Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study

Figures & data

Table I. Baseline characteristics in the unmatched and propensity-matched study population.

Baseline characteristics	Unmatched cohort				Propensity-matched cohort
	All(n = 419)	Thrombocytopenia (n = 144)	No Thrombocytopenia (n = 275)	P	All(n = 274)	Thrombocytopenia (n = 137)	No Thrombocytopenia (n = 137)	P
Age(month), median(IQR)	20(6–84)	24(6.7–74.5)	17(5.8–85)	0.72	24(6.82–86.75)	24(6.78–76.5)	24(6.63–108)	0.76
Gender(male), n(%)	232(55.4)	75(52.1)	157(57.1)	0.33	137(50)	69(50.4)	68(49.6)	0.9
Vasopressor, n(%)	320(76.4)	124(86.1)	196(71.3)	0.001	233(85)	120(87.6)	113(82.5)	0.23
Antibiotics are given within 1 hour, n(%)	304(72.6)	100(69.4)	204(74.2)	0.33	199(72.6)	94(68.6)	105(76.6)	0.14
pSOFA, median(IQR)	9(6–12)	13(10–15)	7(5–10)	<0.001	10(8–14)	13(10–15)	9(6–11.5)	<0.001
PIM-3, median(IQR)	0.07(0.04–0.12)	0.08(0.05–0.16)	0.06(0.04–0.10)	<0.001	0.08(0.05–0.14)	0.08(0.05–0.15)	0.08(0.04–0.14)	0.25
pSIC, median(IQR)	4(3–5)	6(5–6)	4(2–4)	<0.001	4(3.75–6)	6(5–6)	4(3–4)	<0.001
ISTH, median(IQR)	4(3–5)	5(4–6)	3(2–4)	<0.001	4(3–5)	5(4–6)	3(2–4)	<0.001
Tumour, n(%)	6(1.4)	0(0)	6(2.2)	0.07	-	-	-	-
PID, n(%)	21(5)	13(9)	8(2.9)	0.006	15(5.5)	7(5.1)	8(5.8)	0.79
Rheumatism, n(%)	36(8.6)	14(9.7)	22(8)	0.51	27(9.9)	14(10.2)	13(9.5)	0.84
WBC (×10^9/L), median(IQR)	6.9(4–14.9)	6.8(2.8–11.9)	8.3(4.8–16.5)	0.001	7.4(3.82–14.49)	6.8(2.83–11.9)	9.5(4.96–17.64)	0.002
N(%), median(IQR)	69(50.9–83)	67.9(50–81.2)	71(52–84)	0.17	69.7(50–83)	67(50–80.8)	72(51.5–85)	0.09
L(%), median(IQR)	24(13–42)	25(14–43.5)	24(13–40)	0.28	23.95(12–42)	25(13.5–43)	21.3(11–41)	0.17
Hb (g/l), median(IQR)	98(83–115)	93(77–109)	100(85–117)	0.001	98(80–115.25)	93(76.5–109)	103(87–118.5)	<0.001
PLT(×10^9/L), median(IQR)	143(68–280)	39(17–71)	236(145–353)	<0.001	100(39.75–200.25	40(17–71)	200(134–336)	<0.001
CRP (mg/l), median(IQR)	37(8–76)	37(14–74.5)	37(8–77.4)	0.39	36.5(11–74.25)	37(14.5–75.5)	35(8–73)	0.3
PCT (ng/ml), median(IQR)	22.9(3.6–96.6)	30(5.3–84.2)	15.9(2.5–100)	0.04	28.7(5–100)	30(5.32–83.15)	23.8(2.59–100)	0.33
Lactate(mmol/L), median(IQR)	2(1.1–4.5)	2.9(1.3–6.9)	1.6(0.9–3.6)	<0.001	2.2(1.2–5.7)	2.9(1.35–6.75)	2(1–4.15)	0.01
ALT (U/L), median(IQR)	50.6(28.5–126.1)	75.7(34.12–174.8)	41.5(26.5–103.5)	<0.001	53.1(29–141.27)	73(34.35–193.2)	41.5(26.5–103.5)	0.001
Albumin(g/L), median(IQR)	25.8(22.2–31.2)	23.9(19.8–27.5)	27.7(22.9–33)	<0.001	24.95(21.5–30.25)	23.8(19.75–27.45)	27.7(22.95–33)	<0.001
Glucose (mmol/L), median(IQR)	5.8(4.6–7.8)	5.65(4.0–7.6)	6.2(4.8–8.3)	0.17	5.8(4.6–8)	5.7(4.3–7.6)	6.2(4.8–8.3)	0.17
Serum creatinine(mg/dL), median(IQR)	0.5(0.3–1.0)	0.6(0.4–1.2)	0.5(0.3–0.9)	0.01	0.6(0.38–1.08)	0.61(0.43–1.26)	0.58(0.33–1.03)	0.22
Total bilirubin(μmol/L), median(IQR)	6.6(3–15.5)	8.9(4.1–22)	5.7(2.8–12.4)	<0.001	7.05(3.2–17.95)	9(4.1–22.2)	5.7(2.15–11.5)	<0.001
INR, median(IQR)	1.4(1.2–1.9)	1.6(1.3–2.6)	1.4(1.1–1.7)	<0.001	1.48(1.21–1.97)	1.6(1.27–2.7)	1.3(1.16–1.78)	<0.001
APTT(s), median(IQR)	47.3(35.6–68.9)	60.6(43.3–97.1)	43.4(33.9–58.3)	<0.001	51(36.75–77.37)	61.9(43.4–97.45)	44.8(34.25–60.35)	<0.001
Fibrinogens(g/L), median(IQR)	2.4(1.2–3.9)	1.8(0.8–3.1)	2.6(1.5–4.3)	<0.001	2.15(1.04–3.46)	1.7(0.7–3.07)	2.4(1.46–3.69)	0.001
D-dimer(mg/L), median(IQR)	4.6(2.1–11.3)	6.3(3.6–13.7)	4.6(1.7–9.9)	0.001	5.02(2.25–13.35)	6.4(3.59–14.72)	4.6(1.72–12.14)	0.004
Gram-positive, n(%)	89(21.2)	25(17.4)	64(23.3)	0.22	55(20.1)	24(17.5)	31(22.6)	0.29
Gram-negative, n(%)	107(25.5)	39(27.1)	68(24.7)	0.61	73(26.6)	38(27.7)	35(25.5)	0.68
Fungal, n(%)	22(5.3)	8(5.6)	14(5.1)	0.8	16(5.8)	8(5.8)	8(5.8)	1
Culture-negative, n(%)	194(46.3)	66(45.8)	128(46.5)	0.96	124(45.3)	62(45.3)	62(45.3)	1

Abbreviations: pSOFA pediatric sequential organ failure assessment, PIM-3 international society of pediatric index of mortality-3, pSIC pediatric sepsis-induced coagulation score, ISTH-DIC score international society on thrombosis and hemostasis disseminated intravascular coagulation score, PID primary immunodeficiency disease, WBC white blood cells, N% neutrophil percentage, L% lymphocyte percentage, Hb hemoglobin, PLT platelet, CRP C-reactive protein, PCT procalcitonin, ALT alanine aminotransferase, INR international normalized ratio, APTT activated partial thromboplastin time, IQR interquartile range

¹Patients could have >1 type of infection.

Table II. Site of infection.

	Unmatched cohort				Propensity-matched cohort
	All(n = 419)	Thrombocytopenia (n = 144)	No Thrombocytopenia (n = 275)		All(n = 274)	Thrombocytopenia (n = 137)	No Thrombocytopenia (n = 137)
P	–	–	–	0.21	–	–	–	0.25
Respiratory, n(%)	148(35.3)	45(31.3)	103(37.5)	–	100(36.5)	42(30.7)	58(42.3)	–
Bloodstream, n(%)	15(3.6)	7(4.9)	8(2.9)	–	8(2.9)	7(5.1)	1(0.7)	–
Intraabdominal, n(%)	156(37.2)	53(36.8)	103(37.5)	–	95(34.7)	51(37.2)	44(32.1)	–
Urinary tract, n(%)	2(0.5)	0(0)	2(0.7)	–	2(0.2)	0(0)	2(1.5)	–
Nervous system, n(%)	42(10)	12(8.3)	30(10.9)	–	31(11.3)	12(8.8)	19(13.9)	–
Skin and soft tissue, n(%)	30(7.2)	13(9)	17(6.2)	-	21(7.7)	13(9.5)	8(5.8)	–
Other, n(%)	5(1.2)	2(1.4)	3(1.1)	–	2(0.7)	2(1.5)	0(0)	-
Unknow, n(%)	21(5)	12(8.3)	9(3.3)	–	15(5.5)	10(7.3)	5(3.6)	–

Table III. Organ dysfunction for patients with and without thrombocytopenia.

	Unmatched cohort				Propensity-matched cohort
	All(n = 419)	Thrombocytopenia (n = 144)	No Thrombocytopenia (n = 275)	P	All(n = 274)	Thrombocytopenia (n = 137)	No Thrombocytopenia (n = 137)	P
Respiratory failure, n(%)	322(76.8)	126(87.5)	196(71.3)	<0.001	227(82.8)	120(87.6)	107(78.1)	0.03
AKI, n(%)	117(27.9)	57(39.6)	60(21.8)	<0.001	90(32.8)	54(39.4)	36(26.3)	0.02
DIC, n(%)	30(7.2)	20(13.9)	10(3.6)	<0.001	28(10.2)	20(14.6)	8(5.8)	0.01

Abbreviations: AKI acute kidney injury, DIC disseminated intravascular coagulation

Table IV. Clinical outcome in the unmatched and propensity-matched study population.

	Unmatched cohort				Propensity-matched cohort
	All(n = 419)	Thrombocytopenia (n = 144)	No Thrombocytopenia (n = 275)	P	All(n = 274)	Thrombocytopenia (n = 137)	No Thrombocytopenia (n = 137)	P
Need of mechanical ventilation, n(%)	329(78.5)	126(87.5)	203(78.5)	0.001	228(83.2)	120(87.6)	108(78.8)	0.05
Ventilator-free days within 28d, median(IQR)	18(0–27)	0(0–21.7)	22(0–27.9)	<0.001	7(0–25)	0(0–21.5)	19(0–27)	0.001
Need of CRRT, n(%)	106(25.3)	53(36.8)	53(29.3)	<0.001	86(31.4)	51(37.2)	35(25.5)	0.03
The length of CRRT (days), median(IQR)	2(1–3)	2(1–3.5)	2(1–3.5)	0.61	0(0–1)	0(0–1)	0(0–0.7)	0.04
PICU-free days within 28d, median(IQR)	13(0–22)	0(0–19)	17(0–23)	<0.001	0(0–21.25)	0(0–19.5)	13(0–23)	0.003
28-day mortality, n(%)	164(39.1)	81(56.3)	83(30.2)	<0.001	129(47.1)	76(55.5)	53(38.7)	0.005
Gastrointestinal hemorrhage, n(%)	69(16.5)	29(20.1)	40(14.5)	0.14	51(18.6)	28(20.4)	23(16.8)	0.43
Epistaxis, n(%)	15(3.6)	13(9)	2(0.7)	<0.001	15(5.5)	13(9.5)	2(1.5)	0.003
Pulmonary hemorrhage, n(%)	39(9.3)	25(17.4)	14(5.1)	<0.001	34(12.4)	24(17.5)	10(7.3)	0.01
Intracranial hemorrhage, n(%)	16(3.8)	11(7.6)	5(1.8)	0.003	15(5.5)	11(8)	4(2.9)	0.06
Bleeding from other parts, n(%)	13(3.1)	5(3.5)	8(2.9)	0.75	9(3.3)	4(2.9)	5(3.6)	0.73
Platelet transfusion, n(%)	95(22.7)	63(43.8)	32(11.6)	<;0.001	79(28.8)	60(43.8)	19(13.9)	<0.001
PRBC transfusion, n(%)	231(55.1)	97(67.4)	134(48.7)	<0.001	159(58)	93(67.9)	66(48.2)	0.001
FFP transfusion, n(%)	178(42.5)	86(59.7)	92(33.5)	<0.001	135(49.3)	82(59.9)	53(38.7)	<0.001
Cryoprecipitate transfusion, n(%)	97(23.2)	48(33.3)	49(17.8)	<0.001	71(25.9)	47(34.3)	24(17.5)	0.002

Abbreviations: CRRT continuous renal replacement therapy, PRBC packed red blood cells, FFP fresh frozen plasma, IQR interquartile range, PICU pediatric intensive care unit

Table V. Clinical outcomes in thrombocytopenia patients.

	Unmatched cohort			Propensity-matched cohort
	Platelet count (×10^9/L)			Platelet count (×10^9/L)
	< = 50(n = 82)	51–100(n = 62)	P	< = 50(n = 77)	51–100(n = 60)	P
Need of mechanical ventilation, n(%)	72(87.8)	54(87.1)	0.89	68(88.3)	52(86.7)	0.77
Ventilator-free days within 28d, median(IQR)	0(0–21)	6.5(0–22.25)	0.08	0(0–21)	6.5(0–22.75)	0.98
Need of CRRT, n(%)	28(34.1)	25(40.3)	0.45	26(33.8)	25(41.7)	0.34
The length of CRRT (days), median(IQR)	0(0–1)	0(0–2)	0.11	0(0–1)	0(0–2)	0.85
PICU-free days within 28d, median(IQR)	0(0–17.25)	0(0–20)	0.14	0(0–17.5)	0(0–20)	0.17
28-day mortality, n(%)	53(64.6)	28(45.2)	0.02	49(63.6)	27(45)	0.02

Abbreviations: CRRT continuous renal replacement therapy, IQR interquartile range, PICU pediatric intensive care unit

Table VI. Multivariate logistic regression model to identify risk factors for development of thrombocytopenia.

Variable	Odds ratio	95% confidence interval	P
PIM-3	2.71	0.64–11.4	0.17
WBC	0.97	0.95–0.99	0.003
Lactate	1.11	1.04–1.17	0.001
ALT	1.00	1.00–1.00	0.66
PCT	1.03	0.99–1.00	0.78

Abbreviations: PIM-3 international society of pediatric index of mortality-3, WBC white blood cells, ALT alanine aminotransferase, PCT procalcitonin

Figure 1. A: Kalpan-Meier survival curves between thrombocytopenia and no thrombocytopenia groups before propensity score matching. B: Kalpan-Meier survival curves between thrombocytopenia and no thrombocytopenia groups after propensity score matching.