| Part Ⅰ The prophylactic effect of aspirin and low molecular weight heparin in preeclampsiaObjectiveTo evaluate the effects of prophylactic low-dose aspirin and low molecular weight heparin on maternal and perinatal outcomes in high-risk populations of preeclampsia.MethodsA total of 512 pregnant women with a high risk of preeclampsia who underwent regular antenatal examination and terminated pregnancy in our hospital were collected and divided into medication group(n=164)and control group(n=348)according to the prophylactic use of LDA or LMWH in early pregnancy.The maternal and fetal outcomes of the two groups were compared.According to the specific medication methods,the medication group was further divided into the LDA group(n=114),the LMWH group(n=13),and the combined group(n=37).The clinical adverse events of the three groups were compared.ResultsThe results showed that prophylactic medication could significantly reduce the probability of preeclampsia(OR=0.54,95%CI 0.36～0.80),44%of preeclampsia less than 37 weeks of delivery(OR=0.56,95%CI 0.37～0.86),60%of preeclampsia less than 34 weeks of delivery(OR=0.41,95%CI 0.23～0.73),and 80%of preeclampsia patients requiring therapeutic induced labor(OR＝0.20,95%CI 0.06～0.68).However,it did not have benefits for term preeclampsia and did not increase the risk of placental abruption and postpartum hemorrhage(p>0.05).At the same time,it had no significant effect on different delivery methods and neither on adverse maternal outcomes such as as preterm delivery,fetal growth restriction,small for gestational age and etc.In patients with preeclampsia during pregnancy,there was no significant difference in the onset of gestatonal age,blood pressure for admission,and the use of antihypertensive drugs between the two groups,but preventive medication can significantly prolong the gestaional week of admission(33.53 ±3.31 vs.31.44 ± 5.79,p<0.05)and delivery(35.36± 2.77 vs.34.01±6.61,p<0.05).In the study of neonatal outcomes,preventive medication can increase the survival rate of newborns,reduce the number of days in NICU,reduce the incidence of NRDS and the rate of mechanical ventilation(p<0.05).The NICU hospitalization days,the incidence of NRDS and the use of mechanical ventilation in this study may be underestimated because the control group has a higher rate of abandoning rescue.Finally,this study found that the three medication regimens had no statistically significant difference between maternal and neonatal outcomes(p>0.05),which may indicate that the use of LMWH also has certain preventive potential.Conclusion1.LDA and LMWH can reduce the risk of preeclampsia in high-risk pregnant women,did not increase the risk of postpartum hemorrhage,placental abruption,and adverse maternal outcomes such as premature birth,fetal growth restriction,and small-for-gestational age.2.Preventive medication has nothing to do with the onset of gestational week for women with preeclampsia,the blood pressure standard for admission and the use of antihypertensive drugs,but it can prolong the gestational week of admission and delivery.3.Preventive medication can increase the survival rate of newborns,reduce the NICU hospitalization days,and reduce the incidence of NRDS and the use of mechanical ventilation.4.There was no significant difference between three medication regimens,which may indicate that LMWH also has certain preventive potential.Part Ⅱ The value of thromboelastography and thrombus biomarkers in evaluating coagulation and fibrinolysis in preeclampsiaObjectiveRoutine coagulation assay,thromboelastography,and thrombus biomarkers were used to explore the blood coagulation and fibrinolysis state of normal pregnancy and preeclampsia,and compare the capabilities of these three detection methods in diagnosing preeclampsia and reflecting anticoagulation or antithrombotic therapy.MethodsFrom December 2019 to December 2020,24 pregnant women with severe preeclampsia in our hospital were collected for the study group.Then normal pregnant women were randomly selected as the control group in the same period.We divided the control group into three groups according to different pregnant stages.First,we compared the differences of routine coagulation assay,TEG and thrombus biomarkers in the study group and the control group.Then,the ROC curve was used to explore the best method and single index for predicting preeclampsia.Next,36 patients at high risk of thromboembolism who began antithrombotic therapy in early pregnancy were collected to explore the clinical value of three detection methods in guiding antithrombotic or anticoagulant therapy.Finally,we compared different pregnant stages in the control group and established the reference range of the TEG and thrombus biomarkers.Results1.In the case-control study,PLT in the study group was lower than that in the control group,PDW,APTT and D-dimer in the study group were higher than those in the normal control,and INR and ATⅢ were lower than those in the control group(p<0.05).There was no significant difference in MPV,PT,FIB and TT between the two groups.The R and K values of patients with severe preeclampsia were prolonged,and the values of Angle,MA and CI were decreased,which were significantly different from those of normal pregnant women(p<0.05).The values of TM and t-PAIC in patients with severe preeclampsia were significantly higher than those in normal pregnant women(p<0.05).2.The ROC curve was used to explore the ability of three detection methods to predict preeclampsia,and the results found that the AUC of the thrombus biomarkers was 0.972,the sensitivity was 99.4%,and the specificity was 90.6%,suggesting that thrombus biomarkers had strongest abilities to predict preeclampsia.The R and K in TEG,the TAT,TM and t-PAIC in thrombus biomarkers had AUC greater than 0.7,and among them,the AUC of t-PAIC was 0.974,the sensitivity was 90.5%,the specificity was 92.9%,and the cutoff value was 7.85 ng/ml,which indicated that the t-PAIC was the best prediction index.3.Among the 36 high-risk patients who received LMWH or LDA,TEG Changed significantly after treatment,where R and K values were greater than before medication,and CI were reduced.However there were no significant differences in the parameters of thrombus biomarkers before and after medication(p>0.05).In overall,it indicated that TEG may have a certain clinical value in guiding anticoagulation or antithrombotic therapy for high-risk pregnant women.4.The comparison of routine coagulation assay in normal pregnant women showed that PLT decreased in the third trimester,PDW,PT,APTT increased in the second trimester,FIB and DD increased in the third trimester.There were no significant differences in TEG indices among three groups of normal pregnant women.In the detection of thrombus biomarkers,the TAT and TM values in the third trimester were higher than those in the first and second trimester.Therefore,it is necessary to establish the normal reference range for pregnant women.5.We finally established the reference range of the TEG in normal pregnant women:R value(min):3.9-5.4/4.2-5.8/4.3-5.6;K value(min):1.1-1.4/1.1-1.4/1.1-1.5;Angle(deg):68.9-73.4/70.1-73.5/68.8-73.7;MA(min):65.2-70.9/66.4-71.1/66.4-72.1;CI value:-1.5-3.0/1.7-3.1/1.6-3.4;EPL and LY30(%):0.1-0.1/0.1-0.1/0.1-0.1;the reference range of thrombus biomarkers is also determined:TAT(ng/ml):1.9-3.3/2.5-5.4/7.0-10.6;PIC(ug/ml):0.6-0.8/0.5-0.8/0.5-0.7;TM(TU/ml):6.8-8.1/6.8-8.2/8.0-9.8;t-PAIC(ng/ml):4.0-6.2/4.1-5.7/4.8-7.0.Conclusion1.There were significant differences in several indexes of routine coagulation assay between the study group and the control group,which made it difficult to judge the coagulation state.TEG showed a hypocoagulable state in the study group,and thrombus biomarkers suggested endothelial dysfunction and fibrinolysis inhibition.2.Thrombus biomarkers and TEG have certain clinical values in predicting preeclampsia and guiding anticoagulant or antithrombotic therapy in high-risk obstetrics.The t-PAIC was the best prediction index because its sensitivity was 90.5%,the specificity was 92.9%,and the cutoff value was 7.85 ng/ml.3.Normal pregnant women showed hypercoagulability in the third trimester of pregnancy.Several indices of routine coagulation assay changed significantly in the second and third trimesters.The changes of TEG indexes in pregnant stages were similar,and the values of TAT and TM increased in the third trimester.Therefore,the determination of the reference range of TEG and thrombus biomarkers in normal pregnant women is necessary and helpful for early detection and diagnosis of preeclampsia,aiming to reduce adverse pregnancy complications,and finally improve prognosis. |
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