The Association of Red Blood Cell Distribution Width to Platelet Count Ratio and 28-Day Mortality of Patients with Sepsis: A Retrospective Cohort Study

Figures & data

Table 1 Characteristics of the Patients with Sepsis

	Survivor(n=6215)	Non-Survivor(n=1316)	P-value
Age (years)	67.56 (54.34–78.98)	75.50 (61.68–83.51)	<0.001
Male	3325 (53.50%)	700 (53.19%)	0.839
Mechanical ventilation on first day	3547 (57.07%)	677 (51.44%)	<0.001
Renal replacement therapy on first day	297 (4.78%)	95 (7.22%)	<0.001
SOFA	5.00 (4.00–7.00)	7.00 (4.00–9.00)	<0.001
Length of ICU stay (days)	4.22 (2.22–9.52)	4.38 (2.27–8.67)	0.427
Elixhauser Comorbidity Index (SID30)	17.00 (9.00–26.00)	24.00 (15.00–33.00)	<0.001
Platelet	178.00 (115.00–249.00)	166.00 (89.00–253.25)	<0.001
RDW	14.90 (13.90–16.40)	16.20 (14.70–18.00)	<0.001
RPR	0.09 (0.06–0.13)	0.10 (0.06–0.19)	<0.001
White blood cell	13.30 (9.60–18.80)	13.90 (9.17–19.70)	0.187
Hemoglobin	9.80 (8.50–11.20)	9.40 (8.40–10.80)	<0.001
Comorbidities
Congestive heart failure	2152 (34.63%)	531 (40.35%)	<0.001
Cardiac arrhythmias	1998 (32.15%)	520 (39.51%)	<0.001
Valvular disease	834 (13.42%)	173 (13.15%)	0.791
Pulmonary circulation disorder	505 (8.13%)	119 (9.04%)	0.273
Peripheral vascular disorder	734 (11.81%)	151 (11.47%)	0.731
Hypertension	3305 (53.18%)	650 (49.39%)	0.012
Paralysis	277 (4.46%)	44 (3.34%)	0.069
Other neurological disease	890 (14.32%)	183 (13.91%)	0.696
Chronic pulmonary disease	1303 (20.97%)	303 (23.02%)	0.098
Uncomplicated diabetes	1353 (21.77%)	240 (18.24%)	0.004
Complicated diabetes	481 (7.74%)	80 (6.08%)	0.037
Hypothyroidism	647 (10.41%)	141 (10.71%)	0.743
Renal failure	1193 (19.20%)	285 (21.66%)	0.041
Liver disease	636 (10.23%)	231 (17.55%)	<0.001
Peptic ulcer	13 (0.21%)	2 (0.15%)	1.000
AIDS	97 (1.56%)	15 (1.14%)	0.252
Lymphoma	157 (2.53%)	58 (4.41%)	<0.001
Metastatic cancer	270 (4.34%)	206 (15.65%)	<0.001
Solid tumor	298 (4.79%)	75 (5.70%)	0.170
Rheumatoid arthritis	212 (3.41%)	35 (2.66%)	0.164
Coagulopathy	1369 (22.03%)	396 (30.09%)	<0.001
Obesity	407 (6.55%)	53 (4.03%)	<0.001
Weight loss	477 (7.67%)	118 (8.97%)	0.115
Fluid and electrolyte disorders	2847 (45.81%)	724 (55.02%)	<0.001
Blood loss anemia	184 (2.96%)	35 (2.66%)	0.555
Deficiency anemia	1601 (25.76%)	280 (21.28%)	<0.001
Alcohol abuse	565 (9.09%)	101 (7.67%)	0.100
Drug abuse	266 (4.28%)	23 (1.75%)	<0.001
Psychoses	304 (4.89%)	31 (2.36%)	<0.001
Depression	577 (9.28%)	86 (6.53%)	0.001

Notes: Patients were divided into two groups according to the 28-day survival status. Data were expressed as median (interquartile range) or n (%), Kruskal–Wallis and Chi-square (or Fisher’s exact) tests were used to analyze continuous and categorical variables, respectively. Statistically significant p-values (p< 0.05) iare shown in bold. Comorbidities were defined using International Classification of Diseases, 9th edition (ICD-9) criterion (Table S1).

Abbreviations: SOFA, Sequential Organ Failure Assessment; AIDS, acquired immune deficiency syndrome; RDW, red blood cell distribution width; RPR, red blood cell distribution width to platelet count ratio.

Table 2 Association of RPR with Clinical Outcomes

	Non-Adjusted		Model I		Model II
	HR/OR (95% CI)	P	HR/OR (95% CI)	P	HR/OR (95% CI)	P
28-day mortality	1.07 (1.06, 1.09)	<0.001	1.03 (1.01, 1.05)	0.001	1.04 (1.02, 1.06)	<0.001
90-day mortality	1.07 (1.06, 1.08)	<0.001	1.03 (1.01, 1.04)	<0.001	1.04 (1.02, 1.06)	<0.001
ICU mortality	1.13 (1.10, 1.16)	<0.001	1.06 (1.02, 1.09)	0.001	1.05 (1.02, 1.09)	0.003

Notes: HR/OR represent the increased risk of mortality per 0.1 increase of RPR. Adjusted Model I was adjusted for age, gender, SOFA, mechanical ventilation on the first day, renal replacement therapy on the first day, Elixhauser Comorbidity Index (SID30) and hemoglobin. Adjusted Model II was adjusted for age, gender, SOFA, mechanical ventilation on the first day, renal replacement therapy on the first day, hemoglobin, and comorbidities (congestive heart failure, pulmonary circulation disorder, hypertension, chronic pulmonary disease, uncomplicated diabetes, complicated diabetes, renal failure, liver disease, AIDS, lymphoma, metastatic cancer, solid tumor, rheumatoid arthritis, coagulopathy, obesity, fluid and electrolyte disorders). Statistically significant p-values (p< 0.05) iare shown in bold.

Abbreviations: SOFA, Sequential Organ Failure Assessment; RPR, red blood cell distribution width to platelet count ratio; OR, odds ratio; HR, hazard ratio; CI, confidence interval.

Table 3 Threshold Effect Analysis of RPR on 28-Day Mortality with Piecewise Linear Regression

Non-Segmented Regression Model
	HR (95% CI)	P
	1.04 (1.02, 1.06)	<0.001
Segmented regression model
	HR (95% CI)	P
RPR<0.134	0.86 (0.71, 1.04)	0.110
RPR≥0.134	1.04 (1.02, 1.06)	<0.001
Log-likelihood ratio test: P=0.047

Note: HR represents the increased risk of 28-day mortality per 0.1 increase of RPR and was adjusted for Model II in Table 2. Statistically significant p-values (p< 0.05) are shown in bold.

Abbreviations: HR, hazard ratio; CI, confidence interval, RPR, red blood cell distribution width to platelet count ratio.

Figure 1 Smooth curve fitting for the association between RPR and 28-day mortality. A non-linear relationship was detected after adjusting for Model II in Table 2.

Table 4 Stratified Analyses of the Association Between RPR and 28-Day Mortality

	RPR		p	p for Interaction
	<0.134	≥0.134
Total	1.00	1.16 (1.01, 1.34)	0.047
Gender				0.420
Male	1.00	1.23 (1.01, 1.49)	0.035
Female	1.00	1.09 (0.88, 1.35)	0.418
Age				0.116
<65 years	1.00	1.32 (1.01, 1.73)	0.041
≥65 years	1.00	1.06 (0.89, 1.27)	0.491
SOFA score				0.013
<6	1.00	1.01 (0.76, 1.34)	0.947
≥6	1.00	1.38 (1.17, 1.63)	<0.001
Length of ICU stay				0.008
<4 days	1.00	1.00 (0.79, 1.26)	1.000
≥4 days	1.00	1.19(0.98, 1.45)	0.075
MV or RRT				0.819
No	1.00	1.17 (0.95, 1.44)	0.146
Yes	1.00	1.11 (0.91, 1.35)	0.288
Hematological disorder				0.688
No	1.00	1.25 (1.02, 1.53)	0.035
Yes	1.00	1.18 (0.98, 1.42)	0.075

Notes: Cox proportional hazards model was adjusted for Model II in Table 2. Variable was excluded from the adjusted model when considered as a stratification variable. Statistically significant p-value (p< 0.05) was shown in bold.

Abbreviations: MV, mechanical ventilation on the first day; RPR, red blood cell distribution width to platelet count ratio;RRT, renal replacement therapy on the first day; SOFA, Sequential Organ Failure Assessment.

Figure 2 Kaplan–Meier curve of 28-day survival in sepsis patients. Patients were divided into two groups according to RPR (RPR<0.134 and RPR ≥0.134).

Figure 3 Forest plot for stratified analyses.

Notes: Cox proportional hazards model was adjusted for Model II in Table 2. Variable was excluded from the adjusted model when considered as a stratification variable. Statistically significant p-value (p< 0.05) was shown in bold.Abbreviations: MV, mechanical ventilation on the first day; RRT, renal replacement therapy on the first day; SOFA, Sequential Organ Failure Assessment.