Elaine Neary

Coagulation indices in very preterm infants from cord blood and postnatal samples

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests.

Effect of platelet-derived β-thromboglobulins on coagulation

BACKGROUND β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of βTG on coagulation is unknown. AIM/METHODS Clotting times, thrombin generation, chromogenic clotting factor assays, and surface plasmon resonance (SPR) were used to assess the effect of purified βTG on coagulation. RESULTS In normal pooled plasma, βTG shortened the lagtime and time to peak thrombin generation of tissue factor (TF)-dependent and TF-independent thrombin generation. In factor VIII and factor IX-deficient plasmas, βTG induced thrombin generation in the absence of a TF stimulus and in the presence of anti-TF and factor VIIa inhibitory antibodies. The procoagulant effect was not observed when thrombin generation was independent of factor X activation (supplementation of factor X-deficient plasma with factor Xa). Cleavage of a factor Xa-specific chromogenic substrate was observed when βTG was incubated with factor X, suggesting a direct interaction between βTG and factor X. Using SPR, βTG were found to bind to immobilised factor X in a dose dependent manner. CONCLUSION βTG modulate coagulation in vitro via an interaction with factor X.

Timing of administration of antenatal magnesium sulfate and umbilical cord blood magnesium levels in preterm babies

Abstract Background: The optimum timing of administration of magnesium sulfate (MgSO4) in relation to delivery is not known. The general consensus is to achieve administration to the mother at least 4 hours prior to preterm delivery. Objective: To investigate potential predictors of umbilical cord blood magnesium (Mg) concentrations, in particular, timing of antenatal MgSO4 administration in relation to delivery. Study design: A prospective observational study of infants delivered at less than 32 weeks’ gestational age. Cord bloods samples were collected at delivery and Mg levels analyzed. Results: Of the 81 included cases, five received no antenatal MgSO4, 65 received a 4 g bolus only, and 11 received a 4 g bolus and 1 g/hour infusion. The median time of bolus administration before delivery was 104 minutes (IQR: 57–215). The mean magnesium level was 0.934 mmol/L in the no antenatal MgSO4 group, 1.018 mmol/L in the bolus only group, and 1.225 mmol/L in the bolus and infusion group (p < .05). In the bolus only group, the highest mean magnesium concentration (1.091 mmol/L) was achieved with administration 1–2 hours before delivery, but the difference was small and not statistically significant. On multiple regression analysis, lower birthweight Z scores and gestational age were independently associated with higher cord blood Mg levels. Conclusions: In the bolus only group, the highest mean Mg levels were observed with administration 1–2 hours before delivery, but the findings were not statistically significant. Compared to the rest of the cohort, higher Mg levels were found when a bolus was followed by an infusion. Following a MgSO4 bolus, some growth restricted extremely preterm babies may have higher Mg levels than would be otherwise expected.

Dual endothelin-1 receptor antagonism attenuates platelet-mediated derangements of blood coagulation in Eisenmenger syndrome

Essentials Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology. Calibrated automated thrombography was used to assess these coagulation derangements. Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function. Endothelin‐1 antagonism appeared to ameliorate these derangements.

Endothelial barrier protective properties of low molecular weight heparin: A novel potential tool in the prevention of cancer metastasis?

Essentials Inhibition of tumor cell trans‐endothelial migration inhibits metastasis formation. Low molecular weight heparin (LMWH)‐mediated endothelial barrier protection was investigated. LMWH enhanced endothelial barrier activity and attenuated tumor cell transmigration. The cytoprotective activity of LMWH did not appear to be dependent on anticoagulant activity.

Coagulation values in extreme premature infants.

We read with interest the recent publication by Christensen and colleagues. Standard coagulation test results vary with gestational age. Consequently, gestationspecific reference ranges for these variables are required. The paucity of published reference values for coagulation variables in extremely premature neonates represents a challenge for neonatologists managing infants at greatest risk of intraventricular hemorrhage and other bleeding complications. The data presented by Christensen and coworkers pertaining to infants of less than 28 weeks’ gestation are helpful, but were based on a small sample size of 24 infants. Moreover, tests were performed on cord blood. An equivalency comparison of samples obtained from cord and peripheral blood was limited to full blood count variables. Fetal plasma clotting times vary with maturation and do not necessarily correlate with published reference ranges for delivered premature infants at equivalent gestations. Physiologic changes and medical interventions (including vitamin K administration) after delivery appear to influence these variables. We have recently published data pertaining to the extremely premature neonatal population (n = 183) born at less than 27 weeks’ gestation. In this large patient cohort, we observed longer clotting times than those reported by Christensen and coworkers in a similar but smaller patient population. In our cohort, median (range 5th-95th percentile) prothrombin time (PT) and activated partial thromboplastin time (APTT) values were 20.2 (14.8-32.6) and 67.4 (43.3-130.2) seconds, respectively. In our population the coagulation values were obtained using combination of PT-S (20042008) and PT-Recombinant PlasTin 2G reagent (20082010) for PT values and APTT-SP reagent (2004-2008) and lupus-sensitive silica-based APTT reagent SytnASIL (20082010) for APTT values compared with Diagnostica Stago kits used by Christensen and colleagues. Of particular note, the blood source differed between the two studies. Christensen and colleagues report results obtained from plasma prepared from cord blood. In contrast, blood was obtained from peripheral catheters in our study, before instillation of heparinized saline. The degree to which coagulation variables derived from cord blood correlate with those obtained from peripheral blood in newly delivered extremely premature infants remains unclear. Coagulation values are dynamic and vary with gestational and postnatal age and other environmental stressors and therefore the different sources of blood may account for some of the differences in values observed. We aimed to pragmatically evaluate coagulation test results in a large cohort of infants born at less than 27 weeks in a retrospective study design. Until recently, interpretation of coagulation test results in this patient population was virtually impossible. We hope that the data described herein and future large prospective studies will further define reference ranges for coagulation variables in this high-risk patient cohort and ultimately guide clinical decision making in extremely premature infants.

Coagulation values in extreme premature infants: Letters to the Editor

We read with interest the recent publication by Christensen and colleagues. Standard coagulation test results vary with gestational age. Consequently, gestationspecific reference ranges for these variables are required. The paucity of published reference values for coagulation variables in extremely premature neonates represents a challenge for neonatologists managing infants at greatest risk of intraventricular hemorrhage and other bleeding complications. The data presented by Christensen and coworkers pertaining to infants of less than 28 weeks’ gestation are helpful, but were based on a small sample size of 24 infants. Moreover, tests were performed on cord blood. An equivalency comparison of samples obtained from cord and peripheral blood was limited to full blood count variables. Fetal plasma clotting times vary with maturation and do not necessarily correlate with published reference ranges for delivered premature infants at equivalent gestations. Physiologic changes and medical interventions (including vitamin K administration) after delivery appear to influence these variables. We have recently published data pertaining to the extremely premature neonatal population (n = 183) born at less than 27 weeks’ gestation. In this large patient cohort, we observed longer clotting times than those reported by Christensen and coworkers in a similar but smaller patient population. In our cohort, median (range 5th-95th percentile) prothrombin time (PT) and activated partial thromboplastin time (APTT) values were 20.2 (14.8-32.6) and 67.4 (43.3-130.2) seconds, respectively. In our population the coagulation values were obtained using combination of PT-S (20042008) and PT-Recombinant PlasTin 2G reagent (20082010) for PT values and APTT-SP reagent (2004-2008) and lupus-sensitive silica-based APTT reagent SytnASIL (20082010) for APTT values compared with Diagnostica Stago kits used by Christensen and colleagues. Of particular note, the blood source differed between the two studies. Christensen and colleagues report results obtained from plasma prepared from cord blood. In contrast, blood was obtained from peripheral catheters in our study, before instillation of heparinized saline. The degree to which coagulation variables derived from cord blood correlate with those obtained from peripheral blood in newly delivered extremely premature infants remains unclear. Coagulation values are dynamic and vary with gestational and postnatal age and other environmental stressors and therefore the different sources of blood may account for some of the differences in values observed. We aimed to pragmatically evaluate coagulation test results in a large cohort of infants born at less than 27 weeks in a retrospective study design. Until recently, interpretation of coagulation test results in this patient population was virtually impossible. We hope that the data described herein and future large prospective studies will further define reference ranges for coagulation variables in this high-risk patient cohort and ultimately guide clinical decision making in extremely premature infants.

PO-0696 Baseline Coagulation Times Do Not Influence Likelihood Of Intraventricular Haemorrhage (ivh) In Extremely Premature Neonates

Background Derangements of haemostasis are implicated in IVH. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen level are frequently monitored in premature infants. Neonates frequently receive frozen plasma (FP) in attempt to correct perceived haemostatic abnormalities based on laboratory results. Methods Prospective observational study was performed. Blood was drawn into citrated tubes from neonates (<30/40) on admission (n = 76) from non-heparinised lines. Platelet poor plasma was obtained by centrifugation of whole blood; PT, APTT, and fibrinogen were measured and correlated with IVH. Results Infants with IVH (n = 30) had no significant difference in PT (p = 0.949), APTT (p = 0.405) and fibrinogen (p = 0.560) than those without IVH (n = 46). There was no association between IVH grade and APTT (p = 0.937). There was no significant difference in APTT in those with or without IVH, excluding infants with IVH on admission (p = 0.534). Of patients administered FP, there was no significant difference in IVH (p = 0.38). FP is frequently administered when APTT >100 s. In this subgroup; IVH rates in those that received FP (n = 17) vs. those that did not (n = 4) was not significantly different (p = 0.447). There was no significant difference in IVH development in high risk (APTT >100 s, Administered FP) vs. low risk infants (APTT <100 s, No treatment), (p = 1.00) or when comparing infants with lesser degrees of coagulopathy (APTT 60 s-80 s vs. 80 s-100 s, p = 0.6334). Conclusions Justification of FP based on coagulation values is unclear. In this study, IVH rates following FP administration was not increased. Coagulation values were not predicative of IVH, indicating lack of therapeutic window for intervention.