OBJECTIVES/GOALS: Low-dose aspirin is an established treatment to prevent preeclampsia, a leading cause of maternal and perinatal complications. Nevertheless, aspirin failure is not uncommon. We are investigating whether a gain-of-function genetic polymorphism in a platelet thrombin receptor is associated with aspirin failure in the prevention of preeclampsia. METHODS/STUDY POPULATION: Women who had preeclampsia in an initial pregnancy who then received low-dose aspirin in a subsequent pregnancy will be evaluated. We will compare between women who developed preeclampsia despite aspirin (aspirin non-responders) to women who did not develop preeclampsia with aspirin treatment (aspirin responders). Specifically, we will evaluate the allelic frequency of a single nucleotide variant (rs773902) in PAR4 thrombin receptor on platelets. This variant is associated with increased platelet function and potentially aspirin resistance. In addition, we will analyze the platelet response to PAR4 activation before and 1 hour after administering a single 81 mg enteric-coated aspirin tablet. RESULTS/ANTICIPATED RESULTS: We hypothesize that the prevalence of the PAR4 variant will be significantly higher among women who had recurrence of preeclampsia despite aspirin therapy. We also postulate that women who developed preeclampsia despite aspirin prophylaxis and have the polymorphism will have increased platelet aggregation in response to activation of PAR4, either by thrombin or peptides that activate the receptor, both at baseline and 1 hour after aspirin administration. DISCUSSION/SIGNIFICANCE: If our hypothesis that aspirin failure in preeclampsia prevention is associated with the gain-of-function polymorphism in the platelet PAR4 thrombin receptor, there may be justification for additional experimental studies to assess whether better pregnancy outcomes can be obtained by targeting thrombin itself using low molecular weight heparin.

Mosonik, a 3.25 Ma extensively dissected stratovolcano located in the North Tanzanian Divergence of the East African Rift, consists predominantly of phonolite and three types of phonolitic nephelinite distinguished by the presence or absence of amphibole or garnet antecrysts and differing populations of complexly zoned antecrystal and phenocrystal pyroxenes. The antecryst–phenocryst assemblage is typical of hybrid lavas derived by magma mixing. Compositional data are given for all major minerals. Owing to the high modal proportions (30–60 vol. %) of antecrysts and phenocrysts of pyroxene and nepheline plus the hybrid character of the lavas, bulk-rock compositions do not represent those of the parental liquids. Thus, assimilation–fractional crystallization modelling of the bulk-rock major- and trace-element abundances is inappropriate and an unevolved parental magma cannot as yet be defined. Sr–Nd isotopic data for Mosonik and other Older Extrusive Series rocks suggest derivation by partial melting of ancient metasomatized lithospheric mantle with mixing of Sr and Nd from two sources coupled with minor lower crustal contamination, melting being induced by the plume currently impinging on the Tanzanian craton, and representing the initial interaction of the plume with the cratonic lithosphere. In contrast, the Younger Extrusives, as exemplified by Oldoinyo Lengai nephelinite–carbonatite volcanism, could be derived from this ancient metasomatized lithospheric mantle plus a recent plume-derived asthenospheric component and no contamination by crustal material. The isotopically and genetically distinct Natron–Engaruka melilitites are considered to represent direct adiabatic melting of the Tanzanian plume without lithospheric contributions. Carbonatites and melilite-bearing nephelinites also occur at Mosonik but are not considered in this study as they are only a very minor volumetric component of the volcano.