The rebirth of the cool: a narrative review of the clinical outcomes of cold stored low titer group O whole blood recipients compared to conventional component recipients in trauma

Figures & data

Table 1. Design and demographics of the analyzed studies. CCT = conventional component therapy, IQR = interquartile range, LTOWB = low titer group O whole blood. The italicized studies are of pediatric patients.

Reference	Year of publication	Study design	Age of patients	Number of patients		Titer threshold of LTOWB	Quantity of transfused LTOWB*
				LTOWB	CCT
44**	2013	Randomized controlled trial	Adult	55 modified WB + CCT	52	ABO-specific	Not stated separately from conventional components
26	2016	Retrospective single center	Adult	47 LTOWB + CCT	145	<50	Mean (SD): 24 h: 1.74 (0.61)
13	2018	Propensity match	Adult	135 LTOWB + CCT	135	<50	Median (IQR): 24 h: 2 (1–2)
40	2019	Propensity match	Adult	91 LTOWB + CCT	182	<200	Median (IQR): 4 h: 1.0 (0); 24 h: 1.0 (1.0)
37	2020	Retrospective national database review	Adult	280 LTOWB + CCT	8214	Not specified	Median (IQR): 24 h: 1 (1–1)
31	2020	Retrospective single center	Adult	42 LTOWB + CCT	83	<200	Median (IQR): 24 h: 6.5 (3–11)
30	2020	Retrospective 2 center	Adult	198 LTOWB + CCT	152	<256	Pre-hospital: 78% 1 unit, 22% 2 units; ED: 65% 1 unit, 26% 2 units, 9% 3–4 units
38	2020	Retrospective single center	Adult	44 LTOWB + CCT	42	<200	Median (IQR): 72 h: 23.6 (11.9–45.2) ml/kg
39	2021	Prospective single center	Adult	73 LTOWB + CCT	180	<256	Median (IQR): 24 h: 2 (1–3)
55	2021	Retrospective single center	Adult	34 LTOWB only, 87 LTOWB + CCT	95	<256	Median (IQR): 4 h: LTOWB only 3 (1–5), LTOWB + CCT 3 (1–5); 24 h: LTOWB only 3 (1–5), LTOWB + CCT 3 (1–6)
42***	2021	Propensity match	Adult	92 LTOWB + CCT	92	<50	Median (IQR): 24 h: 4 (3–6)
1	2018	Retrospective single center	Pediatric	18 LTWOB + CCT	0	<50	Median (IQR): 24 h: 15 (9–23) ml/kg
48	2020	Propensity match	Pediatric	28 LTOWB + CCT	28	<50	Median (IQR): 24 h: 15 (10–22) ml/kg
47	2021	Propensity match	Pediatric	36 LTOWB + CCT	36	<50	Median (IQR): 24 h: 15 (9–23) ml/kg
46	2021	Propensity match	Pediatric	135 LTOWB + CCT	270	Not specified	Median (IQR): 4: hour 13 (9–20) ml/kg, 24 h: 14 (10–23) ml/kg

*In units unless specified otherwise.

**Intent-to-treat analysis, see text for other analyses; platelet-depleted WB, patients were supplemented with conventional PLTs after 6 WB units.

***Comparisons are for the propensity score match analysis; see text for coarsened exact match analysis.

Table 2. Mortality and non-mortality clinical outcomes between the LTOWB and conventional component groups in the studies analyzed. Studies that only analyzed biochemical markers of hemolysis are not included. A significant p-value indicates a significant difference in favor of the LTOWB group unless indicated otherwise. Blank cells indicate that the study did not evaluate this parameter. The italicized studies are of pediatric patients. ARDS = acute respiratory distress syndrome, CCT = conventional component therapy, ICU = intensive care unit, IQR = interquartile range, LOS = length of stay, LTOWB = low titer group O whole blood, MODS = multi-organ dysfunction score, NS = not significant, PLT = platelet, RBC = red blood cell.

Reference	Year	Mortality benefit (LTOWB vs CCT)						Other Clinical outcomes
		ED	6-hour	24-hour	28-day	30-day	Overall/In-hospital
44*	2013			p=0.83		p=0.26		NS for all comparisons
26	2016						p=0.27	NS for all comparisons
13	2018		p=0.74	p=0.33			p=0.24	NS for all comparisons
40	2019	p=0.039		p>0.05		p>0.05
37	2020			p=0.006**			p=0.011**	p=0.013** ^+
31	2020			p=0.8		p=0.2
30	2020					p=0.047***
38	2020			p=0.017∼	p=0.059∼			NS for all MODS comparisons
39	2021	p=0.04∼∼					p=0.22	Significantly lower ARDS and ventilator days in overall cohort of LTOWB patients
55	2021			p=0.45∼∼∼		p=0.05∼∼∼	p=0.06∼∼∼	NS for all comparisons#
42^	2021		p=1.00	p=0.835		p=0.43		NS for all clinical outcome comparisons
1	2018							Significantly faster time to receive LTOWB than a single unit of RBC, plasma, and PLT
48	2020						p=0.40	NS for all morbidity comparisons, but significantly faster correction of base deficit following LTOWB transfusion
47	2021						p=0.60	NS for all comparisons except for significantly shorter ICU LOS and ICU-free days, both p=0.03
46	2021			p=0.546			p=0.502	p=0.021 for Ventilation days, NS for other outcomes

*Intent-to-treat analysis, see text for other analyses; platelet-depleted WB, patients were supplemented with conventional PLTs after 6 WB units.

**Logistic regression analysis, see text for details.

+Also fewer complications and shorter hospital LOS for LTOWB recipients stratified by blunt and penetrating injuries.

***Multivariate analysis.

∼Adjusted mortality analysis; see text for survival analysis.

∼∼Higher mortality observed in the LTOWB group; OR, ICU, and overall mortality NS.

∼∼∼comparing all 3 groups of recipients.

^Comparisons are for the propensity score match analysis; see text for coarsened exact match analysis.

Table 3. Volume of blood products transfused between the LTOWB and conventional component groups in the studies analyzed. A significant p-value indicates a significant difference in favor of the LTOWB group unless indicated otherwise. Blank cells indicate that the study did not evaluate this parameter. The italicized studies are of pediatric patients. ED = emergency department, PLT = platelet, RBC = red blood cell.

Reference	Year	Reduced blood transfusion volumes (LTOWB vs CCT)
		RBC	Plasma	PLT	Total products
44*	2013	24 h: p=0.78	24 h: p=0.71	24 h: p=0.41	24 h: 0.61
26	2016	24 h: p=0.078	24 h: p=0.012**	24 h: p=0.0001**
13	2018	24 h: p=1.00	24 h: p<0.01**	24 h: p<0.01**
40	2019	4 h: p=0.061, 24 h: 0.269	4 h: p=0.503, 24 h: p=0.107	4 h: p=0.322, 24 h: p=0.078
37	2020	24 h: p=0.542	24 h: p=0.791	24 h: p=0.169
31	2020	24 h: p=0.003	24 h: p=0.01	24 h: p=0.20	24 h: p=0.19
30	2020	ED RBC: p=0.04, post-ED: p<0.001	ED RBC: p=0.065, post-ED: p=0.018	ED RBC: p=0.216, post-ED: p=0.231	Post-ED: p=0.001
38	2020				72 h: p=0.093
39	2021	24 h: p<0.001	24 h: p=0.04	24 h: p=0.96
55	2021	4 h: p=0.64, 24 h, p=0.77***	4 h: p=0.50, 24 h: p=0.17***	4 h: p=0.10, 24 h: p=0.06***	4 h: p<0.001, 24 h: p<0.001∼
42∼∼	2021	24 h: p=0.251	24 h: p=0.639	24 h: p=0.035
48	2020	24 h: p=0.01	24 h: p=0.04	24 h: p=0.03	24 h: p=0.08
47	2021	24 h: p=0.12	24 h: p=0.84	24 h: p=0.63	24 h: p=0.74
46∼∼∼	2021	4 h: p=0.008, 24 h: p<0.001	4 h: p<0.001, 24 h: p<0.001	4 h: p<0.001, 24 h: p<0.001	4 h: p=0.013, 24 h: p<0.001

*Intent-to-treat analysis, see text for other analyses; platelet-depleted WB, patients were supplemented with conventional PLTs after 6 WB units.

**Significantly fewer units were transfused in the conventional component group.

***Comparing LTOWB + CCT to CCT.

∼Comparing all 3 groups.

∼∼Comparisons are for the propensity score match analysis; similar trends were observed for the coarsened exact match analysis.

∼∼∼These p-values are for the median (IQR) values; the trends were identical when the data were presented as mean (SD).