Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease

Table 1 Comparison of baseline characteristics of cirrhosis patients with platelet counts < 20 × 10⁹/L, 20-50 × 10⁹/L and > 50 × 10⁹/L

Characteristics	Total (n = 913)	Platelet count < 20 × 109/L (n = 23)	Platelet count 20-50 × 109/L (n = 168)	Platelet count > 50 × 109/L (n = 722)	P value
Age (years)	45 (35-54)	42.0 (33-46)	43 (34-53)	45 (36-54)	0.068
Sex (Males:Female)	762 (83.5): 151 (16.5)	20 (87.0): 3 (13.0)	136 (81.0): 32 (19.0)	606 (83.9): 116 (16.1)	0.581
Heart rate (per minute)	96 (86-110)	94 (86-100)	94 (85-110)	96 (86-110)	0.397
MAP (mm of Hg)	82 (74-89)	81 (74-84)	81 (75-88)	82 (73-89)	0.771
Hemoglobin (g/dl)	7.6 (6.1-9.4)	8.3 (5.7-9.6)	7.4 (6.0-8.7)	7.8 (6.1-9.5)	0.168
TLC (×109/L)	6.5 (3.8-9.2)	6.9 (3.7-9.6)	5.1 (3.1-7.9)	6.8 (4.2-9.7)	< 0.001b
Platelet count (×109/L)	96 (55-135)	12.0 (10.0-15.0)	40.0 (34.0-46.0)	118.0 (80.0-150.0)	< 0.001b,c
INR	1.5 (1.3-1.9)	1.7 (1.3-2.0)	1.6 (1.3-1.9)	1.5 (1.3-1.9)	0.337
Serum urea (mg/dL)	37 (24-64)	45 (22-101)	36 (23-55)	37 (25-66)	0.298
Creatinine (mg/dL)	0.8 (0.6-1.2)	1.1 (0.7-2.0)	0.8 (0.6-1.1)	0.8 (0.6-1.3)	0.010a
Sodium (meq/L)	139 (135-142)	137 (131-141)	140 (136-143)	139 (135-142)	0.065
Bilirubin (mg/dL)	1.6 (0.9-3.1)	2.1 (1.0-7.7)	1.7 (0.9-3.4)	1.6 (0.9-2.9)	0.317
AST (IU/L)	51 (34-86)	49.0 (35.0-103.0)	56.0 (38.0-82.0)	50.0 (33.0-87.0)	0.410
ALT (IU/L)	35 (23-55)	36.0 (23.0-120.0)	37.0 (24.0-56.0)	34.0 (22.0-54.0)	0.500
Albumin (g/dL)	3.2 (2.7-3.8)	2.8 (2.1-3.7)	3.1 (2.7-3.8)	3.2 (2.7-3.8)	0.146
CTP	7 (6-9)	8.0 (7.0-10.0)	7.0 (6.0-10.0)	7.0 (6.0-9.0)	0.044c
MELD scores	14.7 (11.1-20.3)	17.2 (10.0-28.3)	14.4 (11.3-19.6)	14.8 (11.1-20.3)	0.551
Ascites	456 (49.9)	12 (52.2)	97 (57.7)	347 (48.1)	0.076
HCC	35 (3.8)	0	8 (4.8)	27 (3.7)	0.515
HE	93 (10.2)	2 (8.7%)	22 (13.1)	69 (9.6)	0.382
Endotherapy					0.815
No therapy	202 (22.1)	7 (30.4)	34 (20.2)	161 (22.3)
Glue	105 (11.5)	1 (4.3)	19 (11.2)	85 (11.8)
Ethoxysclerol	43 (4.7)	2 (8.7)	6 (3.6)	35 (4.8)
EVL	537 (58.8)	12 (52.2)	102 (60.7)	423 (58.6)
APC	2 (0.2)	0	1 (0.6)	1 (0.1)
Glue and EVL	24 (2.6)	1 (4.3)	6 (3.6)	17 (2.4)
Child Class					0.047
A	374 (41.0)	5 (21.7)	65 (38.7)	304 (42.1)
B	361 (39.5)	10 (43.5)	61 (36.3)	290 (40.2)
C	178 (19.5)	8 (34.8)	42 (25.0)	128 (17.7)
Etiology					0.772
Alcohol	393 (43.0)	9 (39.1)	76 (45.2)	308 (42.7)
Others	520 (57.0)	14 (60.9)	92 (54.8)	414 (57.3)
RBC					0.548
0	542 (59.4)	12 (52.2)	91 (54.2)	439 (60.8)
1	143(15.7)	4 (17.4)	29 (17.3)	110 (15.2)
≥2	228 (25.0)	7 (30.4)	48 (28.6)	173 (24.0)
FFP transfusion	108 (11.8)	3 (13.0)	23 (13.7)	82 (11.4)	0.689
Number of FFP transfusion	3 (3-4)	3 (3-3)	3 (3-4)	3 (3-4)	0.728
Platelets transfusion	91 (10.0)	10 (43.5)	53 (31.5)	28 (3.9)	< 0.001a
Number of platelet transfusion	3 (3-3)	3 (2.7-3.2)	3 (3-3)	3 (3-3.7)	0.728
Rescue therapy (Radiological intervention)	17 (1.9)	2 (8.7)	7 (4.2)	8 (1.1)	0.001a
Grade of varices low:high	128 (14.0): 785 (86.0)	4 (17.4): 19 (82.6)	24 (14.3): 144 (85.7)	100 (13.9): 622 (86.1)	0.885
Cause of bleed variceal					0.898
Esophageal	789 (86.4)	21 (91.3)	148 (88.1)	620 (85.9)
Fundal	55 (6.0)	1 (4.3)	9 (5.4)	45 (6.2)
Esophageal and Fundal	69 (7.6)	1 (4.3)	11 (6.5)	57 (7.9)

^a20 × 10⁹/L vs 20-50 × 10⁹/L.

^b20-50 × 10⁹/L vs > 50 × 10⁹/L.

^c< 20 × 10⁹/L vs > 50 × 10⁹/L. All values are represented as n (%) or median (IQR).

APC: Argon plasma Coagulation, AST: Aspartate Transaminase, ALT: Alanine Transaminase, CTP: Child-Turcotte-Pugh score, INR: Internationalized Normalized Ratio, EVL: Endoscopic Variceal Ligation, FFP: Fresh Frozen Plasma, HE: Hepatic Encephalopathy, HCC: Hepatocellular carcinoma, MAP: Mean Arterial Pressure, MELD: Model for End Stage Liver Disease, RBC: Red blood cells, TLC: Total Leucocyte Count

Table 2 Rebleed rates at 5 days and 42 days, and mortality at 42 days in cirrhosis patients with platelet counts < 20 × 10⁹/L, 20-50 × 10⁹/L and > 50 × 10⁹/L

Characteristics	Total (n = 913)	Platelet count < 20 × 109/L (n = 23)	Platelet count 20-50 × 109/L (n = 168)	Platelet count > 50 × 109/L (n = 722)	P value
Rebleed at 5 d	48 (5.3)	3 (13.0)	11 (6.5)	34 (4.7)	0.150
Rebleed at 42 d	138 (15.1)	5 (21.7)	29 (17.3)	104 (14.4)	0.433
Death at 42 d	166 (18.2)	3 (13.0)	39 (23.2)	124 (17.2)	0.153

All values are represented as n (%).

Table 3 Comparison of baseline characteristics of cirrhosis patients who received platelet and those who did not

	Before PSM analysis			After PSM analysis
Characteristics	Platelets transfusion (n = 91)	No platelets transfusion (n = 822)	P value	Platelet transfusion (n = 89)	No platelet transfusion (n = 89)	P value
Age (yr)	42 (34-50)	45 (35-54)	0.012	42 (34-50)	40 (30-50)	0.716
Sex (Male:Female)	77 (84.6): 14 (15.4)	685 (83.3): 137 (16.7)	0.882	75 (84.3): 14 (15.7)	80 (89.9): 9 (10.1)	0.372
Heart rate (per minute)	90 (84-100)	96 (86-110)	0.016	90 (85-100)	89 (82-100)	0.546
MAP (mm of Hg)	81 (75-87)	82 (74-90)	0.341	81 (75-87)	81 (73-88)	0.968
Hemoglobin (g/dL)	7.7 (6.1-9.4)	7.6 (6.1-9.4)	0.890	7.7 (6.1-9.4)	7.5 (6.3-9.0)	0.720
TLC (× 109/L)	5.6 (3.1-8.3)	6.6 (4.0-9.4)	0.012	5.6 (3.1-8.3)	7.0 (4.4-12.0)	0.002
Platelet count (× 109/L)	40.0 (32.0-58.0)	100.0 (63.0-139.0)	< 0.001	40.0 (32.0-58.0)	81 (57-126)	< 0.001
INR	1.6 (1.3-2.0)	1.5 (1.3-1.9)	0.266	1.6 (1.3-2.0)	1.7 (1.4-2.2)	0.402
Serum urea (mg/dL)	41 (28-60)	36 (24-64)	0.864	41 (28-61)	34 (24-69)	0.369
Creatinine (mg/dL)	0.7 (0.5-1.0)	0.8 (0.6-1.3)	0.003	0.7 (0.5-1.0)	0.8 (0.6-1.4)	0.040
Sodium (meq/L)	140.2 (137.0-143.0)	139.0 (135.0-142.0)	0.023	140 (137-143)	140 (135-143)	0.529
Bilirubin (mg/dL)	1.7 (0.9-3.8)	1.6 (0.9-3.0)	0.771	1.7 (0.9-3.8)	2.4 (1.3-4.8)	0.071
AST (IU/L)	49 (34-79)	51 (34-88)	0.570	49 (34-79)	67 (38-119)	0.019
ALT (IU/L)	32 (22-58)	35 (23-54)	0.905	32 (22-58)	41 (30-67)	0.029
Albumin (g/dL)	3.2 (2.7-3.8)	3.2 (2.7-3.8)	0.897	3.2 (2.7-3.8)	3.1 (2.6-3.6)	0.355
CTP	7 (6-10)	7 (6-9)	0.119	8 (6-10)	8 (6-10)	0.186
MELD	14.6 (10.9-20.2)	14.7 (11.1-20.3)	0.878	14.6 (10.9-20.2)	16.1 (12.5-24.1)	0.079
Ascites	59 (64.8)	397 (48.3)	0.003	59 (66.3)	58 (65.2)	1.000
HCC	6 (6.6)	29 (3.5)	0.150	6 (6.7)	4 (4.5)	0.747
HE	15 (16.5)	78 (9.5)	0.044	15 (16.9)	22 (24.7)	0.268
Endotherapy (yes)	71 (78.0)	640 (77.9)	1.000	72 (80.9)	71 (79.8)	1.000
Child class			0.210			0.313
A	33 (36.3)	341 (41.5)		31 (34.8)	22 (24.7)
B	34 (37.4)	327 (39.8)		34 (38.2)	37 (41.6)
C	24 (26.4)	154 (18.7)		24 (27.0)	30 (33.7)
Etiology			0.824			0.176
Alcohol	38 (41.8)	355 (43.2)		37 (41.6)	47 (52.8)
Other	53 (58.2)	467 (56.8)		52 (58.4)	42 (47.2)
RBC			0.483			0.294
0	49 (53.8)	493 (60.0)		48 (53.9)	56 (62.9)
1	15 (16.5)	128 (15.6)		14 (15.7)	15 (16.9)
≥ 2	27 (29.7)	201 (24.5)		27 (30.3)	18 (20.2)
FFP transfusion	22 (24.2)	86 (10.5)	< 0.001	22 (24.7)	22 (24.7)	1.000
Grade of varices low:high	71 (78.0)	714 (86.9)	0.026	69 (77.5)	84 (94.4)	0.002

All values are represented as n (%) or median (IQR). AST: Aspartate transaminase; ALT: Alanine transaminase; CTP: Child-Turcotte-Pugh score; INR: Internationalized normalized ratio; EVL: Endoscopic variceal ligation; FFP: Fresh frozen plasma; HE: Hepatic encephalopathy; HCC: Hepatocellular carcinoma; MAP: Mean arterial pressure; MELD: Model for end stage liver disease; RBC: Red blood cells; TLC: Total leucocyte count.

Table 4 Cox-proportional analysis of variables associated with 42-days rebleeding in the whole cohort and after propensity score matching

	Whole cohort		After propensity score matching
Characteristics	Univariate analysis HR (95%CI)	P value	Univariate analysis HR (95%CI)	P value	Model 1 (Excluding CTP)		Model 2 (Including CTP)
					Adjusted HR (95%CI)	P value	Adjusted HR (95%CI)	P value
Age (yr)	1.000 (0.987-1.013)	0.973	1.007 (0.984-1.031)	0.584
Sex
Male	1		1
Female	0.662 (0.393-1.114)	0.120	1.330 (0.560-3.158)	0.517
Heart rate (per minute)	0.995 (0.986-1.004)	0.298	1.011 (0.996-1.026)	0.157
MAP (mm of Hg)	0.979 (0.965-0.992)	0.002	0.966 (0.938-0.996)	0.024	9.972 (0.938-1.008)	0.131	0.968 (0.936-1.001)	0.057
Hemoglobin (g/dL)	0.969 (0.906-1.036)	0.349	0.914 (0.800-1.045)	0.189
TLC (× 109/L)	1.023 (0.995-1.053)	0.111	0.991 (0.933-1.052)	0.761
Platelet count (× 109/L)	0.999 (0.997-1.001)	0.360	0.995 (0.989-1.001)	0.129
INR	1.528 (1.296-1.802)	< 0.001	1.427 (0.976-2.086)	0.067	1.341 (0.784-2.295)	0.284
Serum urea (mg/dL)	1.005 (1.001-1.008)	0.012	1.004 (0.997-1.011)	0.237
Creatinine (mg/dL)	1.158 (1.021-1.314)	0.023	1.031 (0.805-1.319)	0.811
Sodium (meq/L)	0.993 (0.966-1.022)	0.647	0.980 (0.929-1.033)	0.451
Bilirubin (mg/dL)	1.065 (1.045-1.086)	< 0.001	1.016 (0.976-1.058)	0.434
AST (IU/L)	1.001 (1.000-1.001)	0.005	1.001 (1.000-1.002)	0.002	1.001 (1.000-1.002)	0.284	1.001 (1.000-1.002)	0.021
ALT (IU/L)	1.000 (0.998-1.002)	0.920	1.000 (0.998-1.003)	0.761
Albumin (g/dL)	0.833 (0.672-1.031)	0.093	0.543 (0.363-0.811)	0.003	0.690 (0.431-1.105)	0.122
CTP	1.255 (1.177-1.337)	< 0.001	1.169 (1.048-1.303)	0.005	-		1.081 (0.959-1.220)	0.203
MELD	1.057 (1.038-1.077)	< 0.001	1.028 (0.995-1.063)	0.102	-
Ascites, yes	2.525 (1.757-3.630)	< 0.001	1.906 (0.939-3.870)	0.074	0.857 (0.376-1.953)	0.713
HCC, yes	2.532 (1.367-4.690)	0.003	0.370 (0.051-2.687)	0.326
HE, yes	3.969 (2.700-5.836)	< 0.001	2.489 (1.324-4.679)	0.005	1.791 (0.836-3.836)	0.134
Endotherapy (yes)	0.702 (0.480-1.027)	0.069	0.999 (0.463-2.155)	0.998
Child class
A	1		1
B	1.849 (1.187-2.879)	0.007	1.811 (0.738-4.444)	0.195
C	4.653 (2.988-7.245)	< 0.001	3.695 (1.567-8.715)	0.003
Etiology
Alcohol	1	0.095	1	0.124
Other	0.753 (0.539-1.051)		0.622 (0.339-1.140)
RBC (units)
0	1		1		1		1
1	1.482 (0.944-2.327)	0.087	1.162 (0.464-2.910)	0.748	1.173 (0.460-2.992)	0.738	1.253 (0.493-3.180)	0.636
≥ 2	1.434 (0.979-2.098)	0.064	2.571 (1.349-4.902)	0.004	1.998 (0.962-4.152)	0.064	1.900 (0.942-3.831)	0.073
FFP transfusion	3.078 (2.096-4.518)	< 0.001	1.490 (0.777-2.858)	0.220
Platelet transfusion	2.613 (1.735-3.936)	< 0.001	2.204 (1.165-4.172)	0.015	2.924 (1.448-5.903)	0.003	2.702 (1.345-5.429)	0.005
Grade of varices (high)	0.829 (0.526-1.308)	0.421	0.671 (0.311-1.446)	0.308

AST: Aspartate transaminase; ALT: Alanine transaminase; CTP: Child-Turcotte-Pugh score; INR: Internationalized normalized ratio; EVL: Endoscopic variceal ligation; FFP: Fresh frozen plasma; HE: Hepatic encephalopathy; HCC: Hepatocellular carcinoma; MAP: Mean arterial pressure; MELD: Model for end stage liver disease; RBC: Red blood cells; TLC: Total leucocyte count.

Table 5 Cox-proportional analysis of variables associated with 42-days mortality in the whole cohort and after propensity score matching

	Whole cohort		After propensity score matching
Characteristics	Univariate analysis HR (95%CI)	P value	Univariate analysis HR (95%CI)	P value	Adjusted HR (95%CI)	P value
Age (yr)	1.010 (0.998-1.022)	0.118	1.016 (0.993-1.039)	0.174
Sex
Male	1		1
Female	0.682 (0.427-1.088)	0.108	0.889 (0.350-2.256)	0.804
Heart rate (per minute)	0.999 (0.990-1.007)	0.759	1.004 (0.989-1.021)	0.581
MAP (mm of Hg)	0.988 (0.976-1.000)	0.046	0.996 (0.967-1.027)	0.816
Hemoglobin (g/dL)	0.949 (0.892-1.010)	0.100	0.992 (0.872-1.128)	0.903
TLC (× 109/L)	1.047 (1.023-1.071)	< 0.001	1.034 (0.986-1.084)	0.172
Platelet count (× 109/L)	0.998 (0.995-1.000)	0.053	0.998 (0.992-1.003)	0.422
INR	1.903 (1.689-2.143)	< 0.001	1.656 (1.246-2.201)	0.001	1.361 (0.825-2.244)	0.228
Serum urea (mg/dL)	1.009 (1.006-1.012)	< 0.001	1.005 (0.998-1.012)	0.142
Creatinine (mg/dL)	1.374 (1.263-1.495)	< 0.001	1.205 (1.004-1.446)	0.046	0.985 (0.771-1.258)	0.901
Sodium (meq/L)	0.991 (0.966-1.017)	0.494	0.996 (0.943-1.052)	0.876
Bilirubin (mg/dL)	1.077 (1.061-1.094)	< 0.001	1.040 (1.010-1.072)	0.010	1.013 (0.967-1.061)	0.588
AST (IU/L)	1.001 (1.001-1.002)	< 0.001	1.001 (1.001-1.002)	< 0.001	1.001 (1.000-1.002)	0.113
ALT (IU/L)	1.002 (1.001-1.002)	< 0.001	1.001 (0.999-1.003)	0.249
Albumin (g/dL)	0.671 (0.548-0.821)	< 0.001	0.641 (0.433-0.948)	0.026	0.964 (0.619-1.501)	0.871
CTP	1.369 (1.294-1.448)	< 0.001	1.239 (1.114-1.378)	< 0.001
MELD	1.097 (1.080-1.115)	< 0.001	1.060 (1.029-1.091)	< 0.001
Ascites, yes	2.673 (1.911-3.739)	< 0.001	1.876 (0.926-3.799)	0.080	1.043 (0.431-2.525)	0.925
HCC, yes	1.637 (0.836-3.206)	0.150	1.258 (0.390-4.063)	0.701
HE, yes	5.686 (4.102-7.881)	< 0.001	3.825 (2.014-6.953)	< 0.001	2.586 (1.260-5.307)	0.010
Endotherapy, yes	0.548 (0.394-0.760)	< 0.001	0.423 (0.226-0.790)	0.007	0.589 (0.296-1.169)	0.130
Child class
A	1		1
B	1.771 (1.142-2.747)	0.011	1.002 (0.395-2.538)	0.997
C	6.785 (4.502-10.227)	< 0.001	3.759 (1.698-8.321)	0.001
Etiology
Alcohol	1		1		1
Other	0.641 (0.473-0.870)	0.004	0.600 (0.329-1.094)	0.096	0.920 (0.470-1.799)	0.808
RBC
0	1		1
1	1 0.966 (0.629-1.484)	0.874	1.158 (0.522-2.567)	0.718
≥ 2	0.741 (0.505-1.086	0.125	1.024 (0.504-2.081)	0.948
FFP transfusion	2.532 (1.762-3.637)	< 0.001	1.923 (1.040-3.555)	0.037	1.066 (0.510-2.230)	0.865
Platelet transfusion	1.489 (0.958-2.312)	0.077	1.098 (0.608-1.984)	0.757
Grade of varices (high)	1.348 (0.826-2.198)	0.232	0.880 (0.392-1.975)	0.757

AST: Aspartate transaminase; ALT: Alanine transaminase; CTP: Child-Turcotte-Pugh score; INR: Internationalized normalized ratio; EVL: Endoscopic variceal ligation; FFP: Fresh frozen plasma; HE: Hepatic encephalopathy; HCC: Hepatocellular carcinoma; MAP: Mean arterial pressure; MELD: Model for end stage liver disease; RBC: Red blood cells; TLC: Total leucocyte count.