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 http://www.thejh.org

Original Article

Volume 8, Number 1, March 2019, pages 17-25

Retrospective Cohort Study of Venous Thromboembolism Rates in Ambulatory Cancer Patients: Association With Khorana Score and Other Risk Factors

Figure 1. STROBE diagram to illustrate patient eligibility for the potentially preventable VTE risk factor analysis. VTE: venous thromboembolism.

Figure 2. Total VTE (a) and potentially preventable VTE (b) rates for tumor groups. (a) Total VTE rates in the first year of diagnosis were 26.8% in the pancreatic cancer cohort, 5.7% in endometrial cancer, 9.8% in colorectal cancer and 10.2% in ovarian cancer. No non-hospital associated VTE were identified in the cervical cancer cohort. (b) Excluding VTE present at diagnosis, the rates of VTE in the first year that were potentially preventable with thromboprophylaxis were 16.5% in pancreatic cancer, 3.8% in endometrial cancer, 9.8% in colorectal cancer and 8.7% in the ovarian cancer cohort.

Figure 3. VTE rate by low risk (< 3) and high risk (≥ 3) Khorana score in pancreatic (a), endometrial (b), colorectal (c) and ovarian (d) cancer patients. Cervical cancer cohort not included as no VTE events. High risk Khorana score predicted VTE in endometrial cancer (VTE rate high-risk Khorana: 4/24 (16.7%) vs. low-risk: 2/130 (1.5%); P < 0.001) but not in other cancer groups.

**Table 1.** Khorana Score (Adapted From reference [9])
Patient characteristics	Score
BMI: body mass index.
Site of cancer
Very high risk (stomach and pancreas)	2
High risk (lung, lymphoma, gynecological, bladder and testicular)	1
Pre-chemotherapy platelet count 350 × 10⁹ or more	1
Hemoglobin level less than 100 g/L or use of red cell growth factors	1
Pre-chemotherapy leucocyte count more than 11 × 10⁹/L	1
BMI 35 kg/m² or more	1

Table 1. Khorana Score (Adapted From reference [9])

Patient characteristics

Score

BMI: body mass index.

Site of cancer

Very high risk (stomach and pancreas)

High risk (lung, lymphoma, gynecological, bladder and testicular)

Pre-chemotherapy platelet count 350 × 10⁹ or more

Hemoglobin level less than 100 g/L or use of red cell growth factors

Pre-chemotherapy leucocyte count more than 11 × 10⁹/L

BMI 35 kg/m² or more

**Table 2.** Patient and Treatment Characteristics of Patients Included in the VTE Risk Factor Analysis
	Pancreatic (N = 87)	Colorectal (N = 205)	Endometrial (N = 154)	Ovarian (N = 193)	Cervical (N = 91)
VTE: venous thromboembolism; SD: standard deviation; IQR: interquartile range; bin: binary; CRP: C-reactive protein; BMI: body mass index. Early and advanced stages of cancer for pancreatic patients are defined as curative and non-curative surgery, respectively. *Khorana score not calculated for patients with abdominal VTE.
Age	n = 84	n = 199	N = 151	n = 190	n = 91
Mean (SD)	66.2 (11.3)	64.0 (14.4)	67.5 (10.7)	60.2 (15.1)	48.9 (16.1)
Range	37 - 91	18 - 92	34 - 92	15 - 97	24 - 90
Chemotherapy, n (%)	n = 85	n = 201	n = 154	n = 192	n = 91
Yes	56 (64.4)	116 (56.6)	44 (28.6)	148 (76.7)	51 (56.0)
No	29 (33.3)	85 (41.5)	110 (71.4)	44 (22.8)	40 (44.0)
Indwelling lines, n (%)	n = 78	n = 204	n = 154	n = 192	n = 91
Yes	23 (26.4)	62 (30.2)	8 (5.2)	22 (11.4)	6 (6.6)
No	55 (63.2)	142 (69.3)	146 (94.8)	170 (88.1)	85 (93.4)
Radiotherapy, n (%)	n = 86	n = 205	n = 154	n = 171	n = 91
Yes	13 (14.9)	39 (19.0)	94 (61.0)	5 (2.6)	60 (65.9)
No	73 (83.9)	166 (81.0)	60 (39.0)	166 (86.0)	31 (34.1)
CRP	n = 60	n = 67	n = 23	n = 61	n = 16
Median (IQR)	14.9 (7 - 50.5)	5.7 (1.9 - 34)	11 (4.4 - 40.4)	17.9 (7 - 48)	20.4 (4.5 - 66)
Range	0 - 199	0.6 - 253	0 - 231	0.7 - 214	0 - 207
CRP, n (%)	n = 60	n = 67	n = 23	n = 61	n = 16
> 5.0 mg/L (high risk)	48 (55.2)	35 (17.1)	17 (11.0)	51 (26.4)	11 (12.1)
≤ 5.0 mg/L (low risk)	12 (13.8)	32 (15.6)	6 (3.9)	10 (5.2)	5 (5.5)
Surgery, n (%)	n = 87	n = 205	n = 153	n = 193	n = 90
Yes	15 (17.2)	156 (76.1)	144 (93.5)	165 (85.5)	82 (90.1)
No	72 (82.8)	49 (23.9)	9 (5.8)	28 (14.5)	8 (8.8)
Platelet count	n = 87	n = 205	n = 154	n = 193	n = 91
Mean (SD)	270.0 (97.9)	303.5 (115.0)	319.1 (139.5)	362.8 (138.7)	308.2 (106.3)
Range	99 - 510	81 - 754	124 - 1,239	31 - 920	127 - 682
Platelet count, n (%)	n = 87	n = 205	n = 154	n = 193	n = 91
≥ 350 (high risk)	23 (26.4)	51 (24.9)	46 (29.9)	86 (44.6)	27 (29.7)
< 350 (low risk)	64 (73.6)	154 (75.1)	108 (70.1)	107 (55.4)	64 (70.3)
Hemoglobin (g/L)	n = 87	n = 205	n = 154	n = 193	n = 91
Mean (SD)	117.9 (18.5)	122.6 (23.7)	123.3 (23.1)	72.7 (55.0)	97.9 (48.7)
Range	57 - 163	10 - 168	10 - 159	5.2 - 159	6.9 - 160
Hemoglobin, n (%)	n = 87	n = 205	n = 154	n = 193	n = 91
< 100 g/L (high risk)	10 (11.5)	26 (12.7)	16 (10.4)	95 (49.2)	31 (34.1)
≥ 100 g/L (low risk)	77 (88.5)	179 (87.3)	138 (89.6)	98 (50.8)	60 (65.9)
Leukocyte	n = 87	n = 205	n = 154	n = 193	n = 91
Mean (SD)	8.8 (3.3)	8.0 (3.3)	8.6 (3.2)	9.3 (9.5)	8.4 (3.5)
Range	2.1 - 23	3.5 - 32	3.5 - 30.8	2.1 - 132	2.7 - 22.4
Leukocyte, n (%)	n = 87	n = 205	n = 154	n = 193	n = 91
> 11 (high risk)	21 (24.1)	23 (11.2)	25 (16.2)	29 (15.0)	17 (18.7)
≤ 11 (low risk)	66 (75.9)	182 (88.8)	129 (83.8)	164 (85.0)	74 (81.3)
BMI, n (%)	n = 77	n = 197	n = 152	n = 190	n = 90
< 35 (low risk)	75 (86.2)	192 (93.7)	135 (87.7)	179 (92.8)	83 (91.2)
≥ 35 (high risk)	2 (2.3)	5 (2.4)	17 (11.0)	11 (5.7)	7 (7.7)
Stage of cancer*, n (%)	n = 87	n = 196	n = 148	n = 190
Early	12 (13.8)	I-III: 162 (79.0)	I-II: 106 (68.8)	I-II: 59 (30.6)
Advanced	75 (86.2)	IV: 34 (16.6)	III-IV: 42 (27.3)	III-IV: 131 (67.9)
Khorana score**, n (%)	n = 82	n = 203	n = 154	n = 193	n = 91
0	-	136 (67.0)	-	-	-
1	-	35 (17.2)	78 (50.7)	46 (23.8)	42 (46.2)
2	37 (45.1)	30 (14.8)	52 (33.8)	84 (43.5)	24 (26.4)
3	37 (45.1)	2 (1.0)	20 (13.0)	52 (26.9)	17 (18.7)
4	8 (9.8)	-	4 (2.6)	11 (5.7)	8 (8.8)
Khorana score** (bin), n (%)	n = 82	n = 203	n = 154	n = 193	n = 91
≥ 3 (high risk)	45 (54.9)	2 (1.0)	24 (15.6)	63 (32.6)	25 (27.5)
< 3 (low risk)	37 (45.1)	201 (99.0)	130 (84.4)	130 (67.4)	66 (72.5)

Table 2. Patient and Treatment Characteristics of Patients Included in the VTE Risk Factor Analysis

Pancreatic (N = 87)

Colorectal (N = 205)

Endometrial (N = 154)

Ovarian (N = 193)

Cervical (N = 91)

VTE: venous thromboembolism; SD: standard deviation; IQR: interquartile range; bin: binary; CRP: C-reactive protein; BMI: body mass index. *Early and advanced stages of cancer for pancreatic patients are defined as curative and non-curative surgery, respectively. **Khorana score not calculated for patients with abdominal VTE.

Age

n = 84

n = 199

N = 151

n = 190

n = 91

Mean (SD)

66.2 (11.3)

64.0 (14.4)

67.5 (10.7)

60.2 (15.1)

48.9 (16.1)

Range

37 - 91

18 - 92

34 - 92

15 - 97

24 - 90

Chemotherapy, n (%)

n = 85

n = 201

n = 154

n = 192

n = 91

Yes

56 (64.4)

116 (56.6)

44 (28.6)

148 (76.7)

51 (56.0)

29 (33.3)

85 (41.5)

110 (71.4)

44 (22.8)

40 (44.0)

Indwelling lines, n (%)

n = 78

n = 204

n = 154

n = 192

n = 91

Yes

23 (26.4)

62 (30.2)

8 (5.2)

22 (11.4)

6 (6.6)

55 (63.2)

142 (69.3)

146 (94.8)

170 (88.1)

85 (93.4)

Radiotherapy, n (%)

n = 86

n = 205

n = 154

n = 171

n = 91

Yes

13 (14.9)

39 (19.0)

94 (61.0)

5 (2.6)

60 (65.9)

73 (83.9)

166 (81.0)

60 (39.0)

166 (86.0)

31 (34.1)

CRP

n = 60

n = 67

n = 23

n = 61

n = 16

Median (IQR)

14.9 (7 - 50.5)

5.7 (1.9 - 34)

11 (4.4 - 40.4)

17.9 (7 - 48)

20.4 (4.5 - 66)

Range

0 - 199

0.6 - 253

0 - 231

0.7 - 214

0 - 207

CRP, n (%)

n = 60

n = 67

n = 23

n = 61

n = 16

> 5.0 mg/L (high risk)

48 (55.2)

35 (17.1)

17 (11.0)

51 (26.4)

11 (12.1)

≤ 5.0 mg/L (low risk)

12 (13.8)

32 (15.6)

6 (3.9)

10 (5.2)

5 (5.5)

Surgery, n (%)

n = 87

n = 205

n = 153

n = 193

n = 90

Yes

15 (17.2)

156 (76.1)

144 (93.5)

165 (85.5)

82 (90.1)

72 (82.8)

49 (23.9)

9 (5.8)

28 (14.5)

8 (8.8)

Platelet count

n = 87

n = 205

n = 154

n = 193

n = 91

Mean (SD)

270.0 (97.9)

303.5 (115.0)

319.1 (139.5)

362.8 (138.7)

308.2 (106.3)

Range

99 - 510

81 - 754

124 - 1,239

31 - 920

127 - 682

Platelet count, n (%)

n = 87

n = 205

n = 154

n = 193

n = 91

≥ 350 (high risk)

23 (26.4)

51 (24.9)

46 (29.9)

86 (44.6)

27 (29.7)

< 350 (low risk)

64 (73.6)

154 (75.1)

108 (70.1)

107 (55.4)

64 (70.3)

Hemoglobin (g/L)

n = 87

n = 205

n = 154

n = 193

n = 91

Mean (SD)

117.9 (18.5)

122.6 (23.7)

123.3 (23.1)

72.7 (55.0)

97.9 (48.7)

Range

57 - 163

10 - 168

10 - 159

5.2 - 159

6.9 - 160

Hemoglobin, n (%)

n = 87

n = 205

n = 154

n = 193

n = 91

< 100 g/L (high risk)

10 (11.5)

26 (12.7)

16 (10.4)

95 (49.2)

31 (34.1)

≥ 100 g/L (low risk)

77 (88.5)

179 (87.3)

138 (89.6)

98 (50.8)

60 (65.9)

Leukocyte

n = 87

n = 205

n = 154

n = 193

n = 91

Mean (SD)

8.8 (3.3)

8.0 (3.3)

8.6 (3.2)

9.3 (9.5)

8.4 (3.5)

Range

2.1 - 23

3.5 - 32

3.5 - 30.8

2.1 - 132

2.7 - 22.4

Leukocyte, n (%)

n = 87

n = 205

n = 154

n = 193

n = 91

> 11 (high risk)

21 (24.1)

23 (11.2)

25 (16.2)

29 (15.0)

17 (18.7)

≤ 11 (low risk)

66 (75.9)

182 (88.8)

129 (83.8)

164 (85.0)

74 (81.3)

BMI, n (%)

n = 77

n = 197

n = 152

n = 190

n = 90

< 35 (low risk)

75 (86.2)

192 (93.7)

135 (87.7)

179 (92.8)

83 (91.2)

≥ 35 (high risk)

2 (2.3)

5 (2.4)

17 (11.0)

11 (5.7)

7 (7.7)

Stage of cancer*, n (%)

n = 87

n = 196

n = 148

n = 190

Early

12 (13.8)

I-III: 162 (79.0)

I-II: 106 (68.8)

I-II: 59 (30.6)

Advanced

75 (86.2)

IV: 34 (16.6)

III-IV: 42 (27.3)

III-IV: 131 (67.9)

Khorana score**, n (%)

n = 82

n = 203

n = 154

n = 193

n = 91

136 (67.0)

35 (17.2)

78 (50.7)

46 (23.8)

42 (46.2)

37 (45.1)

30 (14.8)

52 (33.8)

84 (43.5)

24 (26.4)

37 (45.1)

2 (1.0)

20 (13.0)

52 (26.9)

17 (18.7)

8 (9.8)

4 (2.6)

11 (5.7)

8 (8.8)

Khorana score** (bin), n (%)

n = 82

n = 203

n = 154

n = 193

n = 91

≥ 3 (high risk)

45 (54.9)

2 (1.0)

24 (15.6)

63 (32.6)

25 (27.5)

< 3 (low risk)

37 (45.1)

201 (99.0)

130 (84.4)

130 (67.4)

66 (72.5)

**Table 3.** Risk Factors of Potentially Preventable VTE by Cancer Type, Univariate Associations (χ²) and Stepwise Regression Using Backward Elimination
Risk factors for potentially preventable VTE	Pancreatic (N = 87)	Colorectal (N = 205)	Endometrial (N = 154)	Ovarian (N = 193)
VTE: venous thromboembolism; CRP: C-reactive protein; Sig.: remained statistically significant at the P < 0.05 level in stepwise regression; NS: not significant in stepwise regression. Statistically significant at the P < 0.05 level. *Khorana score not calculated for patients with abdominal VTE.
Chemotherapy (yes/no)	0.061	Sig.	< 0.001*	NS	0.035*	NS	0.252	NS
Indwelling lines (yes/no)	0.024*	NS	< 0.001*	Sig.	0.002*	Sig.	0.015*	Sig.
Radiotherapy (yes/no)	0.746	NS	0.629	NS	0.572	NS	0.498	NS
CRP (> 5.0 mg/L)	0.638	-	0.594	-	0.379	-	0.481	-
Surgery (yes/no)	0.043*	NS	0.221	NS	< 0.001*	Sig.	0.011*	Sig.
Platelet count (≥ 350)	0.162	NS	0.270	NS	0.045*	NS	0.769	NS
Hemoglobin level (< 100 g/L)	0.061	Sig.	0.277	NS	0.001*	NS	0.852	NS
Leukocyte count (> 11)	0.462	NS	0.190	NS	0.022*	NS	0.082	NS
BMI (≥ 35)	0.463	NS	0.460	NS	0.375	NS	0.020*	Sig.
Stage of cancer (early/advanced)	0.077	NS	0.115	NS	0.009*	NS	0.004*	NS
Khorana score** (low risk/high risk)	0.530	-	0.658	-	< 0.001*	-	0.807	-

Table 3. Risk Factors of Potentially Preventable VTE by Cancer Type, Univariate Associations (χ²) and Stepwise Regression Using Backward Elimination

Risk factors for potentially preventable VTE

Pancreatic (N = 87)

Colorectal (N = 205)

Endometrial (N = 154)

Ovarian (N = 193)

P value

Stepwise selection

P value

Stepwise selection

P value

Stepwise selection

P value

Stepwise selection

VTE: venous thromboembolism; CRP: C-reactive protein; Sig.: remained statistically significant at the P < 0.05 level in stepwise regression; NS: not significant in stepwise regression. *Statistically significant at the P < 0.05 level. **Khorana score not calculated for patients with abdominal VTE.

Chemotherapy (yes/no)

0.061

Sig.

< 0.001*

0.035*

0.252

Indwelling lines (yes/no)

0.024*

< 0.001*

Sig.

0.002*

Sig.

0.015*

Sig.

Radiotherapy (yes/no)

0.746

0.629

0.572

0.498

CRP (> 5.0 mg/L)

0.638

0.594

0.379

0.481

Surgery (yes/no)

0.043*

0.221

< 0.001*

Sig.

0.011*

Sig.

Platelet count (≥ 350)

0.162

0.270

0.045*

0.769

Hemoglobin level (< 100 g/L)

0.061

Sig.

0.277

0.001*

0.852

Leukocyte count (> 11)

0.462

0.190

0.022*

0.082

BMI (≥ 35)

0.463

0.460

0.375

0.020*

Sig.

Stage of cancer (early/advanced)

0.077

0.115

0.009*

0.004*

Khorana score** (low risk/high risk)

0.530

0.658

< 0.001*

0.807