1. Maraya N. Camazine, BS AABB October 24, 2016
Outcomes Related to the Use of Frozen Plasma or Pooled Solvent/Detergent Treated Plasma in Critically Ill Children
Maraya N. Camazine, BS
AABB
October 24, 2016

2. Disclosures
Spinella: consultant for Octapharma, Cerus, and TerumoBCT

3. Learning Objective Describe current plasma use
Describe solvent detergent plasma processing
Present results of study comparing outcomes for children transfused with plasma vs. solvent detergent plasma
Q&A

4. Background 3.5 million plasma units used annually in the U.S.1
Hospital audits of adult patients reveal use outside of AABB guidelines for nearly half of all FFP transfusions 2
1Whitaker Barbee I RS, Harris Andrea The 2013 AABB Blood Collection, Utilization, and Patient Blood Management Survey Report 2013: 21-8.
2Stanworth SJ, Grant-Casey J, Lowe D, et al. The use of fresh-frozen plasma in England: high levels of inappropriate use in adults and children. Transfusion 2011;51:

5. Solvent/Detergent (S/D) Plasma (Octaplas-LG)
Pooled plasma product from approx donors
All donors are screened for non-enveloped viruses
Retested 6 months after donation
S/D treatment inactivates all enveloped viruses.
Filtration removes cells, cell fragments and aggregates.
Removing intracellular pathogens
Sterile filtration removes bacteria and parasites

6. SD Plasma- Improved Safety Profile
Reduced viral infection risk
Donor screening and SD treatment
Reduced Transfusion Related Acute Lung Injury and POSSIBLY Transfusion Related Immunomodulation
Pooling dilution of anti HLA and HNA antibodies
Extraction Phase and Filtering
Removal of microparticles and biologic reactive mediators

8. PlasmaTV: Subset Analysis
Title: Outcomes Related to the Use of Frozen Plasma or Pooled Solvent/Detergent Treated Plasma in Critically Ill Children
Hypothesis: Apriori hypothesized that SDP will be associated with improved safety and equal efficacy
Methods: Compared children given exclusively SDP vs. FFP/FP24
Primary efficacy outcome: Compare INR reduction
Primary safety outcome: ICU mortality
Statistics: Multivariate analysis to adjust for confounding variables with outcomes of interest.

9. Results Demographics 419 critically ill children were analyzed
Male: 42% (177/419)
Median age: 1 year (IQR, )

10. Table 1. Relationship between plasma type and population characteristics
Candidate independent variables
FFP/FP24
SDP
(N = 357)
(N = 62) P*
Gender, N (%)
0.78
Male
152 (42.6)
25 (40.3)
  Female
205 (57.4)
37 (59.7)
Age, yrs, Median (IQR)
1.1 (0.2, 6.4)
0.8 (0.3, 6.3)
0.80
Reason for admission, N (%)
0.88
  Medical only
142 (39.8)
23 (37.1)
  Surgical only
133 (37.3)
Combination of med and surgical
82 (23.0)
14 (22.6)
Primary indication for plasma transfusion, N (%)
<0.001*
  No bleeding, no procedure (n=145)
128 (35.9)
17 (27.4)
  Critical Bleeding (n=91)
81 (22.7)
10 (16.1)
  Minor Bleeding (n=91)
64 (17.9)
27 (43.6)
  Preparation/Planned procedure (n=60)
44 (12.3)
6 (10.0)
  High risk of postop bleeding (n=42)
40 (11.2)
2 (3.2)

11. Results Table 2. Severity of illness measures by study group
Candidate independent variables
FFP/FP24
SDP
(N = 357)
(N = 62) P*
PELOD-2 score at transfusion, median (IQR)
7 (5, 10)
7 (5, 9)
0.26
INR prior to transfusion, median (IQR)
1.6 (1.3, 2.0)
1.5 (1.2, 1.9)
0.89
Highest lactate on day of transfusion, median (IQR)
2.6 (1.5, 5.0)
2.3 (1.6, 4.3)
0.72
ECLS during transfusion, N (%)
36 (10.1)
4 (6.5)
0.49
CRRT during transfusion, N (%)
28 (7.8)
6 (9.7)
0.62
Intermittent hemodialysis
4 (1.1 )
1 (1.6)
0.55
Total volume of plasma (mL/Kg), median (IQR)
21.4 (11.1, 55.4)
15.0 (10.0, 40.9)
0.07

12. Results Table 3. Primary outcomes by patient study group
Candidate independent variables
FFP/FP24
SDP
(N = 357)
(N = 62) P*
Change in INR, post-tx minus pre-tx, median (IQR)
-0.2 (-0.4, 0)
-0.2 (-0.3, 0)
0.80
ICU Mortality, N (%)
104 (29.1)
9 (14.5)
0.02*

13. Results
Table 3. ICU mortality rates according to type of plasma transfused and indication
 Candidate independent variables
FFP/FP24
SDP
(N = 357)
(N = 62) P*
Primary indication for plasma transfusion
32%
23.5%
0.58
No bleeding, no procedure
37%
20%
0.48
Critical bleeding
18.8%
7.4%
0.22
Minor bleeding
30%
16.7%
0.66
Preparation/Planned procedure
0.0%
1.00
High risk of postop bleeding

14. Results
Table 4. Univariate analysis of variables and intensive care unit mortality
Candidate independent variables
OR (95% CI) P*
Reason for admission
0.0002*
Surgical Only
ref
Medical Only
3.11 ( )
<0.0001*
Combination of medical and surgical
2.54 ( )
0.003*
Primary indication for plasma transfusion
0.02*
No bleeding, no procedure
Critical bleeding
1.21 ( )
0.51
Minor bleeding
0.40 ( )
0.008*
Preparation/Planned procedure
0.86 ( )
0.69
High risk of postop bleeding
0.52 ( )
0.13

15. Results
Table 4. Table 4. Univariate Analysis of variables and intensive care unit mortality
Candidate independent variables
OR (95% CI) P*
PELOD-2 score at transfusion
1.31 ( )
<0.0001*
INR prior to transfusion
1.39 ( )
0.0006*
Highest log lactate on day of transfusion
2.27 ( )
Plasma type
FFP/FP24
ref
SDP
0.41 ( )
0.02*
ECLS during transfusion, Y vs N
3.08 ( )
0.0009*
CRRT during transfusion, Y vs N
4.49 ( )
Log total volume of plasma (mL/Kg)
1.52 ( )

16. Table 5. Multiple logistic regression model of independent variables and intensive care unit mortality
Candidate independent variables
OR (95% CI)
P value
Reason for admission
0.01*
Surgical only
ref
Medical only
2.76 ( )
0.004*
Combination of medical and surgical
2.09 ( )
0.07*
Day 1 PELOD-2 score
1.24 ( )
<0.0001*
Highest log lactate on day of transfusion
1.45 ( )
0.05*
Plasma type
FFP/FP24
SDP
0.40 ( )
CRRT during transfusion, Y vs N
2.50 ( )
0.03*
Log total volume of plasma (mL/Kg)
1.59 ( )

17. To assess the strength of the model we created a ROC Curve
To assess the strength of the model we created a ROC Curve. The area under the curve is 0.85 indicating a strong model.

18. Discussion No difference in INR reduction between study groups
Although INR reduction may not be best measure of efficacy
Association of SD plasma with reduced mortality
May be due to its improved safety profile
Could be increased efficacy based on other parameters of hemostatic function

19. Limitations Lack of randomization and risk of selection bias
Inability to adjust for
RBC or platelet volumes transfused
Center Effect
No cause of death for patients
There was more critical bleeding in the FFP group

20. Conclusions
SD plasma had similar effect on INR reduction compared to FFP/FP24
SD plasma association on reduced ICU mortality was marginally significant compared to FFP/FP24
Results support development of prospective trials to determine if SD plasma use can improve outcomes in critically ill children compared to FFP/FP24

21. Acknowledgements The PlasmaTV Steering Committee
Dr. Philip Spinella
Dr. Oliver Karam
Dr. Pierre Demaret
Dr. Alison Shefler
Dr. Stephane Leteurtre
Dr. Simon Stanworth
Dr. Marisa Tucci
Pediatric Critical Care Blood Research Network

22. QUESTIONS

23. Critical bleeding was defined as massive bleeding (transfusion of all blood produce > 80 ml/kg within 24 h), bleeding in specific sites (intracranial, intraocular, retroperitoneal, intraspinal, pericardial, nontraumatic intraarticular) or bleeding requiring a surgical intervention or drainage (hemothorax requiring drainage)