- Academic Editor
Background: The aim of this study was to evaluate the relationship and
impact of D-dimer levels and preeclamptic pregnancies at different ages in women.
Methods: We conducted an observational retrospective cohort study of 325
pregnant women who delivered in Wenzhou People’s Hospital from January 2018 to
December 2021. Clinical data including age, neutrophils, lymphocytes, platelets,
fibrinogen, gestational age, D-dimer/fibrinogen, blood pressure at admission, and
fetal weight were collected from the medical record database. All measurements
were made using the same methods. Data for continuous variables were
expressed as X
Preeclampsia is a specific disease which is relatively common pregnancy
complications and great harm to the mother and child [1], with an incidence of
2–8% [2]. The disease is characterized by hypertension (140/90 mmHg) after 20
weeks of gestation, with or without proteinuria (
We enrolled and analyzed the data of pregnant women who gave birth in Wenzhou People’s Hospital between January 2018 and December 2021, and volunteered to be included in this retrospective cohort study. A total of 325 pregnant women were included, including 200 in the normotensive pregnancy group (preeclampsia control group) and 125 in the preeclampsia group, as shown in Fig. 1. This study was approved by the Hospital Research Ethics Committee.
Inclusion criteria and exclusion criteria for study population.
The inclusion criteria were based on the latest American College of
Obstetricians and Gynecologists guidelines (ACOG), the diagnosis of preeclampsia
[11] is the onset of hypertension after 20 weeks of gestation (systolic blood
pressure
Clinical data including age, neutrophils, lymphocytes, platelets, fibrinogen,
gestational age, D-dimer/fibrinogen, blood pressure at admission, and fetal
weight were collected from the medical record database. Blood samples were
collected prior to hospitalization for delivery, and tests for D-dimer and
fibrinogen quantification were performed according to the manufacturer’s
guidelines. The D-dimer level was determined by immunoturbidimetric method, and
the fibrinogen level was determined by Klaus method. All measurements were made
using the same instruments and method. The Kolmogorov-Smirnov test was used to
analyze the normality of the data. Data for continuous variables were expressed
as X
A total of 325 pregnant women were enrolled in this study and divided into four
groups according to their blood pressure and age: Normal blood pressure young
group (
Parameter | Normal pregnancy group | Pre-eclampsia group |
The number of primipara | 79 | 62 |
Age (Y) | 26 (24, 28) | 22 (25, 28) |
Neutrophils (10 |
6 (5.15, 6.75) | 6.2 (5.1, 7) |
Lymphocyte (10 |
1.600 |
1.759 |
Platelets (10 |
195 (165, 233) | 198 (152.5, 235) |
D-dimer (mg/L) | 1.412 |
1.641 |
Fibrinogen (g/L) | 4.045 |
4.298 |
D-dimer/fibrinogen | 0.34 (0.27, 0.80) | 0.35 (0.27, 0.47) |
Fetal weight (g) | 3361 |
3048 |
Systolic blood pressure (mmHg) | 113.8 |
150.3 |
Diastolic blood pressure (mmHg) | 73.59 |
97.33 |
Paramete | Normal pregnancy group | Pre-eclampsia group |
The number of primipara | 11 | 19 |
Age (Y) | 32 (31, 34) | 33 (31, 36.75) |
Neutrophils (10 |
5.7 (5, 6.7) | 5.65 (4.725, 7.175) |
Lymphocyte (10 |
1.515 |
1.710 |
Platelets (10 |
174 (149, 199) | 186.5 (154.75, 241) |
D-dimer (mg/L) | 1.367 |
2.087 |
Fibrinogen (g/L) | 4.009 |
4.240 |
D-dimer/fibrinogen | 0.34 (0.27, 0.40) | 0.41 (0.30, 0.56) |
Fetal weight (g) | 3333 |
2907 |
Systolic blood pressure (mmHg) | 113.8 |
153.5 |
Diastolic blood pressure (mmHg) | 72.46 |
95.66 |
The mean value of D-dimer in the normotensive pregnancy group was (1.412
D-dimer and D-dimer/fibrinogen in middle-aged pregnant women.
(A) D-dimer in middle–aged pregnant women, ****: p
The D-dimer/fibrinogen ratio was not different in the young group. However, there were differences among the middle-aged groups, as shown in Fig. 2B. The median and quad values of D-dimer/fibrinogen ratio were [0.34 (0.27, 0.80)] in the young normotensive pregnancy group, [0.35 (0.27, 0.47)] in the young preeclampsia group, [0.34 (0.27, 0.40)] in the middle-aged normotensive pregnancy group, and [0.41 (0.30, 0.56)] in the middle-aged preeclampsia group. The median and quad values of D-dimer/fibrinogen ratio were [0.34 (0.27, 0.40)] in the middle-aged normotensive pregnancy group, and [0.41 (0.30, 0.56)] in the middle-aged preeclampsia group. There was a statistical difference between the middle-aged pregnant women (p = 0.0039).
The difference in fetal birth weight between the middle-aged normotensive pregnancy group
and the middle-aged preeclampsia group was significant (p
Fetal weight of different age pregnant women. (A) Fetal weight
of young pregnant women, ****: p
The relationship between D-dimer and pregnant women with preeclampsia at different ages was evaluated by ROC curve analysis. Table 3 shows detailed ROC curve analysis data. This model suggests that the predicted area of D-dimer for preeclampsia in middle-aged pregnant women is significantly higher than that in young women. Meanwhile, in middle-aged pregnant women, the predicted area of D-dimer for preeclampsia was 70.2% (95% confidence interval (CI) 60–80.43%, p = 0.0002) (Fig. 4). At the same time, logistic regression analysis was used to verify the correlation between D-dimer and preeclampsia again. The odds ratio (OR) value of D-dimer was 3.290 and was positively correlated with preeclampsia. The age also was positively correlated with preeclampsia which suggesting that D-dimer was more valuable in predicting preeclampsia in the middle-aged group (Table 4).
Variable | Cut off value | Sensitivity of sensitivity | Degree of specificity | Area under curve | p | 95% CI | |
Lower limit | Upper limit | ||||||
D-dimer of youth group | 1.86 | 28% | 89% | 0.596 | 0.02 | 0.5 | 0.6779 |
D-dimer of middle group | 1.67 | 56% | 84% | 0.702 | 0.0002 | 0.6 | 0.8043 |
PE, preeclampsia; ROC, receiver operating characteristics; CI, confidence interval.
ROC curve of D-dimer and pregnant women with preeclampsia at different ages.
Variables in the Equation | |||||||||
B | SE | Wald | df | Sig | Exp(B) | 95% CI for Exp(B) | |||
Lower limit | Upper limit | ||||||||
Step 1 |
Age | 0.040 | 0.033 | 1.411 | 1 | 0.235 | 1.040 | 0.975 | 1.111 |
D-dimer | 1.191 | 0.251 | 22.434 | 1 | 3.290 | 2.010 | 5.385 | ||
Delivery (1) | –0.154 | 0.292 | 0.279 | 1 | 0.597 | 0.857 | 0.483 | 1.520 | |
Constant | –3.391 | 1.113 | 9.290 | 1 | 0.002 | 0.034 |
a. Variable(s) entered on step 1: Age, D-dimer, Delivery.
B, beta; df, degree of freedom; SE, standar erro; CI, confidence interval.
Preeclampsia is a pregnancy-specific disease that causes adverse outcomes for
mothers and infants [12]. In order to predict preeclampsia earlier, many studies
are still trying to find ideal markers [13]. It is well known that D-dimer is a
potential predictor of preeclampsia [14], and we further clarified the predictive
value of D-dimer in different age groups of preeclampsia. No similar studies have
been reported.
The level of D-dimer is high during pregnancy, which is a normal physiological
phenomenon. Our study also confirmed that the level of D-dimer in the
preeclampsia group was significantly higher than that in normotensive pregnancy
[8]. Further studies found that the D-dimer levels of preeclampsia women over 30
years of age were significantly higher than those of preeclampsia women below 30
years of age. D-dimer is the final degradation product of fibrin, reflecting the
level of polymerization and decomposition of fibrin [15]. In order to increase
placental blood perfusion, the body compensatively promotes vascular
constriction, resulting in high blood pressure and further promoting the
occurrence of preeclampsia [16]. Placental ischemia can increase the production
of sFlt-1, angiotensin II (Ang II) type 1 autoantibodies and TNF-
The damage of vascular endothelial cells is the basic pathological change of preeclampsia. D-dimer levels have been found to correlate with C-reactive protein (CRP) [21]. Elevated D-dimer is likely associated with vasculitic status. PTX3 is a novel inflammatory marker, which can lead to the prothrombotic state caused by endothelial dysfunction [22]. In studies of disease severity in COVID-19 patients, PTX3 is positively correlated with plasma D-dimer and is involved in coagulation dysfunction [23]. Silvia Galbiati et al. [24] found that serum PTX3 was significantly elevated in pregnant women with preeclampsia, which supports our conclusion.
In the acute phase caused by tissue and blood vessel injury, fibrinogen is a key
component of thrombosis and hemostasis [25]. By detecting plasma fibrinogen
Elevated D-dimer was an independent factor associated with increased incidence of venous thromboembolism, myocardial infarction, and cerebral infarction [27]. If the D-dimer of pregnancy body is high, it is easy to activate the coagulation system. The mother-to-fetus interface vascular endothelium is easy to be damaged. Next, amniotic fluid enters the maternal circulation through potential channels, leading to the occurrence of amniotic fluid embolism. Research shows that preeclampsia increases the risk of an ominous complication such as amniotic fluid embolism [28].
If D-dimer is high in an older pregnant woman during prenatal examination, the clinician should closely monitor the pregnancy blood pressure, urine routine, placental growth factor, etc. Notably, this was the first study to describe the D-dimer levels associated with blood pressure differences among pregnant women of different ages. However, the sample size of this study was so small that the results could be biased. Large prospective trials are needed to investigate the predictive value of D-dimer in preeclampsia at different ages.
Prenatal D-dimer level maybe associated with preeclampsia occurrence in pregnant women over 30 years of gestational age than in women before 30 years of age.
All data generated or analyzed during this study are included in this published article.
The experimental ideas are designed by TTL. HPZ and TTL interpretate the data for work and write the discussion of the manuscript. YJH designed and made critical revisions to the paper. SHC and JYZ collected and analyzed data. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. All authors read and approved the final manuscript.
All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Wenzhou People’s Hospital (approval number: 2021-346).
Not applicable.
This study was funded by the Wenzhou Science and Technology Bureau (Y20210027).
The authors declare no conflict of interest.
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