The Journal of Pediatrics
Volume 160, Issue 2 , Pages 185-186, February 2012

Use of Fresh Frozen Plasma in Children

  • Kenneth S. Azarow, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Kenneth S. Azarow, MD, University of Nebraska College of Medicine, Pediatric Surgery, 111 North 84th Street, Omaha, NE 68114.

Department of Pediatric Surgery, University of Nebraska College of Medicine, Omaha, Nebraska

published online 10 October 2011.

Article Outline

FFP, Fresh frozen plasma, ICU, Intensive care unit

 

See related articles, p 204 and p 210

This issue of The Journal includes two articles that examine the use of fresh frozen plasma (FFP). At first glance, the authors appear to have differing views as to the benefits and overall utilization strategy of FFP use. Hendrickson et al1 describe how coagulopathy is independently associated with mortality and morbidity in trauma patients who are injured severely enough to require a transfusion within the first 24 hours of admission. The inference is that early use of FFP in this setting may be an effective way to treat the coagulopathy that can be anticipated. The other article, by Puetz et al,2 reviews an administrative database that demonstrates the use of FFP across the United States, then refers the reader to the literature, where FFP has been shown generally to not improve outcomes in controlled trials. The end result is that one study infers that FFP may be useful as an upfront resuscitative tool to correct coagulopathy and improve morbidity and mortality secondary to traumatic injury, whereas the other study infers that FFP is grossly overused in the United States and suggests more limited use or at least an increase in the monitoring of FFP use. What message is the reader to take away?

Hendrickson et al1 report a combined retrospective and prospective analysis from a single trauma health care system. The overall mortality was approximately 30%, and the only independent predictor of mechanism was head injury. Some 77% of patients requiring blood transfusion in the first 24 hours also had coagulopathy. This is higher than would be expected in an adult population. Coagulopathy, as defined by prothrombin time, partial thromboplastin time, and thrombocytopenia, was associated with mortality. However, coagulopathy was not proportionally related to the severity of injury, as indicated by the Injury Severity Score. The Injury Severity Score was associated with mortality. When corrected for Injury Severity Score, coagulopathy still was a predictor of mortality. The authors provide a nice discussion as to why coagulopathy is more prevalent in patients with head injury, specifically in a pediatric population. The inference from the data is that anticipating the coagulopathy and providing early correction may have potential benefits in a pediatric trauma population. A curious question not addressed in the discussion is why 50 patients were collected retrospectively over a 3-year period (2006-2008) and 52 patients were collected prospectively over a 1-year period (2009-2010). Given the large number of trauma patients in this system, the most likely conclusion is that there is already a bias developing toward providing transfusions in patients who had more severe injury earlier on in their hospital course.

We know that in patients with severe trauma, coagulopathy, acidosis, and hypothermia are interrelated, and that each is an independent predictor of mortality.3 We also know that head injury, for the reasons to which the authors allude to in their discussion, is perhaps the one type of injury in which even a perceived initial minor injury can lead to a cascade of events resulting in coagulopathy, acidosis, hypothermia, and death. Furthermore, bleeding accentuates each of these factors proportional to the amount of blood loss. Replacing blood with fresh warm whole blood is perhaps the best approach to counteracting the consequences of acute blood loss.4 Although this is not an everyday practical solution, it is the rationale for massive transfusion protocols and the relatively new concept that product replacement in this setting should be in a ratio of 1 packed red blood cells:1 fresh frozen plasma:1 platelets. This has been shown to improve outcomes in massive transfusion situations (ie, acute loss of greater than half a blood volume) situations caused by traumatic injuries.5 Based on the significant military experience over the past decade, many trauma transfusion protocols across the country have already adopted this strategy.

Puetz et al2 use an administrative database to capture the use of FFP in the United States. I agree with the authors’ use of the data, including the exclusion of one institution due to the lack of intensive care unit (ICU) admission codes, despite the known limitations of this type of database, as the authors discussed in depth. This database included more than 3 million hospital admissions, of which 2.85% were associated with FFP use. That rate did not change over the 8 years of the study. What did change was the predilection for ICU utilization in patients who received FFP. In addition, the overall mortality in these patients decreased. Furthermore, thrombosis rates of 10% venous and 5% arterial, for a total thrombosis rate of 15%, were noted. Finally, the incidence of transfusion-related lung injury was reported to be 0.026%, as would be predicted. Based on these rates of complications and the few controlled studies that show a proven benefit from prophylactic use of FFP, the authors conclude that FFP use should be closely monitored, and they infer that it currently is being overused. In fact, they call for blood utilization committees to limit the use of FFP.

Although Puetz et al do note that there are limitations to this type of database review, the specific limitations of this study need to be expanded on. First, we do not know for what diagnosis the patients in the study received transfusions. Although patients undergoing cardiopulmonary bypass surgery and those receiving massive transfusion for trauma are noted exceptions, they represent only one-third of the total population. The authors state that few controlled trials are available to show benefit for all the other diagnoses. Of note, the authors list only 2 surgical or periprocedural situations in which FFP use has been studied, and those references actually refer to postprocedural use.6, 7 To address this question, it would have been interesting to note how many transfusions were provided in the operating room setting rather than simply lumping that in with all other locations.

Second, although the authors do state they cannot correlate the use of FFP with thrombotic complications, they did not collect any data on bleeding-related codes. When using FFP in this setting, the risk of a thrombotic complication is always scaled against the risk of a bleeding complication. Hypothetically, if there were no subsequent bleeding issues, and thus no need for packed red blood cell transfusions after FFP use, it would be reasonable to conclude that most clinicians would accept a thrombosis rate even higher than 15%. Furthermore, the authors state that many factors can lead to thrombotic complications. When evaluating thrombosis rates in this setting, one of the first mitigating factors to consider is the incidence of central or long-term catheter use.8 These catheters have an increased rate of thrombosis independent of FFP. As I read this study, the conclusion that I came away with concerning FFP and thrombosis was that without knowing the severity of the complications, thrombosis was not as significant a problem as I thought it might be.

The fact that FFP was more likely to be given in an ICU setting over time probably reflects the national trends comparing outcomes in ICU settings versus non-ICU settings, and thus the increased utilization in ICUs in general.9 The inference is that FFP is being increasingly used in more appropriate settings.

The authors call for blood utilization committees to limit the prophylactic use of FFP. Although I agree with this conclusion in practice, I believe that this conclusion, as derived from the study data presented, goes a bit too far. The author could have easily concluded that the incidence of FFP use remains the same while the safety and efficacy of FFP use is being more effectively monitored by increased utilization of ICU settings. Although FFP prophylaxis has been reported to be ineffective in many settings, it has been shown to be of benefit in patients undergoing cardiopulmonary bypass surgery and those requiring massive transfusions. Given that data, the use of FFP may be difficult to curtail. However, several studies have shown that blood utilization committees requiring pretransfusion approval for FFP use in prophylactic situations have been able to decrease unnecessary transfusion rates by 30%-40%.10 As a result, hospitals should continue to increase the monitoring of FFP use and be encouraged that monitored settings are being used when FFP is given.

Reading these two articles, I am struck by the different approaches that can be taken to the use of a blood product. The take-home message for me is that patients who require FFP are generally sicker. FFP probably does have a benefit in certain circumstances, especially pediatric trauma. This benefit may extend to other circumstances, but probably does not translate across all diagnoses and all ages. The use of FFP should be monitored closely by blood utilization committees in general, given that FFP is likely being used in situations where it has no proven benefit. However, global guidelines restricting its use should be applied with caution except in instances where class 1 data exist to support that decision.

Back to Article Outline

References 

  1. Hendrickson JE, Shaz BH, Pereira G, Atkins E, Johnson KK, Bao GB, et al. Coagulopathy is prevalent and associated with adverse outcomes in transfused pediatric trauma patients. J Pediatr. 2012;160:204–209
  2. Puetz J, Witmer C, Huang Y-SV, Raffini L. Widespread use of fresh frozen plasma in US children's hospitals despite limited evidence demonstrating a beneficial effect. J Pediatr. 2012;160:210–215
  3. Niles S, McLaughlin DF, Perkins JG, Wade CE, Li Y, Spinella PC, et al. Increased mortality associated with the early coagulopathy of trauma in combat casualities. J Trauma. 2008;64:1459–1465
  4. Spinella PC, Perkins JG, Grathwohl KW, Beekley AC, Holcomb JB. Warm fresh whole blood is independently associated with improved survival for patients with combat related traumatic injuries. J Trauma. 2009;66:S69–S76
  5. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007;62:307–310
  6. Trimble A, Osborn J, Kerth W, Gerbode F. The prophylactic use of fresh frozen plasma after extracorporeal circulation. J Thorac Cardiovasc Surg. 1964;48:314–316
  7. Chong Sung K, Kum Suk P, Mi Ja Y, Kyoung Ok K. Effects of intravascular volume therapy using hydroxyethyl starch (130/0.4) on post-operative bleeding and transfusion requirements in children undergoing cardiac surgery: a randomized clinical trial. Acta Anaesthesiol Scand. 2006;50:108–111
  8. Baskin JL, Pui CH, Reiss U, Wilimas JA, Metzger ML, Ribeiro RC, et al. Management of occlusion and thrombosis associated with long-term indwelling central venous catheters. Lancet. 2009;374:159–169
  9. Halpern NA, Palstores SM. Critical care medicine in the United States 2000-2005: an analysis of bed numbers, occupancy rates, payer mix, and costs. Crit Care Med. 2010;38:65–71
  10. Damiani G, Pinnarelli L, Sommelia L, Farelli V, Mele L, Menichella G, et al. Appropriateness of fresh frozen plasma usage in hospital settings: a meta-analysis of the impact of organizational interventions. Transfusion. 2010;50:139–144

PII: S0022-3476(11)00892-4

doi:10.1016/j.jpeds.2011.08.062

Refers to article:

  • Coagulopathy is Prevalent and Associated with Adverse Outcomes in Transfused Pediatric Trauma Patients , 20 September 2011

    Jeanne E. Hendrickson, Beth H. Shaz, Greg Pereira, Elizabeth Atkins, Karen K. Johnson, Gaobin Bao, Kirk A. Easley, Cassandra D. Josephson
    The Journal of Pediatrics February 2012 (Vol. 160, Issue 2, Pages 204-209.e3)

  • Widespread Use of Fresh Frozen Plasma in US Children’s Hospitals Despite Limited Evidence Demonstrating a Beneficial Effect , 16 September 2011

    John Puetz, Char Witmer, Yuan-Shung V. Huang, Leslie Raffini
    The Journal of Pediatrics February 2012 (Vol. 160, Issue 2, Pages 210-215.e1)

The Journal of Pediatrics
Volume 160, Issue 2 , Pages 185-186, February 2012

Article Tools