Optimal blood pressure target to prevent severe hypertension in pregnancy: A systematic review and meta-analysis.

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there is still a conflict of opinion on the recommendations of antihypertensive therapy. This study aimed to identify the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Ovid MEDLINE and the Cochrane Library were searched, and only randomized controlled trials (RCTs) were included if they compared the effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments in nonsevere hypertensive pregnant patients. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) for the outcomes. Forty RCTs with 6355 patients were included in the study. BP-lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37-0.56), preeclampsia (RR, 0.82; 95% CI, 0.69-0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17-0.84), placental abruption (RR, 0.52; 95% CI, 0.32-0.86), and preterm birth (< 37 weeks; RR, 0.81; 95% CI, 0.71-0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02-1.54). An achieved systolic blood pressure (SBP) of < 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an SBP of ≥ 140 mmHg, with a significant interaction of the BP levels achieved with BP-lowering therapy. There was no significant interaction between the subtypes of hypertensive disorders of pregnancy and BP-lowering treatment, except for placental abruption. BP-lowering treatment aimed at an SBP < 130 mmHg and accompanied by the careful monitoring of fetal growth might be recommended to prevent severe hypertension.

Randomized, Double-Blinded Trial of Magnesium Sulfate Tocolysis versus Intravenous Normal Saline for Preterm Nonsevere Placental Abruption.

Objective To evaluate the efficacy and safety of magnesium sulfate in the resolution of vaginal bleeding and contractions in nonsevere placental abruption. Study Design Thirty women between 24 and 34 weeks of gestation diagnosed with nonsevere placental abruption were randomized to receive magnesium sulfate tocolysis or normal saline infusion. The primary outcome was the proportion of women undelivered at 48 hours with resolution of vaginal bleeding and uterine contractions. Maternal and neonatal outcomes were also compared. Results Fifteen (50%) women received magnesium sulfate tocolysis and 15 (50%) received intravenous saline. There was no difference in the number of women who were undelivered at 48 hours with resolution of vaginal bleeding and contractions in the magnesium sulfate (80.0%) and saline (66.7%; p-value = 0.68) groups. There were no differences between groups in the gestational age at randomization, time to uterine quiescence, time on study drug, length of hospitalization, days from randomization to delivery, incidence of side effects, or admissions to the neonatal intensive care unit. Conclusions Magnesium sulfate tocolysis did not provide a significant difference in pregnancy prolongation in the management of preterm nonsevere placental abruption. Recruitment goals were not met due to the introduction of the use of magnesium sulfate for neuroprotection.

Intrapartum anti-disseminated intravascular coagulation therapy leading to successful vaginal delivery following intrauterine fetal death caused by placental abruption: a case report.

INTRODUCTION: Disseminated intravascular coagulation due to placental abruption with intrauterine fetal death is not uncommon. It can result in increased maternal mortality rates and the need for hysterectomy or greater transfusion volumes if the delivery is not completed within six to eight hours. However, consensus is lacking regarding the delivery approach for cases in which delivery is prolonged. CASE PRESENTATION: A 37-year-old Japanese woman was transported to our tertiary center two and a half hours after the onset of labor because of a diagnosis of placental abruption with intrauterine fetal death at 40 weeks and three days' gestation. On arrival, although severe hypofibrinogenemia was observed, there was no external hemorrhage. Because her cervical canal dilation was good (Bishop score, 7), labor was induced using oxytocin. Anti-disseminated intravascular coagulation therapy was simultaneously started via transfusion. After her hypofibrinogenemia resolved, delivery progressed rapidly, and the fetus was delivered approximately 10 hours after the onset. To reduce postpartum hemorrhage, 6g of fibrinogen concentrate and tranexamic acid, an antifibrinolytic agent, were administered immediately before extraction of the dead fetus and placenta. Although the amount of intrapartum hemorrhage was 1824g, there was no abnormal bleeding after delivery, and our patient was discharged three days later. CONCLUSION: In cases of placental abruption complicated with disseminated intravascular coagulation, intrapartum administration of coagulation factors can simultaneously promote effective labor and correct hypofibrinogenemia, enabling minimally invasive vaginal delivery.

Low molecular weight heparin versus no treatment in women with previous severe pregnancy complications and placental findings without thrombophilia.

Low molecular weight heparin (LMWH) treatment has been recommended for pregnant women with previous adverse pregnancy and who were diagnosed as having a thrombophilia. We now examined the effect of LMWH on pregnant women without thrombophilias who had severe pregnancy complications and placental vasculopathy in an earlier pregnancy. Seventy-two women with a history of severe preeclampsia, fetal growth restriction (FGR) less than fifth percentile, severe placental abruption and/or stillbirth after 20 weeks, whose thrombophilia workup was negative, were enrolled. Placental vasculopathy was defined as villous infarcts, fibrinoid necrosis of decidual vessels, fetal vessel thrombosis, evidence of placental abruption and perivillous fibrin deposition. The study group consisted of 32 pregnant women who were treated with LMWH and 40 pregnant women who were not treated with LMWH (control group) in their ensuing pregnancy in our institution between 2003 and 2007. The incidences of severe preeclampsia, FGR, placental abruption and stillbirth in the previous pregnancies were similar for both groups. The incidences of severe preeclampsia and placental abruption in the study group in the index pregnancy were significantly lower than the control group (3.13 versus 20%, P = 0.03; and 0 versus 15%, P = 0.03, respectively). The respective incidence of FGR was 6.25 versus 22.5%, and of overall adverse outcome was 9.4 versus 60% (P = 0.001). Treatment with LMWH may reduce the rate of the recurrence of severe pregnancy complications and significant placental vasculopathy in women without thrombophilias.

Enoxaparin for the secondary prevention of placental vascular complications in women with abruptio placentae. The pilot randomised controlled NOH-AP trial.

Administration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18-0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.

[HELLP syndrome and hemorrhagic gestosis]. / Síndrome de HELLP y gestosis hemorrágica.

In the year 1817, Charlotte daughter of Georges IV and princess of Wales, died on an unknown condition with uteroplacental hemorrhage and fetal death called at the time "Uteroplacental Apoplexy" and later "Abruptio Placentae". This affection was described in the classical books as an hemorrhagic complication of labor. In 1961 we have at first related the Abruptio with acute toxemia (preeclampsia) and have proposed the term "Gestosis hemorrágica" to design it. In 1982 Weinstein has described the called HELLP syndrome (Hemolysis, Elevated liver Enzymes, at Low Platelets) which basically is the same pathological picture as the described by us as "hemorrhagic toxemia". The aim of the paper is to demonstrate the identity of both syndromes and to claim for the priority of our definition.

Treatment with tranexamic acid during pregnancy, and the risk of thrombo-embolic complications.

Tranexamic acid (AMCA) is an inhibitor of fibrinolysis used to treat fibrinolytic bleeding (e.g., menorrhagia and gastro-intestinal haemorrhage), and to prevent bleeding at surgery, in cases of abruptio placentae and general haemorrhage. As AMCA stabilises preformed clots and prolongs their dissolution, it has been debated whether treatment with AMCA might predispose to thrombosis by depressing the fibrinolytic system. Pregnant women constitute a group with low fibrinolytic capacity and an increased frequency of thrombosis further increased after Caesarean section, and are thus more likely to be susceptible to antifibrinolytic therapy. We therefore carried out a retrospective analysis of the case records of 2,102 patients with various bleeding disorders during pregnancy. Of the 256 patients treated with AMCA (mean duration of treatment, 46 days), 169 were delivered by Caesarean section. Of the remaining 1,846 patients (i.e., controls), 443 were delivered by Caesarean section. The relationship between the use of AMCA and the occurrence of thrombo-embolism was calculated with 95% confidence limits. Of the AMCA treated group (n = 256), two patients--one of whom belonged to the Caesarean section subgroup (n = 168)--had pulmonary embolism. Of the controls (n = 1,846), three patients had deep vein thrombosis and one had pulmonary embolism, all four cases belonging to the Caesarean section subgroup (n = 443). Thus, the findings in this high risk group of women with complicated pregnancies, frequently entailing delivery by Caesarean section, provided no evidence of any thrombogenic effect of AMCA.

Ritodrine therapy in the presence of chronic abruptio placentae.

BACKGROUND: Betamimetic therapy is usually contraindicated for the treatment of premature labor associated with abruptio placentae. We report prolongation of a pregnancy for 7 weeks using ritodrine despite the presence of placental abruption. CASE: A 33-year-old primigravid woman presented at 25 weeks' gestation with irregular uterine contractions, vaginal bleeding, and sonographic evidence of abruptio placentae. Port wine-colored amniotic fluid was found during amniocentesis, and serial hematocrits decreased from 36 to 25%. A diagnosis of abruptio placentae was made, and because the maternal cardiovascular and fetal biophysical indices were normal, tocolytic therapy was started. Before the administration of ritodrine, the patient and her husband were given an extensive review of the risks, including blood transfusion, adult respiratory distress syndrome, disseminated intravascular coagulopathy, and maternal or fetal death. CONCLUSION: Although clinical suspicion of abruptio placentae remains a contraindication to betamimetic therapy, exceptions may be made if fetal and maternal well-being can be monitored and if a fully staffed operating room is always available for immediate cesarean delivery. The benefits of this management may outweigh the associated risks for carefully chosen, very preterm gestations.

Trasylol in the management of abruptio placentae with consumption coagulopathy and uterine inertia.

A study was conducted on 40 patients with abruptio placentae complicated by intrauterine death of the fetus, consumption coagulopathy and uterine inertia. All patients had severe hyperfibrinolysis (FDP > 300 microgram/ml). Following correction of shock, amniotomy was performed, intrauterine pressure catheters were placed, and oxytocin infusions were begun in all cases. The diagnosis of uterine inertia was made when the cervix failed to dilate following six hours of this treatment. After diagnosing uterine inertia, 18 patients (group B) did not. All but one patient in group A showed a marked improvement in the associated consumption coagulopathy and a rapid reawakening of uterine activity with progress to spontaneous vaginal delivery. Thirteen patients in group B did not show prepartum improvement in consumption coagulopathy or a resumption of uterine activity. These patients required cesarean section. There were two maternal deaths in group B; the overall complication rate in this group was greater than in group A.

Abruptio placentae--treatment with the fibrinolytic inhibitor tranexamic acid.

Abruptio placentae is known to have a bad prognosis for the fetus. Pathologic proteolysis, e.g. a pathologic activation of the coagulation mechanism and/or the fibrinolytic system is known to be a common complication in such cases. Analysis of the coagulation factors and components of the fibronlytic system in the acute stage of 14 cases confirmed the earlier finding of mainly an activation of the fibrinolytic system, which argues for the use of a specific inhibitor. 73 consecutive cases of abruptio placentae were treated with tranexamic acid in the acute stage. 67 of the patients were immediately delivered by cesarean section. The remaining six patients were in early gestational age and were treated for a prolonged period. The perinatal mortality of the entire group was only 8 per cent and the maternal mortality nil. None of the cases were complicated by hemorrhagic diathesis or thromboses. We believe that routine immediate treatment with tranexamic acid can reduce the perinatal mortality in cases of abruptio placentae.

Heparin treatment in abruptio placentae.

Two cases of abruptio placentae with disseminated intravascular coagulation (DIC) were treated with heparin, and coagulation was monitored by thromboelastography as well as the usual hematology tests. The cases demonstrated the vagaries of DIC and both showed decreased overt hemorrhage after heparin treatment was started. Heparin may be indicated for the management of abruptio placentae where delivery is not imminent, where significant disseminated intravascular coagulation exists, and when adequate serial coagulation studies are available.