J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://www.thejh.org

Original Article

Volume 13, Number 3, June 2024, pages 71-78

Predictors of Non-Variceal Hemorrhage in a National Cohort of Patients With Chronic Liver Disease

Figure 1. CONSORT diagram. CLD: chronic liver disease; VTE: venous thromboembolic; INR: international normalized ratio.

**Table 1.** Demographic and Clinical Characteristics of Patients With Chronic Liver Disease
Demographic/clinical characteristics	Total (N = 15,183)	P-value
^aChi-square test. ^bt-test. ^cWilcoxon two-sample test.
Mean age (years)	57.3	58.2	0.02^b
Male (%)	97.3	97	0.58^a
Race (%)			0.02^a
White	82.1	85.6
Black	14.1	11.9
Other	3.9	2.5
Prior bleeding (%)	8.9	8.2	0.48^a
Cardiovascular disease (%)	8.3	7.9	0.75^a
Congestive heart failure (%)	7.3	5.3	0.03^a
Dementia (%)	1	0.5	0.08^a
Chronic lung disease (%)	11.6	12.4	0.54^a
Connective tissue disease (%)	1.3	0.8	0.11^a
Peptic ulcer (%)	1.5	1.6	0.77^a
Diabetes mellitus (%)	22.3	24.4	0.21^a
Hemi- or paraplegia (%)	0.5	0.4	0.81^a
HIV/AIDS (%)	0.6	1	0.32^a
Anemia (%)	26	19.2	< 0.001^a
Alcohol abuse (%)	38	30	0.001^a
Ascites (%)	5.3	4.2	0.15^a
NSAID use (%)	23.4	22.4	0.53^a
Antiplatelet use (%)	17.4	14.7	0.053^a
Median platelet count (/µL)	119,000	121,000	0.49^c
INR (median)	1.4	1.3	< 0.001^c
Median albumin (g/dL)	2.8	3.1	< 0.001^c
Median bilirubin (mg/dL)	1.9	1.6	< 0.001^c
Median creatinine clearance (mL/min)	93.4	89.1	< 0.001^c
Infection (%)	45.1	25.2	< 0.001^a
MELD score > 20 (%)	14	12.8	0.0004^a

Table 1. Demographic and Clinical Characteristics of Patients With Chronic Liver Disease

Demographic/clinical characteristics

Total (N = 15,183)

P-value

Hemorrhage (n = 674)

No hemorrhage (n = 14,509)

^aChi-square test. ^bt-test. ^cWilcoxon two-sample test.

Mean age (years)

57.3

58.2

0.02^b

Male (%)

97.3

0.58^a

Race (%)

0.02^a

White

82.1

85.6

Black

14.1

11.9

Other

3.9

2.5

Prior bleeding (%)

8.9

8.2

0.48^a

Cardiovascular disease (%)

8.3

7.9

0.75^a

Congestive heart failure (%)

7.3

5.3

0.03^a

Dementia (%)

0.5

0.08^a

Chronic lung disease (%)

11.6

12.4

0.54^a

Connective tissue disease (%)

1.3

0.8

0.11^a

Peptic ulcer (%)

1.5

1.6

0.77^a

Diabetes mellitus (%)

22.3

24.4

0.21^a

Hemi- or paraplegia (%)

0.5

0.4

0.81^a

HIV/AIDS (%)

0.6

0.32^a

Anemia (%)

19.2

< 0.001^a

Alcohol abuse (%)

0.001^a

Ascites (%)

5.3

4.2

0.15^a

NSAID use (%)

23.4

22.4

0.53^a

Antiplatelet use (%)

17.4

14.7

0.053^a

Median platelet count (/µL)

119,000

121,000

0.49^c

INR (median)

1.4

1.3

< 0.001^c

Median albumin (g/dL)

2.8

3.1

< 0.001^c

Median bilirubin (mg/dL)

1.9

1.6

< 0.001^c

Median creatinine clearance (mL/min)

93.4

89.1

< 0.001^c

Infection (%)

45.1

25.2

< 0.001^a

MELD score > 20 (%)

12.8

0.0004^a

**Table 2.** Site of Hemorrhage
	Frequency/N (%)
Total (any location)	674 (4.4/year)
Upper gastrointestinal	404 (60.0)
Lower gastrointestinal	130 (19.3)
Intracranial	67 (9.9)
Nasal/respiratory	39 (5.8)
Genitourinary	26 (3.9)
Peritoneum	3 (0.4)
Hemorrhage, unspecified	2 (0.3)
Joint/soft tissue	3 (0.4)

Table 2. Site of Hemorrhage

Frequency/N (%)

Total (any location)

674 (4.4/year)

Upper gastrointestinal

404 (60.0)

Lower gastrointestinal

130 (19.3)

Intracranial

67 (9.9)

Nasal/respiratory

39 (5.8)

Genitourinary

26 (3.9)

Peritoneum

3 (0.4)

Hemorrhage, unspecified

2 (0.3)

Joint/soft tissue

3 (0.4)

**Table 3.** Multivariable Analysis of Risk Factors for Non-Variceal Hemorrhage
Parameter	Adjusted hazard ratio	95% confidence interval	P-value
^aStudied as time-varying variables. ^bCollinearity was tested between these variables (tolerance > 0.92 and condition index < 5). AIDS: acquired immune deficiency syndrome; CrCl: creatinine clearance; HIV: human immunodeficiency virus; HTN: hypertension; INR: international normalized ratio; NSAID: non-steroidal anti-inflammatory drug; PPI: proton pump inhibitor; SBP: systolic blood pressure.
Age	0.99	0.985 - 1.003	0.20
Gender (Ref: male)	1.36	0.84 - 2.20	0.22
Race (Ref: Caucasian)
African American	1.04	0.83 - 1.30	0.74
Others	1.54	1.03 - 2.28	0.03
HTN (SBP > 160 mm Hg)	1.36	0.98 - 1.89	0.06
Albumin (≤ 3.5 g/dL)^{a, b}	3.68	2.84 - 4.77	< 0.0001
Anemia^a	1.30	1.08 - 1.57	0.01
Bilirubin (≥ 2 mg/dL)^{a, b}	1.45	1.19 - 1.76	0.0002
Chronic kidney disease (CrCl < 30 mL/min)^{a, b}	2.63	2.05 - 3.39	< 0.0001
INR > 1.5^{a, b}	1.68	1.39 - 2.04	< 0.0001
Thrombocytopenia (platelets < 50,000/µL)^a	0.96	0.67 - 1.34	0.80
Antiplatelet use^a	1.36	1.02 - 1.82	0.03
NSAID use^a	1.21	0.75 - 1.96	0.43
PPI use^a	1.23	1.05 - 1.43	0.01
Prior hemorrhage (within 5 years)	0.92	0.70 - 1.22	0.56
Alcohol abuse	1.29	1.10 - 1.53	0.002
Ascites^b	1.01	0.71 - 1.43	0.95
Cardiovascular disease	0.85	0.62 - 1.17	0.33
Congestive cardiac failure	1.17	0.84 - 1.62	0.35
Chronic lung disease	0.85	0.66 - 1.10	0.23
Connective tissue disease	1.51	0.74 - 3.08	0.25
Dementia	2.56	1.19 - 5.51	0.02
Diabetes mellitus	0.93	0.76 - 1.14	0.51
HIV/AIDS	0.57	0.22 - 1.51	0.26
Hemi- or paraplegia	0.89	0.27 - 2.89	0.84
Peptic ulcer disease	0.82	0.43 - 1.56	0.55
Infections	2.54	2.12 - 3.05	< 0.0001

Table 3. Multivariable Analysis of Risk Factors for Non-Variceal Hemorrhage

Parameter

Adjusted hazard ratio

95% confidence interval

P-value

^aStudied as time-varying variables. ^bCollinearity was tested between these variables (tolerance > 0.92 and condition index < 5). AIDS: acquired immune deficiency syndrome; CrCl: creatinine clearance; HIV: human immunodeficiency virus; HTN: hypertension; INR: international normalized ratio; NSAID: non-steroidal anti-inflammatory drug; PPI: proton pump inhibitor; SBP: systolic blood pressure.

Age

0.99

0.985 - 1.003

0.20

Gender (Ref: male)

1.36

0.84 - 2.20

0.22

Race (Ref: Caucasian)

African American

1.04

0.83 - 1.30

0.74

Others

1.54

1.03 - 2.28

0.03

HTN (SBP > 160 mm Hg)

1.36

0.98 - 1.89

0.06

Albumin (≤ 3.5 g/dL)^{a, b}

3.68

2.84 - 4.77

< 0.0001

Anemia^a

1.30

1.08 - 1.57

0.01

Bilirubin (≥ 2 mg/dL)^{a, b}

1.45

1.19 - 1.76

0.0002

Chronic kidney disease (CrCl < 30 mL/min)^{a, b}

2.63

2.05 - 3.39

< 0.0001

INR > 1.5^{a, b}

1.68

1.39 - 2.04

< 0.0001

Thrombocytopenia (platelets < 50,000/µL)^a

0.96

0.67 - 1.34

0.80

Antiplatelet use^a

1.36

1.02 - 1.82

0.03

NSAID use^a

1.21

0.75 - 1.96

0.43

PPI use^a

1.23

1.05 - 1.43

0.01

Prior hemorrhage (within 5 years)

0.92

0.70 - 1.22

0.56

Alcohol abuse

1.29

1.10 - 1.53

0.002

Ascites^b

1.01

0.71 - 1.43

0.95

Cardiovascular disease

0.85

0.62 - 1.17

0.33

Congestive cardiac failure

1.17

0.84 - 1.62

0.35

Chronic lung disease

0.85

0.66 - 1.10

0.23

Connective tissue disease

1.51

0.74 - 3.08

0.25

Dementia

2.56

1.19 - 5.51

0.02

Diabetes mellitus

0.93

0.76 - 1.14

0.51

HIV/AIDS

0.57

0.22 - 1.51

0.26

Hemi- or paraplegia

0.89

0.27 - 2.89

0.84

Peptic ulcer disease

0.82

0.43 - 1.56

0.55

Infections

2.54

2.12 - 3.05

< 0.0001