European Journal of Pediatrics

, Volume 176, Issue 5, pp 581–589 | Cite as

Effectiveness of prothrombin complex concentrate (PCC) in neonates and infants with bleeding or risk of bleeding: a systematic review and meta-analysis

Original Article


To systematically evaluate the effectiveness of prothrombin complex concentrate (PCC) in neonates and infants, we performed a systematic review and meta-analysis based on current evidence. Quality of studies was assessed by Cochrane Collaboration’s risk of bias tool and Newcastle-Ottawa quality assessment scale. For dichotomous data, we obtained the number of events and total number and calculated the relative risk (RR) with 95% confidence intervals (CI). For continuous variables, we obtained mean and standard deviation (SD) values and calculated mean difference (MD) with 95% CI. We identified six trials and two cohort studies. For trials, selection bias and performance bias were high, while detection bias, attrition bias, and reporting bias were relatively low. For cohort studies, selection bias was low. Both individual studies and meta-analysis failed to find any benefit of PCC on mortality. Meta-analysis also failed to show any benefit in reducing intracranial hemorrhage. The effectiveness of PCC on the correction of hemostatic defects was inconsistent among studies. In addition, PCC was not more effective than fresh frozen plasma (FFP) in correcting hemostatic defects.

Conclusion: There is insufficient evidence to allow a recommendation for use of PCC in neonates and infants.

What is Known:

• Prothrombin Complex Concentrate is becoming increasingly used off-label for treatment of neonates and infants with severe bleeding or risk of severe bleeding.

• Some case reports showed PCC seemed to be effective for infants and children with coagulation factor deficiency, but evidence about the effectiveness of PCC to reverse serious Vitamin K Deficiency Bleeding is limited.

What is New:

• As far as we know, this is the first systematic review that evaluates the effectiveness of PPC in neonates with bleeding or risk of bleeding.

• There is insufficient evidence to allow a recommendation for use of PCCs in neonates and infants.


Prothrombin complex concentrate Neonates Infants Systematic review Meta-analysis 



Activated partial thromboplastin time


Chinese Biomedical Literature Database


China Dissertation Database


China Doctoral Dissertations and Master’s Theses Full-text Databases


Confidence intervals


China National Knowledge Infrastructure


Food and Drug Administration


Fresh frozen plasma


Hypoxic ischemic encephalopathy


Intracranial hemorrhage


International Clinical Trials Registry Platform


Mean difference


Prothrombin complex concentrate


ProQuest Digital Dissertation


Prothrombin time


Relative risk


Standard deviation


Thrombin generation


World Health Organization



We thank Program for Yangtze River Scholars and Innovative Research Team in University (No. IRT0935) and the Group of People with Highest Risk of Drug Exposure of International Network for the Rational Use of Drugs, China, for its support.

Authorsʼ contributions

Linan Zeng searched and selected the literatures, assessed the quality of studies, and wrote the paper. Imti Choonara analyzed the data and wrote the paper. Lingli Zhang extracted the data and revised the paper. Youping Li wrote and revised the paper. Jing Shi selected the literature and analyzed the data.

Compliance with ethical standards


This study was funded by the Natural Science Foundation of China (No. 81373381) and the National Science Foundation for Young Scholars of China (No. 71503177).

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants performed by any of the authors.

Ethical approval

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Pharmacy/Evidence-Based Pharmacy CenterWest China Second University Hospital, Sichuan UniversityChengduChina
  2. 2.Key Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan University, Ministry of EducationChengduChina
  3. 3.Academic Division of Child HealthUniversity of Nottingham, Derbyshire Children’s HospitalDerbyUK
  4. 4.Chinese Evidence-Based Medicine Centre/Chinese Cochrane CenterWest China Hospital, Sichuan UniversityChengduChina
  5. 5.Department of NeonatologyWest China Second University Hospital, Sichuan UniversityChengduChina

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