Thomas Rehak

Reference values of tricuspid annular peak systolic velocity in healthy pediatric patients, calculation of z score, and comparison to tricuspid annular plane systolic excursion.

The tricuspid annular peak systolic velocity (TAPSV) is an echocardiographic measurement assessing right ventricular systolic function in children and adults. We determined the growth-related changes of the TAPSV to establish the references values for the entire pediatric age group. A prospective study was conducted of a group of 860 healthy pediatric patients (age 1 day to 18 years; body surface area [BSA] 0.14 to 2.30 m(2)). We determined the effects of age, gender, and BSA on the TAPSV values. Stepwise linear multiple regression analysis was used to estimate the TAPSV from the age, BSA, and gender. A correlation of normal TAPSV with normal tricuspid annular plane systolic excursion values was performed. The TAPSV ranged from a mean of 7.2 cm/s (z score ± 2: 4.8 to 9.5 cm/s) in the newborn to 14.3 cm/s (z score ± 2: 10.6 to 18.6 cm/s) in the 18-year-old adolescent. The TAPSV values showed a positive correlation with age and BSA, with a nonlinear course. No significant difference was found in the TAPSV values according to gender. A significant correlation was found between the TAPSV and tricuspid annular plane systolic excursion values in our pediatric population. In conclusion, the z scores of the TAPSV values were calculated, and percentile charts were established to serve as reference data for patients with congenital heart disease.

Elevated thrombin-forming capacity of tissue factor-activated cord compared with adult plasma.

Summary.  Clinically observed excellent hemostasis in neonates despite low levels of clotting factors is not completely understood so far. Therefore, we investigated whether physiological low levels of the inhibitor protein C (PC) facilitate thrombin formation in tissue factor (TF)‐activated plasma samples. PC was activated by endogenously generated thrombin after addition of soluble thrombomodulin (TM). The capability of activated PC (APC) to suppress thrombin formation was significantly more pronounced in adult than in cord plasma. Addition of 4 nm of TM decreased the thrombin potential (TP) in cord plasma by 10%, and in adult plasma by 52% in the presence of 5 pm TF. We demonstrate that this low anticoagulant action of PC is attributable to the low levels of tissue factor pathway inhibitor (TFPI) and antithrombin (AT) physiologically present in cord plasma. Addition of 4 nm TM decreased the TP by 58% in cord plasma adjusted to contain TFPI and AT at adult levels in the presence of 5 pm TF. Thus, the combined low anticoagulant action of the three inhibitors APC, TFPI, and AT in cord plasma allows enhanced thrombin formation associated with shorter clotting times compared with adult plasma when low amounts of TF are applied to initiate clot formation. Although our laboratory experiments do not allow definite conclusions for various clinical situations, our data might contribute to explain excellent hemostasis in neonates despite low levels of procoagulants.

Regional cerebral oxygen saturation in newborn infants in the first 15 min of life after vaginal delivery

The objective of this study was to evaluate regional oxygen saturation of the brain during immediate transition after birth, and to correlate it with pre-ductal arterial oxygen saturation in newborn infants. The prospective observational study including newborn infants in the first 15 min after spontaneous vaginal delivery and uncomplicated transitional period was undertaken. Regional cerebral oxygen saturation (rSO(2)brain) was measured using near-infrared spectroscopy. Arterial oxygen saturation (SpO(2)) and heart rate (HR) were measured on the right wrist by pulse oximetry. rSO(2)brain, SpO(2) and HR measurements were started immediately after birth and were performed in the first 15 min of life. Cerebral fractional tissue oxygen extraction (FTOE) was calculated for each minute. Of 145 newborn infants, 16 were included and the gender allocation was 31 females (49.2%) and 32 males (50.8%). rSO(2)brain increased rapidly from 39% (2 min) to 69% (5 min), SpO(2) increased from 72% (2 min) to 96% (14 min) and FTOE showed a significant decrease from minute 2 (0.47) until minute 4 (0.30) and an increase between 8 to 13 min. rSO(2)brain increased rapidly after vaginal delivery. Although SpO(2) increased within the first 14 min after delivery, rSO(2)brain showed no further significant changes after 5 min. FTOE decreased in the first 4 min and reached standard values subsequently.

Increased shear stress- and ristocetin-induced binding of von Willebrand factor to platelets in cord compared with adult plasma

Multiple indications do exist that the extensive neonatal platelet adhesion and aggregation, and the shorter closure time of neonatal compared with adult whole blood in the platelet function analyzer 100 are attributable to the physiological high plasma concentrations and high concentrations of unusually large von Willebrand factor (vWf) multimers in neonates. However, to date the direct experimental evidence is lacking. Therefore, we compared in the present study the ability of neonatal vWf to bind to platelets to that of adult vWf. Platelet-poor plasma of neonatal or adult origin, containing antibody-stained vWf, was incubated with neonatal or adult platelet suspension. Subsequently, vWf-platelet interaction was induced by exposing the mixture to shear stress by means of a cone/plate measuring system or by incubating the mixture with ristocetin. Finally, samples were analyzed in a FACScan flow cytometer. Detected fluorescence intensities directly correlate with the amount of vWf attached to the platelet surface. We found that significantly higher amounts of neonatal vWf were attached to platelets in the presence of shear stress or ristocetin. This efficient neonatal vWf-platelet interaction is an effect intrinsic to the neonatal vWf, and not to the neonatal platelet: the amount of neonatal vWf attached to neonatal platelets was not different from the amount of neonatal vWf attached to adult platelets. Furthermore, decreasing the vWf content in cord plasma to adult level resulted in significantly suppressed vWf-platelet attachment in the presence of ristocetin, indicating that the high neonatal vWf level contributes to the efficient vWf-platelet binding in neonates.

Phospholipid content, expression and support of thrombin generation of neonatal platelets

Aim: Newborns have, despite low clotting factors and poor in vitro platelet function, a well functioning haemostasis. We investigated whether phospholipids (PL) in neonatal platelets differ from those in adult platelets in their exposure on the platelet surface, and their effect on thrombin generation.

First experience with the Prismaflex HF 20 set in four infants

Purpose Renal replacement therapy (RRT) in infants is challenging due to a lack of widely available technology that is specific to this patient population. We present our initial experience with the newly developed Prismaflex HF2O® disposable set used on the Prismaflex® device in infants with renal failure. Patients Four infants, age 5 to 24 months, were enrolled. Overall 120 treatment sessions were performed over 300 patient-days. Treatment monitoring included patient weight change and fluid balance, treatment efficacy, number of interventions, and alarms. Results Desired fluid balance according to the prescribed weight loss was achieved in all patients (R2=0.86, p<0.0001). Treatment efficacy was monitored by blood urea nitrogen (BUN) and serum creatinine values at the start of RRT (59±17 mg/dL and 5.1±1.1 mg/dL) and their decrease after 4 hours of RRT (23±7 mg/dL and 2.2±0.6 mg/dL). Measured urea and creatinine clearances for the HF20 filter were 23±7 ml/min and 19±4 ml/min, respectively. No complications occurred. Conclusion This is the first report on the use of the Prismaflex HF20 set in infants. No adverse events were observed, treatments were well tolerated in all patients, and flow rate adaptability to infants’ needs was good.

Increased von-Willebrand-Factor-Binding to Platelets in Neonatal Plasma

Platelets of newborns aggregate poorly in-vitro [1, 2]. However, newborns have efficient hemostasis, as illustrated by their short skin bleeding time. It has been demonstrated that elevated von-Willebrand-factor (vWF) concentrations and unusually large vWF multimers, not present in normal adult plasma [3], allow sufficient vWF-collagen binding, probably contributing to the clinically observed effective primary hemostasis of neonates.

Combined effects of melagatran and eptifibatide on platelet aggregation inhibition but not thrombin generation inhibition.

The aim of our study was to investigate the combined in vitro effects of melagatran and eptifibatide on platelet aggregation and thrombin generation under low and high coagulant challenge in tissue-factor-activated, platelet-rich plasma. Increasing amounts of melagatran dose-dependently decreased prothrombin fragment 1.2 and activated factor X values, and dose-dependently prolonged the lag phase until the onset of platelet aggregation. Eptifibatide exerted a dose-dependent anti-aggregating effect under both high and low coagulant challenge. The combination of melagatran and eptifibatide resulted in significant additive prolongation of the lag phase until the onset of platelet aggregation, which was more pronounced under low coagulant challenge. Under low, but not under high, coagulant challenge, the combination of melagatran and eptifibatide had a significant additive inhibitory effect on platelet aggregation. No additive effects on decreasing prothrombin fragment 1.2 and activated factor X values were observed with combined administration of the drugs. The present study demonstrates the additive effect of melagatran and eptifibatide on platelet aggregation inhibition and on prolongation of the lag phase until the onset of platelet aggregation.