Assessment of hemostatic profile in patients with mild to advanced liver cirrhosis

Table 1 Patient characteristics

	MELD 6-11 (n = 25)	MELD ≥ 17 (n = 25)	P value
Age, yr (IQR)	62 (56-69)	58 (56-66)	0.58
Male sex, n (%)	12 (48)	16 (64)	0.39
BMI (SD)	26 (6)	27 (6)	0.43
MELD score (IQR)	8 (7-10)	22 (19-24)	< 0.0001
Primary disease, n (%)			0.20
NASH	2 (8)	4 (16)
Nutritive toxic	15 (60)	9 (36)
Hepatitis B	2 (8)	2 (8)
Hepatitis C	5 (20)	4 (16)
Other	1 (4)	6 (24)
Listed for LT, n (%)	2 (8)	5 (20)	0.41
Renal replacement therapy, n (%)	0 (0)	2 (8)	0.49
Anticoagulants, n (%)	9 (36)	11 (44)	0.77
P2Y12–receptor inhibitor	1 (4)	0 (0)
ASA	5 (20)	8 (32)
LMWH	3 (12)	3 (12)
Laboratory parameters
Bilirubin, mg/dL (SD)	0.9 (0.5)	5.7 (4.4)	< 0.0001
Creatinine, mg/dL (SD)	0.8 (0.19)	1.9 (1.5)	< 0.0001
Urea, mg/dL (SD)	28.7 (9.6)	58.8 (41.6)	< 0.001
INR	1.1 (0.1)	1.7 (0.6)	< 0.0001
aPTT, s (SD)	30 (3.7)	35 (7.5)	0.047
Fibrinogen, mg/dL (SD)	275 (51)	209 (90)	0.006
Platelet count, 103/µL (SD)	145 (51)	138 (49)	0.60
Minimum, 103/µL	80	72
Maximum, 103/µL	275	274
Thrombocytopenia < 150 × 103/µL, n (%)	16 (64)	18 (72)	1.00

Data are given as means except for age which is presented as the median. Data comparisons were made with Mann Whitney U test or χ² test where applicable. BMI: Body mass index; MELD: Model for end-stage liver disease; NASH: Nonalcoholic steatohepatitis; INR: International normalized ratio; aPTT: Activated partial thromboplastin time; ASA: Acetylsalicylic acid; LMWH: Low-molecular-weight heparin; LT: Liver transplantation; IQR: Indicates interquartile range.

Table 2 Results of impedance aggregometric and thrombelastometric assays

	All patients	MELD 6-11	MELD ≥ 17	P value
Impedance aggregometry
AUCADP1, U (IQR)	43 (30-56)	45 (30-56)	42 (29-67)	0.80
AUCADP1< 55 U, n (%)	34 (68)	17 (68)	17 (68)	0.58
AUC ASPI2, U (IQR)	71 (57-99)	72 (57-96)	68 (43-104)	0.53
AUCASPI2 < 79 U, n (%)	22 (44)	12 (48)	10 (40)	0.94
AUCTRAP, U (IQR)	92 (61-106)	94 (80-109)	79 (60-110)	0.26
AUCTRAP < 92 U, n (%)	24 (48)	9 (36)	15 (60)	0.09
Thrombelastometry
EXTEM
CT, s (IQR)	71 (65-79)	70 (65-77)	73 (64-81)	0.52
CT < 42 s, n (%)	1 (2)	0	1 (4)	0.10
CT > 74 s, n (%)	19 (38)	8 (32)	11 (44)	0.38
CFT, s (IQR)	100 (75-115)	103 (82-109)	97 (67-132)	0.96
CFT < 46 s, n (%)	1 (2)	0 (0)	1 (4)	0.10
CFT > 148 s, n (%)	6 (12)	1 (4)	5 (20)	0.18
MCF, mm (IQR)	57 (51-63)	58 (53-63)	52 (46-63)	0.06
MCF <49mm, n (%)	10 (20)	0 (0)	10 (40)	< 0.001
MCF >71mm, n (%)	4 (8)	2 (8)	2 (8)	1.00
α-angle, ° (IQR)	73 (69-77)	74 (70-76)	71 (66-80)	0.31
α-angle < 63°, n (%)	3 (6)	0 (0)	3 (12)	0.23
α-angle > 81°, n (%)	4 (8)	1 (4)	3 (12)	0.60
INTEM
CT, s (IQR)	197 (183-226)	195 (181-217)	202 (185-230)	0.80
CT < 137 s, n (%)	0 (0)	0 (0)	0 (0)	a
CT > 246 s, n (%)	9 (18)	4 (16)	4 (16)	1.00
CFT, s (IQR)	92 (69-110)	91 (80-109)	91 (62-120)	0.55
CFT < 40 s, n (%)	1 (2)	0 (0)	1 (4)	1.00
CFT > 100 s, n (%)	22 (44)	8 (32)	11 (44)	0.56
MCF, mm (IQR)	54 (48-59)	55 (51-59)	52 (42-59)	0.16
MCF < 52 mm, n (%)	20 (40)	8 (32)	11 (44)	0.38
MCF > 72 mm, n (%)	1 (2)	0 (0)	1 (4)	1.00
α-angle, °(IQR)	73 (69-76)	71 (67-75)	74 (69-80)	0.55
α-angle < 71°, n (%)	19 (38)	10 (40)	9 (36)	0.77
α-angle > 82°, n (%)	0 (0)	0 (0)	0 (0)	a
FIBTEM
CT, s (IQR)	63 (56-71)	59 (55-65)	68 (59-79)	0.004
CT < 43 s, n (%)	0 (0)	0 (0)	0 (0)	a
CT > 69 s, n (%)	3 (6)	4 (16)	9 (36)	0.19
MCF, mm (IQR)	17 (12-20)	17 (14-20)	12 (9-21)	0.11
MCF < 9 mm, n (%)	4 (8)	0 (0)	4 (16)	0.11
MCF > 25 mm, n (%)	3 (6)	0 (0)	3 (12)	0.23

Data are presented as the median, with 25^th-75^th percentiles shown within parentheses or count and percentage as indicated. Data comparisons were made with Mann-Whitney U test or χ² test where applicable. Reference ranges of impedance aggregometric tests for area under the curve (AUC, U) were: AUC_ADP: 55-117, AUC_ASPI: 79-141. AUC_TRAP: 92-151[23].

¹One patient on clopidogrel therapy was excluded from analysis;

²13 patients on therapy with acetylsalicylic acid were excluded from analysis. P values are given for comparison between MELD 6-11 and MELD ≥ 17 groups.

^aNo statistics were computed because no measured values were within the given range. AUC: Area under the curve; ADP: Adenosine-5 diphosphate; ASPI: Arachidonic acid; TRAP: Thrombin receptor activator peptide 6; MEA: Multiple electrode aggregometry; IQR: Indicates interquartile range; CT: Clotting time; CFT: Clot formation time, MCF: Maximum clot firmness.