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The aim of this study was to elucidate the fall in von Willebrand factor (VWF) and factor VIII activity (FVIII) after childbirth in women with and without von Willebrand disease (VWD). VWF:RCo, VWF:Ag, and FVIII were obtained in the third trimester of pregnancy, on admission for childbirth, and 10 times postpartum. Specimens were processed within 4 h and analysed centrally. Means were calculated at each time point. Forty women (40 pregnancies) without VWD and 32 women (35 pregnancies) with VWD were enrolled. 15/32 with VWD were treated (30% of those with type 1 and all of those with type 2) in 17 pregnancies. Treatments prior to delivery consisted of desmopressin (2/17), VWF concentrate (15/17) and after delivery VWF concentrate (16/17). Duration of treatment was 0-21 days (median 6). VWF levels peaked at 250% of baseline--4 h postpartum in women with VWD and 12 h postpartum in women without VWD. Thereafter, VWF levels fell rapidly, approached baseline at 1 week and reached baseline at 3 weeks. Except immediately postpartum, when the levels among treated cases were higher, levels among women with VWD appeared to parallel, but were lower than those among women without VWD. Levels were lowest among those who received treatment. VWF levels fall rapidly after childbirth. Except immediately postpartum, current treatment strategies do not raise VWF levels to the levels of women without VWD or even to the levels of women with milder, untreated VWD. Consequently, women with VWD may be at risk of postpartum haemorrhage despite treatment.

Objective Evaluation of "near-miss" maternal mortality is a robust surveillance method to assess the quality of obstetric care and determinants of poor maternal outcome. To evaluate near-miss maternal mortality, we examined patient characteristics and maternal and neonatal outcomes for an obstetric population admitted to intensive care units (ICUs) in a tertiary care center. Methods Pregnant and postpartum patients admitted to Duke University Medical Center ICUs from January 2005 to April 2011 were enrolled. Demographic, diagnostic, and outcome data were abstracted from the medical records for analysis. Results A total of 86 women were included in the study. No participants were included more than once. The mean maternal age (±standard deviation) was 29.8±7.2 years. When racial and ethnic differences were examined, African American women were more likely to be admitted to the ICU. Significant ethnic differences in body mass index (BMI) were noted with African American women (mean BMI 35) and Hispanic women (mean BMI 36) having significantly higher BMIs than white women (mean BMI 28). The majority of patients (87%) were admitted postpartum. The mean length of stay was 10 days. The leading reason for admission to the ICUs was maternal cardiac disease (36%) followed by complications from hemorrhage (29%), sepsis (9%), and hypertensive disorders (9%). No significant racial or ethnic differences in maternal medical comorbidities or neonatal outcome were noted. Conclusion In this obstetric population, the leading reason for ICU admissions was cardiac disease. The increasing prevalence of advanced maternal age, congenital heart disease, obesity, diabetes, and hypertension among women who are of childbearing age may be contributing factors. Level of evidence III.

Background/Aims: The purpose of this study was to determine the relationship between maternal characteristics and severe postpartum hemorrhage (PPH). Methods: Medical records of women who delivered at Duke University Hospital between 2001 and 2004 with an ICD-9 code for PPH were reviewed. Women with PPH who received blood component therapy (severe PPH) were selected as cases and compared with controls matched for age, parity and mode of delivery. Results: Among 12,476 deliveries, there were 109 women with severe PPH. Hispanic women had an almost fourfold increase in the odds of severe PPH [OR 3.9 (1.8, 8.7)] that persisted when controlling for other significant predictors of PPH. Women with PPH were almost two times more likely [OR 1.8 (1.1, 3.1)] to have a BMI Conclusion: Systemic factors as well as obstetrical factors modify the risk of severe PPH. Hispanic women and women with a BMI

This study focuses on the implementation of modulated modularity clustering (MMC) a new cluster algorithm for the identification of molecular signatures of preeclampsia and intrauterine growth restriction (IUGR), and the identification of affected microRNAsEighty-six human placentas from normal (40), growth-restricted (27), and preeclamptic (19) term pregnancies were profiled using Illumina Human-6 Beadarrays. MMC was utilized to generate modules based on similarities in placental transcriptome. Gene Set Enrichment Analysis (GSEA) was used to predict affected microRNAs. Expression levels of these candidate microRNAs were investigated in seventy-one human term placentas as follows: control (29); IUGR (26); and preeclampsia (16).MMC identified two modules, one representing IUGR placentas and one representing preeclamptic placentas. 326 differentially expressed genes in the module representing IUGR and 889 differentially expressed genes in a module representing preeclampsia were identified. Functional analysis of molecular signatures associated with IUGR identified P13K/AKT, mTOR, p70S6K, apoptosis and IGF-1 signaling as being affected. Analysis of variance of GSEA-predicted microRNAs indicated that miR-194 was significantly down-regulated both in preeclampsia (p = 0.0001) and IUGR (p = 0.0304), and miR-149 was significantly down-regulated in preeclampsia (p = 0.0168).Implementation of MMC, allowed identification of genes disregulated in IUGR and preeclampsia. The reliability of MMC was validated by comparing to previous linear modeling analysis of preeclamptic placentas.MMC allowed the elucidation of a molecular signature associated with preeclampsia and a subset of IUGR samples. This allowed the identification of genes, pathways, and microRNAs affected in these diseases.

PRIM2, encoding a subunit of primase involved in DNA replication and transcription, is expressed in the placenta and is crucial for mammalian development and growth. Its role in placental function is not well understood. Recently, PRIM2 was reported as imprinted in human white blood cells (WBC). We report here our failure to confirm imprinting of the PRIM2 locus in human placenta or WBC. The discordance between our results and those of others are likely due to an incorrectly annotated PRIM2 pseudogene found in the human genome database.

The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n = 60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases.

BACKGROUND: The purpose of this study was to examine blood component therapy in the treatment of postpartum hemorrhage. STUDY DESIGN AND METHODS: Records were reviewed for subjects who delivered during the 5-year period between January 1, 2000, and December 31, 2004, at Duke University Medical Center and had postpartum hemorrhage coded as International Classification of Diseases Version 9 (ICD-9) codes 666.0X, 666.1X, and 666.2X. Records were reviewed to determine whether blood components had been transfused. Data were analyzed using descriptive statistics and the chi-square test. RESULTS: During the 5-year period from January 1, 2000, to December 31, 2004, there were 12,476 deliveries at Duke University Medical Center. A total of 671 or 5.4% had a diagnosis of postpartum hemorrhage. A total of 108 (0.87%) required blood component therapy, 106 received red blood cells (RBCs), and 30 (0.24%) received components other than RBCs. Of these 30, all received fresh-frozen plasma (1-20 units); eight received one to two transfusions of cryoprecipitate (each containing 10 units); and five received between one and three transfusions of apheresis or pooled whole blood platelets. None of the women received hemostatic agents such as antifibrinolytic medication, DDAVP, recombinant Factor VIIa, or clotting factor concentrates. None of the women experienced thromboembolic events postpartum. There were no deaths and none of the women developed organ dysfunction as a result of hemorrhage. CONCLUSION: Among 12,476 deliveries at a major United States medical center with a modern blood bank and readily available blood component therapy, there were no deaths or organ dysfunction as a consequence of severe postpartum hemorrhage.

Objective We sought to determine if women with severe postpartum hemorrhage (PPH) secondary to uterine atony received greater amounts of oxytocin during labor compared to women without PPH. Study Design Subjects with severe PPH secondary to uterine atony, who received a blood transfusion, were compared to matched controls. Total oxytocin exposure was calculated as the area under the concentration curve (mU/min*min). Variables were compared using paired t test, χ 2 , and logistic regression. Results Women with severe PPH had a mean oxytocin area under the curve of 10,054 mU compared to 3762 mU in controls ( P Conclusion Women with severe PPH secondary to uterine atony were exposed to significantly more oxytocin during labor compared to matched controls.

OBJECTIVE: The purpose of this study was to estimate the incidence and risk factors associated with coagulopathy from severe postpartum hemorrhage. STUDY DESIGN: After approval by the Institutional Review Board at Duke University Medical Center, records with the ICD-9 code 666.12 for immediate postpartum hemorrhage were reviewed for the 5-year period from January 1, 2000, to December 31, 2004. Severe postpartum hemorrhage was defined as postpartum hemorrhage requiring transfusion. Coagulopathy from postpartum hemorrhage was defined as severe postpartum hemorrhage requiring factor replacement. RESULTS: During this period there were 12,476 deliveries. 108 had severe postpartum hemorrhage. 30/108 became coagulopathic. They received a total of 108 units of fresh frozen plasma (FFP) and 12 units of cryoprecipitate (cryo). 28/30 also received 1 to 20 units of packed red blood cells and 5/30 received 1 to 3 units of platelets. All of the women who received cryo had also received FFP. The trigger for administration of factor replacement was clinical (oozing, continued bleeding) in 13/30 cases and a prolonged partial thromboplastin time (PTT) in 17/30 cases. Peak PTTs ranged from 27 to > 150 seconds. Lowest fibrinogen levels ranged from 27 to 580. In 2 cases, however, no fibrinogen levels were obtained. Hemorrhage was attributed to uterine atony in 11/30 cases, placenta accreta in 6/30, lacerations or incisions in 6/30, HELLP syndrome in 2/30, acute fatty liver of pregnancy in 1/30, amniotic fluid embolism in 1/30, fibroids, in 1/30, hemorrhage into an ovarian fibroma in 1/30, and chronic hepatitis B in 1/30. 22/30 cases were associated with cesarean delivery. In 12/30 cases hysterectomy was performed. Hospital length of stay ranged from 2 to 11 days with a mean of 5.4. 9/30 women spent from 1 to 3 days in the ICU. There were no deaths. 2 women had evidence of organ dysfunction from HELLP syndrome or acute fatty liver of pregnancy, but none developed organ dysfunction as a consequence of severe postpartum hemorrhage. CONCLUSION: 2.4 per 1000 women developed coagulopathy as a result of severe postpartum hemorrhage. They received an average of 4 units of either FFP or cryo. 90% of the units were FFP and 10% were cryo. While 30% of the women required intensive care, all survived with no sequelae.

Objective: Menorrhagia, excessive menstrual bleeding, affects up to 20% of reproductive-aged women. Underlying bleeding disorders, such as von Willebrand’s disease (vWD) and platelet abnormalities, may present as menorrhagia. Gynecologists do not routinely screen women with menorrhagia for bleeding disorders. The purpose of this preliminary study was to detect underlying bleeding disorders in women with menorrhagia using a new screening test. Methods: Reproductive-aged women with a diagnosis of menorrhagia were identified. Participants were screened using the PFA-100 (Dade Behring, Inc., Miami, FL), an in vitro platelet function analyzer found to be both sensitive (95%) and specific (88%) in the detection of vWD and platelet disorders. A positive test result was defined as prolonged time until clot formation. Results were confirmed with additional testing. Results: During the first 8 months of the study, 43 women were enrolled. The median age was 40 years. Twenty-one (49%) were white, 21 (49%) were African American, and 1 (2%) was Asian. Sixteen of the 43 women had a positive PFA-100 test result. Eleven had positive results suggestive of aspirin use. Five (12%) were found to have an underlying bleeding disorder: two with vWD and three with platelet abnormalities. Conclusions: Our preliminary findings suggest that the PFA-100 is useful in the evaluation of women with menorrhagia. A significant number of these women appear to have underlying bleeding disorders.

ObjectiveTo characterize antithrombin (AT) levels in normal pregnancy.MethodsWe performed secondary analyses with data from 3 studies. Using a single measurement from each subject in the first analysis (cross-sectional), we correlated AT levels with gestational age from the middle of the second trimester throughout the third trimester of pregnancy. Using serial measurements in a second analysis (cohort), we compared AT levels between the late first and second trimesters of pregnancy and baseline (the level at 6weeks postpartum). Using serial measurements in a third analysis (cohort), we analyzed the pattern of change in AT levels in the immediate postpartum period. Assays of AT activity were performed using the Dade Behring (Siemens) Berichrom Antithrombin III Chromogenic Assay. AT levels were correlated with gestational age using the Pearson correlation coefficient and compared between the different time points using one-way ANOVA.ResultsOverall, AT levels were 20% lower than baseline during pregnancy (p