Abstract
Objective
; Early-onset preeclampsia is a rare pregnancy-specific disorder associated with significantly
increased maternal and fetal morbidity and mortality. Whilst it is known that even
normotensive pregnancies are associated with changes in clot formation and dissolution,
the nature of how these changes differ in those with early onset preeclampsia has
not been well established.
We sought to evaluate parameters of fibrin formation and fibrinolysis in individuals
with early onset preeclampsia in comparison to both pregnant and non-pregnant controls.
Furthermore, such parameters were correlated with markers of disease severity in this
patient cohort, including the presence of multiorgan involvement, the rate of disease
progression and the extent of the anti-angiogenic state in this condition.
Study design
; Patients with early onset preeclampsia (N = 20) and both pregnant (N = 16) and non
-pregnant (N = 16) controls were recruited from the cohort at a large urban maternity
hospital which saw over 15,000 deliveries during the study period. Platelet poor plasma
was prepared from collected whole blood and analysed for parameters of fibrin formation
and fibrinolysis (lagtime to and rate of fibrin formation; PAI-1; PAI-2; D-dimer;
plasmin-antiplasmin; tPA) in addition to markers of angiogenesis (sFLT-1; Endoglin)
using commercially available specific immunoassays.
Results
; The maximum rate of fibrin formation as well as PAI-1, PAI-2 and D-dimer levels
were all significantly increased in those with early onset preeclampsia and pregnant
controls when compared to non-pregnant controls without significant differences between
the 2 former groups. Plasmin-antiplasmin levels were significantly reduced in a similar
manner. tPA levels were significantly elevated in EOP compared to both pregnant and
non-pregnant controls. EOP was associated with significantly increased anti-angiogenic
factors (sFLT-1; Endoglin) when compared to both pregnant and non-pregnant controls.
Conclusion
; Markers of fibrin formation and fibrinolysis are significantly alerted in early
onset preeclampsia; furthermore, certain markers correlate with disease severity in
this patient cohort.
Abbreviations:
EOP (Early Onset Preeclampsia), PAI-1 (Plasminogen activator inhibitor 1), PAI-2 (Plasminogen activator inhibitor 2), PAP (plasmin-antiplasmin), PC (pregnant controls), PLGF (Placental growth factor), sFLT-1 (soluble fm-like tyrsosine kinase 1), tPA (Tissue Plasminogen activator)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Obstetrics and Gynecology and Reproductive BiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- American college of obstetricians and gynecologists.Task Force on Hypertension in Pregnancy, 2014
- “Make every mother and child count” in “the world health report 2005”.World Health Organization, Geneva, Switzerland2005
- Maternal mortality from preeclampsia/eclampsia.Semin Perinatol. 2012; 36: 56-59
- Pre-eclampsia: more than pregnancy-induced hypertension.Lancet. 1993; 341: 1447-1451
- A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies.Br J Obstet Gynaecol. 1994; 101: 669-674
- Vascular biology of preeclampsia.J Thromb Haemost. 2009; 7: 375-384
- The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).Pregnancy Hypertens. 2013; 3: 44-47
- A critical review of early-onset and late-onset preeclampsia.Obstet Gynecol Surv. 2011; 66: 497-506
- Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease.Am J Obstet Gynecol. 2013; 209 (544 e1-e12.)
- Fibrinolytic system in preeclampsia.Clin Chim Acta. 2013; 416: 67-71
- Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia.Blood. 1989; 74: 1332-1338
National Institute for Health and Care Excellence (2011). Hypertension in pregnancy: diagnosis and management. Clinical Guideline CG107. <https://www.nice.org.uk/guidance/cg107>.
- Current CHS and NHBPEP criteria for severe preeclampsia do not uniformly predict adverse maternal or perinatal outcomes.Hypertens Pregnancy. 2007; 26: 447-462
- Association between level of delivery hospital and neonatal outcomes among South Carolina Medicaid recipients.Am J Obstet Gynecol. 2000; 183: 1504-1511
- Perinatal regionalization and neonatal mortality in North Carolina, 1968-1994.Am J Obstet Gynecol. 2001; 184: 1302-1307
- Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial.Lancet. 2002; 359: 1877-1890
- PZP and PAI-2: Structurally-diverse, functionally similar pregnancy proteins?.Int J Biochem Cell Biol. 2016; 79: 113-117
- Evidence of increased oxidative stress and a change in the plasminogen activator inhibitor (PAI)-1 to PAI-2 ratio in early-onset but not late-onset preeclampsia.Am J Obstet Gynecol. 2009; 201 (597): e1-8
- Coagulation and fibrinolytic systems in pre-eclampsia and eclampsia.Br Med J. 1971; 2: 12-16
- Altered expression of plasminogen activator inhibitor type 1 in placentas from pregnant women with preeclampsia and/or intrauterine fetal growth retardation.Blood. 1994; 84: 143-150
- Markers of intravascular coagulation and fibrinolysis in preeclampsia: association with intrauterine growth retardation.Acta Obstet Gynecol Scand. 1997; 76: 541-546
- Fibrinolysis parameters in Sudanese women with severe preeclampsia.Hypertens Pregnancy. 2016; : 1-6
- A longitudinal study of biochemical variables in women at risk of preeclampsia.Am J Obstet Gynecol. 2002; 187: 127-136
- Screening test for preeclampsia through assessment of uteroplacental blood flow and biochemical markers of oxidative stress and endothelial dysfunction.Am J Obstet Gynecol. 2005; 193: 1486-1491
- Hemostatic variables as independent predictors for fetal growth retardation in preeclampsia.Acta Obstet Gynecol Scand. 1999; 78: 191-197
- Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks.Journal of thrombosis and haemostasis: JTH. 2009; 7: 955-961
- Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia.Circulation. 2012; 125: 911-919
- Circulating angiogenic factors and the risk of preeclampsia.N Engl J Med. 2004; 350: 672-683
- Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.J Clin Invest. 2003; 111: 649-658
- Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.N Engl J Med. 2006; 355: 992-1005
- Soluble endoglin contributes to the pathogenesis of preeclampsia.Nat Med. 2006; 12: 642-649
- The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients.Am J Obstet Gynecol. 2012; 206 (58): e1-8
- Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia.Obstet Gynecol. 2007; 109: 1368-1374
- Uterine artery Doppler and sFlt-1/PlGF ratio: prognostic value in early-onset pre-eclampsia.Ultrasound Obstet Gynecol. 2014; 43: 525-532
- Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia.N Engl J Med. 2016; 374: 13-22
Article info
Publication history
Published online: July 25, 2019
Accepted:
July 24,
2019
Received in revised form:
July 12,
2019
Received:
March 23,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
