Fresh frozen plasma use in the NICU: a prospective,

observational, multicentred study

Dr Prakash. I

What is already known on this topic

The use of FFP in 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 in 17 NICUs received one or more FFP transfusions.

60% were non-compliant with published guidelines.

Coagulation testing did not predict subsequent clinical hemorrhage.

Introduction

FFP administration: most frequent intervention in NICU

Recommended indications for FFP transfusion : characterized by a low level of evidence.

Due to lack of scientific evidence a wide variety of transfusion practice is followed.

Objectives

1. Prospectively quantify FFP usage in NICUs

2. FFP administration according to preset guidelines (appropriateness)

3. Describe haemorrhagic episodes among FFP transfused neonates

4. Statistically assess associations between potential risk factors and actual bleeding episodes.

Design and Setting

Prospective, observational study.

Seventeen Italian NICUs.

Approved by ethics committee

Parents consent taken

Patients and methods

Over period of 12 months (Jan 2011 to Feb 2012):

All neonates that received FFP

Pre-transfusion and post-transfusion laboratory test of hemostasis

Details of all haemorrhagic events.

Data collection Period: 12 months

Admitted 3506

FFP given(no): 609

No of babies received: 290 (8.2%)

% of neonates who received FFP: range from 2.5 to 20 of admissions (median 8.7%).

Mean number of transfusions/patient was 2.1 (range 1–25).

FFP transfusions vs. no FFP transfusion : significantly higher mortality rate (25.5% vs 3.4%; p<0.001), and increased OR for mortality 6.3 (95% CI4.9 to 7.8).

Characteristics pre-transfusion test of hemostasis and variety of hemorrhage among 290 neonates that received FFP transfusion

At least one bleeding episode(received FFP) :107 (37%)

No bleeding episodes(prophylactically): 183 (63%)

Compliant : 244 (40%) FFP transfusions

Noncompliant: 365 (60%)

Main causes of multiple transfusions were liver failure and DIC(compliant).

By logistic regression: abnormal PT, aPTT, fibrinogen and platelet count were not independently associated with bleeding episodes.

Coagulopathy was defined as a PT or APTT ratio >1.5,or as a prolonged PT and/or partial thromboplastin time more than two times the age related

normal values

FFP transfusion

Day Percentage (%)

3 42

5 50

14 75

28 90

Test of hemostasis Pre transfusion: 329 casesPost transfusion:189 cases

Table 3

PT and APTT :significantly longer :pre vs. post FFP administration.

<28 weeks’ gestation, and in those 28–34 weeks: pre and post-transfusion values of fibrinogen were similar

>34 weeks: fibrinogen values were significantly lower before versus after FFP administration

IVH vs no IVH

GA and B wt low , increased APTT

Mechanical ventilation and PDA more frequent in babies with IVH

No difference in PT, fibrinogen or platelet count

Pulmonary hemorrhage

Higher GA and birth weight

Longer PT and lower fibrinogen

Mechanical ventilation(↑)

GI hemorrhage

Longer coagulation time

Minor hemorrhage

Longer coagulation time

Lower fibrinogen

Lower platelets

All grades of IVH: Lower GA

Minor bleeding episodes: Higher GA

Discussion

FFP administration is a relatively frequent intervention(8% of admitted babies)

Six fold increase in the risk of death of FFP transfused neonates(sick babies)

60% transfusion non compliant with guidelines

63% received FFP prophylactically without bleeding episodes

Guidelines used in this study are based on poor quality evidence

Most frequent haemorrhage as an indication for FFP : IVH of all grades (18.6% of FFP-transfused neonates): in preterm neonates

Grade 3 or 4 IVH in 6.6% of FFP-transfused neonates.

Pulmonary haemorrhage 5.5% of transfused neonates : in term neonates.

Mean volume of FFP administered :16 mL/kg, which is in accordance with our recommendations for neonatal transfusion practice.

Sufficient to affect the PT and APTT.

In contrast, in preterm neonates (GA<35 weeks): FFP transfusions did not significantly ↑the fibrinogen value.

May contribute to the pathogenesis of their bleeding

lower GA :in neonates with IVH

higher need of mechanical ventilation :pulmonary haemorrhage

lower platelet counts :cutaneous haemorrhage

The multivariate analysis indicated that no laboratory tests of haemostasis were associated with haemorrhage

Reason for lack of association between coagulation times and haemorrhagic episodes: may be due to poor predictive value of PT and APTT regarding bleeding risk.

Conventional coagulation test: do not account for the physiologically lower concentrations of anticoagulants (protein C and ATIII)

Conventional coagulation test: do not reflect the actual balance between procoagulant and anticoagulant factors.

Tripodi et al: coagulation system of neonates appears normal and balanced between procoagulants and anticoagulants despite prolongations of the PT and APTT.

Thromboelastography (enzymatic phase of coagulation) gives same findings. Despite prolongation of the PT and APTT, clot reaction times by thromboelastography were normal and significantly shorter in neonates, suggesting a normal thrombin generation potential.

Limitations Case series

No control group

1st: Italian NICUs data -may not be representative of other populations or national practices.

2nd: an observational study, data collected only on neonates who received FFP transfusions; (lack of control comparisons).

3rd: although we found a significantly increased mortality rate among FFP recipients, we were unable to identify the factors responsible for this finding.

Thank You