Journal Pre-proof

Practical diagnosis and treatment of suspected venous thromboembolism during

COVID-19 Pandemic

Andrea T. Obi, MD, Geoff D. Barnes, MD, Thomas W. Wakefield, MD, Sandra Brown
RVT, Jonathon L. Eliason, MD, Erika Arndt, BA, Peter K. Henke, MD

PII: S2213-333X(20)30221-3
DOI: https://doi.org/10.1016/j.jvsv.2020.04.009
Reference: JVSV 994

To appear in: Journal of Vascular Surgery: Venous and Lymphatic Disorders

Received Date: 2 April 2020

Accepted Date: 14 April 2020

Please cite this article as: A.T. Obi, G.D. Barnes, T.W. Wakefield, S. Brown RVT, J.L. Eliason, E.
Arndt, P.K. Henke, Practical diagnosis and treatment of suspected venous thromboembolism during
COVID-19 Pandemic, Journal of Vascular Surgery: Venous and Lymphatic Disorders (2020), doi: https://
doi.org/10.1016/j.jvsv.2020.04.009.

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Copyright © 2020 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery.
 1

1 Practical diagnosis and treatment of suspected venous thromboembolism during COVID-

2 19 Pandemic

4 Andrea T. Obi, MDa, Geoff D. Barnes MDb, Thomas W. Wakefield MDa, Sandra Brown RVTa,

5 Jonathon L. Eliason MDa, Erika Arndt, BAa, Peter K. Henke, MDa

a
6 From the Section of Vascular Surgery, Department of Surgery, University of Michigan Health

7 System; b Section of Vascular Medicine, Department of Cardiology, University of Michigan

8 Health System

10 Reprint requests to Peter K. Henke, MD, University of Michigan Health System (UMHS),

11 1500 E. Medical Center Drive, Cardiovascular Center - 5463, Ann Arbor, MI 48109-5867.

12 Email: henke@umich.edu Phone: (734) 763-0250, FAX: (734) 647-9867

13 Conflicts of Interest and Source of Funding: None of the authors report conflicts of interest.

14 Vascular Cures Wiley Foundation Grant (AO)

15

16 Keywords: anticoagulant, deep venous thrombosis, venous thromboembolism, pulmonary

17 embolism, duplex ultrasound

18

19 Article Highlights

20 Type of Research: Evidence based algorithm designed for use in times of extreme scarcity.

21

22 Key Findings: Standard imaging techniques such as duplex ultrasonography and CT may not be

23 available for VTE diagnosis due to sheer volume of patients, difficulty in disinfecting equipment,
 2

1 and inadequate number of qualified imaging personnel. Empiric treatment of suspected VTE

2 may be warranted based upon risk stratification and risk-benefit ratio calculation until imaging is

3 available.

5 Take Home Message: During the COVID-19 pandemic and other times of extreme scarcity,

6 empiric treatment of VTE without confirmatory imaging may need to be undertaken, balancing

7 risk-benefit ratios.

9 Table of Contents Summary

10 Based on evidence review, patients with low pretest probability of DVT or PE by clinical scoring

11 system should be treated with thromboprophylaxis; those at high risk should be treated

12 empirically until imaging is available. The authors advocate for imaging only on a limited basis

13 for patients at high risk of both thrombosis and bleeding, when the results will change

14 management.

15

16

17 Abstract

18 A markedly increased demand for vascular ultrasound laboratory and other imaging studies in

19 COVID-19 positive patients has occurred, due to most with markedly elevated D-dimer, and a

20 presumed prothrombotic state in many of the very ill patients. This article summarizes a broad

21 institutional consensus focusing on evaluation and recommended empirical therapy for COVID-

22 19 positive patients. We recommend following the algorithms with the idea that as more data

23 becomes available that this may well change.

 3

2 Introduction

3 The diagnosis of venous thromboembolism (VTE) traditionally relies upon assessment of

4 the patient for history and physical exam findings consistent with the diagnosis, risk

5 stratification, then imaging with duplex ultrasonography for deep venous thrombosis (DVT) or

6 with computed tomography (CT-PE) for pulmonary embolism.1 This common diagnosis and its

7 work up are a familiar thread in the fabric of all emergency departments, inpatient wards and

8 intensive care units across the country and the world. The COVID-19 pandemic has caused a

9 massive rent in this cloth as hospitals experience a surge of patients: CT PE is often delayed or

10 not performed due to co-morbid renal failure precluding the use of intravenous contrast and

11 cardiopulmonary instability leading to an unacceptable risk for transfer. Similarly, duplex

12 ultrasonography (DUS) for the diagnosis of DVT is difficult to perform due to large number of

13 patients, many of whom will be housed in field hospitals without diagnostic vascular unit labs

14 (DVUs), a contracted registered vascular technician workforce, and length of time associated

15 with and difficulty in completely disinfecting the machines in between patients.

16 Beyond the obligation of “do no harm” to our patient population, a global pandemic also

17 shines light on the moral obligations of and to ancillary healthcare staff. For instance, while it is

18 hotly debated on a national stage whether the physician “duty to treat” moral standard should be

19 upheld without proper personal protective equipment, it is even less clear to what obligation the

20 registered vascular technician (RVTs) should be held to when their services only indirectly

21 impact morbidity and mortality. It is arguably both within the realm of physician capability and

22 obligation to minimize exposure to RVTs in our DVUs, while minimizing harm to patients.

23 Furthermore, with a dedicated skill set requiring the use of expensive equipment, RVTs represent
 4

1 a scare resource during a pandemic, that if depleted, would inhibit our ability to detect other life

2 and limb threatening conditions that require urgent/emergent treatment such as acute limb

3 ischemia, pseudoaneurysms and carotid disease leading to stroke.

4 Facing mounting requests for duplex ultrasonography (DVT scans) for VTE diagnosis

5 during the exponential growth phase of the COVID-19 pandemic in our community, we formed

6 an ad hoc committee of venous thrombosis experts, vascular surgeons, hospitalists and critical

7 care physicians, vascular medicine physicians and RVTs. This committee is charged with rapidly

8 reviewing evidence for VTE diagnosis and treatment and adapt clinical algorithms for use during

9 a time when imaging resources, such as ultrasound machines and sonographers with experience

10 and expertise, are expected to be scarce, recognizing both our moral obligation to our patients

11 and to our vascular sonographers. Underlying these algorithms is the absolute commitment at

12 the institutional level to ensure appropriate diagnostic imaging, long term therapy

13 recommendations and follow up once the surge has passed. As a frame of reference, we are

14 expected to experience a volume of >3,000 patients at our peak in Michigan, and to be several

15 fold in excess of our hospital capacity, utilizing field hospitals for approximately 8 weeks.

16

17 Methods

18 A committee comprised of vascular thrombosis experts, vascular surgeons, vascular medicine

19 physicians, and vascular technologist was convened. We also sought, via multiple conference

20 calls, input from intensivists, pulmonologists, and hematologists for critique and vetting of the

21 algorithms that resulted. Existing published protocols for diagnosis and management of VTE by

22 our faculty practice group were reviewed, alongside current ACCP and National Institution for

23 Health and Care Excellence.1 Our institutional experience with VTE events and utility of
 5

1 empiric low dose anticoagulation with H1N1 viral pneumonia were reviewed, as well as

2 emerging evidence regarding VTE risk in COVID-19 infections. Feedback from content experts

3 in vascular surgery, hematology, pharmacology, internal medicine, cardiology, anesthesiology

4 and critical care was solicited. Implementation was rapidly achieved via dissemination in care

5 bundles, computerized physician order entry (CPOE) sets, and best practice alerts.

7 Results

8 Consensus was achieved regarding 9 critical guiding principles (Table I) based upon best

9 evidence, available resources and ethical obligations to patients and staff. High priority was

10 placed on treating suspected VTE without definitive imaging in the context of acceptable

11 bleeding risk, recognizing the potential to decrease morbidity and mortality. Extreme

12 pragmatism was applied, recognizing the well-being and scarcity of RVTs was paramount over

13 obtaining a diagnosis when clinical management would not be altered.

14 VTE prophylaxis

15 As an institutional standard, all patients are routinely risk assessed with the Caprini risk

16 assessment model upon admission.2 The committee recognized that healthy patients with only a

17 diagnosis may fall into a low risk category that would not warrant VTE prophylaxis. There is a

18 paucity of data on VTE in COVID-19, however one study found a mortality benefit to

19 thromboprophylaxis with subcutaneous unfractionated heparin or low molecular weight heparin

20 amongst COVID-19 positive patients with highly elevated (>3x upper limit of normal) D-dimer

21 and sepsis induced coagulopathy score.3 The true incidence of VTE is unknown, and likely

22 variable across different patient populations, with the highest case reports of pulmonary

23 embolism (PE) in up to 40% of patients with elevated D dimer undergoing CT PE.4-6 These data
 6

1 suggest VTE or primary pulmonary thrombi may be an underlying etiology responsible for

2 mortality in severe COVID-19 infections. In patients who initially present with less severe

3 disease, the risk from failure to reassess and provide timely thromboprophylaxis in an over-

4 capacity healthcare system is much more likely to outweigh the risk of major bleeding from

5 appropriately dosed thromboprophylaxis (~1%).1 Further, while some may choose to use larger

6 doses of thromboprophylaxis, there is no clear evidence basis for this, and we defer to the front

7 line practicioner.7 The committee therefore recommends routine thromboprophylaxis of all

8 hospitalized patients with COVID-19 regardless of risk score (Table II).

9 Suspected Diagnosis of Pulmonary Embolism

10 The existing, published Michigan Medicine faculty practice guidelines recommend utilization of

11 a modified Wells’ score (Table III) to determine pretest probability of a PE.8

12 If the pre-test probability of the modified Wells’ PE score is low (score ≤4, mean probably

13 of PE 1.7-2.2% if D-dimer negative; 5.1-7.8% overall, independent of the D-dimer): The

14 current recommendation is thromboprophylaxis for the non-intubated, admitted patient and the

15 intubated critically ill patient at high risk for bleeding (Figures 1 and 2). The intubated,

16 critically ill patient who is low risk by the Wells’ score may qualify for empiric lower dose

17 anticoagulation if their bleeding risk is low. Higher consideration should be given to empiric

18 low dose anticoagulation if the Partial pressure of arterial oxygen/Fractional inspired oxygen

19 (P/F) ratio is less than 200. We do not recommend that duplex ultrasonography be performed in

20 patients to exclude the diagnosis of PE. The rationale for this is that the use of DVT imaging in

21 the setting of suspected PE has a low accuracy, a sensitivity of 44%, a specificity of 86%, a

22 positive predictive value 58% and a negative predictive value of 77%.9 This data has been

23 substantiated in other studies with reported sensitivities of 25-38% for the diagnosis of
 7

1 thrombosis when being used as a surrogate for PE. Thus, duplex imaging has significant

2 limitations in the diagnosis of PE or in situ pulmonary thrombosis and is not a direct test for PE.

3 A negative D dimer in combination with a low modified Wells’ score is generally sufficient to

4 exclude PE as a diagnosis. However, in the setting of COVID-19 infection, which is associated

5 with elevated D dimer, the clinical utility of D dimer is unknown.10 A clinician may draw a D

6 dimer at their discretion in the setting of a low modified Wells’ score if a negative result will

7 reassure the patient. However, if positive, which is likely, it may distract from pursuing other,

8 more likely diagnoses.

9 If the pre-test probability is of the Wells’ PE score is high (score >4): We recommend full

10 dose anticoagulation for the high risk patient with a low risk for bleeding anticoagulation based

11 on bleeding risk (VTE Bleed score <2, no other risk factors such as thrombocytopenia, cirrhosis,

12 other thrombotic use). Lower dose empiric anticoagulation may be utilized as clinically

13 appropriate in the intubated critically ill patients due to the bleeding risk associated with

14 hemorrhagic pneumonitis with higher Xa levels. For the patient at high risk of bleeding (Table

15 IV), the clinician could consider obtaining a CT PE study, if this would alter management. If a

16 CT PE is unable to be obtained, lower extremity duplex ultrasonography would be an alternative

17 option, recognizing limitations in sensitivity and specificity. Prior to obtaining imaging,

18 clinicians should screen each patient to ensure that testing will not be futile nor redundant (Table

19 V).

20 If the diagnostic study is negative, thromboprophylaxis is recommended. If the study is positive,

21 consideration should be given to full dose anticoagulation in the non-intubated admitted patient

22 and lower dose empiric anticoagulation (either clinician run non-nomogram; or using the ACS

23 nomogram without bolus, Figures 1 and 2) in the intubated critically ill patients due to the
 8

1 bleeding risk, or full dose anticoagulation if felt to be appropriate by the intensivist.

2 Rationale for using anticoagulation at lower than full dose but higher than prophylactic

3 dose in those patients with severe ARDS:

4 Viral pneumonia associated venous thrombotic events resulting in significant mortality were

5 witnessed during the H1N1 2009 pandemic. Patients meeting the following criteria during this

6 time were treated with an empiric low dose anticoagulation protocol: P/F ratio < 200; viral

7 pneumonia suspected or confirmed; no absolute contraindications to anticoagulation. In patients

8 meeting these criteria, the following protocol reduced the risk of VTE and primary pulmonary

9 thrombi without increasing bleeding complications: initiation of non-nomogram heparin infusion

10 with a goal Xa between 0.2-0.3; no bolus dose administered. The lower Xa is necessary given

11 the risk of bleeding with hemorrhagic pneumonitis. Of note, this goal Xa does not match with an

12 existing heparin nomogram at our institution, and requires manual titration by the inpatient

13 team.11 It therefore may be a reasonable, although untested, strategy to utilize the ACS

14 nomogram with lower Xa ranges (0.2-0.5) to reduce clinician workload if bleeding risk is

15 acceptable (Table II). In intubated patients without ARDS, there is a paucity of data regarding

16 risk-benefit ratio of empiric anticoagulation strategies. Patients with thrombocytopenia (platelets

17 < 30) should not be anticoagulated due to attendant bleeding risk, based on expert consensus.

18

19 Suspected Diagnosis of DVT

20 The existing Michigan Medicine faculty practice guidelines recommend utilization of Wells’

21 score to determine pretest probability of a DVT (Table VI).12 We recommend use of this score

22 during the COVID-19 pandemic, recognizing that sensitivity and specificity diminishes in the

23 inpatient setting and performance in the setting of pandemic pneumonia is untested, yet no
 9

1 reasonable alternative exists.12-14

2 If the pre-test probability of the modified Wells’ DVT score is low (score <2, mean

3 probably of DVT 3%): The current recommendation is thromboprophylaxis in the non-

4 intubated admitted patient. The intubated, critically ill patient who is low risk by the Wells’

5 score may qualify for empiric lower dose anticoagulation if their bleeding risk is low (Figures 3

6 and 4). Higher consideration should be given to empiric low dose anticoagulation if the P/F

7 ratio is less than 200. The use of duplex ultrasound testing with a risk of only 3% DVT does not

8 warrant the risk to the technologists of performing the tests in COVID-19 positive patients or

9 those PUI. Anticoagulation would not be used unless the Wells’ scores changes. D dimer can be

10 used only to rule out the presence of DVT; however, is expected to be elevated in COVID-19

11 and should not provide impetus to obtain imaging in the absence of any other clinical

12 manifestation of DVT.

13 If the pre-test probability of the Wells’ DVT score is high(score >2, mean probability of

14 DVT 16.6%-74.6%): With the higher likelihood of DVT in this group, we would recommend

15 anticoagulation based on bleeding risk (VTE-BLEED score). In the low bleeding risk patient

16 (VTE-BLEED score <2), we suggest empiric full dose therapeutic anticoagulation for the non-

17 intubated admitted patient. In the intubated critically ill patient, we recommend empiric lower

18 dose anticoagulation, due to the expected elevated bleeding risk with common comorbid

19 conditions such as renal failure, DIC and hemorrhagic pneumonitis (Figures 3 and 4). In the

20 high bleeding risk patient (VTE-BLEED score >2), a lower extremity DVT scan may be

21 indicated if the patients meets criteria (Table V). We note that the VTE-BLEED score (Table

22 IV) is validated in the outpatient population, and that no similar score exists for use in the

23 acutely hospitalized nor critically ill population. This specific patient cohort may have additional
 10

1 risk factors that increase bleeding risk such as thrombocytopenia, cirrhosis and other anti-

2 thrombotic use that should be taken into consideration by the clinician at the bedside.

3 Furthermore, the VTE-BLEED scan is validated for bleeding risk over a longer time period than

4 expected in most patients treated with this algorithm, therefore physicians may be comfortable

5 with full dose anticoagulation if a patient has multiple risk factors, recognizing the less absolute

6 number of days subjected to risk. If the DVT scan is negative, then thromboprophylaxis is

7 recommended. If the study is positive, consideration should be given to full dose

8 anticoagulation, or an IVC filter. For patients treated with lower dose empiric anticoagulation in

9 the ICU setting, standard full dose anticoagulation should be initiated once they become floor

10 status.

11 Upper extremity DVT

12 Given the low morbidity of upper extremity line associated DVT in our critically ill population,15

13 we do not recommend routine upper extremity duplex ultrasound. If a patient has unilateral

14 symptoms and a high risk for bleeding, the need for upper extremity imaging can be considered

15 on a case by case basis. If low bleeding risk, and high likelihood of DVT, the patient should be

16 empirically treated.

17 Consideration for long term therapy

18 In patients who are treated with anticoagulants and are unable to get diagnostic imaging during

19 the COVID-19 surge, we recommend that they be discharged with a one to two-month supply of

20 direct oral anticoagulants (or vitamin K antagonists), until they are able to undergo diagnostic

21 imaging. For patients deemed moderate to high risk for PE, a CT PE protocol within 1 month

22 should be ordered once they are considered negative for COVID-19. For patients deemed high

23 risk for DVT, a lower extremity duplex ultrasound should be ordered again once they are
 11

1 considered negative for COVID-19. All patients should be followed and provided

2 recommendations for long term duration of therapy. Current efforts are aimed at developing

3 protocols for high through-put imaging post pandemic and diligent follow up via newly

4 expanded video and or telephone visits.

6 Discussion

7 It is said that necessity is the mother of innovation. Just a few short months ago, it was

8 inconceivable that hospitals across the United States and the globe would be stretched far beyond

9 capacity, that essential resources would be rationed, and that even the most mundane, everyday

10 clinical diagnosis and treatment algorithms would be altered. This is the current status as only a

11 small aliquot of hours stand between us and the overwhelming tide of patients throughout the

12 nation and in many parts of the world. Proactive use of an algorithmic approach to care in this

13 setting has the following advantages: (1) decreases variability in care across the healthcare

14 system; (2) relieves stress on the individual provider on determining optimal treatment without

15 appropriate and usual diagnostic tests; (3) harnesses existing healthcare infrastructure to ensure

16 conscientious follow up for patients and restore confidence in the system; (4) protects scare

17 resources; and (5) fulfills our moral obligation to our patients and staff.

18 As we move forward through the inevitable crush of patients, conserving clinicians’

19 mental energy for critical decisions should be of the highest priority given the expected

20 emotional and mental exhaustion in the pandemic setting. As vascular specialists, using our

21 knowledge of clinical scoring systems and risk-benefit ratio, we can extrapolate the current

22 knowledge and standard of care to provide practical and pragmatic straightforward rules for

23 treatment that alleviates the bedside clinician mired in the purgatory of diagnostic uncertainty.
 12

1 In this treatment paradigm, we emphasize preventing VTE related morbidity and mortality at the

2 expense of bleeding complications over a short term while imaging is delayed, and also utilizing

3 therapy that has shown benefit for other severe viral states (H1N1). While direct oral

4 anticoagulants are now more readily available, and have improved bleeding profile, we expect

5 that with such a large influx of patients, bleeding complications are a statistical certainty. With

6 such an approach, the commitment to providing follow up – the DVT scan that would normally

7 be obtained in 24 hours, now will be obtained in 2-4 weeks – must be absolute, meticulous and

8 unwavering.

9 The lack of hospital system beds across the country alongside the press reports of

10 temporary morgues and ventilator rationing may very well serve to undermine the confidence of

11 Americans in the existing healthcare infrastructure. Using content experts and protocolizing

12 treatment plans is one method that can allow us to maintain consistency in care delivery and

13 restore faith in the local hospital system. Undoubtedly, there are areas beyond VTE where

14 vascular surgeons can and are developing protocols that can help to streamline the care of

15 patients during a time of crisis. During the time of crisis, we can further respond by collating

16 data in an organized fashion, adapting protocols as more is learned and disseminating

17 information rapidly. Vascular surgeons are often the quarterback in crisis; but in the current

18 challenge of the COVID-19 pandemic our role is to use our expertise and tools to protect and aid

19 those serving on the frontlines.

20

21

22 References

23 1. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson
 13

1 ME, Wells PS, Gould MK, Dentali F, Crowther M and Kahn SR. Antithrombotic therapy for

2 VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College

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4 e496S.

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6 Venous Thromboembolism Risk Stratification Using the 2005 Caprini Score to Identify the

7 Benefits and Harms of Chemoprophylaxis in Surgical Patients: A Meta-analysis. Ann Surg.

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9 3. Tang N, Bai H, Chen X, Gong J, Li D and Sun Z. Anticoagulant treatment is associated

10 with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J

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13 keypoints in treatment of the critical coronavirus disease 2019 patient]. Zhonghua Jie He He Hu

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17 HM and Parikh SA. Cardiovascular Considerations for Patients, Health Care Workers, and

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21 Xie, Y. Findings of Acute Pulmonary Embolism in COVID-19 Patients. Lancet. 2020.

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23 patients undergoing bariatric surgery. Vasc Health Risk Manag. 2015;11:461-77.

 14

1 8. Bahia A and Albert RK. The modified Wells score accurately excludes pulmonary

2 embolus in hospitalized patients receiving heparin prophylaxis. J Hosp Med. 2011;6:190-4.

3 9. Killewich LA, Nunnelee JD and Auer AI. Value of lower extremity venous duplex

4 examination in the diagnosis of pulmonary embolism. J Vasc Surg. 1993;17:934-8; discussion

5 938-9.

6 10. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L,

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8 for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

9 Lancet. 2020;395:1054-1062.

10 11. Obi AT, Tignanelli CJ, Jacobs BN, Arya S, Park PK, Wakefield TW, Henke PK and

11 Napolitano LM. Empirical systemic anticoagulation is associated with decreased venous

12 thromboembolism in critically ill influenza A H1N1 acute respiratory distress syndrome patients.

13 J Vasc Surg Venous Lymphat Disord. 2019;7:317-324.

14 12. Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, Clement C, Robinson

15 KS and Lewandowski B. Value of assessment of pretest probability of deep-vein thrombosis in

16 clinical management. Lancet. 1997;350:1795-8.

17 13. Silveira PC, Ip IK, Goldhaber SZ, Piazza G, Benson CB and Khorasani R. Performance

18 of Wells Score for Deep Vein Thrombosis in the Inpatient Setting. JAMA Intern Med.

19 2015;175:1112-7.

20 14. Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J, Kovacs G, Mitchell

21 M, Lewandowski B and Kovacs MJ. Evaluation of D-dimer in the diagnosis of suspected deep-

22 vein thrombosis. N Engl J Med. 2003;349:1227-35.

23 15. Underhill J, Sherman MA, Howard R, Hage A, Obi A, Napolitano L and Coleman DM.
 15

1 The natural history and outcomes of line-associated upper extremity deep venous thromboses in

2 critically ill patients. J Vasc Surg Venous Lymphat Disord. 2017;5:630-637.

7
Legends

Figure 1. Algorithm for stable patient with suspected DVT. Note PE = pulmonary embolism;

VTE = venous thromboembolism; AC = anticoagulation; LE = lower extremity; Pt = patient; Dx

= diagnosis.

Figure 2. Algorithm for critically ill patient with suspected DVT. Note PE = pulmonary

embolism; VTE = venous thromboembolism; AC = anticoagulation; ACS = acute coronary

syndrome; LE = lower extremity; Pt = patient; Dx = diagnosis.

Figure 3. Algorithm for stable patient with suspected PE. Note PE = pulmonary embolism; VTE

= venous thromboembolism; AC = anticoagulation; LE = lower extremity; Pt = patient; Dx =

diagnosis.

Figure 4. Algorithm for critically ill patient with suspected PE. Note PE = pulmonary embolism;

VTE = venous thromboembolism; AC = anticoagulation; ACS = acute coronary syndrome; LE =

lower extremity; Pt = patient; Dx = diagnosis.

Table I.
Critical Guiding Principles
1. All patients with COVID-19 or suspected COVID-19 should be treated with
thromboprophylaxis. This statement places value on avoiding the need to reassess
VTE risk when a patient has a change in status, and accepts overall low bleeding risk
associated with use of anticoagulants used at thromboprophylactic doses.
2. Elevated D-dimer is expected with severe COVID infection and should not be a
determinant in the decision to obtain imaging. Negative D-dimer in combination with
a low clinical risk score can still safely exclude VTE and may have limited utility for
this purpose.
3. Current guidelines recommend empiric treatment of suspected PE if imaging is
expected to take > 4 hours, or for DVT if imaging is expected to take > 24 hours. We
expect that due to stress on the healthcare system that imaging may be delayed for up
to a month or greater, but that patients may be safely empirically treated during this
time by determining risk-benefit ratio.
4. Duplex ultrasonography should be utilized when the three following conditions are met
simultaneously: (1) bleeding risk is high, (2) the results will change management (3)
clinical suspicion of pulmonary embolism is high and CT PE is unobtainable or clinical
suspicion of DVT is high (based upon modified Wells and Wells scoring systems).
5. Most patients with confirmed or suspected VTE who are not at high bleeding risk
should receive therapeutic doses of anticoagulation.
6. In patients with ARDS, low dose non-nomogram heparin infusion may reduce risk of
major bleeding while still protecting from thrombotic events. There is no data
available for this treatment strategy in intubated patients without ARDS.
7. Patients treated with low dose anticoagulation protocols should be transitioned to full
dose anticoagulation when no longer ICU status.
8. Referral for CT PE or duplex may be performed once patient has recovered as an
inpatient, however, may need to be completed in the outpatient setting in a resource
scarce setting. CVC venous clinics (or hematology, if a consulting service as inpatient)
will provide continuity of care in reviewing these outpatient imaging tests and
providing long term anticoagulation recommendations to the patient, thereby
expediting discharges without the burden of additional testing and relieving inpatient
providers of burden of follow up.
9. Upper extremity duplex ultrasonography should be limited to patients with unilateral
limb symptoms and criteria as listed in #4 and should not be performed routinely.
Table II. Anticoagulation strategies
Thromboprophylaxis • Low molecular weight heparin 40mg qday (or 30mg bid)
• Subcutaneous heparin 5000 units tid
Full dose • “Heparin Nomogram for DVT/PE”
anticoagulation • Low molecular weight heparin 1.5mg/kg qday (or 1mg/kg bid)
• Direct oral anticoagulant (standard dosing)
Low dose • Many patients can receive “Heparin Nomogram for DVT/PE”
anticoagulation without bolus
protocol • “Heparin Nomogram for ACS/AF” (Xa target 0.2-0.5)
• Non-nomogram Heparin at discretion of attending (Xa target
0.2-0.3)
Table III. Modified Wells Score for Assessment of
Clinical Likelihood for Pulmonary Embolism
Criteria Points
Clinical signs and symptoms of DVT
(objectively measured calf swelling and
3
pain with palpation in the deep vein
region)
An alternative diagnosis is less likely than
3
PE
Heart rate > 100 beats per minute 1.5
Immobilization or surgery in the previous
1.5
four weeks
Previous DVT or PE 1.5
Hemoptysis 1
Malignancy (on treatment, treated in the
1
past six months, or palliative care)
Note: Total score > 4 = PE-likely, ≤ 4 = PE-unlikely
Table IV. Under the following circumstances no further studies should be performed:
1. Patient end of life/comfort care.
2. Patient has another indication for anticoagulation.
3. Patient has a previous CT PE or DVT scan this admission without a change in modified
Wells risk stratification.
4. Patient would not consent to or be a candidate for anticoagulation or IVC filter if offered.
5. Patient has a diagnosis of VTE from OSH study.
Table V. Wells Score for Likelihood Estimation of Lower Extremity Deep Venous
Thrombosis
Clinical Characteristic Score
Active cancer (patient receiving treatment for cancer within the previous 6
1
months or currently receiving palliative treatment)
Paralysis, paresis, or recent casting or immobilization of the lower extremities 1
Recently bedridden for 3 days or more, or major surgery within the previous 12
1
weeks requiring general or regional anesthesia
Localized tenderness along the distribution of the deep venous system 1
Entire leg swollen 1
Calf swelling at least 3 cm larger than that on the asymptomatic side (measured
1
10 cm below the tibial tuberosity)
Pitting edema confined to the symptomatic leg 1
Previously documented DVT 1
Collateral non-varicose superficial veins 1
Alternative diagnosis at least as clinically likely as DVT -2
A score of < 2 is considered low likelihood for DVT. From Wells et al., N Eng J Med
2003;349:1227-1235; Wells et al, Lancet 1997; 350:1795-1798
Table VI. Under the following circumstances no further studies should be performed:
1. Patient end of life/comfort care.
2. Patient has another indication for anticoagulation.
3. Patient has a previous CT PE or DVT scan this admission without a change in modified
Wells risk stratification.
4. Patient would not consent to or be a candidate for anticoagulation or IVC filter if offered.
5. Patient has a diagnosis of VTE from OSH study.

Table 6. VTE-BLEED Score

Factor Score
a
Active cancer 2
Male with uncontrolled arterial
1
hypertensionb
Anemiac 1
d
History of bleeding 1
Age ≥ 60 years old 1
Renal dysfunctione 1
Classification of patients with the VTE-BLEED
score
Total score
Low bleeding risk
<2
Total score
High bleeding risk
≥2
Other factors that contribute to bleeding:
• Thrombocytopenia
• Cirrhosis
• Other anti-thrombotic use
a
Cancer diagnosed within 6 mos. before VTE
(excluding BCC or SCC of the skin), recently
recurrent or progressive cancer or any cancer that
required anti-cancer Tx within 6 mos. before VTE
was diagnosed
b
Males w/ SBP ≥ 140 mmHg at baseline
c
Hgb <13 g/dl in men or <12 g/dl in women
d
Including prior major or non-major clinically
relevant bleeding event, rectal bleeding, frequent
nose bleeding, or hematuria
e
GFR <60 ml/min
Adapted from From Klok FA, etal. Thrombosis
Haemost 2017;117:1164
 Non‐Critically Ill, Admitted Patients

Clinical Suspicion for DVT

Risk Assessment by  High Risk 
Wells Score (≥ 2)

Low Risk 
(< 2)
Assess Bleeding 
Risk (VTE‐BLEED)

Optional
D‐Dimer
Low Risk 
(< 2) High Risk 
(≥ 2)
Thrombo 
Prophylaxis
Full Therapeutic 
Anticoagulation (UFH,  Consider LE DVT Scan
LMWH, or DOAC)
No Anticoagulation on 
D/C Unless Wells Score 
Changes Meets COVID Protocol for VTE:
 Pt. is not in end of life or comfort care
D/C with 1‐2 mos. AC; refer for DVT   DVT Scan would change management
 Pt. would consent to AC
Scan when clinically appropriate with 
 Pt. does not already have Dx of VTE from 
rapid clinic follow‐up another study or other indications for AC

Proceed with LE DVT  Yes No
Scan
 + DVT
Full dose AC (UFH, LMWH, 
No change in 
or DOAC) Thrombo 
 ‐ DVT management
D/C with 3 mos. AC Prophylaxis
 Critically Ill Patients

Clinical Suspicion for DVT

Risk Assessment by 
Wells Score

Low Risk  High Risk 
(< 2) (≥ 2)

Assess Bleeding  Assess Bleeding 
Risk (VTE‐BLEED) Risk (VTE‐BLEED)
Low Risk 
(< 2)
High Risk 
(≥ 2)
Presumptive VTE Treatment with 
High Risk  Heparin:
(≥ 2)  “Heparin Nomogram for DVT/
PE” without bolus (most 
patients)
Consider LE DVT Scan
 “Heparin Nomogram for ACS/AF” 
Thrombo  (Xa target 0.2‐0.5)
 Non‐nomogram Heparin at 
Prophylaxis discretion of attending (Xa target 
0.2‐0.3) Meets COVID Protocol for VTE:
 Pt. is not in end of life or comfort care
 DVT Scan would change management
 Pt. would consent to AC
 Pt. does not already have Dx of VTE from 
 + DVT
another study or other indications for AC
Upon no longer critically ill  Yes
follow the COVID‐19 Algorithm  Proceed with LE DVT  No
for DVT Assessment, Non‐ Scan
Critically Ill, Admitted protocol
No change in 
Thrombo 
 ‐ DVT management
Prophylaxis
 Non‐Critically Ill, Admitted Patients

Clinical Suspicion for PE

Risk Assessment by  PE Likely 
Modified Wells (> 4)

PE Unlikely 
(≤ 4)
Low Risk  Assess Bleeding 
(< 2) Risk (VTE‐BLEED)

Optional
D‐Dimer
High Risk 
Full Therapeutic 
(≥ 2)
Anticoagulation (UFH, 
LMWH, or DOAC)
Thrombo 
Prophylaxis
Consider 1) PE CT or 2) LE DVT scan 
D/C with 1‐2 mos. AC; 
if CT cannot be performed
refer for PE CT when 
clinically appropriate with 
No Anticoagulation on 
D/C Unless Modified  rapid clinic follow‐up1
Meets COVID Protocol for VTE:
Wells Score Changes
 Pt. is not in end of life or comfort care
 PE CT or DVT Scan would change 
management
 Pt. would consent to AC
 Pt. does not already have Dx of VTE from 
another study or other indications for AC
Yes
No
Full dose AC (UFH,  Proceed with CT PE 
LMWH, or DOAC)  + VTE  Protocol or LE DVT if CT  No change in 
D/C with 3 mos. AC cannot be performed
management
Thrombo  *If CT cannot be performed but clinical 
 ‐ VTE 
Prophylaxis* suspicion for PE is high, consider 
therapeutic AC
 Critically Ill Patients

Clinical Suspicion for PE

PE Unlikely  Risk Assessment by  PE Likely 

(≤ 4) Modified Wells (> 4)

Assess 
Low Risk  Assess Bleeding 
Bleeding Risk 
(VTE‐BLEED)
(< 2) Risk (VTE‐BLEED)

Presumptive VTE Treatment  High Risk 
High Risk  with Heparin: (≥ 2)
(≥ 2)  “Heparin Nomogram for 
DVT/PE” without bolus 
(most patients)
 “Heparin Nomogram for 
Thrombo  ACS/AF” (Xa target 0.2‐0.5) Consider 1) PE CT or 2) LE DVT scan  
Prophylaxis  Non‐nomogram Heparin at  if CT cannot be performed
discretion of attending (Xa 
target 0.2‐0.3)

Meets COVID Protocol for VTE:
 Pt. is not in end of life or comfort care
 PE CT or DVT Scan would change 
Once no longer critically ill   + VTE management
follow the COVID‐19 
 Pt. would consent to AC
Algorithm for PE 
 Pt. does not already have Dx of VTE from 
Assessment, Non‐Critically 
another study or other indications for AC
Ill, Admitted protocol
Proceed with CT PE  Yes
No
Protocol or LE DVT if CT 
cannot be performed
 ‐ VTE
Thrombo  *If CT cannot be performed but 
No change in 
Prophylaxis* clinical suspicion for PE is high,  management
consider therapeutic AC