Patients with advanced liver diseases frequently acquire profound alterations in their hemostatic system. Simultaneous changes in procoagulant and anticoagulant systems result in a reset in the hemostatic balance with a relatively neutral net effect, although there are notable hypocoagulable and hypercoagulable features in the hemostatic system in patients with liver disease. Laboratory and clinical studies have demonstrated that patients have a relatively well-preserved hemostatic system even though routine diagnostic tests of hemostasis (prothrombin time, platelet count) suggest a bleeding tendency. Routine diagnostic tests of hemostasis are unsuitable to assess the hemostatic status of patients with liver disease, as these tests are insensitive for the concurrent prohemostatic and antihemostatic changes in these patients. These tests are, however, frequently requested in patients with liver disease, as they are well established indicators of severity of liver disease. This paper will discuss commonly used diagnostic and research-type hemostatic tests and will outline how test results should be interpreted in patients with liver disease.

1.
Lisman
T
,
Porte
RJ
.
Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences
.
Blood
.
2010
;
116
(
6
):
878
-
885
.
doi:10.1182/blood-2010-02-261891.
2.
Lisman
T
,
Bongers
TN
,
Adelmeijer
J
, et al.
Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity
.
Hepatology
.
2006
;
44
(
1
):
53
-
61
.
doi:10.1002/hep.21231.
3.
Lebreton
A
,
Sinegre
T
,
Lecompte
T
,
Talon
L
,
Abergel
A
,
Lisman
T
.
Thrombin generation and cirrhosis: state of the art and perspectives
.
Semin Thromb Hemost
.
2020
;
46
(
6
):
693
-
703
.
doi:10.1055/s-0040-1715102.
4.
Sinegre
T
,
Duron
C
,
Lecompte
T
, et al.
Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis
.
J Thromb Haemost
.
2018
;
16
(
6
):
1132
-
1140
.
doi:10.1111/jth.14011.
5.
Tripodi
A
,
Primignani
M
,
Lemma
L
,
Chantarangkul
V
,
Mannucci
PM
.
Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis
.
J Hepatol
.
2013
;
59
(
2
):
265
-
270
.
doi:10.1016/j.jhep.2013.03.036.
6.
Lisman
T
,
Bos
S
,
Intagliata
NM
.
Mechanisms of enhanced thrombin- generating capacity in patients with cirrhosis
.
J Thromb Haemost
.
2018
;
16
(
6
):
1128
-
1131
.
doi:10.1111/jth.14020.
7.
von Meijenfeldt
FA
,
Lisman
T
.
Fibrinolysis in patients with liver disease
.
Semin Thromb Hemost
.
2021
;
47
(
5
):
601
-
609
.
doi:10.1055/s-0040-1718924.
8.
European Association for the Study of the Liver
.
EASL clinical practice guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis
.
J Hepatol
.
2022
;
76
(
5
):
1151
-
1184
.
doi:10.1016/j.jhep.2021.09.003.
9.
Northup
PG
,
Garcia-Pagan
JC
,
Garcia-Tsao
G
, et al.
Vascular liver disorders, portal vein thrombosis, and procedural bleeding in patients with liver disease: 2020 practice guidance by the American Association for the Study of Liver Diseases
.
Hepatology
.
2021
;
73
(
1
):
366
-
413
.
doi:10.1002/hep.31646.
10.
Roberts
LN
,
Lisman
T
,
Stanworth
S
, et al.
Periprocedural management of abnormal coagulation parameters and thrombocytopenia in patients with cirrhosis: guidance from the SSC of the ISTH
.
J Thromb Haemost
.
2022
;
20
(
1
):
39
-
47
.
doi:10.1111/jth.15562.
11.
O'Shea
RS
,
Davitkov
P
,
Ko
CW
, et al.
AGA clinical practice guideline on the management of coagulation disorders in patients with cirrhosis
.
Gastroenterology
.
2021
;
161
(
5
):
1615
-
1627.e11627e1
.
doi:10.1053/j.gastro.2021.08.015.
12.
Reiniš
J
,
Petrenko
O
,
Simbrunner
B
, et al.
Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis
.
J Hepatol
.
2023
;
78
(
2
):
390
-
400
.
doi:10.1016/j.jhep.2022.09.012.
13.
Fisher
C
,
Patel
VC
,
Stoy
SH
, et al.
Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on- chronic-liver failure
.
J Crit Care
.
2018
;
43
:
54
-
60
.
doi:10.1016/j.jcrc.2017.07.053.
14.
Intagliata
NM
,
Davis
JPE
,
Lafond
J
, et al.
Acute kidney injury is associated with low factor XIII in decompensated cirrhosis
.
Dig Liver Dis
.
2019
;
51
(
10
):
1409
-
1415
.
doi:10.1016/j.dld.2019.03.011.
15.
Zanetto
A
,
Rinder
HM
,
Campello
E
, et al.
Acute kidney injury in decompensated cirrhosis is associated with both hypo-coagulable and hyper- coagulable features
.
Hepatology
.
2020
;
72
(
4
):
1327
-
1340
.
doi:10.1002/hep.31443.
16.
Campello
E
,
Zanetto
A
,
Bulato
C
, et al.
Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure
.
Liver Int
.
2021
;
41
(
10
):
2455
-
2466
.
doi:10.1111/liv.15001.
17.
Zanetto
A
,
Northup
P
,
Roberts
L
,
Senzolo
M
.
Haemostasis in cirrhosis: understanding destabilising factors during acute decompensation
.
J Hepatol
.
2023
;
78
(
5
):
1037
-
1047
.
doi:10.1016/j.jhep.2023.01.010.
18.
Hung
A
,
Garcia-Tsao
G
.
Acute kidney injury, but not sepsis, is associated with higher procedure-related bleeding in patients with decompensated cirrhosis
.
Liver Int
.
2018
;
38
(
8
):
1437
-
1441
.
doi:10.1111/liv.13712.
19.
Tripodi
A
,
Caldwell
SH
,
Hoffman
M
,
Trotter
JF
,
Sanyal
AJ
.
Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease
.
Aliment Pharmacol Ther
.
2007
;
26
(
2
):
141
-
148
.
doi:10.1111/j.1365-2036.2007.03369.x.
20.
Kovalic
AJ
,
Majeed
CN
,
Samji
NS
,
Thuluvath
PJ
,
Satapathy
SK
.
Systematic review with meta-analysis: abnormalities in the international normalised ratio do not correlate with periprocedural bleeding events among patients with cirrhosis
.
Aliment Pharmacol Ther
.
2020
;
52
(
8
):
1298
-
1310
.
doi:10.1111/apt.16078.
21.
Lenting
PJ
,
Christophe
OD
,
Guéguen
P
.
The disappearing act of factor VIII
.
Haemophilia
.
2010
;
16
(
102
):
6
-
15
.
doi:10.1111/j.1365-2516.2008.01864.x.
22.
Bos
S
,
Van Den Boom
B
,
Kamphuisen
PW
, et al.
Haemostatic profiles are similar across all aetiologies of cirrhosis
.
Thromb Haemost
.
2019
;
119
(
2
):
246
-
253
.
doi:10.1055/s-0038-1676954.
23.
Blasi
A
,
Patel
VC
,
Spanke
ENHE
, et al.
Fibrin clot quality in acutely ill cirrhosis patients: relation with outcome and improvement with coagulation factor concentrates
.
Liver Int
.
2022
;
42
(
2
):
435
-
443
.
doi:10.1111/liv.15132.
24.
Drolz
A
,
Horvatits
T
,
Roedl
K
, et al.
Coagulation parameters and major bleeding in critically ill patients with cirrhosis
.
Hepatology
.
2016
;
64
(
2
):
556
-
568
.
doi:10.1002/hep.28628.
25.
Ow
TW
,
Fatourou
E
,
Rabinowich
L
, et al.
Prevalence of bleeding and thrombosis in critically ill patients with chronic liver disease
.
Thromb Haemost
.
2021
;
122
(
6
):
1006
-
1016
.
doi:10.1055/a-1667-7293.
26.
Budnick
IM
,
Davis
JPE
,
Sundararaghavan
A
, et al.
Transfusion with cryoprecipitate for very low fibrinogen levels does not affect bleeding or survival in critically ill cirrhosis patients
.
Thromb Haemost
.
2021
;
121
(
10
):
1317
-
1325
.
doi:10.1055/a-1355-3716.
27.
Hugenholtz
GC
,
Macrae
F
,
Adelmeijer
J
, et al.
Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen
.
J Thromb Haemost
.
2016
;
14
(
5
):
1054
-
1066
.
doi:10.1111/jth.13278.
28.
Witters
P
,
Freson
K
,
Verslype
C
, et al.
Review article: blood platelet number and function in chronic liver disease and cirrhosis
.
Aliment Pharmacol Ther
.
2008
;
27
(
11
):
1017
-
1029
.
doi:10.1111/j.1365-2036.2008.03674.x.
29.
Raparelli
V
,
Basili
S
,
Carnevale
R
, et al.
Low-grade endotoxemia and platelet activation in cirrhosis
.
Hepatology
.
2017
;
65
(
2
):
571
-
581
.
doi:10.1002/hep.28853.
30.
Zanetto
A
,
Campello
E
,
Bulato
C
, et al.
Increased platelet aggregation in patients with decompensated cirrhosis indicates higher risk of further decompensation and death
.
J Hepatol
.
2022
;
77
(
3
):
660
-
669
.
doi:10.1016/j.jhep.2022.03.009.
31.
Tripodi
A
,
Primignani
M
,
Chantarangkul
V
, et al.
Thrombin generation in patients with cirrhosis: the role of platelets
.
Hepatology
.
2006
;
44
(
2
):
440
-
445
.
doi:10.1002/hep.21266.
32.
Basili
S
,
Raparelli
V
,
Napoleone
L
, et al
;
PRO-LIVER Collaborators
.
Platelet count does not predict bleeding in cirrhotic patients: results from the PRO-LIVER study
.
Am J Gastroenterol
.
2018
;
113
(
3
):
368
-
375
.
doi:10.1038/ajg.2017.457.
33.
De Pietri
L
,
Bianchini
M
,
Montalti
R
, et al.
Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial
.
Hepatology
.
2016
;
63
(
2
):
566
-
573
.
doi:10.1002/hep.28148.
34.
Rout
G
,
Shalimar
,
Gunjan
D
, et al.
Thromboelastography-guided blood product transfusion in cirrhosis patients with variceal bleeding: a randomized controlled trial
.
J Clin Gastroenterol
.
2020
;
54
(
3
):
255
-
262
.
doi:10.1097/MCG.0000000000001214.
35.
Seeßle
J
,
Löhr
J
,
Kirchner
M
,
Michaelis
J
,
Merle
U
.
Rotational thrombelastometry (ROTEM) improves hemostasis assessment compared to conventional coagulation test in ACLF and non-ACLF patients
.
BMC Gastroenterol
.
2020
;
20
(
1
):
271
.
doi:10.1186/s12876-020-01413-w.
36.
Lentschener
C
,
Flaujac
C
,
Ibrahim
F
, et al.
Assessment of haemostasis in patients with cirrhosis: relevance of the ROTEM tests? a prospective, cross-sectional study
.
Eur J Anaesthesiol
.
2016
;
33
(
2
):
126
-
133
.
doi:10.1097/EJA.0000000000000322.
37.
Shenoy
A
,
Louissaint
J
,
Shannon
C
,
Tapper
EB
,
Lok
AS
.
Viscoelastic testing prior to non-surgical procedures reduces blood product use without increasing bleeding risk in cirrhosis
.
Dig Dis Sci
.
2022
;
67
(
11
):
5290
-
5299
.
doi:10.1007/s10620-021-07376-6.
38.
Lisman
T
.
Interpreting hemostatic profiles assessed with viscoelastic tests in patients with cirrhosis
.
J Clin Gastroenterol
.
2020
;
54
(
4
):
389
-
391
.
doi:10.1097/MCG.0000000000001327.
39.
Stravitz
RT
,
Lisman
T
,
Luketic
VA
, et al.
Minimal effects of acute liver injury/ acute liver failure on hemostasis as assessed by thromboelastography
.
J Hepatol
.
2012
;
56
(
1
):
129
-
136
.
doi:10.1016/j.jhep.2011.04.020.
40.
Stravitz
RT
,
Fontana
RJ
,
Meinzer
C
, et al
;
ALF Study Group
.
Coagulopathy, bleeding events, and outcome according to rotational thromboelastometry in patients with acute liver injury/failure
.
Hepatology
.
2021
;
74
(
2
):
937
-
949
.
doi:10.1002/hep.31767.
41.
Scavone
M
,
Podda
GM
,
Tripodi
A
,
Cattaneo
M
.
Whole blood platelet aggregation measurement by Multiplate™: potential diagnostic inaccuracy of correcting the results for the sample platelet count
.
Platelets
.
2023
;
34
(
1
):
2156493
.
doi:10.1080/09537104.2022.2156493.
42.
Tripodi
A
,
Salerno
F
,
Chantarangkul
V
, et al.
Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests
.
Hepatology
.
2005
;
41
(
3
):
553
-
558
.
doi:10.1002/hep.20569.
43.
Talon
L
,
Sinegre
T
,
Lecompte
T
, et al.
Hypercoagulability (thrombin generation) in patients with cirrhosis is detected with ST-Genesia
.
J Thromb Haemost
.
2020
;
18
(
9
):
2177
-
2190
.
doi:10.1111/jth.14963.
44.
Wan
J
,
Roberts
LN
,
Hendrix
W
, et al.
Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay
.
J Thromb Haemost
.
2020
;
18
(
4
):
834
-
843
.
doi:10.1111/jth.14751.
45.
Lisman
T
.
Decreased plasma fibrinolytic potential as a risk for venous and arterial thrombosis
.
Semin Thromb Hemost
.
2017
;
43
(
2
):
178
-
184
.
doi:10.1055/s-0036-1585081.
46.
van den Boom
BP
,
Lisman
T
.
Pathophysiology and management of bleeding and thrombosis in patients with liver disease
.
Int J Lab Hematol
.
2022
;
44
(
S1
):
79
-
88
.
doi:10.1111/ijlh.13856.
47.
Lisman
T
.
Bleeding and thrombosis in patients with cirrhosis: what's new?
Hemasphere
.
2023
;
7
(
6
):
e886
.
doi:10.1097/HS9.0000000000000886.
You do not currently have access to this content.