Haematology trials mostly up to 2017 in critical care

1. Quick review
BY: Fadel Kamal
ICU REGISTRAR

2. 1) TRANSFUSE
2) RETIC
3) TRICS III
4) TRIBE
5) TRICOP

3. 1) TRANSFUSE
Age of Red Cells for Transfusion and Outcomes in
Critically Ill Adults
D. James Cooper, M.D., Zoe K. McQuilten, Ph.D., Alistair Nichol, Ph.D., Bridget Ady, M.Clin.Res.Meth., Cécile Aubron, Ph.D., Michael Bailey, Ph.D.,
Rinaldo Bellomo, M.D., Dashiell Gantner, M.B., B.S., David O. Irving, Ph.D., Kirsi-Maija Kaukonen, Ph.D., Colin McArthur, M.B., Ch.B., Lynne Murray,
B.App.Sci., Ville Pettilä, Ph.D., and Craig French, M.B., B.S. for the TRANSFUSE Investigators and the Australian and New Zealand Intensive Care Society
Clinical Trials Group
Background: It is uncertain whether the duration of red-cell
storage affects mortality after transfusion among critically ill
adults.

4. Methods:
 In an international, multicentre, randomized, double-blind
trial, they assigned critically ill adults to receive either the
freshest available, compatible, allogeneic red cells (short-term
storage group) or standard-issue (oldest available),
compatible, allogeneic red cells (long-term storage group).
 The primary outcome was 90-day mortality.

5. Results:
 From November 2012 through December 2016, at 59 centers in
five countries, 4994 patients underwent randomization and
4919 (98.5%) were included in the primary analysis.
 At 90 days, there were 610 deaths (24.8%) in the short-term
storage group and 594 (24.1%) in the long-term storage group
(absolute risk difference, 0.7 percentage points; 95% confidence
interval [CI], −1.7 to 3.1; P=0.57). At 180 days, the absolute
risk difference was 0.4 percentage points (95% CI, −2.1 to 3.0;
P=0.75). Most of the prespecified secondary measures showed
no significant between-group differences in outcome.

6. Conclusion:
 The age of transfused red cells did not affect 90-day mortality
among critically ill adults.
Should we change from current practice of
using the oldest available blood in blood
bank ?
No. TRANSFUSE provides reassurance that
current practice is safe.

7. 2) RETIC
Reversal of trauma-induced coagulopathy using
first-line coagulation factor concentrates or fresh
frozen plasma
Prof Petra Innerhofer, MD, Prof Dietmar Fries, MD, Prof Markus Mittermayr, MD, Nicole Innerhofer, MD, Daniel von Langen, MD, Tobias Hell, PhD, Gottfried
Gruber, MD, Stefan Schmid, MD, Prof Barbara Friesenecker, MD, Prof Ingo H Lorenz, MD, Mathias Ströhle, MD, Verena Rastner, MD, Susanne Trübsbach,
MD, Helmut Raab, MD, Benedikt Treml, MD, Dieter Wally, MD, Benjamin Treichl, MD, Agnes Mayr, MD, Christof Kranewitter, MD, Elgar Oswald, MD
Background
Effective treatment of trauma-induced coagulopathy is important;
so they aimed to compare the efficacy of first-line therapy using
fresh frozen plasma (FFP) or coagulation factor concentrates
(CFC) for the reversal of trauma-induced coagulopathy, the
arising transfusion requirements, and consequently the

8. Methods:
 This single-centre, parallel-group, open-label, randomised trial
was done at trauma centre, Patients aged 18–80 years, with
(ISS) greater than 15, bleeding signs, and plasmatic
coagulopathy identified by abnormal fibrin polymerisation or
prolonged coagulation time using rotational
thermoelectrometry (ROTEM) were eligible.
 Treatment with FFP or CFC (primarily fibrinogen concentrate ).
 The primary clinical endpoint was multiple organ failure .
 Reversal of coagulopathy and need for massive transfusions
were important secondary efficacy endpoints.

11. Findings:
 Between 2012, and 2016, 100 out of 292 screened patients
were included and randomly allocated to FFP (n=48) and CFC
(n=52).
 44 patients in the FFP group and 50 patients in the CFC group
were included in the final interim analysis.
 The study was terminated early for futility and safety reasons
because of the high proportion of patients in the FFP group who
required rescue therapy compared with those in the CFC group
(23 [52%] in the FFP group vs two [4%] in the CFC group; odds
ratio [OR] 25·34 [95% CI 5·47–240·03], p<0·0001) .
 Increased the need for massive transfusion (13 [30%] in the FFP
group vs six [12%] in the CFC group; OR 3·04 [0·95–10·87],
p=0·042) in the FFP group.

12. Conclusion:
• Our results underline the importance of early and effective
fibrinogen supplementation for severe clotting failure in
multiple trauma.
Should we implement this results in our
practice?
YES. Use of fibrinogen and coagulation
factors concentrate should be considered and
superior to FFP.

13. 3) TRICS III
Restrictive or liberal red-cell Transfusion for
cardiac surgery
Dharam J. Kumbhani, MD, SM, FACC
Deepak L. Bhatt, MD, MPH, FACC
Description:
The goal of the trial was to assess the efficacy of a restrictive
blood transfusion strategy to a more liberal one among moderate-
to high-risk patients undergoing cardiac surgery.

14. Study Design:
 Patients scheduled for on-pump cardiac surgery were
randomized in a 1:1 fashion to either a restrictive transfusion
strategy (only if hemoglobin was <7.5 mg/dl) or a more liberal
strategy (hemoglobin <9.5 mg/dl in the operating room and
intensive care unit [ICU], and <8.5 mg/dl on the floors).
 Assigned strategy had to be adhered to until hospital discharge
or 28 days (whichever came first).

15. Principal Findings:
 The primary outcome, all-cause mortality, nonfatal myocardial
infarction (MI), stroke, new-onset renal failure with dialysis, and
between-hospital admission and discharge/28 days, for
restrictive vs. liberal transfusion strategies, was 11.4% vs. 12.5%
(odds ratio 0.90, 95% confidence interval 0.76-1.07, p for
noninferiority < 0.001).
 All-cause mortality: 3.0% vs. 3.6%
 MI: 5.9% vs. 5.9%
 Stroke: 1.9% vs. 2.0%
 New renal failure: 2.5% vs. 3.0%
 On subgroup analysis, the primary endpoint was significantly
reduced among patients ≥75 years (p for interaction = 0.004).

16. Conclusion:
 This trial confirms earlier observations that blood transfusions
to an arbitrary higher threshold may not always be beneficial
and could be associated with potential harm. A more restrictive
strategy appeared to be particularly beneficial among elderly
patients. These are important findings and will likely influence
perioperative guidelines.
Should cardiac surgery patients receive a
restrictive transfusion strategy?
YES. The result of TRICS III is consistent with
the majority of evidence based transfusion
thresholds in critically ill.

17. 4) TRIBE
Transfusion Requirement in Burn Care Evaluation
Palmieri TL1, Holmes JH 4th, Arnoldo B, Peck M, Potenza B, Cochran A, King BT, Dominic W, Cartotto R, Bhavsar D, Kemalyan N, Tredget E, Stapelberg F,
Mozingo D, Friedman B, Greenhalgh DG, Taylor SL, Pollock BH.
BACKGROUND:
Patients with major burns have major (>1 blood volume)
transfusion requirements. Studies suggest that a restrictive
blood transfusion strategy is equivalent to a liberal strategy.
However, major burn injury is precluded from these studies. The
optimal transfusion strategy in major burn injury is thus needed
but remains unknown.

18. METHODS:
 This prospective randomized multicenter trial block randomized
patients to a restrictive (hemoglobin 7-8 g/dL) or liberal
(hemoglobin 10-11 g/dL) transfusion strategy throughout
hospitalization.
 Data collected included demographics, infections, transfusions,
and outcomes which includes blood stream infections ,
mortality and other secondery endpoints.

19. RESULTS:
 18 burn canters enrolled 345 patients with 20% or more TBSA
burn similar in age, TBSA burn, and inhalation injury.
 A total of 7054 units blood were transfused. The restrictive
group received fewer blood transfusions: mean 20.3 ± 32.7
units, median = 8 (interquartile range: 3, 24) versus mean
31.8 ± 44.3 units, median = 16 (interquartile range: 7, 40) in
the liberal group (P < 0.0001, Wilcoxon rank sum).
 BSI incidence, organ dysfunction, ventilator days, and time to
wound healing (P > 0.05) were similar. In addition, there was
no 30-day mortality difference: 9.5% restrictive versus 8.5%
liberal (P = 0.892, χ test).

20. CONCLUSIONS:
 A restrictive transfusion strategy halved blood product
utilization. Although the restrictive strategy did not decrease
BSI, mortality, or organ dysfunction in major burn injury.
Should we use a restrictive transfusion
strategy in burns patients?
Probably. This is consistent with the
evidence-base for transfusion in the critical
ill.

21. 5) TRIBE
Liberal Versus Restrictive Transfusion Strategy in
Critically Ill Oncological Patients:
Fabricio. 2017. Critical Care Medicine 2017;45(5)766-776. doi:10.1097/CCM.0000000000002283
BACKGROUND:
The TRICC study included critically ill patients with acute
anaemia, & the TRISS study included patients with septic shock.
Both studies reported that a restrictive strategy was safe , where
as the TRISOP study reported that major complications and
mortality was reduced with a liberal threshold in surgical
oncology patients. There is the additional concern of the
association of blood transfusion with cancer progression. This
study was therefore performed to try and determine what

22. METHODS:
Randomized controlled trial in a single centre in brazil from june
2012 to may 2014, 300 pt. was enrolled with Solid cancer with
septic shock within 1st 6hrs. Of icu admission.
 Restrictive Group:
 Patients received 1 unit of RBCs each time Hb <7g/dL
 41% of patients had RBC transfusion
 Liberal Group:
 Patients received 1 unit of red blood cells each time Hb <9g/dL
 61% of patients had RBC transfusion

23. RESULTS: 300 pt. were enrolled.
 Primary outcome: liberal vs. restrictive
All-cause mortality at 28 days – no significant difference
 45.0% vs. 55.6% (Hazard ratio 0.74, 95% C.I. 0.53-1.04,
p=0.08).
 Secondary outcomes:
 No significant difference in:
Need for mechanical ventilation , Renal replacement therapy ,
Need for inotropic support , Acute myocardial infarction , ICU LOS
and Hospital LOS.
 Significantly increase 90 day mortality in restrictive group
59.1% vs. 70.2%, HR 0.72 (95% C.I. 0.53-0.97), p=0.03.

24. CONCLUSIONS:
 A survival trend was found favouring the liberal transfusion
strategy
Should we use a liberal transfusion strategy in
critically ill solid tumor oncology patients with
sepsis?
Not at present. The body of evidence does not
support thr use of a libral transfusion
strategy. However , given the results of