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 10, Number 4, August 2021, pages 162-170

Incidence of Venous Thromboembolism and Effect of Anticoagulant Dosing in Hospitalized COVID-19 Patients

**Table 1.** Demographical, Clinical Characteristics and Outcomes of COVID-19 Patients With and Without Venous Thromboembolism (VTE)
	No VTE	VTE	P value
*Median (inter quartile range), number of observations. COVID-19: coronavirus disease 2019; SNF: skilled nursing facility; LTAC: long-term acute care; LOS: length of stay; IQR: interquartile range.
Total	4,394	251
Age, median (IQR)*	66 (52 - 77)	64 (52 - 75)	0.81
Male (%)	51.9	61.4	0.003
Race (%)*			0.08
White	71	67.7
Blacks	8.2	12.8
Hispanic	16.7	14.7
Asian	1.5	2.4
Not disclosed	2.7	2.4
BMI	30 (25.7 - 35.6)	31.3 (26.5 - 37.5)	0.81
Comorbidities (%)
Hypertension	71.7	73.3	0.57
Congestive heart failure	29.4	33.5	0.17
Diabetes mellitus	44	47.4	0.28
Chronic obstructive pulmonary disease	35.7	29.4	0.22
End-stage renal disease	3.5	4.8	0.28
Cirrhosis	12.4	13.2	0.72
Cancer	13.1	11.6	0.47
History of VTE	5.6	10.0	0.004
COVID-19 medications (%)
Tocilizumab	5.6	14.3	< 0.001
Steroids	66.5	47.0	< 0.001
Remdesivir	57.1	61.7	0.017
Died (%)	15.0	28.7	< 0.001
LOS in survivors, median (IQR)	5 (3 - 8)	8 (4 - 27)	< 0.001
Time to death, median (IQR)	10 (5 - 18)	14.5 (9 - 24)	< 0.001
Disposition (%)			< 0.001
Home	65.7	44.1
Home with health	17.6	22.4
SNF/LTAC/rehab	12.5	24.0
Others	4.1	9.5
Readmissions	13.5	11.2	0.37

Table 1. Demographical, Clinical Characteristics and Outcomes of COVID-19 Patients With and Without Venous Thromboembolism (VTE)

No VTE

VTE

P value

*Median (inter quartile range), number of observations. COVID-19: coronavirus disease 2019; SNF: skilled nursing facility; LTAC: long-term acute care; LOS: length of stay; IQR: interquartile range.

Total

4,394

251

Age, median (IQR)*

66 (52 - 77)

64 (52 - 75)

0.81

Male (%)

51.9

61.4

0.003

Race (%)*

0.08

White

67.7

Blacks

8.2

12.8

Hispanic

16.7

14.7

Asian

1.5

2.4

Not disclosed

2.7

2.4

BMI

30 (25.7 - 35.6)

31.3 (26.5 - 37.5)

0.81

Comorbidities (%)

Hypertension

71.7

73.3

0.57

Congestive heart failure

29.4

33.5

0.17

Diabetes mellitus

47.4

0.28

Chronic obstructive pulmonary disease

35.7

29.4

0.22

End-stage renal disease

3.5

4.8

0.28

Cirrhosis

12.4

13.2

0.72

Cancer

13.1

11.6

0.47

History of VTE

5.6

10.0

0.004

COVID-19 medications (%)

Tocilizumab

5.6

14.3

< 0.001

Steroids

66.5

47.0

< 0.001

Remdesivir

57.1

61.7

0.017

Died (%)

15.0

28.7

< 0.001

LOS in survivors, median (IQR)

5 (3 - 8)

8 (4 - 27)

< 0.001

Time to death, median (IQR)

10 (5 - 18)

14.5 (9 - 24)

< 0.001

Disposition (%)

< 0.001

Home

65.7

44.1

Home with health

17.6

22.4

SNF/LTAC/rehab

12.5

24.0

Others

4.1

9.5

Readmissions

13.5

11.2

0.37

**Table 2.** Initial Labs and Inflammatory Markers of COVID-19 Patients With and Without Venous Thromboembolism (VTE)
	No VTE	VTE	P value
^aMedian (inter quartile range), number of observations. COVID-19: coronavirus disease 2019; aPTT: activated partial thromboplastin time; SOFA: Sequential Organ Failure Assessment; INR: international normalized ratio; BUN: blood urea nitrogen; ALT: alanine transaminase; ECHO: echocardiogram; LVEF: left ventricular ejection fraction; TAPSE: tricuspid annular plane systolic excursion; RVSP: right ventricular systolic pressure; CRP: C-reactive protein; LDH: lactate dehydrogenase.
Initial clinical characteristics^a
SOFA score at admission	1 (0 - 2), 4,394	1 (0 - 2), 251	< 0.001
Mean arterial pressure (mm Hg)	90 (80 - 100), 4,383	92 (81 - 102), 249	0.25
Pulse	90 (78 - 104), 4,363	93 (80 - 110), 244	0.007
Respiratory rate	20 (18 - 24), 4,347	23 (19 - 26), 237	0.001
White blood cell count (× 10³)	7.7 (5.6 - 10.8), 4,375	9.6 (6.8 - 13.4), 250	0.001
Lymphocyte count (× 10³)	0.96 (0.66 - 1.41), 4,206	0.93 (0.61 - 1.33), 249	0.28
Hemoglobin (g/dL)	13.1 (11.6 - 14.4), 4,377	13.5 (12.4 - 14.9), 250	0.007
Platelets (× 10³)	205 (158 - 265), 4,367	221 (161 - 291), 250	0.02
Lactate (mmol/L)	1.1 (0.8 - 1.6), 2,449	1.3 (0.9 - 2.0), 200	0.001
Troponin (ng/mL)	0.02 (0.02 - 0.02), 2,216	0.02 (0.02 - 0.12), 138	< 0.001
aPTT	28.8 (26.3 - 31.9), 2,658	28 (25.2 - 31.5), 200	0.05
INR	1.17 (1.09 - 1.29), 3,877	1.21 (1.12 - 1.34), 246	0.02
BUN (mg/dL)	18 (12 - 27), 4,259	21 (15 - 32), 247	< 0.001
Creatinine (mg/dL)	1.08 (0.85 - 1.44), 4,257	1.21 (0.91 - 1.7), 246	< 0.001
ALT (IU/L)	32 (21 - 50), 4,220	37 (25 - 58), 248	< 0.001
Bilirubin (mg/dL)	0.5 (0.4 - 0.8), 4,150	0.6 (0.5 - 0.8), 248	< 0.001
ECHO findings^a
Lowest LVEF	60 (53 - 66), 1,297	60 (53 - 66), 163	0.89
Lowest TAPSE	2 (1.6 - 2.3), 1,460	2 (1.7 - 2.3), 176	0.72
Highest RVSP	35 (27 - 46), 954	36 (26 - 46), 116	0.87
Initial inflammatory markers during hospitalization^a
Ferritin (µg/L)	427 (200 - 874), 3,458	638 (311 - 1197), 232	< 0.001
CRP (mg/L)	7.4 (3.2 - 12.9), 3,474	11 (4.3 - 17.2), 234	< 0.001
LDH (U/L)	311 (238 - 407), 3,129	418 (310 - 582), 206	< 0.001
Fibrinogen (mg/dL)	540 (426 - 673), 3,188	564 (423 - 712), 221	0.46
D-dimer (µg/mL FEU)	0.8 (0.5 - 1.5), 3,433	1.97 (0.9 - 4), 237	< 0.001

Table 2. Initial Labs and Inflammatory Markers of COVID-19 Patients With and Without Venous Thromboembolism (VTE)

No VTE

VTE

P value

^aMedian (inter quartile range), number of observations. COVID-19: coronavirus disease 2019; aPTT: activated partial thromboplastin time; SOFA: Sequential Organ Failure Assessment; INR: international normalized ratio; BUN: blood urea nitrogen; ALT: alanine transaminase; ECHO: echocardiogram; LVEF: left ventricular ejection fraction; TAPSE: tricuspid annular plane systolic excursion; RVSP: right ventricular systolic pressure; CRP: C-reactive protein; LDH: lactate dehydrogenase.

Initial clinical characteristics^a

SOFA score at admission

1 (0 - 2), 4,394

1 (0 - 2), 251

< 0.001

Mean arterial pressure (mm Hg)

90 (80 - 100), 4,383

92 (81 - 102), 249

0.25

Pulse

90 (78 - 104), 4,363

93 (80 - 110), 244

0.007

Respiratory rate

20 (18 - 24), 4,347

23 (19 - 26), 237

0.001

White blood cell count (× 10³)

7.7 (5.6 - 10.8), 4,375

9.6 (6.8 - 13.4), 250

0.001

Lymphocyte count (× 10³)

0.96 (0.66 - 1.41), 4,206

0.93 (0.61 - 1.33), 249

0.28

Hemoglobin (g/dL)

13.1 (11.6 - 14.4), 4,377

13.5 (12.4 - 14.9), 250

0.007

Platelets (× 10³)

205 (158 - 265), 4,367

221 (161 - 291), 250

0.02

Lactate (mmol/L)

1.1 (0.8 - 1.6), 2,449

1.3 (0.9 - 2.0), 200

0.001

Troponin (ng/mL)

0.02 (0.02 - 0.02), 2,216

0.02 (0.02 - 0.12), 138

< 0.001

aPTT

28.8 (26.3 - 31.9), 2,658

28 (25.2 - 31.5), 200

0.05

INR

1.17 (1.09 - 1.29), 3,877

1.21 (1.12 - 1.34), 246

0.02

BUN (mg/dL)

18 (12 - 27), 4,259

21 (15 - 32), 247

< 0.001

Creatinine (mg/dL)

1.08 (0.85 - 1.44), 4,257

1.21 (0.91 - 1.7), 246

< 0.001

ALT (IU/L)

32 (21 - 50), 4,220

37 (25 - 58), 248

< 0.001

Bilirubin (mg/dL)

0.5 (0.4 - 0.8), 4,150

0.6 (0.5 - 0.8), 248

< 0.001

ECHO findings^a

Lowest LVEF

60 (53 - 66), 1,297

60 (53 - 66), 163

0.89

Lowest TAPSE

2 (1.6 - 2.3), 1,460

2 (1.7 - 2.3), 176

0.72

Highest RVSP

35 (27 - 46), 954

36 (26 - 46), 116

0.87

Initial inflammatory markers during hospitalization^a

Ferritin (µg/L)

427 (200 - 874), 3,458

638 (311 - 1197), 232

< 0.001

CRP (mg/L)

7.4 (3.2 - 12.9), 3,474

11 (4.3 - 17.2), 234

< 0.001

LDH (U/L)

311 (238 - 407), 3,129

418 (310 - 582), 206

< 0.001

Fibrinogen (mg/dL)

540 (426 - 673), 3,188

564 (423 - 712), 221

0.46

D-dimer (µg/mL FEU)

0.8 (0.5 - 1.5), 3,433

1.97 (0.9 - 4), 237

< 0.001

**Table 3.** Rate of Venous Thromboembolism (VTE) and Bleeding Complications of Anticoagulation According to Dose
	None (n = 598)	Standard (n = 3,269)	Intermediate (n = 59)	High (n = 719)	P
VTE at admission (%)	19.6	-	-	1.7	< 0.001
VTE during admission (%)	0.5	3.2	5.1	1.8	0.001
Acute intracranial hemorrhage (%)	2.3	1.0	1.7	1.7	0.03
Gastrointestinal bleeding	11.6	4.8	4.2	10.4	< 0.001
Blood transfusion (%)	11.0	7.8	13.6	14.6	< 0.001
Average units of blood transfusions	1.6	0.8	0.4	1.1	< 0.001
Fresh frozen plasma transfusion (%)	1.2	1.5	5.1	4.2	< 0.001
Cryoprecipitate transfusion (%)	1.2	0.5	0	0.6	0.21
Platelets transfusion (%)	2.0	1.1	0	1.4	0.26

Table 3. Rate of Venous Thromboembolism (VTE) and Bleeding Complications of Anticoagulation According to Dose

None (n = 598)

Standard (n = 3,269)

Intermediate (n = 59)

High (n = 719)

VTE at admission (%)

19.6

1.7

< 0.001

VTE during admission (%)

0.5

3.2

5.1

1.8

0.001

Acute intracranial hemorrhage (%)

2.3

1.0

1.7

0.03

Gastrointestinal bleeding

11.6

4.8

4.2

10.4

< 0.001

Blood transfusion (%)

11.0

7.8

13.6

14.6

< 0.001

Average units of blood transfusions

1.6

0.8

0.4

1.1

< 0.001

Fresh frozen plasma transfusion (%)

1.2

1.5

5.1

4.2

< 0.001

Cryoprecipitate transfusion (%)

1.2

0.5

0.6

0.21

Platelets transfusion (%)

2.0

1.1

1.4

0.26

**Table 4.** Factors Associated With Venous Thromboembolism in COVID-19 Patients
	Odds ratio	95% confidence interval	P
*P < 0.05. COVID-19: coronavirus disease 2019; NSAIDs: nonsteroidal anti-inflammatory drugs; CRP: C-reactive protein; LDH: lactate dehydrogenase; SOFA: Sequential Organ Failure Assessment.
Age	0.83	0.55 - 1.25	0.37
Gender (male vs. female)	1.55	1.01 - 2.39	0.04*
Race (black vs. others)	2.00	1.19 - 3.35	0.01*
Diabetes mellitus	1.45	0.96 - 2.19	0.07
End-stage renal disease	1.30	0.50 - 3.37	0.58
Congestive heart failure	1.04	0.66 - 1.65	0.83
Cancer	0.54	0.23 - 1.29	0.16
Cirrhosis	1.07	0.56 - 2.02	0.84
Anticoagulants at home	0.52	0.12 - 2.27	0.39
NSAIDs	0.70	0.37 - 1.31	0.27
P2Y12 inhibitors	0.68	0.23 - 1.99	0.48
Steroid use	0.58	0.30 - 1.11	0.10
Convalescent plasma	2.52	1.58 - 4.01	< 0.001*
Remdesivir	1.22	0.67 - 2.20	0.51
LDH	2.53	1.70 - 3.78	< 0.001*
CRP	1.30	0.99 - 1.72	0.06
D-dimer	1.15	1.06 - 1.24	< 0.001*
SOFA score on admission	1.52	0.82 - 2.80	0.18

Table 4. Factors Associated With Venous Thromboembolism in COVID-19 Patients

Odds ratio

95% confidence interval

*P < 0.05. COVID-19: coronavirus disease 2019; NSAIDs: nonsteroidal anti-inflammatory drugs; CRP: C-reactive protein; LDH: lactate dehydrogenase; SOFA: Sequential Organ Failure Assessment.

Age

0.83

0.55 - 1.25

0.37

Gender (male vs. female)

1.55

1.01 - 2.39

0.04*

Race (black vs. others)

2.00

1.19 - 3.35

0.01*

Diabetes mellitus

1.45

0.96 - 2.19

0.07

End-stage renal disease

1.30

0.50 - 3.37

0.58

Congestive heart failure

1.04

0.66 - 1.65

0.83

Cancer

0.54

0.23 - 1.29

0.16

Cirrhosis

1.07

0.56 - 2.02

0.84

Anticoagulants at home

0.52

0.12 - 2.27

0.39

NSAIDs

0.70

0.37 - 1.31

0.27

P2Y12 inhibitors

0.68

0.23 - 1.99

0.48

Steroid use

0.58

0.30 - 1.11

0.10

Convalescent plasma

2.52

1.58 - 4.01

< 0.001*

Remdesivir

1.22

0.67 - 2.20

0.51

LDH

2.53

1.70 - 3.78

< 0.001*

CRP

1.30

0.99 - 1.72

0.06

D-dimer

1.15

1.06 - 1.24

< 0.001*

SOFA score on admission

1.52

0.82 - 2.80

0.18

**Table 5.** Odds of Developing Venous Thromboembolism (VTE) and Odds of In-Hospital Mortality in COVID-19 Patients According to Anticoagulation (AC) Status
AC dose	For developing VTE	For in-hospital mortality
COVID-19: coronavirus disease 2019; CI: confidence interval.
No AC vs. any	0.05 (0.03 - 0.08)	< 0.001	0.81 (0.49 - 1.32)	0.41
Standard vs. intermediate	1.15 (0.30 - 4.38)	0.83	1.62 (0.65 - 4.05)	0.29
Standard vs. therapeutic	1.30 (0.57 - 2.95)	0.52	0.47 (0.27 - 0.80)	0.006
Standard vs. intermediate/therapeutic	1.26 (0.60 - 2.63)	0.53	0.61 (0.34 - 1.07)	0.08

Table 5. Odds of Developing Venous Thromboembolism (VTE) and Odds of In-Hospital Mortality in COVID-19 Patients According to Anticoagulation (AC) Status

AC dose

For developing VTE

For in-hospital mortality

Odds ratio (95% CI)

COVID-19: coronavirus disease 2019; CI: confidence interval.

No AC vs. any

0.05 (0.03 - 0.08)

< 0.001

0.81 (0.49 - 1.32)

0.41

Standard vs. intermediate

1.15 (0.30 - 4.38)

0.83

1.62 (0.65 - 4.05)

0.29

Standard vs. therapeutic

1.30 (0.57 - 2.95)

0.52

0.47 (0.27 - 0.80)

0.006

Standard vs. intermediate/therapeutic

1.26 (0.60 - 2.63)

0.53

0.61 (0.34 - 1.07)

0.08