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 11, Number 5, October 2022, pages 167-175

Incidence of Venous Thromboembolism in Hospitalized COVID-19 Patients Receiving Thromboprophylaxis

Figure 1. Kaplan-Meier plot of 30-day VTE by TX or PPX group. VTE: venous thromboembolism; PPX: prophylaxis-intensity; TX: therapeutic-intensity.

Figure 2. Kaplan-Meier plot of VTE by TX or PPX group with no truncation at 30 days. Fifty percent to VTE time for PPX group is 39 days vs. undefined for the TX group. VTE: venous thromboembolism; PPX: prophylaxis-intensity; TX: therapeutic-intensity.

Figure 3. Kaplan-Meier plot of 30-day all-cause mortality by TX or PPX group. Fifty percent survival time for the TX group is 22 days vs. undefined for the PPX group. PPX: prophylaxis-intensity; TX: therapeutic-intensity.

Figure 4. Kaplan-Meier plot of mortality by TX or PPX group with no truncation at 30 days. Median time to death for TX group is 27 days vs. undefined for the PPX group. PPX: prophylaxis-intensity; TX: therapeutic-intensity.

**Table 1.** Baseline Characteristics
	Prophylactic anticoagulation (n = 141)	Therapeutic anticoagulation (n = 141)
P < 0.05, Wald’s test. P < 0.05, KW ANOVA post-hoc* Dunn’s test. IQR: interquartile range; BMI: body mass index; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; COPD: chronic obstructive pulmonary disease; HIV/AIDS: human immunodeficiency virus/acquired immunodeficiency syndrome; ICU: intensive care unit; tPA: tissue plasminogen activator; VTE: venous thromboembolism; ESRD: end-stage renal disease; CAD: coronary artery disease; PPI: proton pump inhibitor.
Demographic
Age (years), median (IQR)	66 (54 - 80)	66 (55 - 76)
Male, n (%)	91 (67.4)	99 (70.2)
BMI (kg/m²), median (IQR)	28.8 (26 - 32.7)	30.8 (25.8 - 33.7)
Race/ethnicity
Caucasian, n (%)	87 (61.7)	87 (61.7)
Hispanic, n (%)	36 (24.8)	25 (17.7)
African American, n (%)	10 (7.1)	14 (10.0)
Asian, n (%)	1 (0.7)	1 (0.7)
Other, n (%)	8 (5.7)	14 (9.9)
Comorbidities
Hypertension	85 (60.3)	87 (61.7)
Diabetes	60 (42.6)	62 (44.0)
Asthma	12 (8.5)	19 (13.5)
COPD	10 (7.1)	19 (13.5)*
Atrial fibrillation	12 (8.5)	10 (7.1)
Heart failure	12 (8.5)	9 (6.4)
History of VTE	4 (2.8)	4 (2.8)
CAD	38 (27.0)	36 (26)
Chronic kidney disease	21 (14.9)	10 (7.1)*
ESRD	5 (3.6)	0 (0)*
Liver disease	2 (1.4)	1 (0.7)
Cancer	12 (8.5)	11 (7.8)
HIV/AIDS	2 (1.4)	2 (1.4)
Smoking history	4 (2.8)	5 (3.6)
Charlson Comorbidity Index (median)	3 (1 - 4)	3 (1 - 4)
Hospital interventions
ICU	13 (9.2)	36 (25.5)*
Intubation/ventilator	14 (9.9)	40 (28.4)*
Steroids, n (%)	112 (79.4)	126 (89.4)*
tPA, n (%)	3 (2.1)	14 (9.9)*
Home medications
ACEI/ARBs, n (%)	58 (41.3)	66 (47.1)
Antiplatelet, n (%)	48 (33.7)	48 (34.0)
Anticoagulation, n (%)	17 (12.1)	13 (9.2)
Statins, n (%)	63 (44.7)	65 (46.1)
PPI, n (%)	38 (27.0)	49 (35.0)
Baseline vitals/labs
Systolic blood pressure (mm Hg), median (IQR)	128 (118 - 146)	131 (115 - 142)
Diastolic blood pressure (mm Hg), median (IQR)	76 (67 - 85)	79 (68 - 87)
Respiratory rate (breaths/min), median (IQR)	18 (17 - 20)	18 (18 - 20)
Oxygen saturation, median (IQR)	96 (94 - 98)	96 (94 - 98)
D-dimer (µg/mL), median (IQR)	0.98 (0.61 - 1.82)	1.47 (0.8 - 2.9)
D-dimer > 0.5	88%	91%
Platelet count, median (IQR)	199 (160 - 260)	216 (158 - 291)

Table 1. Baseline Characteristics

Prophylactic anticoagulation (n = 141)

Therapeutic anticoagulation (n = 141)

*P < 0.05, Wald’s test. **P < 0.05, KW ANOVA post-hoc Dunn’s test. IQR: interquartile range; BMI: body mass index; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; COPD: chronic obstructive pulmonary disease; HIV/AIDS: human immunodeficiency virus/acquired immunodeficiency syndrome; ICU: intensive care unit; tPA: tissue plasminogen activator; VTE: venous thromboembolism; ESRD: end-stage renal disease; CAD: coronary artery disease; PPI: proton pump inhibitor.

Demographic

Age (years), median (IQR)

66 (54 - 80)

66 (55 - 76)

Male, n (%)

91 (67.4)

99 (70.2)

BMI (kg/m²), median (IQR)

28.8 (26 - 32.7)

30.8 (25.8 - 33.7)

Race/ethnicity

Caucasian, n (%)

87 (61.7)

Hispanic, n (%)

36 (24.8)

25 (17.7)

African American, n (%)

10 (7.1)

14 (10.0)

Asian, n (%)

1 (0.7)

Other, n (%)

8 (5.7)

14 (9.9)

Comorbidities

Hypertension

85 (60.3)

87 (61.7)

Diabetes

60 (42.6)

62 (44.0)

Asthma

12 (8.5)

19 (13.5)

COPD

10 (7.1)

19 (13.5)*

Atrial fibrillation

12 (8.5)

10 (7.1)

Heart failure

12 (8.5)

9 (6.4)

History of VTE

4 (2.8)

CAD

38 (27.0)

36 (26)

Chronic kidney disease

21 (14.9)

10 (7.1)*

ESRD

5 (3.6)

0 (0)*

Liver disease

2 (1.4)

1 (0.7)

Cancer

12 (8.5)

11 (7.8)

HIV/AIDS

2 (1.4)

Smoking history

4 (2.8)

5 (3.6)

Charlson Comorbidity Index (median)

3 (1 - 4)

Hospital interventions

ICU

13 (9.2)

36 (25.5)*

Intubation/ventilator

14 (9.9)

40 (28.4)*

Steroids, n (%)

112 (79.4)

126 (89.4)*

tPA, n (%)

3 (2.1)

14 (9.9)*

Home medications

ACEI/ARBs, n (%)

58 (41.3)

66 (47.1)

Antiplatelet, n (%)

48 (33.7)

48 (34.0)

Anticoagulation, n (%)

17 (12.1)

13 (9.2)

Statins, n (%)

63 (44.7)

65 (46.1)

PPI, n (%)

38 (27.0)

49 (35.0)

Baseline vitals/labs

Systolic blood pressure (mm Hg), median (IQR)

128 (118 - 146)

131 (115 - 142)

Diastolic blood pressure (mm Hg), median (IQR)

76 (67 - 85)

79 (68 - 87)

Respiratory rate (breaths/min), median (IQR)

18 (17 - 20)

18 (18 - 20)

Oxygen saturation, median (IQR)

96 (94 - 98)

D-dimer (µg/mL), median (IQR)

0.98 (0.61 - 1.82)

1.47 (0.8 - 2.9)

D-dimer > 0.5

88%

91%

Platelet count, median (IQR)

199 (160 - 260)

216 (158 - 291)

**Table 2.** Primary and Secondary Outcomes
	Prophylactic anticoagulation (n = 141)	Therapeutic anticoagulation (n = 141)	Odds ratio (95% CI)	P value
*Statistically significant. CI: confidence interval; VTE: venous thromboembolism; LOS: length of stay; NA: not available.
30-day primary outcomes (n = 266)
VTE, n (%)	3 (2.2)	5 (3.9)	0.56 (0.2 - 2.0)	0.5
Mortality, n (%)	7 (5.2)	33 (25.4)	0.16 (0.08 - 0.39)	< 0.0001*
Unrestricted primary outcomes
VTE, n (%)	6 (2.9)	8 (5.7)	2.02 (0.7 - 5.2)	0.2
Mortality, n (%)	8 (3.8)	38 (27.0)	9.2 (4.0 - 17.7)	< 0.0001*
30-day secondary outcomes (n = 266)
Hemorrhagic events n (%)	14 (10)	21 (16)	0.6 (0.3 - 1.22)	0.2
Hospital LOS, median days (IQR)	6 (4 - 11)	8 (5 - 15)	NA	0.02*
Unrestricted secondary outcomes
Hemorrhagic events n (%)	15 (11)	27 (19)	0.5 (0.3 - 1.0)	0.049*
Hospital LOS, median days (IQR)	6 (3 - 9)	9 (6 - 18)	NA	0.003*

Table 2. Primary and Secondary Outcomes

Prophylactic anticoagulation (n = 141)

Therapeutic anticoagulation (n = 141)

Odds ratio (95% CI)

P value

*Statistically significant. CI: confidence interval; VTE: venous thromboembolism; LOS: length of stay; NA: not available.

30-day primary outcomes (n = 266)

VTE, n (%)

3 (2.2)

5 (3.9)

0.56 (0.2 - 2.0)

0.5

Mortality, n (%)

7 (5.2)

33 (25.4)

0.16 (0.08 - 0.39)

< 0.0001*

Unrestricted primary outcomes

VTE, n (%)

6 (2.9)

8 (5.7)

2.02 (0.7 - 5.2)

0.2

Mortality, n (%)

8 (3.8)

38 (27.0)

9.2 (4.0 - 17.7)

< 0.0001*

30-day secondary outcomes (n = 266)

Hemorrhagic events n (%)

14 (10)

21 (16)

0.6 (0.3 - 1.22)

0.2

Hospital LOS, median days (IQR)

6 (4 - 11)

8 (5 - 15)

0.02*

Unrestricted secondary outcomes

Hemorrhagic events n (%)

15 (11)

27 (19)

0.5 (0.3 - 1.0)

0.049*

Hospital LOS, median days (IQR)

6 (3 - 9)

9 (6 - 18)

0.003*

**Table 3.** Restricted Mean Survival Time (RMST) Analysis
Group	Failed	Total	τ	RMST (τ)^a	Standard error	Lower 95% CI	Upper 95% CI
aEstimates are based on an interval upper limit of τ = 42.0, the smallest maximum observed time among all groups. CI: confidence interval; PPX: prophylaxis-intensity; TX: therapeutic-intensity.
PPX	8	141	42.0	34.9	2.370	30.2	39.5
TX	38	141	42.0	27.4	1.712	24.0	30.7

Table 3. Restricted Mean Survival Time (RMST) Analysis

Group

Failed

Total

RMST (τ)^a

Standard error

Lower 95% CI

Upper 95% CI

aEstimates are based on an interval upper limit of τ = 42.0, the smallest maximum observed time among all groups. CI: confidence interval; PPX: prophylaxis-intensity; TX: therapeutic-intensity.

PPX

141

42.0

34.9

2.370

30.2

39.5

141

42.0

27.4

1.712

24.0

30.7

**Table 4.** Cox Regression of Factors Related to Mortality
Independent variable	Risk ratio	P
^aMeans the P value is referring to patients in the ICU (1) vs. patients not in the ICU (0), likewise for ventilator status. *Statistically significant. COPD: chronic obstructive pulmonary disease; ICU: intensive care unit; PPX: prophylaxis-intensity; TX: therapeutic-intensity.
ICU (1 - 0)	2.1 (1.4 - 3.1)	0.0002*
COPD (1 - 0)	1.75 (1.1 - 2.7)	0.01*
Age (≥ 65 - < 65)	1.56 (1.1 - 2.3)	0.02*
TX group (TX - PPX)	1.34 (0.9 - 2.0)	0.16
Ventilator	1.1 (0.7 - 1.7)	0.7
ICU (1 - 0)^a ventilator (1 - 0)^a	0.46 (0.31 - 0.69)	0.0002*

Table 4. Cox Regression of Factors Related to Mortality

Independent variable

Risk ratio

^aMeans the P value is referring to patients in the ICU (1) vs. patients not in the ICU (0), likewise for ventilator status. *Statistically significant. COPD: chronic obstructive pulmonary disease; ICU: intensive care unit; PPX: prophylaxis-intensity; TX: therapeutic-intensity.

ICU (1 - 0)

2.1 (1.4 - 3.1)

0.0002*

COPD (1 - 0)

1.75 (1.1 - 2.7)

0.01*

Age (≥ 65 - < 65)

1.56 (1.1 - 2.3)

0.02*

TX group (TX - PPX)

1.34 (0.9 - 2.0)

0.16

Ventilator

1.1 (0.7 - 1.7)

0.7

ICU (1 - 0)^a ventilator (1 - 0)^a

0.46 (0.31 - 0.69)

0.0002*