T

Use of Fresh Frozen

Plasma in Children

his issue of The Journal includes two articles that exam-ine the use of fresh frozen plasma (FFP). At first glance,the authors appear to have differing views as to the ben-

efits and overall utilization strategy of FFP use. Hendricksonet al1 describe how coagulopathy is independently associated

See related articles, p 204

and p 210

with mortality andmorbidity in trauma pa-tients who are injured severely enough to re-quire a transfusion within the first 24 hours

of admission. The inference is that early use of FFP in this set-tingmay be an effective way to treat the coagulopathy that canbe anticipated. The other article, by Puetz et al,2 reviews an ad-ministrative database that demonstrates the use of FFP acrossthe United States, then refers the reader to the literature,where FFP has been shown generally to not improve out-comes in controlled trials. The end result is that one study in-fers that FFP may be useful as an upfront resuscitative tool tocorrect coagulopathy and improve morbidity and mortalitysecondary to traumatic injury, whereas the other study infersthat FFP is grossly overused in the United States and suggestsmore limited use or at least an increase in the monitoring ofFFP use. What message is the reader to take away?

Hendrickson et al1 report a combined retrospective andprospective analysis from a single trauma health care system.The overall mortality was approximately 30%, and the onlyindependent predictor of mechanism was head injury.Some 77% of patients requiring blood transfusion in the first24 hours also had coagulopathy. This is higher than would beexpected in an adult population. Coagulopathy, as defined byprothrombin time, partial thromboplastin time, and throm-bocytopenia, was associated with mortality. However, coa-gulopathy was not proportionally related to the severity ofinjury, as indicated by the Injury Severity Score. The InjurySeverity Score was associated with mortality. When correctedfor Injury Severity Score, coagulopathy still was a predictor ofmortality. The authors provide a nice discussion as to whycoagulopathy is more prevalent in patients with head injury,specifically in a pediatric population. The inference from thedata is that anticipating the coagulopathy and providing earlycorrection may have potential benefits in a pediatric traumapopulation. A curious question not addressed in the discus-sion is why 50 patients were collected retrospectively overa 3-year period (2006-2008) and 52 patients were collectedprospectively over a 1-year period (2009-2010). Given thelarge number of trauma patients in this system, the mostlikely conclusion is that there is already a bias developingtoward providing transfusions in patients who had moresevere injury earlier on in their hospital course.

FFP Fresh frozen plasma

ICU Intensive care unit

We know that in patients with severe trauma, coagulop-athy, acidosis, and hypothermia are interrelated, and thateach is an independent predictor of mortality.3 We alsoknow that head injury, for the reasons to which the authorsallude to in their discussion, is perhaps the one type of injury

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in which even a perceived initial minor in-jury can lead to a cascade of events resultingin coagulopathy, acidosis, hypothermia, and

death. Furthermore, bleeding accentuates each of these fac-tors proportional to the amount of blood loss. Replacingblood with fresh warm whole blood is perhaps the best ap-proach to counteracting the consequences of acute bloodloss.4 Although this is not an everyday practical solution, itis the rationale for massive transfusion protocols and the rel-atively new concept that product replacement in this settingshould be in a ratio of 1 packed red blood cells:1 fresh frozenplasma:1 platelets. This has been shown to improve outcomesin massive transfusion situations (ie, acute loss of greaterthan half a blood volume) situations caused by traumatic in-juries.5 Based on the significant military experience over thepast decade, many trauma transfusion protocols across thecountry 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 institutiondue to the lack of intensive care unit (ICU) admission codes,despite the known limitations of this type of database, as theauthors discussed in depth. This database included morethan 3 million hospital admissions, of which 2.85% were as-sociated with FFP use. That rate did not change over the 8years of the study. What did change was the predilectionfor ICU utilization in patients who received FFP. In addition,the overall mortality in these patients decreased. Further-more, thrombosis rates of 10% venous and 5% arterial, fora total thrombosis rate of 15%, were noted. Finally, the inci-dence of transfusion-related lung injury was reported to be0.026%, as would be predicted. Based on these rates of com-plications and the few controlled studies that show a provenbenefit from prophylactic use of FFP, the authors concludethat FFP use should be closely monitored, and they inferthat it currently is being overused. In fact, they call for bloodutilization 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 thisstudy need to be expanded on. First, we do not know forwhat diagnosis the patients in the study received transfusions.Although patients undergoing cardiopulmonary bypass sur-gery and those receiving massive transfusion for trauma are

ont matter. Copyright ª 2012 Mosby Inc.

0.1016/j.jpeds.2011.08.062

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THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 160, No. 2

noted exceptions, they represent only one-third of the totalpopulation. The authors state that few controlled trials areavailable to show benefit for all the other diagnoses. Ofnote, the authors list only 2 surgical or periprocedural situa-tions in which FFP use has been studied, and those referencesactually refer to postprocedural use.6,7 To address thisquestion, it would have been interesting to note how manytransfusions were provided in the operating room settingrather than simply lumping that in with all other locations.

Second, although the authors do state they cannot corre-late the use of FFP with thrombotic complications, they didnot collect any data on bleeding-related codes. When usingFFP in this setting, the risk of a thrombotic complication isalways scaled against the risk of a bleeding complication. Hy-pothetically, if there were no subsequent bleeding issues, andthus no need for packed red blood cell transfusions after FFPuse, it would be reasonable to conclude that most clinicianswould accept a thrombosis rate even higher than 15%. Fur-thermore, the authors state that many factors can lead tothrombotic complications. When evaluating thrombosisrates in this setting, one of the first mitigating factors to con-sider is the incidence of central or long-term catheter use.8

These catheters have an increased rate of thrombosis inde-pendent of FFP. As I read this study, the conclusion that Icame away with concerning FFP and thrombosis was thatwithout knowing the severity of the complications, thrombo-sis 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 set-ting over time probably reflects the national trends compar-ing outcomes in ICU settings versus non-ICU settings, andthus the increased utilization in ICUs in general.9 The infer-ence is that FFP is being increasingly used in more appropri-ate settings.

The authors call for blood utilization committees to limitthe prophylactic use of FFP. Although I agree with this con-clusion in practice, I believe that this conclusion, as derivedfrom the study data presented, goes a bit too far. The authorcould have easily concluded that the incidence of FFP use re-mains the same while the safety and efficacy of FFP use is be-ing more effectively monitored by increased utilization ofICU settings. Although FFP prophylaxis has been reportedto be ineffective in many settings, it has been shown to beof benefit in patients undergoing cardiopulmonary bypasssurgery and those requiring massive transfusions. Giventhat data, the use of FFP may be difficult to curtail. However,several studies have shown that blood utilization committeesrequiring pretransfusion approval for FFP use in prophylac-tic situations have been able to decrease unnecessary transfu-sion rates by 30%-40%.10 As a result, hospitals shouldcontinue to increase the monitoring of FFP use and be en-couraged that monitored settings are being used when FFPis given.

186

Reading these two articles, I am struck by the different ap-proaches that can be taken to the use of a blood product. Thetake-home message for me is that patients who require FFPare generally sicker. FFP probably does have a benefit in cer-tain circumstances, especially pediatric trauma. This benefitmay extend to other circumstances, but probably does nottranslate across all diagnoses and all ages. The use of FFPshould be monitored closely by blood utilization committeesin general, given that FFP is likely being used in situationswhere it has no proven benefit. However, global guidelinesrestricting its use should be applied with caution except in in-stances where class 1 data exist to support that decision. n

Kenneth S. Azarow, MDDepartment of Pediatric Surgery

University of NebraskaCollege of MedicineOmaha, Nebraska

Reprint requests: Kenneth S. Azarow, MD, University of Nebraska College of

Medicine, Pediatric Surgery, 111 North 84th Street, Omaha, NE 68114. E-mail:

kazarow@childrensomaha.org

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