Relationship Between Red Blood Cell Distribution Width and All-Cause Mortality in Disseminated Intravascular Coagulation Patients: A Retrospective Analysis

Figures & data

Table 1 Baseline Characteristics of Participants

Variables	Overall (n = 2098)	Survivors (n = 1529)	Non-Survivors (n = 569)	P-value	P-value*
Age, mean (sd), years	61.64 (16.41)	61.48 (16.81)	62.08 (15.28)	0.457	0.768
Weight, mean (sd), kg	80.15 (21.18)	79.62 (20.19)	81.55 (23.60)	0.066	0.439
Sex, n(%)				0.149	-
Female	898 (42.80%)	669 (43.75%)	229 (40.25%)
Male	1200 (57.20%)	860 (56.25%)	340 (59.75%)
Ethnicity, n(%)				0.001	-
White	1432 (68.26%)	1052 (68.80%)	380 (66.78%)
Black	135 (6.43%)	97 (6.34%)	38 (6.68%)
Hispanic	79 (3.77%)	66 (4.32%)	13 (2.28%)
Asian	68 (3.24%)	58 (3.79%)	10 (1.76%)
Others	384 (18.30%)	256 (16.74%)	128 (22.50%)
Causes of DIC, n(%)				<0.001	-
Sepsis	1507 (71.83%)	1006 (65.79%)	501 (88.05%)
Cardiovascular diseases	449 (21.40%)	413 (27.01%)	36 (6.33%)
Trauma	142 (6.77%)	110 (7.19%)	32 (5.62%)
Scoring systems, mean (sd)
SOFA	8.20 (3.74)	7.31 (3.22)	10.58 (4.00)	<0.001	<0.001
SAPSII	44.51 (15.75)	40.62 (13.62)	54.95 (16.34)	<0.001	<0.001
SIRS	3.17 (0.87)	3.11 (0.89)	3.35 (0.81)	<0.001	<0.001
JAAM-DIC	4.95 (0.93)	4.85 (0.84)	5.21 (1.08)	<0.001	<0.001
Comorbidities, n (%)
Congestive heart failure	519 (24.74%)	382 (25.00%)	137 (24.08%)	0.663	-
Hypertension	919 (43.80%)	704 (46.04%)	215 (37.79%)	<0.001	-
COPD	325 (15.49%)	242 (15.84%)	83 (14.59%)	0.482	-
Diabetes	452 (21.54%)	338 (22.11%)	114 (20.04%)	0.305	-
Renal failure	282 (13.44%)	197 (12.89%)	85 (14.94%)	0.222	-
Liver diseases	677 (32.27%)	407 (26.64%)	270 (47.45%)	<0.001	-
MBP, mean (sd), mmHg	76.32 (10.60)	77.19 (10.31)	73.96 (11.02)	<0.001	<0.001
Temperature, mean (sd),°C	36.86 (0.76)	36.92 (0.69)	36.70 (0.89)	<0.001	<0.001
SPO2, mean (sd), %	97.09 (3.40)	97.54 (2.18)	95.88 (5.29)	<0.001	<0.001
Laboratory parameters, mean (sd)
Hemoglobin, g/dL	9.90 (2.21)	9.95 (2.16)	9.77 (2.33)	0.106	0.117
Hematocrit, %	29.22 (6.60)	29.30 (6.45)	28.99 (6.98)	0.337	0.239
RBC, 10^9/L	3.20 (0.76)	3.22 (0.74)	3.14 (0.80)	0.035	0.032
MCV, fl	91.53 (7.94)	90.69 (7.34)	93.79 (8.98)	<0.001	<0.001
Platelet, 10^9/L	102.85 (106.18)	106.68 (113.40)	92.57 (83.00)	0.007	<0.001
WBC, 10^9/L	11.85 (15.76)	11.46 (14.90)	12.90 (17.86)	0.063	0.620
APTT, seconds	47.00 (27.10)	45.25 (24.90)	51.67 (31.79)	<0.001	<0.001
PT, seconds	18.19 (7.55)	17.52 (6.98)	19.99 (8.66)	<0.001	<0.001
PT - INR	1.87 (1.82)	1.78 (1.98)	2.12 (1.27)	<0.001	<0.001
Creatinine, mEq/L	1.58 (1.60)	1.47 (1.62)	1.89 (1.49)	<0.001	<0.001
Urea nitrogen, mg/dL	31.09 (25.92)	27.34 (23.29)	41.17 (29.68)	<0.001	<0.001
Glucose, mg/dL	151.65 (76.47)	152.15 (75.79)	150.30 (78.33)	0.622	0.100
Potassium, mmol/L	4.19 (0.86)	4.17 (0.87)	4.26 (0.84)	0.033	0.008
Sodium, mmol/L	137.56 (5.52)	137.48 (5.20)	137.76 (6.30)	0.309	0.187
Bicarbonate, mg/dL	21.01 (4.96)	21.58 (4.50)	19.47 (5.76)	<0.001	<0.001
Anion gap, mEq/L	15.18 (5.23)	14.31 (4.58)	17.47 (6.07)	<0.001	<0.001
Treatments, n (%)
Use of CRRT	210 (10.01%)	85 (5.56%)	125 (21.97%)	<0.001	-
Use of vasopressor drugs	1248 (59.49%)	830 (54.28%)	418 (73.46%)	<0.001	-
Use of mechanical ventilation	1508 (71.88%)	1062 (69.46%)	446 (78.38%)	<0.001	-
RDW, mean (sd), %	16.00 (2.68)	15.56 (2.40)	17.19 (3.01)	<0.001	<0.001
RDW (dichotomous), n (%)				<0.001	-
Normal (≤15.5%)	1170 (55.77%)	960 (62.79%)	210 (36.91%)
Elevated (>15.5%)	928 (44.23%)	569 (37.21%)	359 (63.09%)
RDW (quartiles), n (%)				<0.001	-
11.80–14.00%	508 (24.21%)	434 (28.38%)	74 (13.01%)
14.10–15.10%	518 (24.69%)	415 (27.14%)	103 (18.10%)
15.20–17.30%	544 (25.93%)	385 (25.18%)	159 (27.94%)
17.40–29.10%	528 (25.17%)	295 (19.29%)	233 (40.95%)

Note: P* indicated U-test.

Abbreviations: DIC, disseminated intravascular coagulation; SOFA, sequential organ failure assessment; SAPSII, simplified acute physiology score II; SIRS, systemic inflammatory response syndrome; JAAM, Japanese Association of Acute Medicine; COPD, chronic obstructive pulmonary disease; MBP, mean blood pressure; RBC, red blood cell; MCV, mean corpuscular volume; WBC, white blood cell; APTT, activated partial thromboplastin time; PT, prothrombin time; INR, international normalized ratio; CRRT, continuous renal replacement therapy; RDW, red blood cell distribution width.

Figure 1 Flowchart of subject screening.

Table 2 Univariate and Multivariate Results by Cox Regression

Exposure	Non-Adjusted Model HR, 95% CI, P	Minimally-Adjusted Model HR, 95% CI, P	Fully-Adjusted Model HR, 95% CI, P
RDW (continuous)	1.11 (1.08, 1.14) <0.0001	1.12 (1.09, 1.15) <0.0001	1.08 (1.05, 1.12) <0.0001
RDW (dichotomous)
Normal (≤15.5%)	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)
Elevated(>15.5%)	1.87 (1.57, 2.21) <0.0001	1.91 (1.61, 2.27) <0.0001	1.66 (1.36, 2.03) <0.0001
RDW (quartiles)
Q1 (11.80–14.00%)	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)
Q2 (14.10–15.10%)	1.12 (0.83, 1.52) 0.4428	1.07 (0.80, 1.45) 0.6425	0.91 (0.66, 1.25) 0.5536
Q3 (15.20–17.30%)	1.63 (1.23, 2.14) 0.0006	1.56 (1.18, 2.06) 0.0016	1.30 (0.95, 1.76) 0.0982
Q4 (17.40–29.10%)	2.38 (1.83, 3.10) <0.0001	2.42 (1.86, 3.15) <0.0001	1.96 (1.43, 2.69) <0.0001
P for trend	1.37 (1.27, 1.49) <0.0001	1.39 (1.28, 1.51) <0.0001	1.32 (1.19, 1.46) <0.0001

Notes: Non-adjusted model: no covariates was adjusted for. Minimally-adjusted model: we only adjusted for age and sex. Fully-adjusted model: we adjusted for age, sex, ethnicity, care unit, causes of DIC, SOFA score, JAAM-DIC score, liver diseases, use of CRRT, use of vasopressor drugs, use of mechanical ventilation, hemoglobin, RBC, MCV, APTT, bicarbonate, urea nitrogen, anion gap, and potassium.

Abbreviations: HR, hazard ratio; CI, confidence interval; Ref, reference.

Figure 2 The K-M survival curve of normal RDW (≤15.5%) group and elevated RDW (>15.5%) group.

Table 3 Nonlinearity Addressing of RDW and In-Hospital All-Cause Mortality

Exposure	HR, 95% CI, P value
Fitting model by standard Cox proportional-hazards regression model	1.08 (1.05, 1.12) <0.0001
Fitting model using two-piecewise Cox proportional-hazards regression model
Inflection point	19.2%
<19.2%	1.17 (1.11, 1.24) <0.0001
≥19.2%	0.97 (0.91, 1.04) 0.4617*
P for log-likelihood ratio test	<0.001

Notes: *The results indicated that there was a saturation effect on the relationship between RDW and mortality of DIC patients. The linear increase between RDW and mortality reached a peak at a RDW of 19.2%. An elevation in RDW greater than 19.2% did not result in an additional increased risk of mortality. But, DIC patients with RDW ≥19.2% still had a higher mortality than patients with RDW <19.2%.

Figure 3 Nonlinear relationship between RDW and in-hospital all-cause mortality of DIC patients.

Table 4 Subgroup Analysis of the Relationship Between RDW and In-Hospital All-Cause Mortality

Characteristic	Number of Patients	HR (95% CI)	P value	P for Interaction
Sex				0.1537
Female	873	1.12 (1.06, 1.17)	<0.0001
Male	1155	1.07 (1.02, 1.11)	0.0015
Causes of DIC				0.2756
Sepsis	1464	1.09 (1.05, 1.12)	<0.0001
Cardiovascular diseases	432	1.18 (1.01, 1.39)	0.0421
Trauma	141	1.26 (1.01, 1.59)	0.0443
Congestive heart failure				0.8724
No	1519	1.09 (1.05, 1.13)	<0.0001
Yes	509	1.09 (1.03, 1.16)	0.0033
Hypertension				0.7981
No	1142	1.07 (1.03, 1.11)	0.0006
Yes	886	1.06 (1.01, 1.12)	0.0166
COPD				0.2661
No	1707	1.09 (1.06, 1.13)	<0.0001
Yes	321	1.04 (0.95, 1.13)	0.4276
Diabetes				0.0601
No	1590	1.06 (1.02, 1.09)	0.0025
Yes	438	1.13 (1.06, 1.20)	0.0001
Renal failure				0.9512
No	1754	1.07 (1.03, 1.10)	0.0001
Yes	274	1.07 (0.98, 1.16)	0.1427
Liver diseases				0.1749
No	1355	1.09 (1.04, 1.14)	<0.0001
Yes	673	1.05 (1.00, 1.09)	0.0359
Use of CRRT				0.2058
No	1822	1.10 (1.06, 1.14)	<0.0001
Yes	206	1.04 (0.96, 1.12)	0.3019
Use of vasopressor drugs				0.9704
No	813	1.08 (1.02, 1.14)	0.0050
Yes	1215	1.08 (1.05, 1.12)	<0.0001
Use of mechanical ventilation				0.4614
No	558	1.10 (1.04, 1.18)	0.0015
Yes	1470	1.08 (1.04, 1.11)	<0.0001
Hemoglobin				0.4309
<8 g/dL	373	1.11 (1.04, 1.18)	0.0016
≥8 g/dL	1655	1.08 (1.04, 1.11)	<0.0001

Abbreviations: DIC, disseminated intravascular coagulation; COPD, chronic obstructive pulmonary disease; CRRT, continuous renal replacement therapy.