Neonatal Section
Neonatal Plasma Transfusion: An Evidence-Based Review

https://doi.org/10.1016/j.tmrv.2016.07.001Get rights and content

Highlights

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    There is limited available evidence to guide the use of fresh-frozen plasma in the neonatal unit.

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    Routine admission coagulation screening is inappropriate in neonates.

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    Plasma should not be used to correct abnormalities in coagulation studies alone.

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    Plasma should not be used for volume replacement or routinely for prevention of intraventricular hemorrhage.

Abstract

Several clinical scenarios for plasma transfusion are repeatedly identified in audits, including treatment of bleeding in association with laboratory evidence of coagulopathy, correction of disseminated intravascular coagulation, prevention of intraventricular hemorrhage, management of critically ill neonates (eg, during sepsis or as a volume expander), or correction of markers of prolonged coagulation in the absence of bleeding. The findings of at least one national audit of transfusion practice indicated that almost half of plasma transfusions are given to neonates with abnormal coagulation values with no evidence of active bleeding, despite the limited evidence base to support the effectiveness of this practice. Plasma transfusions to neonates should be considered in the clinical context of bleeding (eg, vitamin K dependent), disseminated intravascular coagulation, and very rare inherited deficiencies of coagulation factors. There seems to be no role for prophylactic plasma to prevent intraventricular hemorrhage or for use as a volume expander.

Section snippets

Clinical Scenario

An extremely premature growth–restricted infant at 27 weeks' gestation weighing 500 g was delivered after a planned cesarean birth for suspected fetal compromise. She is admitted to the neonatal intensive care unit (NICU) and routine admission blood tests reveal that the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are elevated outside the reference ranges provided by the laboratory. The attending neonatologist requests plasma from the Blood Blank to prevent an

Background

Up to 15% of neonates admitted to the NICU are transfused with plasma when all birth weights and gestational ages are included [2], [3], [4]. Several clinical scenarios for plasma transfusion exist and are repeatedly identified in audits. Reasons given by health care professionals to support administration of neonatal plasma transfusion commonly include hypovolemia, bleeding with abnormal coagulation test results, abnormal coagulation test results without bleeding, intraoperative bleeding,

Plasma for Neonatal Transfusion

Fresh-frozen plasma is human donor plasma frozen within a short specified period after collection (often 8 hours) and then stored at a defined temperature, typically at −30°C. Plasma frozen at slightly later intervals (typically up to 24 hours) after collection is referred to as FP24. After thawing, although diluted with citrate anticoagulant, plasma contains near normal levels of many plasma proteins, including procoagulant and inhibitory components of the coagulation cascades, acute-phase

Reported Indications for Use of Plasma in Neonates

In neonatal practice, plasma is predominantly given to reduce perceived bleeding risk (prophylaxis) in nonbleeding patients. However, it should be accepted that all critically ill neonates might display some features of bleeding risk, for example, oozing at sites of venepuncture. Other usages include as a volume expander, bleeding with abnormal coagulation test results, intraoperative bleeding, sepsis, partial exchange for polycythemia, and exchange transfusions.

Potential Complications of Plasma Use in Neonates

Use of plasma is not without risks and can lead to transfusion-related acute lung injury, transfusion-related volume overload, febrile reactions, and hemolysis [16], all likely underrecognized and underreported in neonates. There is a reported association between plasma use and thrombotic events in neonatal [17] and pediatric [18] patients. Maruyama et al [17] in a single institutional study found an adjusted odd ratio of 5.88 for venous thrombosis in neonates who received greater than 50 mL/kg

Limitations of Coagulopathy Tests in Neonates

As part of a review of plasma use in neonates, it is important to acknowledge the limitations of coagulopathy tests in neonates. There remains an assumption that coagulation tests predict future bleeding; however, there are no studies that show at what level PT and international normalized ratio (INR) a neonate is at increased risk for bleeding. Several studies in neonates have found that routine admission coagulation tests lead to increased use of plasma but no impact on clinically significant

Search Strategy

To provide a comprehensive overview of the current evidence base for the use of plasma in neonates, a literature review was undertaken (Appendix A). The results of this review were used to inform this article and individual study characteristics are available in Table 1, Table 2.

What Is the Current Evidence to Define Use of Plasma in Neonates?

This review of the current literature revealed a limited number of studies (Appendix A, Fig. A1) providing relatively low levels of evidence to guide plasma use in neonates (Table 1, Table 2).

Commentary

The studies of the highest level of evidence, namely the systematic reviews, are limited by the quality of the studies that inform them [20], [22]. The best-designed and highest-quality study from the NNNI group showed that prophylactic plasma use had no impact on severe cranial ultrasound abnormalities and/or mortality. This study is probably the best guidance health care professionals have on the use of prophylactic plasma use in the NICU. However, because it was published in 1996, it is

Critical Analysis of the Clinical Scenario

How do we respond to previous clinical scenario? At a first level, we recognize the limitations of the tests to provide prediction of bleeding risk [9] and then we recognize the overall pattern of results in clinical trials, although few in number, to indicate very little likelihood of benefit of plasma use as (routine) prophylaxis, certainly at the doses frequently used. It, therefore, seems appropriate in this clinical case to challenge the request for plasma. Careful consideration of the

Gaps in Knowledge and Research Priorities

  • Research priority 1

The development of more accurate tests to define hemostatic problems in neonates is required and to link these with clinically important outcomes. It could be argued that these tests need to be evaluated before planning larger clinical trials to allow for a better understanding of the potential need for plasma and to identify key outcomes. In addition, use of a bleeding assessment tool in such trials would allow for standardization of recording of bleeding for clinical

Recommendations

With the limited evidence available to inform the use of plasma in neonates, it is challenging to make definitive recommendations. However, health care professionals still require guidance for its use and the following are provided acknowledging the limited evidence they are based upon:

  • 1.

    Routine admission coagulation screening is inappropriate because results are difficult to interpret in neonates and routine testing may lead to increased transfusion of plasma without benefit [19] (level III-2

Conclusion

This review of the evidence for use of plasma in neonates reveals its significant limitations to inform clinical practice, both in prophylactic and in therapeutic use. Currently available investigative tests do not accurately allow health care professionals to identify which neonates are at highest risk for bleeding or which will potentially benefit (if at all) from plasma transfusion. For such a commonly used blood product in the NICU, these are sobering findings. The previously outlined

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    Conflict of interest: The authors have no conflicts of interests to declare.

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