Poor quality specimens delay detection of blood disorders in newborns

This sheet describes the right way to take a blood sample from a newborn infant.

Assessing the viability of studying motion indicators of autism spectrum disorders in infants at high and low risk for ASD using a passive motion capture system

Gemstone Team AMIRA

Prediction and prevention of venous thrombosis in pregnancy

Venous thromboembolism (VTE) remains the leading cause of maternal mortality. Reports identified further research is required in obese and women post caesarean section (CS). Risk factors for VTE during pregnancy are periodically absent indicating the need for a simple and effective screening tool for pregnancy. Perturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications. This thesis had 4 main aims: 1) To investigate anticoagulant effects following a fixed thromboprophylaxis dose in healthy women post elective CS. 2) To evaluate the calibrated automated thrombogram (CAT) assay as a potential predictive tool for thrombosis in pregnancy. 3) To compare the anticoagulant effects of fixed versus weight adjusted thromboprophylaxis dose in morbidly obese pregnant women. 4) To investigate the LMWH effects on human haemostatic gene and antigen expression in placentae and plasma from the uteroplacental , maternal and fetal circulation. Tissue factor pathway inhibitor (TFPI), thrombin antithrombin (TAT), CAT and anti-Xa levels were analysed. Real-time PCR and ELISA were used to quantify mRNA and protein expression of TFPI and TF in placental tissue. In women post CS, anti-Xa levels do not reflect the full anticoagulant effects of LMWH. LMWH thromboprophylaxis in this healthy cohort of patients appears to have a sustained effect in reducing excess thrombin production post elective CS. The results of this study suggest that predicting VTE in pregnant women using CAT assay is not possible at present time. The prothrombotic state in pregnant morbidly obese women was substantially attenuated by weight adjusted but not at fixed LMWH doses. LMWH may be effective in reducing in- vivo thrombin production in the uteroplacental circulation of thrombophilic women. All these results collectively suggest that at appropriate dosage, LMWH is effective in attenuating excess thrombin generation, in low risk pregnant women post caesarean section or moderate to high risk pregnant women who are morbidly obese or tested positive for thrombophilia. The results of the studies provided data to inform evidence-based practice to improve the outcome for pregnant women at risk of thrombosis.

Trombose da veia porta em crianças e adolescentes : deficiência das proteínas C, S e Antitrombina e pesquisa das mutações fator V Leiden, G20210A da Protrombina e C677T da Metileno-tetraidrofolato redutase

Objetivo: A trombose da veia porta é uma causa importante de hiper-tensão porta em crianças e adolescentes, porém, em uma proporção importante dos casos, não apresenta fator etiológico definido. O objetivo desse estudo é determinar a freqüência de deficiência das proteínas inibidoras da coagulação – proteínas C, S e antitrombina − e das mutações fator V Leiden, G20210A no gene da protrombina e C677T da metileno-tetraidrofolato redutase em crianças e adolescentes com trom-bose da veia porta, definir o padrão hereditário de uma eventual deficiência das pro-teínas inibidoras da coagulação nesses pacientes e avaliar a freqüência da deficiên-cia dessas proteínas em crianças e adolescentes com cirrose. Casuística e Métodos: Foi realizado um estudo prospectivo com 14 crianças e adolescentes com trombose da veia porta, seus pais (n = 25) e dois gru-pos controles pareados por idade, constituídos por um grupo controle sem hepato-patia (n = 28) e um com cirrose (n = 24). A trombose da veia porta foi diagnosticada por ultra-sonografia abdominal com Doppler e/ou fase venosa do angiograma celíaco seletivo. A dosagem da atividade das proteínas C, S e antitrombina foi determinada em todos os indivíduos e a pesquisa das mutações fator V Leiden, G20210A da pro-trombina e C677T da metileno-tetraidrofolato redutase, nas crianças e adolescentes com trombose da veia porta, nos pais, quando identificada a mutação na criança, e nos controles sem hepatopatia. Resultados: Foram avaliados 14 pacientes caucasóides, com uma média e desvio padrão de idade de 8 anos e 8 meses ± 4 anos e 5 meses e do diagnóstico de 3 anos e 8 meses ± 3 anos e seis meses. Metade dos pacientes pertenciam ao gênero masculino. O motivo da investigação da trombose da veia porta foi hemorra-gia digestiva alta em 9/14 (64,3%) e achado de esplenomegalia ao exame físico em 5/14 (35,7%). Anomalias congênitas extra-hepáticas foram identificadas em 3/14 (21,4%) e fatores de risco adquiridos em 5/14 (35,7%) dos pacientes. Nenhum pa-ciente tinha história familiar de consangüinidade ou trombose venosa. A deficiência das proteínas C, S e antitrombina foi constatada em 6/14 (42,9%) (p < 0,05 vs con-troles sem hepatopatia), 3/14 (21,4%) (p > 0,05) e 1/14 (7,1%) (p > 0,05) pacientes com trombose da veia porta, respectivamente. A deficiência dessas proteínas não foi identificada em nenhum dos pais ou controles sem hepatopatia. A mutação G20210A no gene da protrombina foi identificada em um paciente com trombose da veia porta e em um controle sem hepatopatia (p = 0,999), mas em nenhum desses foi identificado a mutação fator V Leiden. A mutação C677T da metileno-tetraidrofo-lato redutase foi observada na forma homozigota, em 3/14 (21,4%) dos pacientes com trombose da veia porta e em 5/28 (17,9%) controles sem hepatopatia (p = 0,356). A freqüência da deficiência das proteínas C, S e antitrombina nos pacientes com cir-rose foi de 14/24 (58,3%), 7/24 (29,2%) e 11/24 (45,8%), respectivamente (p < 0,05 vs controles sem hepatopatia), sendo mais freqüente nos pacientes do subgrupo Child-Pugh B ou C, que foi de 11/12 (91,7%), 5/12 (41,7%) e 9/12 (75%), respectivamente (p < 0,05 vs controles sem hepatopatia). Conclusões: A deficiência de proteína C foi freqüente nas crianças e adolescentes com trombose da veia porta e não parece ser de origem genética. A deficiência de proteína S, antitrombina e as presenças das mutações G20210A da protrombina e C677T da metileno-tetraidrofolato redutase foram observadas mas não apresentaram diferença estatística significativa em relação ao grupo controle sem hepatopatia. O fator V Leiden não foi identificado. Os resultados deste estudo sugerem que a deficiência da proteína C pode ocorre como conseqüência da hiper-tensão porta. Os distúrbios pró-trombóticos hereditários não parecem apresentar um papel importante em relação à trombose nas crianças e adolescentes estudadas.

International registry on factor XIII deficiency: a basis formed mostly on European data

FXIII deficiency is known as one of the rarest blood coagulation disorders. In this study, the phenotypic and in part genotypic data of 104 FXIII-deficient patients recorded from 1993 - 2005 are presented. The most common bleeding symptoms were subcutaneous bleeding (57%) followed by delayed umbilical cord bleeding (56%), muscle hematoma (49%), hemorrhage after surgery (40%), hemarthrosis (36%), and intracerebral bleeding (34%). Prophylactic treatment was initiated in about 70% of all patients. FXIII-B subunit-deficient patients had a milder phenotype than patients with FXIII-A subunit deficiency. The most frequent mutation affecting the F13A gene was a splice site mutation in intron 5 (IVS5-1G>A). This mutation was found in eight (17%) of 46 analyzed families. The haplotype analysis of patients carrying the IVS5-1A allele was consistent with a founder effect. The international registry (http://www.f13-database.de) will provide clinicians and scientists working on FXIII deficiency with a helpful tool to improve patient care and direct future studies towards better understanding and treatment of the disease.

Human blood coagulation and its disorders,

Bibliography: p. 369-398.

Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans

Dietary alpha-linolenic acid (ALA) can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on risk factors for coronary heart disease (CHID). This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects. A placebo-controlled, parallel study was conducted in 150 moderately hyperlipidemic subjects, age 25-72 y. Subjects were randomly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA, 4.5 or 9.5g/d ALA or control (linoleic acid; LA) for 6 mo. Fatty acids were incorporated into 25 g of fat spread, which replaced the subject's normal spread and three capsules. Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa, VIIc, VIIag, XIIa, XIIag, fibrinogen concentrations, plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control. (n-3) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors.

CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units

Preterm infants in neonatal intensive care units frequently receive red blood cells (RBC) transfusions due to the anemia of prematurity. A number of variables related to gestational age, severity of illness and transfusion practices adopted in the neonatal unit where the neonate was born may contribute to the prescription of RBC transfusions. This study aimed to analyse the frequency and factors associated with RBC transfusions in very-low-birth-weight preterm infants. A prospective cohort of 4283 preterm infants (gestational age: 29.9 ± 2.9 weeks; birth weight: 1084 ± 275 g) carried out at 16 university hospitals in Brazil between January 2009 and December 2011 was analysed. Factors associated with RBC transfusions were evaluated using univariate and multiple logistic regression analysis. A total of 2208 (51.6%) infants received RBC transfusions (variation per neonatal unit: 34.1% to 66.4%). RBC transfusions were significantly associated with gestational age (OR: -1.098; 95%CI: -1.12 to -1.04), SNAPPE II score (1.01; 1.00-1.02), apnea (1.69; 1.34-2.14), pulmonary hemorrhage (2.65; 1.74-4.031), need for oxygen at 28 days of life (1.56; 1.17-2.08), clinical sepsis (3.22; 2.55-4.05), necrotising enterocolitis (3.80; 2.26-6.41), grades III/IV intraventricular hemorrhage (1.64; 1.05-2.58), mechanical ventilation (2.27; 1.74-2.97), use of umbilical catheter (1.86; 1.35-2.57), parenteral nutrition (2.06; 1.27-3.33), >60 days of hospitalization (5.29; 4.02-6.95) and the neonatal unit where the neonate was born. The frequency of RBC transfusions varied among neonatal intensive care units. Even after adjusting for adverse health conditions and therapeutic interventions, the neonatal unit continued to influence transfusion practices in very-low birth-weight infants.

Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia

Background Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Methods Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30), chorioamnionitis (n = 33) and asphyxia (n = 25) were compared to a control group of preterm and term (n = 155) neonates. Results Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419). Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p < 0.0001). Neonates born after vaginal compared to cesarean delivery had elevated copeptin levels (p < 0.0001). Copeptin correlated strongly with umbilical artery pH (Spearman's Rho -0.50, p < 0.0001), umbilical artery base excess (Rho -0.67, p < 0.0001) and with lactate at NICU admission (Rho 0.54, p < 0.0001). No difference was found when comparing copeptin cord blood concentrations between neonates with EOS and controls (multivariate p = 0.30). The highest copeptin concentrations were found in neonates with asphyxia (median 993 pmol/l). Receiver-operating-characteristic curve analysis showed that copeptin cord blood concentrations were strongly associated with asphyxia: the area under the curve resulted at 0.91 (95%-CI 0.87-0.96, p < 0.0001). A cut-off of 400 pmol/l had a sensitivity of 92% and a specifity of 82% for asphyxia as defined in this study. Conclusions Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS.