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Van Lingen et al, Heparin in arterial catheters
J. Perinat. Med. 20(1992)39-46
The effect of heparin in arterial catheters on the coagulation in preterm infants Richard A. Van Lingen13, Wim J. D. Hofhuis2, Ina Dekker2, Wim Baerts1, Karel Hählen2, and Pieter J. J. Sauer1
Department of Pediatrics, Division of Neonatology and 2Division of Hematology, Erasmus University und University Hospital Rotterdam/Sophia Children's Hospital, Rotterdam, The Netherlands
1
Introduction
In many neonatal intensive care units heparin is used routinely to maintain patency of indwelling arterial umbilical or periferal catheters [7, 13]. The optimal concentration of heparin in the infusion to keep the lines patent is not very well known. Recently it was suggested to use 5 IU heparin per ml [5]. The effect of this dose of heparin on the coagulation of the preterm appropriate for gestational age (AGA) or small for gestational age infant (SGA) is unknown. There might be an increased risk for peri- and intraventricular hemorrhage (PIVH) already at a dose of 1 lU/ml [7]. In our unit we have been using a heparin concentration of 5 lU/ml for a prolonged period of time. Concerned about potential effects on the clotting status of our infants, we undertook a study to evaluate these effects. Secondly, we evaluated if samples obtained from the arterial line showed results comparable with venous samples. 2
Patients and methods
Curriculum vitae RICHARD VAN LINGEN, M.D., was bom in 1953 in Leeuwarden, The Netherlands. In 1980 he graduated from the University of Groningen. From 1982 to 1986 he was a pediatric resident in the Zuiderziekenhuis and the Sophia Childrens Hospital in Rotterdam. From 1986 to 1991 he worked as a neonatologist in the Sophia Childrens Hospital and the University Hospital Groningen. Presently he is a staffmember of the Perinatal Center, Sophia Hospital Zwolle, The Netherlands. His main fields of interest are nutrition, thermogenesis and hematology.
ventilated nor had an arterial catheter served as controls. Control infants showing clinical signs of hemostatic disorders were excluded from the study. All study infants and control infants received 1 mg of vitamin K shortly after birth. Informed consent from one or both of the parents was obtained.
From August 1987 till April 1988 all infants admitted to our NICU with a birth weight < 2000 grams, a gestational age > 27 weeks and with a platelet count > 100 109/liter, who did The heparin solution used contains 5 lU/ml hepnot receive indomethacin or whose mothers had arin (TromboliquineR, Organon Teknika, The not received indomethacin to prevent premature Netherlands) in NaCl 0.9%, at an infusion rate labor and received an arterial catheter on the of 0.5 ml per hour and flushes using the same day of admittance were eligible for inclusion in solution were given after sampling for bloodthe study. Infants meeting the same criteria as gasses. The total amount of heparin given in Brought24tohr youprior by | Michigan State University was measured. the study infants except that they were not being to the bloodsampling 1992 by Walter de Gruyter & Co. Berlin · New York
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Van Lingen et al, Heparin in arterial catheters
Between 48 and 72 hours after birth bloodsamples were taken in both study infants and controls. A venipuncture was performed, the first 0.5 ml of blood was used for other laboratory data, then 2 ml of blood was drawn into a siliconized plastic syringe aseptically and gently flushed into a siliconized plastic tube, containing 0.225 ml of a sterile buffer solution of sodium citrate (0.11 mol/1), theophyllin, adenosin and dipyramidol (CTAD, Boehringer Mannheim, Germany) to prevent neutralization of heparin in vitro by platelet factor four [2] and mixed carefully. In the study infants blood was also taken from the arterial catheter using the following technique [8]: a. 0.7 ml of fluid in catheter and stopcock is drawn into a siliconized plastic syringe aseptically and discarded. b. Five milliliters of blood are drawn into another siliconized plastic syringe aseptically. c. After removing the stopcock two milliliters of blood flowed freely into a tube containing CTAD as mentioned before and mixed carefully. d. The original five milliliters of blood was returned aseptically to the patient and the catheter was flushed.
a one-stage clotting assay, using rabbit brain thromboplastin (Dade thromboplastin-FS). ATIII activity was determined chromogenically (Boehringer Mannheim). To analyze if abnormal results of APTT and TT might be correlated to heparin levels in the sample, two heparin assays were performed, analysing both the anti-Xa effect of heparin in the presence of AT-III (Hepaclot, Stago) and its anti-IIa effect (Heparin Low Dose, Boehringer Mannheim). Ultrasound studies of the brain were performed by one investigator (WB). All infants were scanned at least twice during the first week of life. Statistical analysis was performed by means of the Wilcoxon signed rank test for the paired data and the Wilcoxon ranking test for unpaired data (Mann-Whitney test). 3 Results Twenty infants were eligible for inclusion in the study, five of them were excluded. One infant died within 36 hour after birth, in two cases the catheter was removed electively before the day of study and in two cases clotting of the sample occurred before centrifugation. In 13 of the remaining 15 infants an arterial and venous sample was obtained, in 2 infants no venous sample could be obtained. Data of these 13 infants are included in the analysis. All catheters were placed in the radial artery, 10 in the right radial artery, 5 in the left.
All blood sampling was done by the same investigator (RVL). The samples were put on melting ice and within ten minutes centrifugated with 4000 rpm for ten minutes and then again with 20.000 rpm for thirty minutes at a temperature of 4° Celsius. The samples were devided in three From the 26 eligible control infants, 10 were fractions and stored at — 80° Celsius until serial excluded; 7 because of clotting of the sample and analysis was performed. The possible effect of 3 because of clinical symptoms of coagulation heparin on the coagulation was analyzed using disorder (i.e. bleeding from digestive tract or the activated partial thromboplastin time (APIT) prolonged bleeding from puncture sites or peteand the thrombin time (TT). To evaluate if pos- chiae), before the sample was obtained. Clinical sible abnormal results might be caused by a more details of the two groups are shown in table I. general coagulation disorder, we also measured There was no significant difference in birth Antithrombin III (AT-III), bathroxobin time and weight or gestational age (as determined by Balfactors I, II, V and VII. The APTT was measured lard scores and maternal ultrasound dates) beusing rabbit brain cephalin (Dade Actin). tween the two groups. On the day of bloodsamThrombin time was determined photometrically pling all arterial catheters were patent, nine of (Behring Werke). Bathroxobin time (ReptilaseR), those were removed electively later on; mean a test with a proteolytic enzyme from Bothrops duration of patency in these infants was 3.63 atrox, that measures fibrinolytic activity as the ± 1.75 days (range 2.04-6.92 days). Six cathethrombin time but is not influenced by thrombin ters were removed because of complications as inhibitors such as heparin [3] was also deter- blood oozing next to the catheter (one), or when mined photometrically (Behring Werke). Fibri- no more samples from the arterial catheter could nogen (factor I) was measured according to VON be drawn (five). Mean duration of patency in CLAUSS' method [6]. Coagulation factors II, V these infants was 9.77 ±5.81 days (range you by | Michigan and VII clotting activities were performedBrought with to2-18.4 days). State University Authenticated Download Date | 6/17/15 1:01 AM
J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters Table I. Clinical details of the study group and controls
(n = 13)
Study group
Controls (n = 16)
Weight (g) (mean ± SD)
1391 + 308 (range 1060 -1930)
1440 + 200.6 (range 1100-1835)
Gestational age (wks) (mean + SD)
30.15 + 1.36 (range 27 -31. 86)
32 ± 2.39 (range 28 -35.57)
study group arterial
study group venous
V//A
100
AT III (%)
factor II (%) factor V (%) factor VII (%)
factor I (g/l)
Figure 1. Mean values + SD for arterial and venous samples of the study infants and control for AT III and factors I, II, V and VII. * Neither the arterial nor the venous data of the study infants are statistically significant different from the control infants.
The amount of heparin administered to the study time were not significantly different between the infants was 103 ± 29 IU/day and 86.7 ± 29 IU/ study infants and the controls (table II). kg/day. Figure I shows the results for AT-III and factors In ten of the twelve infants heparin could not be I, II, V and VII for the arterial and venous detected in the venous sample, in two infants a samples from the study infants and the venous very low amount of heparin was detected. The values of the arterial samples showed a samples from the control infants. There were no mean significant lenghtened APTT and thrombin time significant differences between venous samples compared with the venous samples of the from the two groups nor between the arterial same infants andboth with control infants. Moreover and venous values from the study group. the results of the arterial samples showed a The mean values of the venous samples of the higher variability. In three infants the APTT was Broughtmore to youthan by | Michigan Statethe University APTT, the thrombin time and the bathroxobin four times mean of the controls, J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters
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43
Van Lingen et al, Heparin in arterial catheters
the thrombin time was also lengthened in these infants. The bathroxobin time, in which is corrected for possible heparin effects, showed no elevation in any of these three samples. Heparin was detectable in almost all arterial samples by the heparin anti-Xa as well as by the heparin anti-IIa test. The heparin level was more than 0.1 lU/ml, as measured by both tests, in all three arterial samples in which the APTT and thrombin time was elevated. No correlation between heparin intake and coagulation tests, either from venous or from arterial samples, could be found. Ultrasound diagnoses for PIVH were made in three out of thirteen study infants (one PIVH I, two PIVH II) and in one out of sixteen control infants (PIVH I) [9]. 4 Discussion
the influence of the amount of heparin given with this regime on the coagulation of preterm infants [5]. Venous samples are the best indicators to study possible systemic effects of heparin given via the intraarterial route in order to keep a catheter patent. In only 2 of the 13 study infants, a small amount of heparin activity in the venous samples was found. All heparin independent coagulationtests were found to be in the same range as in the control infants (figure 1) indicating that there was no more general coagulation disorder present. This was also the case for the APTT and TT (table II) and bathroxobin time. Only one child with a detectable heparin anti-IIa level in the venous sample had a prolonged APTT (but a normal TT). Thus, it can be concluded that an intraarterial infusion of 5 lU/ml heparin given at an infusion rate of 0.5 ml/hr has no detectable effect on the coagulation in preterm infants.
It is important to note that the values for the Although it is presently possible to measure oxdifferent coagulation parameters were not difygen tension and oxygen saturation transcutaferent between the more sick, ventilated infants neously, arterial bloodgas analysis and intraarand the more healthy, not ventilated infants. terial monitoring of blood pressure are still necMoreover the values we obtained are in good essary in ventilated newborn infants. As infants agreement with values reported recently by other can react on arterial punctures with unrest and investigators in "healthy" preterm infants [1,11]. crying and thereby give false results of their The incidence of intracranial hemorrhage was steady state bloodgas status, arterial catheters not different between study and control infants. are of great importance in these infants [10]. In The coagulation tests in the study infants showview of the limited number of arteries available ing a grade I or II bleeding were not different for the insertion of these lines, it is important from the control infants. Because the study popthat they remain patent as long as possible withulation is too small to detect a significant differout side effects. Heparin is used since a long time ence we conclude that heparin given in a dose in the fluids used for continuous infusion and/ as presented in this study, does not appear to or flushes. BOSQUE and WEAVER showed that a increase the risk for a PIVH. continuous heparin infusion is to be preferred above intermittent heparin flushes to keep the Finally, the comparison of the results of the umbilical artery catheter patent. While using a samples obtained by venipuncture and from the solution containing l IU heparin per ml at dif- arterial catheters show that the data from the ferent rates with a mean intake of 120 IU/kg/ arterial catheters have to be interpreted in reladay (range 80-220 IU/kg/day), the mean du- tion to the possibility of contamination of these ration of patency of an umbilical catheter was samples with heparin. The coagulation tests that only 66.9 hrs [4]. RANDEL et al described their are independent of heparin were as expected not results with periferal artery catheters; also using influenced by the route they were obtained, so a 1 lU/ml heparin solution at a rate of 2 ml/hr. the heparin independent tests can be taken from With this regime, the mean duration of the pat- (heparinized) arterial catheters. In contrast to ency of the radial catheters that were not elec- MERENSTEIN, however, we found that falsely high tively removed was 87.8 hr [12]. BUTT et al sug- results can be obtained for coagulation tests that gested recently to use a solution containing 5 IU/ are influenced by the presence of heparin, as ml at a rate of 1 ml/hr as they showed that the heparin is detectable in almost all samples, even peripheral arterial catheters remained longer pat- if the technique of blood sampling is as careful ent with this solution compared with a 1 lU/ml as in the present study [8]. As no heparin could Broughtbeto detected you by | Michigan University containing solution. They did not study however in the State venous samples of the same J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters
infants, the heparin found in the arterial samples must be caused by contamination from the arterial line. Especially when the heparin level found in the same sample is more than 0.1 IU/ ml, the results of the APTT and thrombin time should be regarded with extreme caution. In conclusion, a solution containing 5 lU/ml of heparin infused intraarterially at a rate of 0.5
ml/hour does not affect systemic coagulation in premature infants. Bloodsamples taken from arterial catheters in the way described before can be used for coagulation studies for bathroxobin, AT-III and factors I, II, V and VII. This might also be valid for APTT and thrombin time as long as the heparin concentration is less than 0.1 lU/ml.
Abstract
The coagulation of 16 healthy preterm infants (control infants) was compared with 15 ventilated preterm infants (study infants) receiving 0.5 ml/hr of a solution containing 5 lU/ml heparin intra-arterially in order to keep a radial artery catheter patent. A venous sample was obtained in both groups, in the study group a sample from the arterial catheter was also taken. Both the heparin dependent (APTT, thrombin time) and the heparin independent coagulation factors (AT-III, Clotting Factors I, II, V and VII) were not different between the venous samples of both groups. The arterial samples showed a significantly elevated APTT and thrombin time compared with venous samples, espe-
cially when the heparin level in the sample was higher than 0.1 lU/ml. These elevations are due to heparin in the sample from the arterial line as the venous sample in the same patient did not show any heparin effect. The heparin non-dependent factors were not different between venous and arterial samples. We conclude that a solution containing 5 lU/ml heparin given at a rate of 0.5 ml/hr does not influence coagulation in preterm infants. Determination of heparin independent coagulation factors can be done in both venous samples and samples taken from the arterial catheter, in these arterial samples the heparin dependent factors can be influenced by the heparin present in the catheters.
Keywords: Arterial catheter, clotting, coagulation, heparin, preterm infants.
Zusammenfassung Einfluß yon Heparin in intraarteriellen Kathetern auf die Gerinnung bei Frühgeborenen
zwischen den beiden Gruppen keine Unterschiede: Alle Kinder wogen weniger als 2000g, hatten ein Gestationsalter von mehr als 27 Wochen und Thrombozyten von mehr als 100 109/1. Weder die Kinder noch die Mütter vor der Geburt hatten Indomethacin erhalten. Alle Kinder bekamen jedoch l mg Vitamin K kurz nach der Geburt. Kinder aus der Kontrollgruppe, die klinische Zeichen einer Störung der Haemostase zeigten, wurden aus der Studie ausgeschlossen. Die Blutentnahme erfolgte wie oben beschrieben [2, 8]. Die Proben wurden in schmelzendes Eis gegeben, zentrifugiert, in drei Portionen aufgeteilt und bei — 80 °C bis zur Analyse aufbewahrt. Um mögliche Effekte des Heparins auf die Koagulation zu erfassen, wurden APTT und Thrombin-Zeit (TT) bestimmt; die Messung des AT III, der Bathroxobin-Zeit und der Faktoren I, II, V und VII erfolgte, um möglicherweise abweichende Ergebnisse, die aber durch übergeordnete Störungen der Blutgerinnung verursacht sind, zu erfassen. Um zu analysieren, ob abnorme APTT- und TT-Werte mit einem erhöhten Heparin-Spiegel in der Probe korreliert sind, wurden zwei Assays angesetzt, mit denen der Anti-XA- und Anti-IIA-Effekt des Heparins geprüft wurde.
Um intraarterielle Katheter bei Neugeborenen durchgängig zu halten, wird einer kontinuierlichen Heparinisierung gegenüber intermittierenden Zugaben der Vorzug gegeben. Bei einer Heparin-Konzentration von l lU/ml war die Dauer der Durchgängigkeit signifikant kürzer als bei Konzentrationen von 5 lU/ml [4, 5, 12]. Bisher wurde jedoch nicht der Einfluß des infundierten Heparins auf die Gerinnung der Frühgeborenen untersucht. Wir untersuchten 46 Kinder, um die Wirkung des Heparins, das intraarterielle Katheter offenhalten soll, auf die Gerinnung von Frühgeborenen zu erfassen und um zu sehen, ob Proben aus den arteriellen Kathetern vergleichbare Ergebnisse mit denen aus venösen Proben aufweisen. 20 dieser Kinder wurden beatmet. Alle erhielten eine salzhaltige Lösung einer Dosis von 0,5 ml/Std. über einen arteriellen Katheter, die 5 lU/ml Heparin/ml enthielten. Nach Blutentnahme wurde mit der gleichen Lösung durchgespült. Zwischen 48 und 72 Std. post partum wurden die Gerinnungsparameter in venösen Blutproben sowie in arteriellen Proben aus dem Katheter bestimmt. Die Ergebnisse verglichen wir mit den Werten von 26 gesunden Kindern (Kontrollgruppe), die nicht beatmet waren und keinen arteriellen Katheter hatten. Im Hinblick auf andere Parameter Brought gab es to you by | Michigan State University Authenticated Download Date | 6/17/15 1:01 AM
J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters Die statistische Bearbeitung erfolgte über den WILCOXON-Test für paarweise angeordnete Meßwerte und den WILCOXON-Test für nicht gepaarte Daten (MANN-WHITNEY-Test). Fünf Kinder aus der Untersuchungsgruppe und 10 Kinder aus der Kontrollgruppe wurden aus der Studie ausgeschlossen, weil der Katheter entfernt werden mußte, die Blutprobe geronnen war oder bei den Kontroll-Kindern klinische Zeichen einer Blutgerinnungsstörung auftraten. Tabelle I enthält die klinischen Befunde der 15 Untersuchungs- und 16 Kontroll-Kinder. Wurden die Katheter elektiv entfernt, betrug die mittlere Dauer der Durchgängigkeit 3,6 ±1,7 Tage, bei den anderen Kathetern 9,8 ± 5,8 Tage. Zwischen den arteriellen und venösen Proben im Untersuchungskollektiv gab es keine signifikanten Unterschiede bezüglich des AT III und der Faktoren I, II, V und VII. Dasselbe gilt für die venösen Blutproben der Untersuchungs- bzw. Kontrollgruppe (Abb. 1). Bezogen auf das APTT und die TT, lagen jedoch die Mittelwerte der arteriellen Proben signifikant höher als
die aus den venösen Proben der Katheter-Kinder und Kontroll-Kinder. Die Bathroxobin-Zeit, mit der mögliche Heparin-Effekte eliminiert werden, war in keiner Probe erhöht. Zwischen den venösen Proben aus Untersuchungs- und Kontrollgruppe gab es keine signifikanten Unterschiede (Tab. II). In allen arteriellen Proben war Heparin nachweisbar; in drei Proben lagen die Spiegel höher als 0,1 lU/ml, wobei APTT und TT erhöht waren. Der HeparinSpiegel im Blut korrelierte nicht mit den Gerinnungstests. Wir schließen daraus, daß eine Infusion von 5 IU Heparin/ml, die über 0,5 ml/Std. intraateriell gegeben wird, keinen nachweisbaren Einfluß auf die Koagulation bei Frühgeborenen hat. Zwischen beeinträchtigten und beatmeten Kinder sowie gesunden, nicht beatmeten Kindern gab es keine Unterschiede. Selbst bei sorgfaltiger Blutentnahme können die Proben aus Kathetern mit Heparin kontaminiert seinl. Liegt der Spiegel über 0,1 lU/ml, sollten die APTT- und TT-Werte zurückhaltend interpretiert werden.
Schlüsselwörter: Arterieller Katheter, Frühgeborene, Gerinnselbildung, Gerinnung.
Resume Effets de l'heparine au niveau des catheters arteriels sur regu d'Indometacine. Tous les nouveaux nes ont regu la coagulation des prematures l mg de vitamine K, peu de temps apres la naissance. Afln de conserver les catheters arteriels, chez les pre- Les nouveaux nes controles, presentant des signes climatures, il est preferable de faire appel a une hepari- niques de troubles de Fhemostase, ont ete exclus de nisation continue, plutot qu'a des flashs intermittents; l'etude. une solution comportant l Ul/ml d'heparine a une Les prelevements sanguins ont ete effectues comme duree d'hypocoagulabilite plus breve que celle conte- cela a ete decrit anterieurement. nant 5 Ul/ml [4, 5, 12]. L'influence de l'heparine per- Les echantillons sont places dans de la glace pilee, fusee sur la coagulation des prematures, cependant, centrifuges, separes en trois fractions et Stockes a — 80° n'a pas ete etudiee. Pour evaluer Feffet de l'heparine, centigrade jusqu'ä la realisation des analyses en serie. utilisee pour maintenir une hypocoagulabilite au ni- On s'est servi de FAPTT et du temps de thrombine veau des catheters arteriels, sur la coagulation des pour analyser les effets possible de l'heparine sur la prematures, et pour voir si les prelevements, obtenus coagulation; on a dose L'AT III, le temps de bathroxoä partir des catheters arteriels montrent des resultats bine, et les facteurs l, 2, 5 et 7, afin d'evaluer des comparables a ceux des prelevements veineux, on a resultats anormaux eventuels, provoques par un etudie 46 nouveaux nes. trouble de la coagulation plus general. Vingt de ces enfants etaient ventiles (nouveaux nes etudies), ils recevaient tous 0,5 ml/hr de serum sale, Pour analyser si les resultats anormaux de l'APTT et contenant 5 Ul/ml d'heparine, par le catheter arteriel du TT peuvent etre correles au taux d'heparine dans ainsi que eds ringages, apres prelevements sanguins, les prelevements, on a effectue deux dosages d'hepaavec la meme solution. On a compare leur coagulation, rine, en analysant les effets anti-XA et anti-IIA de sur des prelevements veineux et sur des prelevements l'heparine. du catheter arteriel, efectues entre 48 et 72 heures apres On a effectue une analyse statistique ä l'aide du test la naissance, avec la coagulation, au niveau de prele- de Wilcoxon pour les donnees appariees et du test pour vements veineux, de 28 nouveaux nes, prematures, en les donnees non-appariees (Mann-Whitney test). bonne sante (nouveaux nes controles), non ventiles et On a exclu cinq enfants etudies et dix enfants controles sans catheters arteriels. Sous tous les autres aspects, il de l'etude, en raison de l'ablation du catheter, de la n'y a pas de differences entre les deux groupes, tous coagulation du prelevement ou, pour le groupe les nouveaux nes pesaient moins de 2000 grammes, controle, de signes cliniques dec troubles de la coaguavaient un age gestationnel > 27 semaines, et une lation. numeration plaquettaire > 100 10—9/litre. Ni les Les details cliniques des 15 nouveaux nes etudies et Broughtdes to you by | Michigan Statedans University nouveaux nes, ni leurs meres, avant la naissance n'ont 10 controles figurent le tableau I. J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters
La duree moyenne de 1'hypocoagulabilite au niveau des catheters enleves electivement est de 3,6 + ou — 1,7 jours; et de 9,8 4- ou — 5,8 jours pour les autres catheters. Les resultats de FAT III et des facteurs 1, 2, 5 et 7, des prelevements veineux et arteriels du groupe etudie ne montrent pas de differences significatives, de meme que les prelevements veineux des deux groupes (figure 1). Les valeurs moyennes des prelevements arteriels, comparees, a la fois avec les prelevements veineux des memes enfants et des enfants controles, sont significativement plus elevees pour PAPTT et le temps de thrombine; le temps de bathroxobine, qui est corrige pour les effets possibles de 1'heparine, n'est eleve dans aucun des prelevements. Les prelevements veineux du groupe etudie versus ceux des controles ne sont pas signiflcativement differents (tableau II).
L'heparine est detectee dans tous les prelevements arteriels, dans trois prelevements, les taux sont superieurs a 0,1 UI/ml, alors que l'APTT et le taux de thrombine sont eleves. L'apport d'heparine n'est pas correle avec les tests de coagulation. Nous concluons qu'une perfusion de 5 UI/ml d'heparine, au rythme de 0,5 ml/hr, en intra-arteriel, n'a pas d'effets detectables sur la coagulation de nouveaux nes prematures. II n'y a pas de differences entre les nouveaux nes malades ventiles, et ceux en meilleure sante non ventiles. Meme avec une technique soigneuse de prelevement sanguin, les echantillons provenant du catheter arteriel peuvent etre contamines par I'heparine, lorsque les taux d'heparine retrouves dans les prelevements sont superieurs a 0,1 UI/ml, les resultats de l'APTT et du temps de thrombine doivent etre regardes avec une extreme prudence.
Mots-cles: Caillot, catheter arteriel, coagulation, heparine, prematures. Acknowledgements: The authors wish to thank the nurses of their NICU for monitoring the heparin infusions and the personnel of the hematologic laboratory for performing the coagulation tests.
References
[1] ANDREW M, B PAES, R MILNER et al: Develop[9] PAPILE LA, J BURSTEIN, R BURSTEIN, H KOFFLER: ment of the human coagulation system in the Incidence and evolution of subependymal and healthy premature infant. Blood 72-5 (1988) intraventricular hemorrhage: A study of infants with birthweight less than 1500 gram. J Pediatr 1651 [2] BESSELAAR VAN DEN AMHP, J MEEUWISSE-BRAUN, 92 (1978) 529 R JANSEN-GRÜTER, RM BERTINA: Monitoring [10] PEARSE RG: Percutaneous catheterization of the radial artery in newborn babies using transilluheparin therapy by the activated partial thrommination. Arch Dis Child 53 (1978) 549 boplastin time — the effect of pre-analytical conditions. Thrombosis and haemostasis 57 (1987) [11] PETERS M, C BREEDERVELD, LH KAHLE, JW TEN CATE: Rapid microanalysis of coagulation para226 meters by automated chromogenic substrate [3] BLOMBÄCK B, M BLOMBÄCK, JM NILSSON: Comethods — application in neonatal patients. agulation studies on "Reptilase", an extract of the Thromb Res 28 (1982) 773 venom from Bothrops jararaca. Thromb Diathes [12] RANDEL SN, BHL TSANG, JT WUNG, JM DRISHaemorrh (Stuttg) 1 (1957) 76 COLL, LS JAMES: Experience with percutaneous [4] BOSQUE E, L WEAVER: Continuous versus interindwelling peripheral arterial catheterization in mittent heparin infusion of umbilical artery cathneonates. Am J Dis Child 141 (1987) eters in the newborn infant. J Pediatr 108 (1986) [13] SPEAR ML, GE STAHL, M HAMOSH et al: Effect 141 of heparin dose and infusion rate on lipid clear[5] BUTT W, F SHANN, G MCUONNNELL, J HUDSON: ance and bilirubin binding in premature infants Effect of heparin concentration and infusion rate receiving intravenous fat emulsions. J Pediatr 112 on the patency of arterial catheters. Crit Care (1988) Med 15 (1987) 230 [6] CLAUSS A, VON: Gerinnungsphysiologische Received. May 25, 1991. Accepted May 30, 1991. Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol (Basle) 17 (1957) 237 [7] LESKO SM, AA MITCHELL, MF EPSTEIN, C LOUIK, Prof. Dr. P. J. J. Sauer Department of Pediatrics GP GIACOIA, S SHAPIRO: Heparin use as a risk factor for intraventricular hemorrhage in low Division of Neonatology birth weight infants. N Engl J Med 314 (1986) Sophia Children's Hospital 1156 Gordelweg 160 [8] MERENSTEIN GB: Heparinized catheters and coNL-3038 GE Rotterdam by | Michigan State University agulation studies. J Pediatr 79 (1971) 117 Brought to you The Netherlands Authenticated Download Date | 6/17/15 1:01 AM
J. Perinat. Med. 20 (1992)
Van Lingen et al, Heparin in arterial catheters
J. Perinat. Med. 20(1992)39-46
The effect of heparin in arterial catheters on the coagulation in preterm infants Richard A. Van Lingen13, Wim J. D. Hofhuis2, Ina Dekker2, Wim Baerts1, Karel Hählen2, and Pieter J. J. Sauer1
Department of Pediatrics, Division of Neonatology and 2Division of Hematology, Erasmus University und University Hospital Rotterdam/Sophia Children's Hospital, Rotterdam, The Netherlands
1
Introduction
In many neonatal intensive care units heparin is used routinely to maintain patency of indwelling arterial umbilical or periferal catheters [7, 13]. The optimal concentration of heparin in the infusion to keep the lines patent is not very well known. Recently it was suggested to use 5 IU heparin per ml [5]. The effect of this dose of heparin on the coagulation of the preterm appropriate for gestational age (AGA) or small for gestational age infant (SGA) is unknown. There might be an increased risk for peri- and intraventricular hemorrhage (PIVH) already at a dose of 1 lU/ml [7]. In our unit we have been using a heparin concentration of 5 lU/ml for a prolonged period of time. Concerned about potential effects on the clotting status of our infants, we undertook a study to evaluate these effects. Secondly, we evaluated if samples obtained from the arterial line showed results comparable with venous samples. 2
Patients and methods
Curriculum vitae RICHARD VAN LINGEN, M.D., was bom in 1953 in Leeuwarden, The Netherlands. In 1980 he graduated from the University of Groningen. From 1982 to 1986 he was a pediatric resident in the Zuiderziekenhuis and the Sophia Childrens Hospital in Rotterdam. From 1986 to 1991 he worked as a neonatologist in the Sophia Childrens Hospital and the University Hospital Groningen. Presently he is a staffmember of the Perinatal Center, Sophia Hospital Zwolle, The Netherlands. His main fields of interest are nutrition, thermogenesis and hematology.
ventilated nor had an arterial catheter served as controls. Control infants showing clinical signs of hemostatic disorders were excluded from the study. All study infants and control infants received 1 mg of vitamin K shortly after birth. Informed consent from one or both of the parents was obtained.
From August 1987 till April 1988 all infants admitted to our NICU with a birth weight < 2000 grams, a gestational age > 27 weeks and with a platelet count > 100 109/liter, who did The heparin solution used contains 5 lU/ml hepnot receive indomethacin or whose mothers had arin (TromboliquineR, Organon Teknika, The not received indomethacin to prevent premature Netherlands) in NaCl 0.9%, at an infusion rate labor and received an arterial catheter on the of 0.5 ml per hour and flushes using the same day of admittance were eligible for inclusion in solution were given after sampling for bloodthe study. Infants meeting the same criteria as gasses. The total amount of heparin given in Brought24tohr youprior by | Michigan State University was measured. the study infants except that they were not being to the bloodsampling 1992 by Walter de Gruyter & Co. Berlin · New York
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Van Lingen et al, Heparin in arterial catheters
Between 48 and 72 hours after birth bloodsamples were taken in both study infants and controls. A venipuncture was performed, the first 0.5 ml of blood was used for other laboratory data, then 2 ml of blood was drawn into a siliconized plastic syringe aseptically and gently flushed into a siliconized plastic tube, containing 0.225 ml of a sterile buffer solution of sodium citrate (0.11 mol/1), theophyllin, adenosin and dipyramidol (CTAD, Boehringer Mannheim, Germany) to prevent neutralization of heparin in vitro by platelet factor four [2] and mixed carefully. In the study infants blood was also taken from the arterial catheter using the following technique [8]: a. 0.7 ml of fluid in catheter and stopcock is drawn into a siliconized plastic syringe aseptically and discarded. b. Five milliliters of blood are drawn into another siliconized plastic syringe aseptically. c. After removing the stopcock two milliliters of blood flowed freely into a tube containing CTAD as mentioned before and mixed carefully. d. The original five milliliters of blood was returned aseptically to the patient and the catheter was flushed.
a one-stage clotting assay, using rabbit brain thromboplastin (Dade thromboplastin-FS). ATIII activity was determined chromogenically (Boehringer Mannheim). To analyze if abnormal results of APTT and TT might be correlated to heparin levels in the sample, two heparin assays were performed, analysing both the anti-Xa effect of heparin in the presence of AT-III (Hepaclot, Stago) and its anti-IIa effect (Heparin Low Dose, Boehringer Mannheim). Ultrasound studies of the brain were performed by one investigator (WB). All infants were scanned at least twice during the first week of life. Statistical analysis was performed by means of the Wilcoxon signed rank test for the paired data and the Wilcoxon ranking test for unpaired data (Mann-Whitney test). 3 Results Twenty infants were eligible for inclusion in the study, five of them were excluded. One infant died within 36 hour after birth, in two cases the catheter was removed electively before the day of study and in two cases clotting of the sample occurred before centrifugation. In 13 of the remaining 15 infants an arterial and venous sample was obtained, in 2 infants no venous sample could be obtained. Data of these 13 infants are included in the analysis. All catheters were placed in the radial artery, 10 in the right radial artery, 5 in the left.
All blood sampling was done by the same investigator (RVL). The samples were put on melting ice and within ten minutes centrifugated with 4000 rpm for ten minutes and then again with 20.000 rpm for thirty minutes at a temperature of 4° Celsius. The samples were devided in three From the 26 eligible control infants, 10 were fractions and stored at — 80° Celsius until serial excluded; 7 because of clotting of the sample and analysis was performed. The possible effect of 3 because of clinical symptoms of coagulation heparin on the coagulation was analyzed using disorder (i.e. bleeding from digestive tract or the activated partial thromboplastin time (APIT) prolonged bleeding from puncture sites or peteand the thrombin time (TT). To evaluate if pos- chiae), before the sample was obtained. Clinical sible abnormal results might be caused by a more details of the two groups are shown in table I. general coagulation disorder, we also measured There was no significant difference in birth Antithrombin III (AT-III), bathroxobin time and weight or gestational age (as determined by Balfactors I, II, V and VII. The APTT was measured lard scores and maternal ultrasound dates) beusing rabbit brain cephalin (Dade Actin). tween the two groups. On the day of bloodsamThrombin time was determined photometrically pling all arterial catheters were patent, nine of (Behring Werke). Bathroxobin time (ReptilaseR), those were removed electively later on; mean a test with a proteolytic enzyme from Bothrops duration of patency in these infants was 3.63 atrox, that measures fibrinolytic activity as the ± 1.75 days (range 2.04-6.92 days). Six cathethrombin time but is not influenced by thrombin ters were removed because of complications as inhibitors such as heparin [3] was also deter- blood oozing next to the catheter (one), or when mined photometrically (Behring Werke). Fibri- no more samples from the arterial catheter could nogen (factor I) was measured according to VON be drawn (five). Mean duration of patency in CLAUSS' method [6]. Coagulation factors II, V these infants was 9.77 ±5.81 days (range you by | Michigan and VII clotting activities were performedBrought with to2-18.4 days). State University Authenticated Download Date | 6/17/15 1:01 AM
J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters Table I. Clinical details of the study group and controls
(n = 13)
Study group
Controls (n = 16)
Weight (g) (mean ± SD)
1391 + 308 (range 1060 -1930)
1440 + 200.6 (range 1100-1835)
Gestational age (wks) (mean + SD)
30.15 + 1.36 (range 27 -31. 86)
32 ± 2.39 (range 28 -35.57)
study group arterial
study group venous
V//A
100
AT III (%)
factor II (%) factor V (%) factor VII (%)
factor I (g/l)
Figure 1. Mean values + SD for arterial and venous samples of the study infants and control for AT III and factors I, II, V and VII. * Neither the arterial nor the venous data of the study infants are statistically significant different from the control infants.
The amount of heparin administered to the study time were not significantly different between the infants was 103 ± 29 IU/day and 86.7 ± 29 IU/ study infants and the controls (table II). kg/day. Figure I shows the results for AT-III and factors In ten of the twelve infants heparin could not be I, II, V and VII for the arterial and venous detected in the venous sample, in two infants a samples from the study infants and the venous very low amount of heparin was detected. The values of the arterial samples showed a samples from the control infants. There were no mean significant lenghtened APTT and thrombin time significant differences between venous samples compared with the venous samples of the from the two groups nor between the arterial same infants andboth with control infants. Moreover and venous values from the study group. the results of the arterial samples showed a The mean values of the venous samples of the higher variability. In three infants the APTT was Broughtmore to youthan by | Michigan Statethe University APTT, the thrombin time and the bathroxobin four times mean of the controls, J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters
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43
Van Lingen et al, Heparin in arterial catheters
the thrombin time was also lengthened in these infants. The bathroxobin time, in which is corrected for possible heparin effects, showed no elevation in any of these three samples. Heparin was detectable in almost all arterial samples by the heparin anti-Xa as well as by the heparin anti-IIa test. The heparin level was more than 0.1 lU/ml, as measured by both tests, in all three arterial samples in which the APTT and thrombin time was elevated. No correlation between heparin intake and coagulation tests, either from venous or from arterial samples, could be found. Ultrasound diagnoses for PIVH were made in three out of thirteen study infants (one PIVH I, two PIVH II) and in one out of sixteen control infants (PIVH I) [9]. 4 Discussion
the influence of the amount of heparin given with this regime on the coagulation of preterm infants [5]. Venous samples are the best indicators to study possible systemic effects of heparin given via the intraarterial route in order to keep a catheter patent. In only 2 of the 13 study infants, a small amount of heparin activity in the venous samples was found. All heparin independent coagulationtests were found to be in the same range as in the control infants (figure 1) indicating that there was no more general coagulation disorder present. This was also the case for the APTT and TT (table II) and bathroxobin time. Only one child with a detectable heparin anti-IIa level in the venous sample had a prolonged APTT (but a normal TT). Thus, it can be concluded that an intraarterial infusion of 5 lU/ml heparin given at an infusion rate of 0.5 ml/hr has no detectable effect on the coagulation in preterm infants.
It is important to note that the values for the Although it is presently possible to measure oxdifferent coagulation parameters were not difygen tension and oxygen saturation transcutaferent between the more sick, ventilated infants neously, arterial bloodgas analysis and intraarand the more healthy, not ventilated infants. terial monitoring of blood pressure are still necMoreover the values we obtained are in good essary in ventilated newborn infants. As infants agreement with values reported recently by other can react on arterial punctures with unrest and investigators in "healthy" preterm infants [1,11]. crying and thereby give false results of their The incidence of intracranial hemorrhage was steady state bloodgas status, arterial catheters not different between study and control infants. are of great importance in these infants [10]. In The coagulation tests in the study infants showview of the limited number of arteries available ing a grade I or II bleeding were not different for the insertion of these lines, it is important from the control infants. Because the study popthat they remain patent as long as possible withulation is too small to detect a significant differout side effects. Heparin is used since a long time ence we conclude that heparin given in a dose in the fluids used for continuous infusion and/ as presented in this study, does not appear to or flushes. BOSQUE and WEAVER showed that a increase the risk for a PIVH. continuous heparin infusion is to be preferred above intermittent heparin flushes to keep the Finally, the comparison of the results of the umbilical artery catheter patent. While using a samples obtained by venipuncture and from the solution containing l IU heparin per ml at dif- arterial catheters show that the data from the ferent rates with a mean intake of 120 IU/kg/ arterial catheters have to be interpreted in reladay (range 80-220 IU/kg/day), the mean du- tion to the possibility of contamination of these ration of patency of an umbilical catheter was samples with heparin. The coagulation tests that only 66.9 hrs [4]. RANDEL et al described their are independent of heparin were as expected not results with periferal artery catheters; also using influenced by the route they were obtained, so a 1 lU/ml heparin solution at a rate of 2 ml/hr. the heparin independent tests can be taken from With this regime, the mean duration of the pat- (heparinized) arterial catheters. In contrast to ency of the radial catheters that were not elec- MERENSTEIN, however, we found that falsely high tively removed was 87.8 hr [12]. BUTT et al sug- results can be obtained for coagulation tests that gested recently to use a solution containing 5 IU/ are influenced by the presence of heparin, as ml at a rate of 1 ml/hr as they showed that the heparin is detectable in almost all samples, even peripheral arterial catheters remained longer pat- if the technique of blood sampling is as careful ent with this solution compared with a 1 lU/ml as in the present study [8]. As no heparin could Broughtbeto detected you by | Michigan University containing solution. They did not study however in the State venous samples of the same J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters
infants, the heparin found in the arterial samples must be caused by contamination from the arterial line. Especially when the heparin level found in the same sample is more than 0.1 IU/ ml, the results of the APTT and thrombin time should be regarded with extreme caution. In conclusion, a solution containing 5 lU/ml of heparin infused intraarterially at a rate of 0.5
ml/hour does not affect systemic coagulation in premature infants. Bloodsamples taken from arterial catheters in the way described before can be used for coagulation studies for bathroxobin, AT-III and factors I, II, V and VII. This might also be valid for APTT and thrombin time as long as the heparin concentration is less than 0.1 lU/ml.
Abstract
The coagulation of 16 healthy preterm infants (control infants) was compared with 15 ventilated preterm infants (study infants) receiving 0.5 ml/hr of a solution containing 5 lU/ml heparin intra-arterially in order to keep a radial artery catheter patent. A venous sample was obtained in both groups, in the study group a sample from the arterial catheter was also taken. Both the heparin dependent (APTT, thrombin time) and the heparin independent coagulation factors (AT-III, Clotting Factors I, II, V and VII) were not different between the venous samples of both groups. The arterial samples showed a significantly elevated APTT and thrombin time compared with venous samples, espe-
cially when the heparin level in the sample was higher than 0.1 lU/ml. These elevations are due to heparin in the sample from the arterial line as the venous sample in the same patient did not show any heparin effect. The heparin non-dependent factors were not different between venous and arterial samples. We conclude that a solution containing 5 lU/ml heparin given at a rate of 0.5 ml/hr does not influence coagulation in preterm infants. Determination of heparin independent coagulation factors can be done in both venous samples and samples taken from the arterial catheter, in these arterial samples the heparin dependent factors can be influenced by the heparin present in the catheters.
Keywords: Arterial catheter, clotting, coagulation, heparin, preterm infants.
Zusammenfassung Einfluß yon Heparin in intraarteriellen Kathetern auf die Gerinnung bei Frühgeborenen
zwischen den beiden Gruppen keine Unterschiede: Alle Kinder wogen weniger als 2000g, hatten ein Gestationsalter von mehr als 27 Wochen und Thrombozyten von mehr als 100 109/1. Weder die Kinder noch die Mütter vor der Geburt hatten Indomethacin erhalten. Alle Kinder bekamen jedoch l mg Vitamin K kurz nach der Geburt. Kinder aus der Kontrollgruppe, die klinische Zeichen einer Störung der Haemostase zeigten, wurden aus der Studie ausgeschlossen. Die Blutentnahme erfolgte wie oben beschrieben [2, 8]. Die Proben wurden in schmelzendes Eis gegeben, zentrifugiert, in drei Portionen aufgeteilt und bei — 80 °C bis zur Analyse aufbewahrt. Um mögliche Effekte des Heparins auf die Koagulation zu erfassen, wurden APTT und Thrombin-Zeit (TT) bestimmt; die Messung des AT III, der Bathroxobin-Zeit und der Faktoren I, II, V und VII erfolgte, um möglicherweise abweichende Ergebnisse, die aber durch übergeordnete Störungen der Blutgerinnung verursacht sind, zu erfassen. Um zu analysieren, ob abnorme APTT- und TT-Werte mit einem erhöhten Heparin-Spiegel in der Probe korreliert sind, wurden zwei Assays angesetzt, mit denen der Anti-XA- und Anti-IIA-Effekt des Heparins geprüft wurde.
Um intraarterielle Katheter bei Neugeborenen durchgängig zu halten, wird einer kontinuierlichen Heparinisierung gegenüber intermittierenden Zugaben der Vorzug gegeben. Bei einer Heparin-Konzentration von l lU/ml war die Dauer der Durchgängigkeit signifikant kürzer als bei Konzentrationen von 5 lU/ml [4, 5, 12]. Bisher wurde jedoch nicht der Einfluß des infundierten Heparins auf die Gerinnung der Frühgeborenen untersucht. Wir untersuchten 46 Kinder, um die Wirkung des Heparins, das intraarterielle Katheter offenhalten soll, auf die Gerinnung von Frühgeborenen zu erfassen und um zu sehen, ob Proben aus den arteriellen Kathetern vergleichbare Ergebnisse mit denen aus venösen Proben aufweisen. 20 dieser Kinder wurden beatmet. Alle erhielten eine salzhaltige Lösung einer Dosis von 0,5 ml/Std. über einen arteriellen Katheter, die 5 lU/ml Heparin/ml enthielten. Nach Blutentnahme wurde mit der gleichen Lösung durchgespült. Zwischen 48 und 72 Std. post partum wurden die Gerinnungsparameter in venösen Blutproben sowie in arteriellen Proben aus dem Katheter bestimmt. Die Ergebnisse verglichen wir mit den Werten von 26 gesunden Kindern (Kontrollgruppe), die nicht beatmet waren und keinen arteriellen Katheter hatten. Im Hinblick auf andere Parameter Brought gab es to you by | Michigan State University Authenticated Download Date | 6/17/15 1:01 AM
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Van Lingen et al, Heparin in arterial catheters Die statistische Bearbeitung erfolgte über den WILCOXON-Test für paarweise angeordnete Meßwerte und den WILCOXON-Test für nicht gepaarte Daten (MANN-WHITNEY-Test). Fünf Kinder aus der Untersuchungsgruppe und 10 Kinder aus der Kontrollgruppe wurden aus der Studie ausgeschlossen, weil der Katheter entfernt werden mußte, die Blutprobe geronnen war oder bei den Kontroll-Kindern klinische Zeichen einer Blutgerinnungsstörung auftraten. Tabelle I enthält die klinischen Befunde der 15 Untersuchungs- und 16 Kontroll-Kinder. Wurden die Katheter elektiv entfernt, betrug die mittlere Dauer der Durchgängigkeit 3,6 ±1,7 Tage, bei den anderen Kathetern 9,8 ± 5,8 Tage. Zwischen den arteriellen und venösen Proben im Untersuchungskollektiv gab es keine signifikanten Unterschiede bezüglich des AT III und der Faktoren I, II, V und VII. Dasselbe gilt für die venösen Blutproben der Untersuchungs- bzw. Kontrollgruppe (Abb. 1). Bezogen auf das APTT und die TT, lagen jedoch die Mittelwerte der arteriellen Proben signifikant höher als
die aus den venösen Proben der Katheter-Kinder und Kontroll-Kinder. Die Bathroxobin-Zeit, mit der mögliche Heparin-Effekte eliminiert werden, war in keiner Probe erhöht. Zwischen den venösen Proben aus Untersuchungs- und Kontrollgruppe gab es keine signifikanten Unterschiede (Tab. II). In allen arteriellen Proben war Heparin nachweisbar; in drei Proben lagen die Spiegel höher als 0,1 lU/ml, wobei APTT und TT erhöht waren. Der HeparinSpiegel im Blut korrelierte nicht mit den Gerinnungstests. Wir schließen daraus, daß eine Infusion von 5 IU Heparin/ml, die über 0,5 ml/Std. intraateriell gegeben wird, keinen nachweisbaren Einfluß auf die Koagulation bei Frühgeborenen hat. Zwischen beeinträchtigten und beatmeten Kinder sowie gesunden, nicht beatmeten Kindern gab es keine Unterschiede. Selbst bei sorgfaltiger Blutentnahme können die Proben aus Kathetern mit Heparin kontaminiert seinl. Liegt der Spiegel über 0,1 lU/ml, sollten die APTT- und TT-Werte zurückhaltend interpretiert werden.
Schlüsselwörter: Arterieller Katheter, Frühgeborene, Gerinnselbildung, Gerinnung.
Resume Effets de l'heparine au niveau des catheters arteriels sur regu d'Indometacine. Tous les nouveaux nes ont regu la coagulation des prematures l mg de vitamine K, peu de temps apres la naissance. Afln de conserver les catheters arteriels, chez les pre- Les nouveaux nes controles, presentant des signes climatures, il est preferable de faire appel a une hepari- niques de troubles de Fhemostase, ont ete exclus de nisation continue, plutot qu'a des flashs intermittents; l'etude. une solution comportant l Ul/ml d'heparine a une Les prelevements sanguins ont ete effectues comme duree d'hypocoagulabilite plus breve que celle conte- cela a ete decrit anterieurement. nant 5 Ul/ml [4, 5, 12]. L'influence de l'heparine per- Les echantillons sont places dans de la glace pilee, fusee sur la coagulation des prematures, cependant, centrifuges, separes en trois fractions et Stockes a — 80° n'a pas ete etudiee. Pour evaluer Feffet de l'heparine, centigrade jusqu'ä la realisation des analyses en serie. utilisee pour maintenir une hypocoagulabilite au ni- On s'est servi de FAPTT et du temps de thrombine veau des catheters arteriels, sur la coagulation des pour analyser les effets possible de l'heparine sur la prematures, et pour voir si les prelevements, obtenus coagulation; on a dose L'AT III, le temps de bathroxoä partir des catheters arteriels montrent des resultats bine, et les facteurs l, 2, 5 et 7, afin d'evaluer des comparables a ceux des prelevements veineux, on a resultats anormaux eventuels, provoques par un etudie 46 nouveaux nes. trouble de la coagulation plus general. Vingt de ces enfants etaient ventiles (nouveaux nes etudies), ils recevaient tous 0,5 ml/hr de serum sale, Pour analyser si les resultats anormaux de l'APTT et contenant 5 Ul/ml d'heparine, par le catheter arteriel du TT peuvent etre correles au taux d'heparine dans ainsi que eds ringages, apres prelevements sanguins, les prelevements, on a effectue deux dosages d'hepaavec la meme solution. On a compare leur coagulation, rine, en analysant les effets anti-XA et anti-IIA de sur des prelevements veineux et sur des prelevements l'heparine. du catheter arteriel, efectues entre 48 et 72 heures apres On a effectue une analyse statistique ä l'aide du test la naissance, avec la coagulation, au niveau de prele- de Wilcoxon pour les donnees appariees et du test pour vements veineux, de 28 nouveaux nes, prematures, en les donnees non-appariees (Mann-Whitney test). bonne sante (nouveaux nes controles), non ventiles et On a exclu cinq enfants etudies et dix enfants controles sans catheters arteriels. Sous tous les autres aspects, il de l'etude, en raison de l'ablation du catheter, de la n'y a pas de differences entre les deux groupes, tous coagulation du prelevement ou, pour le groupe les nouveaux nes pesaient moins de 2000 grammes, controle, de signes cliniques dec troubles de la coaguavaient un age gestationnel > 27 semaines, et une lation. numeration plaquettaire > 100 10—9/litre. Ni les Les details cliniques des 15 nouveaux nes etudies et Broughtdes to you by | Michigan Statedans University nouveaux nes, ni leurs meres, avant la naissance n'ont 10 controles figurent le tableau I. J. Perinat. Med. 20 (1992)
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Van Lingen et al, Heparin in arterial catheters
La duree moyenne de 1'hypocoagulabilite au niveau des catheters enleves electivement est de 3,6 + ou — 1,7 jours; et de 9,8 4- ou — 5,8 jours pour les autres catheters. Les resultats de FAT III et des facteurs 1, 2, 5 et 7, des prelevements veineux et arteriels du groupe etudie ne montrent pas de differences significatives, de meme que les prelevements veineux des deux groupes (figure 1). Les valeurs moyennes des prelevements arteriels, comparees, a la fois avec les prelevements veineux des memes enfants et des enfants controles, sont significativement plus elevees pour PAPTT et le temps de thrombine; le temps de bathroxobine, qui est corrige pour les effets possibles de 1'heparine, n'est eleve dans aucun des prelevements. Les prelevements veineux du groupe etudie versus ceux des controles ne sont pas signiflcativement differents (tableau II).
L'heparine est detectee dans tous les prelevements arteriels, dans trois prelevements, les taux sont superieurs a 0,1 UI/ml, alors que l'APTT et le taux de thrombine sont eleves. L'apport d'heparine n'est pas correle avec les tests de coagulation. Nous concluons qu'une perfusion de 5 UI/ml d'heparine, au rythme de 0,5 ml/hr, en intra-arteriel, n'a pas d'effets detectables sur la coagulation de nouveaux nes prematures. II n'y a pas de differences entre les nouveaux nes malades ventiles, et ceux en meilleure sante non ventiles. Meme avec une technique soigneuse de prelevement sanguin, les echantillons provenant du catheter arteriel peuvent etre contamines par I'heparine, lorsque les taux d'heparine retrouves dans les prelevements sont superieurs a 0,1 UI/ml, les resultats de l'APTT et du temps de thrombine doivent etre regardes avec une extreme prudence.
Mots-cles: Caillot, catheter arteriel, coagulation, heparine, prematures. Acknowledgements: The authors wish to thank the nurses of their NICU for monitoring the heparin infusions and the personnel of the hematologic laboratory for performing the coagulation tests.
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