Cell cycle, apoptosis, cell differentiation, and lipid metabolism gene expression in endometriotic tissue and exposure to parabens and benzophenones.

AIM: To describe the expression profile in endometriotic tissue of genes involved in four signaling pathways related to the development and progression of endometriosis (cell cycle, apoptosis, cell differentiation and lipid metabolism) and to explore its relationship with the women exposure to chemicals with hormonal activity released from cosmetics and personal care products (PCPs). METHODS: This cross-sectional study, encompassed within the EndEA study, comprised a subsample of 33 women with endometriosis. Expression levels of 13 genes (BMI1, CCNB1, CDK1, BAX, BCL2L1, FOXO3, SPP1, HOXA10, PDGFRA, SOX2, APOE, PLCG1 and PLCG2) in endometriotic tissue and urinary concentrations of 4 paraben (PB) and 3 benzophenone (BP) congeners were quantified. Bivariate linear and logistic regression analyses were performed to explore the associations between exposure and gene expression levels. RESULTS: A total of 8 out 13 genes (61.5 %) were expressed in >75 % of the samples. Exposure to congeners of PBs and/or BPs was associated with the overexpression of CDK1 gene (whose protein drives cells through G2 phase and mitosis), HOXA10 and PDGFRA genes (whose proteins favor pluripotent cell differentiation to endometrial cells), and APOE (whose protein regulates the transport and metabolism of cholesterol, triglycerides and phospholipids in multiple tissues) and PLCG2 genes (whose protein creates 1D-myo-inositol 1,4,5-trisphosphate and diacylglycerol, two important second messengers). CONCLUSIONS: Our findings suggest that women exposure to cosmetic and PCP-released chemicals might be associated with the promotion of cell cycle and cell differentiation as well as with lipid metabolism disruption in endometriotic tissue, three crucial signaling pathways in the development and progression of endometriosis. However, further studies should be accomplished to confirm these preliminary data.

Biomonitoring bisphenols, parabens, and benzophenones in breast milk from a human milk bank in Southern Spain.

BACKGROUND: Human breast milk is considered the optimal source of nutrition for infants. Milk from breast milk banks offers an alternative to infant formulas for vulnerable hospitalized neonates most likely to benefit from exclusive human milk feeding. However, breast milk can also be a source of exposure to environmental contaminants, including endocrine-disrupting chemicals (EDCs). AIM: To evaluate concentrations of phenolic EDCs, including bisphenols, parabens (PBs), and benzophenones (BPs), in samples from a human milk bank in Granada, Southern Spain and to explore sociodemographic, reproductive, and lifestyle factors related to their concentrations in the milk. METHODS: Concentrations of three bisphenols [bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS)], four PBs [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP)], and six BPs [BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP] were determined in milk samples from 83 donors. Information on potential explanatory variables was gathered using the milk bank donor form and an ad hoc questionnaire. Multiple linear and logistic regression models were fitted. RESULTS: Detectable concentrations were found of at least one of the analyzed compounds in all donor breast milk samples and at least five compounds in one-fifth of them. The most frequently detected compounds were MeP (90.5%), BP-3 (75.0%), EtP (51.2%), n-PrP (46.4%), and BPA (41.7%). Median concentrations ranged between <0.10 ng/mL (n-PrP, n-BuP, BP-1) and 0.59 ng/mL (BP-3). No sample contained detectable concentrations of BPF, BPS, or most BPs (BP-2, BP-6, BP-8, and 4- hydroxy-BP). Breast milk phenol concentrations were associated with parity, the utilization of deodorants, mouthwash, skin care products, and cosmetics, and the intake of nutritional supplements. CONCLUSIONS: Results reveal the widespread presence of BPA, PBs, and BP-3 in donor breast milk samples, highlighting the need for preventive measures to enhance the benefits of breast milk from milk banks and from breastfeeding women in general.

Hyperinsulinemic hypoglycemia in adolescents: case report and systematic review.

BACKGROUND: Hyperinsulinemic hypoglycemia is the most common cause of severe and persistent hypoglycemia in neonates and children. It is a heterogeneous condition with dysregulated insulin secretion, which persists in the presence of low blood glucose levels. CASE PRESENTATION: We report a case of a 15 year-old male with hyperinsulinemic hypoglycemia, who underwent a subtotal pancreatectomy after inadequate response to medical therapy. Pathological examination was positive for nesidioblastosis (diffuse ß-cell hyperplasia by H-E and immunohistochemical techniques). The patient's blood glucose levels normalized after surgery and he remains asymptomatic after 1 year of follow-up. The systematic review allowed us to identify 41 adolescents from a total of 205 cases reported in 22 manuscripts, from a total of 454 found in the original search done in PubMed and Lilacs. CONCLUSIONS: Although very well reported in children, hyperinsulinemic hypoglycemia can occur in adolescents or young adults, as it happens in our reported case. These patients can be seen, treated and reported by pediatricians or adult teams either way due to the wide age range used to define adolescence. Most of them do not respond to medical treatment, and subtotal distal pancreatectomy has become the elected procedure with excellent long-term response in the vast majority.

Determination of bisphenols, parabens, and benzophenones in placenta by dispersive liquid-liquid microextraction and gas chromatography-tandem mass spectrometry.

Human exposure to endocrine disrupting chemicals (EDCs) is of particular concern during development. Bisphenols, parabens, and benzophenones are EDCs widely used in the manufacture of numerous goods, personal care products, and cosmetics. The aim of this study was to develop a new and practical method for determining three bisphenols, four parabens, and five benzophenones in placenta samples. It uses dispersive liquid-liquid microextraction (DLLME) in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS). Several chemometric approaches were employed to optimize the experimental parameters. Limits of detection ranged from 0.04 to 0.08 ng g-1 and inter-day variabilities (evaluated as relative standard deviation) from 4.2% to 13.4%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percentages ranged from 87.1% to 113.2%. Finally, the method was used to measure target compounds in 20 placental tissue samples from voluntary donors. This analytical procedure can provide information on the exposure of the fetus to non-persistent EDCs.

Assessment of perfluoroalkyl substances in placenta by coupling salt assisted liquid-liquid extraction with dispersive liquid-liquid microextraction prior to liquid chromatography-tandem mass spectrometry.

The widespread use of perfluoroalkyl substances (PFAS) is resulting in a broad human exposure to these endocrine disrupting chemicals (EDCs), prompting biomonitoring research to evaluate its magnitude and impact, especially during critical windows of exposure such as fetal and perinatal periods. This study was focused on developing a method to determine 10 PFAS in placental tissue by combining salt-assisted liquid-liquid extraction with dispersive liquid-liquid microextraction and using liquid chromatography-tandem mass spectrometry. Chemometric strategies were applied to optimize the experimental parameters. The limit of quantification was 0.02 ng g-1 for all analytes, and the inter-day variability (as relative standard deviation) ranged from 7.9% to 13.8%. Recoveries ranged from 88.2% to 113.9%. The suitableness of the procedure was demonstrated by assessing the targeted compounds in 20 placenta samples. The highest concentrations were recorded for perfluorooctanoic acid and perfluorooctane sulfonate, with maximum concentrations of 0.62 and 1.02 ng g-1 and median concentrations of 0.13 and 0.53 ng g-1, respectively. Median concentrations of the other PFAS ranged from detected values to 0.08 ng g-1. This analytical procedure yields useful data on fetal exposure to PFAS.

Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: results from the EndEA study.

AIM: To explore the relationship of urinary concentrations of different congeners of benzophenones and parabens with the utilization of cosmetics and personal care products (PCPs) and their impact on the risk of endometriosis, and to evaluate the influence of oxidative stress on associations found. METHODS: This case-control study comprised a subsample of 124 women (35 cases; 89 controls). Endometriosis was confirmed (cases) or ruled out (controls) by laparoscopy, with visual inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Urinary concentrations of benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-hydroxibenzophenone (4-OH-BP), methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP), and biomarkers of oxidative stress [lipid peroxidation (TBARS) and total antioxidant power (TAP)] were quantified. Information was gathered on the frequency of use of cosmetics and PCPs. Associations between the frequency of cosmetics/PCP use, urinary concentrations of benzophenones and parabens, oxidative stress, and endometriosis risk were explored in logistic and linear multivariable regression analyses. RESULTS: The frequency of utilization of certain cosmetics and PCPs was significantly associated with urinary concentrations of benzophenones and parabens. After adjustment for potential confounders, the risk of endometriosis was increased in women in the second versus first terciles of MeP (OR = 5.63; p-value<0.001), BP-1 (OR = 5.12; p-value = 0.011), BP-3 (OR = 4.98; p-value = 0.008), and Æ©BPs (OR = 3.34; p-value = 0.032). A close-to-significant relationship was observed between TBARS concentrations and increased endometriosis risk (OR = 1.60, p-value = 0.070) and an inverse association between TAP concentrations and this risk (OR = 0.15; p-value = 0.048). Oxidative stress results did not modify associations observed between benzophenone/paraben exposure and endometriosis risk. CONCLUSIONS: Our findings indicate that the frequency of cosmetics and PCP utilization is a strong predictor of exposure to certain benzophenone and paraben congeners. These compounds may increase the risk of endometriosis in an oxidative stress-independent manner. Further studies are warranted to corroborate these findings.

Intra-host dynamics and co-receptor usage of HIV-1 quasi-species in vertically infected patients with phenotypic switch.

HIV-1 infection through vertical transmission provides a good model to evaluate intra-host viral evolution and allows to gain insight into the dynamics of viral populations. Our aim was to assess the diversity and dynamics of X4- and R5-using HIV-1 variants in vertically infected children who presented a switch in SI/ NSI phenotype in MT-2 cell assays during chronic infection. Through molecular cloning and next generation sequencing of the C2-V5 env fragment, we investigated HIV-1 evolution and co-receptor usage based on V3 loop prediction bioinformatic tools of longitudinal samples obtained from 4 children. In all cases, the phylogenetic relationships were assessed by Maximum-Likelihood trees constructed with MEGA 6.0. In two cases, V3 loop sequences predicted exclusively R5-using and or X4-using strains, while in another two a higher degree of concordance was observed between the phenotypic and genotypic characteristics. In 3 of the 4 cases, C2-V5 env sequences from different time points were intermingled in phylogenetic trees, with no segregation neither by time or tropism. In only one case monophyletic clustering defined groups of sequences with different co-receptor usage. Comparison of amino acid frequency between isolates with SI and NSI phenotype allowed the identification of 9 possible genetic determinants in subtype F C2-V5 region of env associated to SI/ NSI phenotype in these patients, one of which had previously been reported for subtype B. Overall, we found a low degree of correlation between phenotypic and genotypic properties of HIV-1 quasispecies in patients under chronic infection. Whether HIV-1 subtype or other factors influence the evolution of HIV-1 in vivo will require further research.

Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain.

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n = 144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(ß) = 1.20, p = 0.060] and decreased levels of reduced glutathione (GSH) [exp(ß) = 0.55, p = 0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(ß) = 0.83, exp(ß) = 0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(ß) = 1.73, p-value = 0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(ß) < 0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.

Determination of bisphenol A and bisphenol S concentrations and assessment of estrogen- and anti-androgen-like activities in thermal paper receipts from Brazil, France, and Spain.

Bisphenol A (BPA) is a high-production-volume chemical with endocrine disrupting properties commonly used as color developer in thermal paper. Concerns about the potential hazards of human BPA exposure have led to the increasing utilization of alternatives such as bisphenol S (BPS) and bisphenol F (BPF). This study was designed to assess: (i) BPA, BPS, and BPF concentrations in 112 thermal paper receipts from Brazil, France, and Spain by liquid chromatography coupled to mass spectrometry (LC-MS); and (ii) hormone-like activities of these receipts using two receptor-specific bioassays, the E-Screen for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 95.3% of receipts from Spain, 90.9% of those from Brazil, and 51.1% of those from France at concentrations up to 20.27 mg/g of paper. Only two samples from Brazil, two from Spain, and ten from France had a BPS concentration ranging from 6.46 to 13.29 mg/g; no BPA or BPS was detected in 27.7% of French samples. No BPF was detected in any receipt. Estrogenic activity was observed in all samples from Brazil and Spain and in 74.5% of those from France. Anti-androgenic activity was observed in > 90% of samples from Brazil and Spain and in 53.2% of those from France. Only 25.5% of French samples were negative for both estrogenic and anti-androgenic activity. Estrogenic and anti-androgenic activities per gram of paper were up to 1.411 µM estradiol (E2) equivalent units (E2eq) and up to 359.5 mM procymidone equivalent units (Proceq), respectively. BPA but not BPS concentrations were positively correlated with both estrogenic and anti-androgenic activities. BPA still dominates the thermal paper market in Brazil and Spain, and BPS appears to be one of the main alternatives in France. There is an urgent need to evaluate the safety of alternatives proposed to replace BPA as developer in thermal printing. The large proportion of samples with hormonal activity calls for the adoption of preventive measures.

Anogenital distance and reproductive outcomes in 9- to 11-year-old boys: the INMA-Granada cohort study.

BACKGROUND: Studies examining the association of anogenital distance (AGD), a biomarker of prenatal androgen exposure, with sexual development in children are lacking. OBJECTIVE: To assess the association between AGD measures and reproductive outcomes, including puberty onset, testicular volume, reproductive hormone levels, and urogenital malformations in boys aged 9-11 years. MATERIALS AND METHODS: A cross-sectional study was conducted among children belonging to the Spanish Environment and Childhood (INMA) Project, a population-based birth cohort study. The present sample included 279 boys for whom data were available on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was measured from the center of the anus to the base of the scrotum. Pubertal development was assessed according to Tanner stage of genital development (G1-G5), and testicular volume was measured with an orchidometer. RESULTS: After adjusting for potential confounders, logistic regression analysis showed that AGD was positively associated with testicular volume but not with Tanner stage (>G1 vs. G1), serum hormone levels, or undescended testis. Regardless of their age, body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10% increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm). DISCUSSION: Longer AGD was associated with testicular growth, an indicator of gonadarche, but not with other reproductive outcomes. CONCLUSIONS: Although AGD was positively associated with testicular volume, it remains unclear whether AGD predicts testis size at puberty or is related to puberty onset.

Environmental phenols and parabens in adipose tissue from hospitalized adults in Southern Spain.

Urinary concentrations of non-persistent environmental pollutants (npEPs) are widely assessed in biomonitoring studies under the assumption that they are metabolised and eliminated in urine. However, some of these chemicals are moderately lipophilic, and their presence in other biological matrices should also be evaluated to estimate mid/long-term exposure to npEPs and its impact on human health. The present study aims to explore concentrations and potential determinants of npEPs in adipose tissue from a hospital-based adult cohort (GraMo cohort, Southern Spain). Concentrations of bisphenol-A (BPA), benzophenone-3 (BP-3), triclosan (TCS), three chlorophenols (2,4-DCP, 2,5-DCP and 2,4,5-TCP) and two phenylphenols (2-PP and 4-PP), triclocarban (TCCB) and parabens [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP and i-PrP), butyl- (n-BuP and i-BuP) and benzyl-paraben (BzP)] were analysed in adipose tissue samples from a subcohort of 144 participants. Spearman correlation tests were performed, followed by stepwise multivariable linear regression analyses to assess determinants of the exposure. Detection frequencies and median concentrations were: BPA (86.8%, 0.54 ng/g tissue), BP-3 (79.2%, 0.60 ng/g tissue), TCS (45.8%,

QuEChERS and ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of parabens and ultraviolet filters in human milk samples.

Concerns are growing about human exposure to endocrine disrupting chemicals (EDCs), especially during developmental stages. Parabens (PBs) and ultraviolet filters (UVFs) are prevalent EDCs widely used as additives in cosmetics and personal care products (PCPs). The objective of this study was to develop a method to determine four PBs and ten UVFs in human milk using QuEChERS treatment and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Multivariate strategies were applied to optimize experimental parameters. Limits of quantification ranged from 0.1 to 0.2 ng mL-1 and inter-day variability (evaluated as relative standard deviation) from 6% to 13%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percentages ranged from 87% to 112%. The method was satisfactorily applied to assess target compounds in human milk samples from 15 donors. This analytical procedure can provide information on newborn exposure to these EDCs.

Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum.

The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24h. Benzophenone-3 (BP-3; range of values: 70% of adipose tissue samples, while bisphenol-A (BPA; 40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals.

Assessment of parabens and ultraviolet filters in human placenta tissue by ultrasound-assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

Increasing concerns have been raised over recent decades about human exposure to Endocrine Disrupting Chemicals (EDCs), especially about their possible effects on embryo, foetus, newborn, and child. Parabens (PBs) and ultraviolet filters (UV-filters) are prevalent EDCs widely used as additives in cosmetics and personal care products (PCPs). The objective of this study was to determine the presence of four PBs and ten UV-filters in placental tissue samples using a novel analytical method based on ultrasound-assisted extraction (UAE) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Multivariate optimization strategies were used to accurately optimize extraction and clean-up parameters. Limits of quantification ranged from 0.15 to 0.5µgkg-1, and inter-day variability (evaluated as relative standard deviation) ranged from 3.6% to 14%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percents ranged from 94.5% to 112%. The method was satisfactorily applied for the determination of the target compounds in human placental tissue samples collected at delivery from 15 randomly selected women. This new analytical procedure can provide information on foetal exposure to compounds, which has been little studied.

Radiofrequency exposure in the Neonatal Medium Care Unit.

The aims of this study were to characterize electromagnetic fields of radiofrequency (RF-EMF) levels generated in a Neonatal Medium Care Unit and to analyze RF-EMF levels inside unit's incubators. Spot and long-term measurements were made with a dosimeter. The spot measurement mean was 1.51±0.48V/m. Higher values were found in the proximity to the window and to the incubator evaluated. Mean field strength for the entire period of 17h was 0.81 (±0.07)V/m and the maximum value was 1.58V/m for long-term RF-EMF measurements in the incubator. Values found during the night period were higher than those found during the day period. It is important to consider RF-EMF exposure levels in neonatal care units, due to some evidence of adverse health effects found in children and adults. Characterization of RF-EMF exposure may be important to further investigate the mechanisms and underlying effects of electromagnetic fields (EMF) on infant health. A prudent avoidance strategy should be adopted because newborns are at a vulnerable stage of development and the actual impact of EMF on premature infants is unknown.

Determination of personal care products -benzophenones and parabens- in human menstrual blood.

Benzophenones and parabens are synthetic chemicals used in many personal care products, foods and pharmaceuticals. Benzophenones are used to protect the skin and materials from the adverse effects of UV-radiation, and parabens are used as preservatives. Despite their widespread occurrence and proven endocrine disrupting activity, relatively little is known about human exposure to these compounds. In the present work, an analytical method based on sample treatment using dispersive liquid-liquid microextraction (DLLME) for the extraction of six benzophenones (benzophenone-1, -2, -3, -6, -8 and 4-hydroxybenzophenone) and four parabens (methyl-, ethyl-, propyl- and butyl- paraben) from human menstrual blood samples, followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is proposed and validated. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. The limits of detection ranged from 0.1 to 0.3ngmL-1, with recoveries of 93.8% to 108.9%, and precision (evaluated as relative standard deviation) lower than 14% for all selected compounds. This method was successfully applied for the determination of the target compounds in 25 samples of human menstrual blood. Methylparaben and benzophenone-3 were the most frequently detected compounds (96%).

Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery.

INTRODUCTION: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment. AIM: To determine the efficacy and safety of rIX-FP in the perioperative setting. METHODS: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required. RESULTS: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP. CONCLUSION: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.

Practical aspects of factor concentrate use in patients with von Willebrand disease undergoing invasive procedures: a European survey.

INTRODUCTION: The bleeding propensity in von Willebrand disease (VWD) is usually moderate or mild and patients with VWD do not need continuous treatment, but do require extra increased haemostatic cover when undergoing dental or surgical procedures. Desmopressin can be effective in certain patient groups and this has been considered in a previous publication. AIM: This paper now seeks to evaluate current knowledge and practice in the use of factor concentrate in the management of VWD patients undergoing invasive procedures. METHODS: A literature search was performed on the use of factor concentrates to cover invasive procedures and a survey of current practice in a number of specialist haematology centres across Europe represented by the European Haemophilia Strategy Board was conducted. RESULTS: Our review of the literature and the results of the survey showed considerable heterogeneity in treatment regimens, and a lack of consistency in reporting of the variables that determine factor concentrate dosing and monitoring. CONCLUSION: By analysing the literature, examining guidelines and using consensus deliberation, this survey allowed the group to develop recommendations for management of VWD patients undergoing invasive procedures.