Predictors of Aspirin Failure in Preeclampsia Prevention

Summary

Hypertensive disorders of pregnancy (including preeclampsia) are among the leading causes of pregnancy complications and maternal deaths worldwide. They also increase the risks to the babies. Numerous interventions have been suggested in order to reduce the rate of preeclampsia. Low-dose aspirin is the most beneficial prophylactic approach in this regard. Nevertheless, aspirin failure is not uncommon. The genetic, laboratory, and clinical factors associated with low-dose aspirin failure in the prevention of preeclampsia are largely unknown. The presence of a genetic variant in PAR4 receptor expressed on platelets, is associated with increased platelet function and possibly with aspirin failure.

Timeline

Start

2023-04-13

Primary completion

2026-11-01

Completion

2026-11-01

Publications

• Background Bokslag A, van Weissenbruch M, Mol BW, de Groot CJ. Preeclampsia; short and long-term consequences for mother and neonate. Early Hum Dev. 2016 Nov;102:47-50. doi: 10.1016/j.earlhumdev.2016.09.007. Epub 2016 Sep 20.
• Background Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99. doi: 10.1016/S0140-6736(05)17987-2.
• Background Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659. doi: 10.1002/14651858.CD004659.pub2.
• Background Redman CW, Bonnar J, Beilin L. Early platelet consumption in pre-eclampsia. Br Med J. 1978 Feb 25;1(6111):467-9. doi: 10.1136/bmj.1.6111.467.
• Background Roberts MS, Joyce RM, McLeod LJ, Vial JH, Seville PR. Slow-release aspirin and prostaglandin inhibition. Lancet. 1986 May 17;1(8490):1153-4. doi: 10.1016/s0140-6736(86)91865-9. No abstract available.
• Background Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.
• Background Tolcher MC, Sangi-Haghpeykar H, Mendez-Figueroa H, Aagaard KM. Low-dose aspirin for preeclampsia prevention: efficacy by ethnicity and race. Am J Obstet Gynecol MFM. 2020 Nov;2(4):100184. doi: 10.1016/j.ajogmf.2020.100184. Epub 2020 Jul 21.
• Background Johnson JD, Louis JM. Does race or ethnicity play a role in the origin, pathophysiology, and outcomes of preeclampsia? An expert review of the literature. Am J Obstet Gynecol. 2022 Feb;226(2S):S876-S885. doi: 10.1016/j.ajog.2020.07.038. Epub 2020 Jul 24.
• Background Edelstein LC, Simon LM, Lindsay CR, Kong X, Teruel-Montoya R, Tourdot BE, Chen ES, Ma L, Coughlin S, Nieman M, Holinstat M, Shaw CA, Bray PF. Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race. Blood. 2014 Nov 27;124(23):3450-8. doi: 10.1182/blood-2014-04-572479. Epub 2014 Oct 7.
• Background Edelstein LC, Simon LM, Montoya RT, Holinstat M, Chen ES, Bergeron A, Kong X, Nagalla S, Mohandas N, Cohen DE, Dong JF, Shaw C, Bray PF. Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nat Med. 2013 Dec;19(12):1609-16. doi: 10.1038/nm.3385. Epub 2013 Nov 10.

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