Downloaded from fn.bmj.com on July 8, 2014 - Published by group.bmj.com
Original article
Fresh frozen plasma use in the NICU: a prospective, observational, multicentred study Mario Motta,1 Antonio Del Vecchio,2 Barbara Perrone,3 Stefano Ghirardello,4 Maurizio Radicioni5 1 Children’s Hospital of Brescia, Brescia, Italy 2 Ospedale Di Venere, Bari, Italy 3 “G.Salesi” Children’s Hospital, Ancona, Italy 4 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy 5 Santa Maria della Misericordia Hospital, Perugia, Italy
Correspondence to Dr Mario Motta, Neonatology and Neonatal Intensive Care Unit, Children’s Hospital of Brescia, P.le Spedali Civili, Brescia 25123, Italy; mario. [email protected] Received 27 June 2013 Revised 3 February 2014 Accepted 25 February 2014 Published Online First 19 March 2014
ABSTRACT Objectives To examine the use of fresh frozen plasma (FFP) in Italian neonatal intensive care units (NICUs); specifically to quantify compliance with guideline recommendations and to evaluate the relationship between coagulation tests and subsequent bleeding episodes. Design Prospective, observational study. Setting Seventeen Italian NICUs. Patients and methods Over a period of 12 months, for all neonates that received FFP we recorded specific characteristics, pretransfusion and post-transfusion laboratory test of haemostasis, and details of all haemorrhagic events. Results Among 3506 NICU admissions, 290 (8.2%) received one or more FFP transfusions during their hospital stay. Of these, 37% received FFP because of active bleeding and 63% received FFP prophylactically with the intention of preventing haemorrhage. A total of 609 FFP transfusions were administered (mean 2.1/ transfused patient—range 1–25). Using previously agreed upon criteria, we judged that 60% of the 609 FFP transfusions were not compliant with guideline recommendations. By logistic regression, abnormalities in the prothrombin time, activated partial thromboplastin time, fibrinogen and platelet count were not independently associated with bleeding episodes. Conclusions FFP transfusion is a relatively frequent intervention in the NICU. In the present analysis, we found a remarkably high proportion of FFP transfusions given to non-bleeding neonates for indications not compliant with guideline recommendations. Platelet counts and coagulation studies were poor predictors of clinical bleeding.
INTRODUCTION
To cite: Motta M, Del Vecchio A, Perrone B, et al. Arch Dis Child Fetal Neonatal Ed 2014;99: F303–F308.
The use of fresh frozen plasma (FFP) in neonatal intensive care units (NICUs) appears to be a frequent intervention despite a lack of supporting evidence. In a recent study from England, Stanworth et al1 showed that 2.3% of all patients receiving FFP were children (aged 1–15 years) and 4.4% of these were less than 1 year old. He also reported that 62% of infants who received FFP did not have clinical bleeding and that 14% of infants treated with FFP did not have coagulation tests before the FFP administration.1 Puetz et al2 reported that FFP was administered to 2.85% of admissions to paediatric hospitals in the USA and that 29% of these transfusions were given to neonates. A variety of guidelines on transfusion of blood components in neonates have been published.3–5 In 2002, Roseff et al3 reviewed the appropriateness of transfusions in paediatric populations, including
What is already known on this topic ▸ The use of fresh frozen plasma (FFP) in neonatal intensive care units (NICUs) is not evidence-based and practice varies. ▸ Coagulation testing is sometimes used to identify candidates for FFP transfusion.
What this study adds ▸ During a 12-month period, 8.2% of newborns cared for in 17 Italian NICUs received one or more FFP transfusions. ▸ Of these transfusions, 60% were non-compliant with published guidelines. ▸ Coagulation testing did not predict subsequent clinical haemorrhage.
recommendations of FFP transfusion that were mainly based on expert opinion. In 2004, the British Committee for Standards in Haematology updated its document on transfusion guidelines for neonates and older children.4 In this document, the strength of recommendations was graded by using the quality of evidence and, apart from a few conditions where the use of FFP is not supported by results of controlled clinical studies, the recommended indications for FFP transfusion were characterised by a low level of evidence. Although guidelines highlight that the use of plasma products in neonates should be limited to specific conditions, the lack of scientific evidence in the majority of clinical settings may lead to a wide variety of transfusion practice among neonatologists. We previously reported results of a national Italian survey on neonatal transfusion practice, where 11% of NICUs reported administering FFP for clinical indications alone without coagulation testing. We also reported that 26% of NICUs administered FFP outside guideline-based indications.6 Several reports have evaluated the potential usefulness of FFP transfusions in neonates7 8; however, detailed data are lacking. Consequently, we aimed to (1) prospectively quantify FFP usage in representative Italian NICUs, (2) judge the appropriateness of each FFP administration according to preset guidelines, (3) describe and quantify all haemorrhagic episodes among FFP-transfused neonates and (4) statistically assess associations between potential risk factors and actual bleeding episodes.
Motta M, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F303–F308. doi:10.1136/archdischild-2013-304747
F303
Downloaded from fn.bmj.com on July 8, 2014 - Published by group.bmj.com
Original article METHODS Participating centres, study subjects and ethical approval In total, 17 (21.5%) out of 79 tertiary-level NICUs in Italy participated in this study. All neonates in these NICUs who received a FFP transfusion were eligible for prospective enrolment. Participating NICUs supported recruitment for a 12-month period from January 2011 to February 2012. The study was approved by the Ethics Committee of the Children’s Hospital of Brescia, which was the coordinating study centre. Written informed consent was obtained from the parents of all neonates included in the study.
Data collection and statistical analysis Baseline data included gestational age, birth weight, postnatal age at transfusion, dose (mL/kg) of FFP administered, pretransfusion and post-transfusion laboratory tests of haemostasis, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and pretransfusion platelet count. Pretransfusion and post-transfusion laboratory tests of haemostasis were considered as those tests performed within 24 h before and up to 24 h after FFP administration. A list of potential indications for FFP use (compliant and non-compliant with guideline recommendations) was included in the data collection form (table 2). For each FFP transfusion administered, the indication for the transfusion was recorded from an attending senior neonatologist during or immediately after ordering. Haemorrhage as an indication for FFP was classified as intraventricular haemorrhage (IVH), pulmonary haemorrhage, gastrointestinal haemorrhage or minor haemorrhage. IVH was diagnosed by cranial sonography and graded by the classification of Papile et al.9 Pulmonary haemorrhage was defined as a significant amount of blood suctioned from the endotracheal tube with a chest radiograph consistent with pulmonary bleeding. Gastrointestinal haemorrhage was defined as a significant amount of blood suctioned from the stomach or repeated episodes of haematochezia or melena. Minor haemorrhage included mucocutaneous bleeding, such as light blood staining of oral, nasogastric or endotracheal secretions, or the occurrence of microhematuria or ecchymosis. The timing of cranial sonography and the specific laboratory assessments of haemostasis were not mandated by the study. All data were reviewed by the coordinating study centre, and the indications of each FFP administration were grouped as compliant or non-compliant with respect to published standards and guidelines for neonatal transfusion.3–5 In addition, in order to compare the mortality rate of FFP transfusion recipients with that of the general NICU population, data on the total number of neonatal admissions and on the total neonatal mortality rate during the study period were collected from each NICU participating in the study. The characteristics of study neonates were analysed by descriptive statistics. Continuous variables with symmetrical distribution were presented as mean±SD, continuous variables with asymmetrical distribution were presented as median and interquartile range and categorical variables were presented as absolute number and percentage. Comparisons between pretransfusion and post-transfusion values of PT, APTT and fibrinogen were performed by Mann–Whitney U test. Transfusion events were grouped according to different types of haemorrhagic episodes, as specified above, and characteristics of each different subgroups were compared with the group of FFP-transfused neonates without bleedings using Mann– F304
Whitney U or Fisher’s exact tests. Logistic regression analysis was used to evaluate the possible association between gestational age, birth weight and pretransfusion values of PT, APTT, fibrinogen and platelet count as continuous independent variables, and the occurrence of different subtypes of haemorrhages as categorical dependent variables. All computations were performed using two statistical packages (Statistica, StatSoft, Tulsa, Oklahoma, USA; MedCalc for Windows, Mariakerke, Belgium). All results were considered statistically significant at p
Original article
Fresh frozen plasma use in the NICU: a prospective, observational, multicentred study Mario Motta,1 Antonio Del Vecchio,2 Barbara Perrone,3 Stefano Ghirardello,4 Maurizio Radicioni5 1 Children’s Hospital of Brescia, Brescia, Italy 2 Ospedale Di Venere, Bari, Italy 3 “G.Salesi” Children’s Hospital, Ancona, Italy 4 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy 5 Santa Maria della Misericordia Hospital, Perugia, Italy
Correspondence to Dr Mario Motta, Neonatology and Neonatal Intensive Care Unit, Children’s Hospital of Brescia, P.le Spedali Civili, Brescia 25123, Italy; mario. [email protected] Received 27 June 2013 Revised 3 February 2014 Accepted 25 February 2014 Published Online First 19 March 2014
ABSTRACT Objectives To examine the use of fresh frozen plasma (FFP) in Italian neonatal intensive care units (NICUs); specifically to quantify compliance with guideline recommendations and to evaluate the relationship between coagulation tests and subsequent bleeding episodes. Design Prospective, observational study. Setting Seventeen Italian NICUs. Patients and methods Over a period of 12 months, for all neonates that received FFP we recorded specific characteristics, pretransfusion and post-transfusion laboratory test of haemostasis, and details of all haemorrhagic events. Results Among 3506 NICU admissions, 290 (8.2%) received one or more FFP transfusions during their hospital stay. Of these, 37% received FFP because of active bleeding and 63% received FFP prophylactically with the intention of preventing haemorrhage. A total of 609 FFP transfusions were administered (mean 2.1/ transfused patient—range 1–25). Using previously agreed upon criteria, we judged that 60% of the 609 FFP transfusions were not compliant with guideline recommendations. By logistic regression, abnormalities in the prothrombin time, activated partial thromboplastin time, fibrinogen and platelet count were not independently associated with bleeding episodes. Conclusions FFP transfusion is a relatively frequent intervention in the NICU. In the present analysis, we found a remarkably high proportion of FFP transfusions given to non-bleeding neonates for indications not compliant with guideline recommendations. Platelet counts and coagulation studies were poor predictors of clinical bleeding.
INTRODUCTION
To cite: Motta M, Del Vecchio A, Perrone B, et al. Arch Dis Child Fetal Neonatal Ed 2014;99: F303–F308.
The use of fresh frozen plasma (FFP) in neonatal intensive care units (NICUs) appears to be a frequent intervention despite a lack of supporting evidence. In a recent study from England, Stanworth et al1 showed that 2.3% of all patients receiving FFP were children (aged 1–15 years) and 4.4% of these were less than 1 year old. He also reported that 62% of infants who received FFP did not have clinical bleeding and that 14% of infants treated with FFP did not have coagulation tests before the FFP administration.1 Puetz et al2 reported that FFP was administered to 2.85% of admissions to paediatric hospitals in the USA and that 29% of these transfusions were given to neonates. A variety of guidelines on transfusion of blood components in neonates have been published.3–5 In 2002, Roseff et al3 reviewed the appropriateness of transfusions in paediatric populations, including
What is already known on this topic ▸ The use of fresh frozen plasma (FFP) in neonatal intensive care units (NICUs) is not evidence-based and practice varies. ▸ Coagulation testing is sometimes used to identify candidates for FFP transfusion.
What this study adds ▸ During a 12-month period, 8.2% of newborns cared for in 17 Italian NICUs received one or more FFP transfusions. ▸ Of these transfusions, 60% were non-compliant with published guidelines. ▸ Coagulation testing did not predict subsequent clinical haemorrhage.
recommendations of FFP transfusion that were mainly based on expert opinion. In 2004, the British Committee for Standards in Haematology updated its document on transfusion guidelines for neonates and older children.4 In this document, the strength of recommendations was graded by using the quality of evidence and, apart from a few conditions where the use of FFP is not supported by results of controlled clinical studies, the recommended indications for FFP transfusion were characterised by a low level of evidence. Although guidelines highlight that the use of plasma products in neonates should be limited to specific conditions, the lack of scientific evidence in the majority of clinical settings may lead to a wide variety of transfusion practice among neonatologists. We previously reported results of a national Italian survey on neonatal transfusion practice, where 11% of NICUs reported administering FFP for clinical indications alone without coagulation testing. We also reported that 26% of NICUs administered FFP outside guideline-based indications.6 Several reports have evaluated the potential usefulness of FFP transfusions in neonates7 8; however, detailed data are lacking. Consequently, we aimed to (1) prospectively quantify FFP usage in representative Italian NICUs, (2) judge the appropriateness of each FFP administration according to preset guidelines, (3) describe and quantify all haemorrhagic episodes among FFP-transfused neonates and (4) statistically assess associations between potential risk factors and actual bleeding episodes.
Motta M, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F303–F308. doi:10.1136/archdischild-2013-304747
F303
Downloaded from fn.bmj.com on July 8, 2014 - Published by group.bmj.com
Original article METHODS Participating centres, study subjects and ethical approval In total, 17 (21.5%) out of 79 tertiary-level NICUs in Italy participated in this study. All neonates in these NICUs who received a FFP transfusion were eligible for prospective enrolment. Participating NICUs supported recruitment for a 12-month period from January 2011 to February 2012. The study was approved by the Ethics Committee of the Children’s Hospital of Brescia, which was the coordinating study centre. Written informed consent was obtained from the parents of all neonates included in the study.
Data collection and statistical analysis Baseline data included gestational age, birth weight, postnatal age at transfusion, dose (mL/kg) of FFP administered, pretransfusion and post-transfusion laboratory tests of haemostasis, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and pretransfusion platelet count. Pretransfusion and post-transfusion laboratory tests of haemostasis were considered as those tests performed within 24 h before and up to 24 h after FFP administration. A list of potential indications for FFP use (compliant and non-compliant with guideline recommendations) was included in the data collection form (table 2). For each FFP transfusion administered, the indication for the transfusion was recorded from an attending senior neonatologist during or immediately after ordering. Haemorrhage as an indication for FFP was classified as intraventricular haemorrhage (IVH), pulmonary haemorrhage, gastrointestinal haemorrhage or minor haemorrhage. IVH was diagnosed by cranial sonography and graded by the classification of Papile et al.9 Pulmonary haemorrhage was defined as a significant amount of blood suctioned from the endotracheal tube with a chest radiograph consistent with pulmonary bleeding. Gastrointestinal haemorrhage was defined as a significant amount of blood suctioned from the stomach or repeated episodes of haematochezia or melena. Minor haemorrhage included mucocutaneous bleeding, such as light blood staining of oral, nasogastric or endotracheal secretions, or the occurrence of microhematuria or ecchymosis. The timing of cranial sonography and the specific laboratory assessments of haemostasis were not mandated by the study. All data were reviewed by the coordinating study centre, and the indications of each FFP administration were grouped as compliant or non-compliant with respect to published standards and guidelines for neonatal transfusion.3–5 In addition, in order to compare the mortality rate of FFP transfusion recipients with that of the general NICU population, data on the total number of neonatal admissions and on the total neonatal mortality rate during the study period were collected from each NICU participating in the study. The characteristics of study neonates were analysed by descriptive statistics. Continuous variables with symmetrical distribution were presented as mean±SD, continuous variables with asymmetrical distribution were presented as median and interquartile range and categorical variables were presented as absolute number and percentage. Comparisons between pretransfusion and post-transfusion values of PT, APTT and fibrinogen were performed by Mann–Whitney U test. Transfusion events were grouped according to different types of haemorrhagic episodes, as specified above, and characteristics of each different subgroups were compared with the group of FFP-transfused neonates without bleedings using Mann– F304
Whitney U or Fisher’s exact tests. Logistic regression analysis was used to evaluate the possible association between gestational age, birth weight and pretransfusion values of PT, APTT, fibrinogen and platelet count as continuous independent variables, and the occurrence of different subtypes of haemorrhages as categorical dependent variables. All computations were performed using two statistical packages (Statistica, StatSoft, Tulsa, Oklahoma, USA; MedCalc for Windows, Mariakerke, Belgium). All results were considered statistically significant at p
