets did not significantly differ between these two groups. The levels of cyclic AMP formation in both resting and prostaglandin E(1) (10 microM)-treated platelets from pregnant subjects were significantly lower than those in nonpregnant subjects. Nitric oxide production was measured by a chemiluminescence detection method in this study. The extent of nitrate production in either resting or collagen-stimulated platelets from pregnant subjects did not significantly differ from that of platelets from the nonpregnant group. We conclude that the agonist-induced hyperaggregability of platelets from normal pregnancy may be due, at least partly, to an increase in TxA(2) formation and a lowering of the level of cyclic AMP formation, which leads to increased [Ca(2+)](i) mobilization and finally to enhanced platelet aggregation and ATP release.

Platelet behaviour on von Willebrand Factor changes in pregnancy: Consequences of haemodilution and intrinsic changes in platelet function

“…However, haemodilution cannot account for reduced platelet translocation speeds on VWF during pregnancy, a reduction we found to be independent of both platelet count and HCT. These reduced translocation speeds may result from an intrinsic change in the function of platelets that occurs uniquely during pregnancy, consistent with the enhanced platelet reactivity commonly observed in late pregnancy 3–5, 20–22 . The transient tethering of platelets to exposed VWF via the action of GPIbα is necessary to slow translocating platelets in the flowing blood stream as a prelude to stable (non-translocating) adhesion; thus, GPIbα-VWF interactions are a key determinant of translocation velocity.…”

“…Platelet function studies in healthy pregnant females compared with healthy non-pregnant female controls have yielded conflicting results, with studies reporting either decreased 2 , increased 3–5 , or no change 6–8 in either platelet reactivity or platelet activation, as assayed using ex - vivo methods.…”

A Review of Hemostasis in Normal Pregnancy and Puerperium

“…Platelet hyperaggregation during third trimester was reported in a number of studies suggesting hyper functioning platelets near labor [38][39][40] . Recently reduced platelet aggregation was observed using a modified technology in light transmission aggregometry [41].…”

Platelet Adhesion and Thrombus Formation in Whole Blood at Arterial Shear Rate at the End of Pregnancy

“…Changes in platelet function during healthy pregnancy remain less documented . Increased in vitro platelet aggregation has been reported in the third trimester of normal pregnancy . It may be due to elevated intracellular Ca 2+ mobilization, increased thromboxane A 2 formation and reduced levels of cyclic AMP (cAMP), a negative regulator of platelet activation .…”

“…Increased in vitro platelet aggregation has been reported in the third trimester of normal pregnancy . It may be due to elevated intracellular Ca 2+ mobilization, increased thromboxane A 2 formation and reduced levels of cyclic AMP (cAMP), a negative regulator of platelet activation . Platelet intracellular Ca 2+ and plasma levels of beta‐thromboglobulin (βTG) were found significantly higher during the third trimester in pregnant women compared to non‐pregnant women .…”