An Approach for Management of VTE Patients in

New Normal

MA-M_RIV-ID-0091-1
Disclaimer
◆ These slides are for scientific and educational purposes only and is the
copyright of Bayer
◆ Bayer does not support or recommend the use of rivaroxaban in any countries or
indications in which it is not approved
◆ In Indonesia, Xarelto® is registered for indications :
• Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or
knee replacement surgery
• To reduce the risk of stroke and systemic embolism in patients with non-valvular atrial
fibrillation
– With previous history of stroke or TIA
– With CHADS2 Score ≥ 2
• Treatment of deep vein thrombosis (DVT) in which duration of treatment should be based
on the underlying disease
• Treatment of patients with hemodynamically stable pulmonary embolism (PE) which is
must be confirmed by spiral CT imaging
VTE Is a Leading Cause of Death Worldwide
VTE is estimated to cause >500,000 deaths
in Europe every year1

An estimated
300,000
VTE-related
deaths occur
in the US
each year2 VTE is estimated to cause at least
3 million deaths a year worldwide3
1. Cohen AT et al, Thromb Haemost 2007;98:756–764; 2. Heit JA et al, Blood 2005;106:Abstract 910;
3. ISTH Steering Committee for World Thrombosis Day J Thromb Haemost 2014;12:1580–1590
Risk Factors for VTE
Exposing risk factors Predisposing risk factors
(acute conditions or trauma, surgery) (patient characteristics)

History of VTE
Chronic heart failure
Surgery Advanced age

Trauma Varicose veins

Cancer
Obesity
Acute medical illness
Immobility or paresis
Acute heart failure* Inflammatory
Myeloproliferative disorders
Acute respiratory failure diseases
Pregnancy/postpartum period
Central venous catheterization Inherited or acquired thrombophilia
Hormone therapies
Renal insufficiency

Risk factors from: 1. Geerts WH et al, Chest 2004;126:338S–400S *New York Heart Association classification III and IV
ACCP 2016 Guidelines:
Acute Treatment and Secondary Prevention of VTE
ACCP recommendation Grade of
recommendation
Initial anticoagulation
Acute DVT or haemodynamically NOAC preferred to LMWH/VKA 2B
stable PE and no cancer LMWH/VKA preferred to LMWH alone 2C
PE with hypotension Thrombolytic therapy (systemic rather than catheter-directed unless 2B (2C)
bleeding risk is high)
DVT or PE with cancer LMWH suggested over NOAC or VKA 2C
Duration of anticoagulant therapy
Proximal DVT or PE 3 months recommended over shorter duration 1B
First proximal DVT or PE provoked 3 months 1B
by surgery or other transient risk (2B if low/moderate
factor bleeding risk; 1B if
high)
Unprovoked DVT or PE Extended therapy if bleeding risk is low/moderate 2B
3 months if bleeding risk is high 1B
DVT or PE associated with Extended therapy recommended over 3 months’ therapy 1B
active cancer (2B if high bleeding
risk)
Kearon C et al, Chest 2016;149:315–352
2019 ESC PE Guidelines: Treatment Recommendations
Recommendations for duration of oral anticoagulation Class of Level of
recommendation evidence

Therapeutic anticoagulation for ≥3 months is recommended for all patients with PE I A

For patients with first PE/VTE secondary to a major transient/reversible risk factor,
I B
discontinuation of therapeutic oral anticoagulation is recommended after 3 months
Oral anticoagulant treatment of indefinite duration is recommended for patients
presenting with recurrent VTE not related to a major transient or reversible I B
risk factor
Oral anticoagulant treatment with a VKA for an indefinite period is recommended
I B
for patients with antiphospholipid antibody syndrome
Extended oral anticoagulation of indefinite duration should be considered for
IIa A
patients with a first episode of PE and no identifiable risk factor
Recommendations for early discharge and home treatment Class of Level of
recommendation evidence
Carefully selected patients with low-risk PE should be considered for early IIa A
discharge and continuation of treatment at home, if proper outpatient care and
anticoagulant treatment can be provided

Konstantinides SV et al, Eur Heart J 2019; doi:10.1093/eurheartj/ehz405

Anticoagulant Therapy for VTE Patients
Traditional Anticoagulants: Drawbacks
◆ UFH1 ◆ Oral VKAs2
• Parenteral administration • Narrow therapeutic window
• Monitoring and dose adjustment required • Interaction with food and drugs
• Risk of HIT • Frequent monitoring and
◆ LMWH1 dose adjustment required
• Parenteral administration
• Weight-adjusted dosing

1. Hirsh J et al, Chest 2008;133;141S–159S; 2. Ansell J et al, Chest 2008;133;160S–198S

Need for Monitoring According to Guidelines
VKAs
Unpredictable anticoagulation response that necessitates regular monitoring1,2
PT/INR testing to ensure patients are within INR range2,3

LMWHs
Routine coagulation monitoring not normally needed, except for
patients with severe renal failure and pregnant women2
Anti-Factor Xa assay can be used2

UFH
Anticoagulant response varies among patients;
UFH (intravenous and subcutaneous) requires monitoring
(weight-based subcutaneous UFH does not)2,4
aPTT test to be used to maintain doses that correspond to therapeutic heparin levels 2

1. Merli G et al, Ann Surg 2009;250:219–228; 2. Kearon C et al, Chest 2008;133:454S–545S;

3. Ansell J et al, Chest 2008;133:160S–198S; 4. Hirsh J et al, Chest 2008;133:141S–159S
Newer Anticoagulants That Have Single Targets

TF VIIa

Initiation
X IX
Indirect
Fondaparinux AT

Propagation IXa
Xa

Inactive factor Direct II Prothrombin

Rivaroxaban
Active factor Apixaban Direct
Edoxaban Lepirudin
Transformation Bivalirudin
Betrixaban
IIa Argatroban
Catalysis
Thrombin Dabigatran
TGN-167

Clot formation Fibrinogen Fibrin

Adapted from: 1. Spyropoulos AC. Expert Opin Investig Drugs 2007;16:431–440

Single-NOAC Approach Can Be Used for VTE Treatment and
Prevention of Recurrence
ACUTE INTERMEDIATE CHRONIC

Conventional Bridging*
treatment1
Initial Early maintenance Long-term secondary prevention
Unfractionated heparin, VKA (INR 2.0–3.0) VKA (INR 2.0–3.0)
LMWH, fondaparinux ≥3 months ≥3 months, years or indefinite with
≥5 days periodic assessment

PE/DVT treatment schemes with NOACs

Dabigatran2 Parenteral agent Switch to a NOAC
Edoxaban3
Rivaroxaban4
Single-drug approach
Apixaban5
*Administration of heparins or fondaparinux should overlap during at least 5 days with that of VKAs. The parenteral drug can be stopped when the anticoagulant
concentration induced by VKA has reached an INR of 2.0. 1. Adapted from Goldhaber SZ et al. Lancet 2012;379:1835–1846; 2. Boehringer Ingelheim Limited. Pradaxa®
(dabigatran) SmPC. https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf; 3. Daiichi Sankyo Europe GmbH. Lixiana®
(edoxaban) SmPC. https://www.ema.europa.eu/en/documents/product-information/lixiana-epar-product-information_en.pdf; 4. Bayer AG. Xarelto® (rivaroxaban) SmPC.
https://www.ema.europa.eu/en/documents/product-information/xarelto-epar-product-information_en.pdf; 5. Bristol-Myers Squibb-Pfizer. Eliquis® (apixaban) SmPC.
https://www.ema.europa.eu/en/documents/product-information/eliquis-epar-product-information_en.pdf.
EINSTEIN DVT and PE: Pooled Analysis
Treatment of Acute Symptomatic DVT and/or PE and
Secondary Prevention of VTE
Rivaroxaban EINSTEIN Phase III: Study Designs

EINSTEIN DVT1 and EINSTEIN PE2 (non-inferiority studies)

Treatment period of 3, 6 or 12 months
Confirmed acute
symptomatic DVT
Rivaroxaban Rivaroxaban

30-day observation after

without
N=3449

treatment cessation
symptomatic PE
15 mg bid 20 mg od

N=4832 Enoxaparin 1.0 mg/kg bid for at least 5 days, followed

Confirmed acute by VKA to start ≤48 hours, target INR range 2.0–3.0
symptomatic PE
with or without
symptomatic DVT Day 1 Day 21

1. The EINSTEIN Investigators, N Engl J Med 2010;363:2499–2510; 2. The EINSTEIN–PE Investigators, N Engl J Med 2012; 366:1287–1297
EINSTEIN DVT and PE Pooled Analysis: Efficacy Similar to
Enoxaparin/VKA for DVT and PE Treatment
Rivaroxaban Enoxaparin/VKA
n/N (%) n/N (%)
3.0 86/4150 95/4131
Enoxaparin/VKA (n=4131)
(2.1) (2.3)

Cumulative event rate (%)

2.5

2.0
Rivaroxaban (n=4150)
1.5
HR=0.89
1.0 95% CI 0.66–1.19
p<0.001
0.5

0.0
0 30 60 90 120 150 180 210 240 270 300 330 360
Time to event (days)
Number of patients at risk
Rivaroxaban 4150 4018 3969 3924 3604 3579 3283 1237 1163 1148 1102 1034 938
Enoxaparin/VKA 4131 3932 3876 3826 3523 3504 3236 1215 1149 1109 1071 1019 939
Recurrent VTE measured in the ITT population; all analyses were based on the first event
1. Prins MH et al, Thromb J 2013;11:21
EINSTEIN DVT and PE Pooled Analysis:
Principal Safety Outcome
First major or clinically relevant non-major bleeding
Enoxaparin/VKA (n=4116)
14

Cumulative event rate (%)

12

10
Rivaroxaban (n=4130)
8
HR=0.93; 95% CI 0.81–1.06; p=0.272
6
Rivaroxaban Enoxaparin/VKA HR (95% CI)
4 n/N (%) n/N (%) p-value
388/4130 412/4116 0.93 (0.81–1.06)
2 (9.4) (10.0) p=0.27

0
0 30 60 90 120 150 180 210 240 270 300 330 360
Time to event (days)
Number of patients at risk
Rivaroxaban 4130 3768 3671 3406 3270 3210 1928 1051 1009 936 878 853 453
Enoxaparin/VKA 4116 3738 3618 3330 3186 3125 1711 1025 981 907 857 823 369
Safety population
1. Prins MH et al, Thromb J 2013;11:21
Significant Reduction in Major Bleeding Events Compared with
Enoxaparin/VKA
Rivaroxaban Enoxaparin/VKA HR (95% CI)
n/N (%) n/N (%) p-value
3.0 40/4130 72/4116 0.54 (0.37–0.79) HR=0.54
(1.0) (1.7) p=0.002 95% CI 0.37–0.79
2.5 p=0.002

Cumulative event rate (%)

Enoxaparin/VKA (n=4116)
2.0
46%
RRR
1.5 0.8% ARR

1.0
Rivaroxaban (n=4130)
0.5

0.0
0 30 60 90 120 150 180 210 240 270 300 330 360
Time to event (days)
Number of patients at risk
Rivaroxaban 4130 3921 3862 3611 3479 3433 2074 1135 1095 1025 969 947 499
Enoxaparin/VKA 4116 3868 3784 3525 3394 3348 1835 1109 1065 990 950 916 409

Safety population
1. Prins MH et al, Thromb J 2013;11:21
Summary of EINSTEIN DVT and PE: Pooled Analysis
• In the pooled analysis of EINSTEIN DVT and EINSTEIN PE, rivaroxaban had non-inferior
efficacy with respect to the primary efficacy endpoint compared with enoxaparin/VKA1
• This treatment effect was apparent by day 21 – the end of the intensified rivaroxaban treatment
phase (15 mg bid for 21 days),1 during which the risk of recurrence is the highest2
• Pooled results reflected the non-inferiority achieved with rivaroxaban in the individual EINSTEIN
DVT and EINSTEIN PE studies3,4
• Oral rivaroxaban, 15 mg bid for 21 days followed by 20 mg od, could provide clinicians and
patients with a simple, single-drug approach for the acute treatment of DVT/PE and continued
treatment of PE that potentially improves the benefit–risk profile of anticoagulation

1.Prins MH, et al. Thromb J 2013;11:21; 2. Limone BL et al. Thromb Res 2013;132:420–426;
3. The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510; 4. The EINSTEIN–PE Investigators. N Engl J Med 2012;366:1287–1297
Management of VTE in COVID-19 Pandemic Era
Risk factors for Severe COVID-19 Disease Overlap With Risk
Factors for Thromboembolic Events
Risk factors for severe Risk factors for
COVID-19 disease1 thromboembolism2–5

Old age Female

sex*
Cancer/ Respiratory
chemotherapy conditions
Liver Heart
Hypertension*
disease disease

Kidney
Diabetes*
failure
Ischaemic
Obesity events

Additionally, people who live in a nursing home or care facility, and who therefore may
be less mobile, are at increased risk of severe COVID-19 disease1
*Risk factors of thromboembolism for patients with AF.
1. Centers for Disease Control and Prevention. People who are at higher risk for severe illness. Available at: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-
precautions/people-at-higher-risk.html [accessed 6 April 2020]; 2. Barbar S et al. J Thromb Haemost 2010;8:2450–7; 3. Lip GY et al. Chest 2010;137:263–72;
4. Ocak J et al. J Thromb Haemost 2013;11:627–33; 5. Fox KA et al. Eur Heart J 2011;32:2387–94.
Contemporary Challenges During the COVID-19 Pandemic

Health system
A worldwide heparin/LMWH shortage, which is unlikely to be helped
capacity challenges
because of COVID-19 restrictions, and China is a major supplier1,2
for routine care

Optimal
Pragmatic guidance recommends switching/bridging COVID-19
anticoagulation for
inpatients requiring anticoagulation to LMWH or unfractionated
COVID-19 patients
heparin3
unknown

Global travel Continuity of medical care required for vulnerable patients during self-
restrictions/local isolation and social distancing, but need to minimise person-to-
isolation policies person exposure risk for patients needing INR tests4,5

1.McCarthy CP et al. Lancet 2020;395:534–536; 2. Rosovsky RP et al. Oncologist 2020;doi: 10.1634/theoncologist.2019-0910 [Epub ahead of print];
3. ISTH. Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19; 4.
Royal College of General Practitioners. Royal College of General Practitioners Guidance on workload prioritisation during COVID-19. Available at: https://www.rcgp.org.uk/-
/media/Files/Policy/A-Z-policy/2020/covid19/RCGP%20guidance/202003233RCGPGuidanceprioritisationroutineworkduringCovidFINAL [accessed 6 April 2020]; 5.
Anticoagulation Forum. Frequently asked questions. Available at: https://acforum.org/web/downloads/AC_Forum_COVID-19_FAQ_Document.pdf [accessed 6 April 2020].
 All hospitalized COVID-19 pneumonia patients should receive
VTE risk assessment
Clinical conditions
Age≥40 yrs, bed rest>3 days,
confirmed COVID-19
pneumonia
Confirmed hospitalized
COVID-19 pneumonia cases
Confirmed COVID-19
pneumonia cases with elective
surgical procedures or trauma
Pregnant / puerperal women
with COVID-19 pneumonia
VTE risk assessment method
Classified as high VTE risk if complicated with one of the following diseases or risk factors:
• Age≥75 yrs., acute infectious disease (especially severe infections or sepsis)
• Respiratory failure, heart failure (NYHA class III or IV)
• Obesity (BMI≥30 kg/m2), previous VTE history
• Acute exacerbation of chronic obstructive pulmonary disease, acute cerebral infarction,
acute coronary syndrome
• Lower extremity varicose veins, malignancies, inflammatory bowel disease, chronic renal
diseases
• Padua scoring is recommended for VTE risk assessment
• Patients with total score≥4 are considered as VTE high risk patients, <4 considered VTE low
risk
• Caprini risk assessment model is recommended
• Complicated with the following risk factors:
• Immobilization, VTE history, pre-eclampsia or intrauterine growth retardation,
thrombophilia, transfusion, postpartum infection, systemic lupus erythematosus, heart
diseases and sickle cell disease etc. suggest high VTE risk;
• Other risk factors include: obesity, multiple pregnancy, postpartum hemorrhage etc.
Pulmonary Embolism and Pulmonary Vascular Disease Group, Respiratory Medicine Branch, Chinese Medical Association.
National Medical Journal of China, 2020. DOI: 10.3760/cma.j.issn.0376-2491.2020.0007
 Bleeding risk assessment for COVID-19 Pneumonia patients
If any of the following factors are present, a balance of bleeding risks to prevention strategies, protocol, medication
and dosage must be considered
Underlying diseases
Patient factors
(1) Active bleeding, uncontrolled GI ulcer, etc.
(2) Previous ICH or other major hemorrhage history
(3) Uncontrolled hypertension, SBP>180 and/or DBP>110 mmHg
Age ≥ 85 yrs (4) Intracranial diseases which might lead to severe hemorrhage,
Coagulation disorder eg. Acute stroke (within 3 months)
(5) Diabetes
Platelet<50×109/L etc. (6) Malignancies
(7) Severe renal failure or hepatic failure etc.

Bleeding-related
Concomitent medication Invasive operations
risk factors

Anticoagulants Undergoing operation

Antiplatelet drugs Lumbar puncture and epidural anesthesia
Thrombolytic drugs, etc. 4 h before and 12 h after etc.

Pulmonary Embolism and Pulmonary Vascular Disease Group, Respiratory Medicine Branch, Chinese Medical Association.
National Medical Journal of China, 2020. DOI: 10.3760/cma.j.issn.0376-2491.2020.0007
VTE prevention strategies for severe or critical COVID-19
patients
Patients type Recommended prevention measures

General condition • Drug prevention preferred, such as LMWH etc.

Severe renal failure (CCR<30

• Unfractionated heparin (UFH) recommended
ml/min)
Low • Drug preventions and/or mechanical prevention
Admitted to ICU
bleeding recommended
risk Extrasomatic membrane • Additional drug prevention is not required if
oxygenation (ECMO) support heparinization is already used
Complicated with
thrombocytopenia or HIT during • Non-heparin anticoagulants recommended
heparin administration
• Correct factors that might lead to bleeding and conduct
mechanical prevention (e.g. IPC, GCS). Drug
High bleeding risk
prevention might be restored after bleeding risk
decreases
Pulmonary Embolism and Pulmonary Vascular Disease Group, Respiratory Medicine Branch, Chinese Medical Association.
National Medical Journal of China, 2020. DOI: 10.3760/cma.j.issn.0376-2491.2020.0007
VTE prevention strategies for mild and general COVID-19
pneumonia patients

Patient type Recommended preventative strategy

Hospital isolation/home quarantine
Complicated VTE high or intermediate-
high risk based on Padua
with medical
or Caprini model
or surgical
If VTE risk persists at
conditions discharge
Pregnant women with VTE risks
Pregnant women with high VTE risks or
women after C-section delivery
• Avoid prolonged sitting and dehydration. Physical
activities and adequate water intake are encouraged
• Drug prevention, such as LMWH, should be considered if
no anticoagulation contraindications are presented
✓ In principal, drug prevention should last for at least 7～
10 d, or until risk factors eliminated
• Continued prevention outside the hospital could be
considered
• Mechanical prevention (GCS and IPC) recommended if
contraindications of drug prevention are present
• Drug prevention and/or mechanical prevention are
recommended
✓ Drug prevention can be extended to 6 weeks after
pregnancy, or until VTE risk factors are eliminated

Pulmonary Embolism and Pulmonary Vascular Disease Group, Respiratory Medicine Branch, Chinese Medical Association.
National Medical Journal of China, 2020. DOI: 10.3760/cma.j.issn.0376-2491.2020.0007
Guidance for Prophylaxis and Treatment of VTE during COVID-19
Era

Spyropoulos, A.C. et al (2020).. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14929

VTE Prophylaxis in non-ICU Hospitalized COVID-19 Patients

• A universal strategy of routine thromboprophylaxis with standard-

dose UFH or LMWH should be used after careful assessment of
bleed risk, with LMWH as the preferred agent. Intermediate-dose
LMWH may also be considered (30% of respondents).

• VTE prophylaxis recommendations should be modified based on

extremes of body weight, severe thrombocytopenia (i.e. platelet
counts of 50,000 x 109 per liter or 25,000 x 109 per liter) or
deteriorating renal function.

Spyropoulos, A.C. et al (2020).. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14929

VTE Prophylaxis in Sick ICU Hospitalized COVID-19 Patients

• Routine thromboprophylaxis with prophylactic-dose UFH or LMWH

should be used after careful assessment of bleed risk. Intermediate-
dose LMWH (50% of respondents) can also be considered in high risk
patients. Patients with obesity as defined by actual body weight or BMI
should be considered for a 50% increase in the dose of
thromboprophylaxis. Treatment-dose heparin should not be considered
for primary prevention until the results of randomized controlled trials
are available.
• Multi-modal thromboprophylaxis with mechanical methods (i.e.,
intermittent pneumonic compression devices) should be considered
(60% of respondents)

Spyropoulos, A.C. et al (2020).. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14929

Duration of VTE Prophylaxis for Hospitalized COVID-19 Patients

• Extended post-discharge thromboprophylaxis should be considered for

all hospitalized patients with COVID-19 that meet high VTE risk criteria.
The duration of post-discharge thromboprophylaxis can be
approximately 14 days at least (50% of respondents), and up to 30 days
(20% of respondents).

Spyropoulos, A.C. et al (2020).. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14929

VTE treatment in hospitalized COVID-19 patients
• Established guidelines should be used to treat patients with confirmed VTE,
with advantages of LMWH in the inpatient setting and DOACs in the post-
hospital discharge setting. A change from treatment-dose DOAC or VKA to in-
hospital LMWH should be considered especially for patients in critical care
settings or with relevant concomitant medications, and dependent on renal
function and platelet counts. Anticoagulant regimens should not change based
solely on D-dimer levels.
• A change of anticoagulant regimen (i.e. from prophylactic or intermediate-dose
to treatment-dose regimen) can be considered in patients without established
VTE but deteriorating pulmonary status or ARDS (50% of respondents).
• The duration of treatment should be at least 3 months (50% of respondents).

Spyropoulos, A.C. et al (2020).. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14929

Consideration for VTE Management in “New Normal”
How Can We Continue to Protect the Most Vulnerable Patients?

“Past experience has shown that patients will die from

non-COVID-19 related illnesses in addition to COVID-19 itself
as we divert all of our health care resources towards it”1

Patients still need A good balance of Fast onset and

protection against efficacy and safety offset of action
thrombosis
Fixed oral dosing
Wide therapeutic window
regimen
Desirable
characteristics for Low risk of food and No need for routine
anticoagulation drug interactions coagulation monitoring
therapy2

1. Royal College of General Practitioners. Royal College of General Practitioners Guidance on workload prioritisation during COVID-19. Available at:
https://www.rcgp.org.uk/-/media/Files/Policy/A-Z-policy/2020/covid19/RCGP%20guidance/202003233RCGPGuidanceprioritisationroutineworkduringCovidFINAL [accessed
6 April 2020]; 2. Figure adapted from Ahmad Y and Lip GYH. Curr Cardiol Rev 2012;8:290–301.
Switching from warfarin to NOACs is recommended by
several societies

British Society for Haematology1

• Patients on oral anticoagulation with warfarin require regular INR testing, which can be problematic at a time
when we are trying to minimise visits to hospitals, GP surgeries and other testing facilities. This monitoring is
however an essential component of safe anticoagulation that cannot be omitted due to social distancing

• To help minimise the number of patient visits, consider whether a DOAC that does not require monitoring can
be used instead of warfarin

Royal College of General Practitioners2

“Converting patients from
• For patients on warfarin, consider switching to treatment with a DOAC if warfarin to DOAC is
appropriate reasonable to minimise the
need for frequent
monitoring and clinic
Canadian Cardiovascular Society4
COVID-19 Rapid Response Team visits” – Anticoagulation
• Consider switching patients from warfarin to a direct oral anticoagulant to limit Forum3
INR monitoring
1. British Society for Haematology. INR testing for out-patients on warfarin during COVID-19 restrictions. Available at: https://b-s-h.org.uk/media/18162/inr-testing-for-out-patients-on-warfarin-during-
covid-19-restrictions_23-03-2020.pdf [accessed 6 April 2020]; 2. Royal College of General Practitioners. Royal College of General Practitioners Guidance on workload prioritisation during COVID-19.
Available at: https://www.rcgp.org.uk/-/media/Files/Policy/A-Z-policy/2020/covid19/RCGP%20guidance/202003233RCGPGuidanceprioritisationroutineworkduringCovidFINAL [accessed 6 April 2020];
3. Anticoagulation Forum.
Frequently asked questions. Available at: https://acforum.org/web/downloads/AC_Forum_COVID-19_FAQ_Document.pdf [accessed 6 April 2020]; 4. Guidance from the CCS COVID-19 Rapid
Response Task Force. Available at: http://www.ccs.ca/images/Images_2020/Tips_Pitfalls__Red_Flags_FINAL.pdf [accessed 22 April 2020].
When should patients on chronic warfarin therapy be
transitioned to a DOAC in the setting of the COVID-19 pandemic?
◆ Many patients who take chronic warfarin therapy are concerned about the potential risk of
COVID-19 exposure while managing their warfarin:
• Exposure risk while providing the laboratory sample for INR measurement
• Interacting with their anticoagulation provider
◆ For many patients, providing reassurance about appropriate preventative measures (e.g.,
wearing a mask, washing hands, maintaining social distance) may be sufficient.
◆ However, other patients may be eligible to switch to DOAC therapy, thereby reducing the need
for frequent laboratory draws.
◆ Care must be taken to select appropriate patients for whom DOAC therapy is indicated and can
be initiated and maintained.
◆ Careful assessment of weight, renal function, liver function, drug interactions, indication for
anticoagulation, and in-depth review of the year-round cost implications should be performed
prior to switching from warfarin to a DOAC.

Barnes et al. Journal of Thrombosis and Thrombolysis (2020) 50:72–81 https://doi.org/10.1007/s11239-020-02138-z

Recommendation
◆ Anticoagulation clinics use standardized educational materials for their warfarin-treated patients
about safety precautions when obtaining INR blood draws to reduce the risk of COVID-19
infection
◆ Patients who would not be eligible for DOAC therapy prior to the COVID-19 pandemic not be
switched to DOAC therapy during the COVID-19 pandemic. This includes (but is not limited to)
patients with mechanical heart valves, severe liver dysfunction, or combined renal dysfunction
and/or drug-drug interactions that preclude safe DOAC use. Ability to reliably obtain and take
DOACs is another important consideration when assessing eligibility to switch.
◆ Clinics interested in transitioning patients from warfarin to a DOAC develop a standardized
screening protocol to identify eligible patients.
◆ Patients taking chronic oral anticoagulant in the outpatient setting be switched to shorter acting
agents (e.g., LMWH or UFH) when initially hospitalized for COVID-19 in case of clinical
deterioration, changes in renal function, or need for invasive procedures.

Barnes et al. Journal of Thrombosis and Thrombolysis (2020) 50:72–81 https://doi.org/10.1007/s11239-020-02138-z

Conclusion

◆ VTE risk assessment and prevention is particularly important during the

comprehensive treatment of COVID-19 pneumonia patients.
◆ The conditions of some patients change quickly. VTE risks and bleeding risks
may also change during treatment.
◆ Risk factors for severe COVID-19 disease overlap with risk factors for
thromboembolic events and patients with COVID-19 have increased risk of
coagulation.
◆ During the new normal period, we need to consider the risk of VTE patients, act
in accordance with the guidelines for their management and at the same time
bring the greatest possible convenience to the patients.