Trimester-Specific Dynamics of Haematological, Coagulation, Biochemical And Angiogenic Biomarkers In Pregnancies At Risk Of Early-Onset Preeclampsia: A Prospective Comparative Study Of Early Diagnosis And Complex Treatment
Keywords:
Preeclampsia, angiogenic factors, sFlt-1/PlGF ratio, coagulogramAbstract
Background. Preeclampsia (PE) is driven by systemic endothelial dysfunction and an angiogenic imbalance. We characterised the trimester dynamics of haematological, coagulation, biochemical and angiogenic biomarkers and assessed the impact of early diagnosis and complex treatment. Materials and Methods. In this prospective comparative study, 102 pregnant women were allocated to a control group (physiological pregnancy, n=30), an early-diagnosed and treated group (n=32) and an untreated group (n=40). Complete blood count, coagulogram, C-reactive protein (CRP), lactate dehydrogenase (LDH), urea, creatinine, VEGF, TGF-β2, EGF, sFlt-1, PlGF and the sFlt-1/PlGF ratio were measured each trimester. Between-group differences were tested by one-way ANOVA or Kruskal–Wallis with post-hoc correction; longitudinal change by linear mixed models; α=0.05. Results. By the third trimester, untreated women showed anaemia (haemoglobin 80.1±6.2 g/L), thrombocytopenia (150.9±14.2×10⁹/L) and hypercoagulation (fibrinogen 7.6±1.0 g/L; PT 8.7 s). CRP rose 5.2-fold, LDH 2.9-fold (648.9±34.0 U/L), and creatinine reached 107.4±5.4 µmol/L. VEGF fell 2.5-fold while the sFlt-1/PlGF ratio rose 10.6-fold versus controls (all p<0.001, large effect sizes). All derangements were significantly attenuated in the treated group (p<0.001). Conclusion. PE at risk of early onset produces coordinated multi-system biomarker derangement proportional to severity. The sFlt-1/PlGF ratio was the strongest discriminator, and early diagnosis with complex treatment markedly limited progression.
References
Chappell LC, Cluver CA, Kingdom J, Tong S. Pre-eclampsia. Lancet. 2021;398(10297):341–354. [Full text]
Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019;124(7):1094–1112. [Full text]
Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019;366:l2381. [Full text]
Magee LA, Brown MA, Hall DR, et al. The 2021 ISSHP classification, diagnosis and management recommendations for pregnancy hypertension. Pregnancy Hypertens. 2022;27:148–169. [Full text]
American College of Obstetricians and Gynecologists. Gestational hypertension and preeclampsia: ACOG Practice Bulletin No. 222. Obstet Gynecol. 2020;135(6):e237–e260. [Full text]
Zeisler H, Llurba E, Chantraine F, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13–22. [Full text]
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–683. [Full text]
Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649–658. [Full text]
Verlohren S, Herraiz I, Lapaire O, et al. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders. Am J Obstet Gynecol. 2012;206(1):58.e1–58.e8. [Full text]
Stepan H, Herraiz I, Schlembach D, et al. Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy. Ultrasound Obstet Gynecol. 2015;45(3):241–246. [Full text]
Karumanchi SA. Angiogenic factors in preeclampsia: from diagnosis to therapy. Hypertension. 2016;67(6):1072–1079. [Full text]
Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol. 2014;10(8):466–480. [Full text]
Poon LC, Shennan A, Hyett JA, et al. The FIGO initiative on pre-eclampsia: first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145(Suppl 1):1–33. [Full text]
Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613–622. [Full text]
Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth. 2009;9:8. [Full text]
Ceyhan T, Beyan C, Baser I, et al. The effect of pre-eclampsia on complete blood count, platelet count and mean platelet volume. Ann Hematol. 2006;85(5):320–322. [Full text]
Han L, Liu X, Li H, et al. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies. PLoS One. 2014;9(12):e114488. [Full text]
Bramham K, Parnell B, Nelson-Piercy C, et al. Chronic kidney disease and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2013;347:f6564. [Full text]
Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–1594. [Full text]
Roberts JM, Escudero C. The placenta in preeclampsia. Pregnancy Hypertens. 2012;2(2):72–83. [Full text]
Tannetta D, Sargent I. Placental disease and the maternal syndrome of preeclampsia: missing links? Curr Hypertens Rep. 2013;15(6):590–599. [Full text]
Redman CWG, Staff AC. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. Am J Obstet Gynecol. 2015;213(4 Suppl):S9.e1–S9.e11. [Full text]
Duhig KE, Myers J, Seed PT, et al. Placental growth factor testing to assess women with suspected pre-eclampsia (PARROT): a stepped-wedge cluster-randomised controlled trial. Lancet. 2019;393(10183):1807–1818. [Full text]
Agrawal S, Cerdeira AS, Redman C, Vatish M. Meta-analysis and systematic review to assess the role of soluble FMS-like tyrosine kinase-1 and placenta growth factor ratio in prediction of preeclampsia. Hypertension. 2018;71(2):306–316. [Full text]
Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15(5):275–289. [Full text]
Brown MA, Magee LA, Kenny LC, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24–43. [Full text]
World Health Organization. WHO recommendations on prevention and treatment of pre-eclampsia and eclampsia. Geneva: World Health Organization; 2011. [Full text]
Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631–644. [Full text]
