The document discusses anticoagulation in COVID-19 patients. It notes that COVID-19 infection can cause a cytokine storm and increased risk of thrombosis. Studies have shown that 1/3 of hospitalized COVID-19 patients develop thrombotic complications. Several guidelines recommend prophylactic anticoagulation for hospitalized COVID-19 patients to reduce the risk of thromboembolism and lower mortality. Early initiation of prophylactic anticoagulation is associated with a 27% reduced risk of death within 30 days. The document discusses diagnostic tests for coagulopathy in COVID-19 patients and potential radiological findings of thromboembolic complications.

1. Anticoagulation in
COVID-19 patients
An overview
Dr.Pankaj Jariwala
MD,DNB,DNB,MNAMS,FICPS,FACC,FSCAI
Consultant Interventional Cardiologist
Yashoda Hospitals,Somajiguda

2. The COVID19 Pandemic – A Health Crisis
Reference: 1. Majeed J, Ajmera P, Goyal RK. Delineating clinical characteristics and comorbidities among 206 COVID-19 deceased patients in India:
Emerging significance of renin angiotensin system derangement. Diabetes Res Clin Pract. 2020;167:108349.
The first case of
coronavirus disease
(COVID19) was
reported in China in
2019 and the disease
continues to have
devastating impacts
on health across the
globe.
The United Nations
has called this
pandemic as the
'Worst global
humanitarian crisis,
since World War II.
Preliminary
researches have
demonstrated that
'elderly population'
and people with
comorbidities such
as cardiovascular
diseases, diabetes
mellitus, cancer,
hypertension, or lung
diseases are at
higher risk.
Weak immune
mechanism along
with cytokine surge
due to COVID19
infection is one of
the major reported
causes of death

3. COVID19 infection and comorbidities
Reference: 1. Majeed J, Ajmera P, Goyal RK. Delineating clinical characteristics and comorbidities among 206 COVID-19 deceased patients in India:
Emerging significance of renin angiotensin system derangement. Diabetes Res Clin Pract. 2020;167:108349.
A retrospective study conducted on the data
obtained from 176 deceased cases was used to
describe the clinical characteristics and
prevalence of underlying comorbidities.
Around half of the deceased (53.4%) were elderly
and predominantly males (69.3%)
Around half of the deceased (50.5%) had
pre-existing co-morbidities; diabetes was present
in 27.8% cases and hypertension was present in
22.1% cases, 6.2% had cardiac problems.

4. COVID19 and the pathophysiology of inflammation
References: 1. Komiyama M, Hasegawa K. Anticoagulant Therapy for Patients with Coronavirus Disease 2019: Urgent Need for Enhanced Awareness. Eur Cardiol. 2020 Aug 7;15:e58.
2. Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020 Oct 1;40:37.
Interleukin (IL)-2, IL-7, IL-10, tumor necrosis factor (TNF), granulocyte colony- stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP1; also known as CCL2), macrophage in- flammatory protein 1 alpha (MIP1α; also known as CCL3), CXC-chemokine ligand 10 (CXCL10),;
nuclear factor kappa B (NF-κB) ; IL-6-signal transducer and activator of transcription 3 (STAT3).
There is an increased risk of thrombosis in viral
infections
As compared to other infections, COVID-19
imparts a greater hypercoagulability.
In SARS-CoV-2 infection, there is production of a
'cytokine storm'.

5. Thrombotic complications in patients with COVID19
References: 1. Gąsecka A, Borovac JA, Guerreiro RA, et al. Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment. Cardiovasc Drugs Ther. 2021
Apr;35(2):215-229.
ICU =Intensivecareunit
1/3rd of hospitalized patients with COVID19 patients develop macro-vascular thrombotic
complications such as venous thromboembolism (VTE), stroke and acute myocardial infarction.
VTE has an overall
incidence of 21.9%
About 22-31% patients
admitted to the ICU
with COVID19 suffer
from myocardial injury.
Microvascular
complications include
thrombotic
microangiopathies and
disseminated
intravascular
coagulation.

6. Diagnostic evaluations for coagulopathy in patients
with COVID19
Reference: 1. Omar S, Habib R, Motawea A. Radiological findings of COVID-19-related thromboembolic complications
The Egyptian Journal of Radiology and Nuclear Medicine. 2021 Jan;52(1).
In hospitalized and ICU admission patients with COVID19, testing should be for coagulation markers
such as D-dimers, PT and/or international normalized ratio (INR), aPTT, platelet count, and fibrinogen.
Based on the preliminary results, testing should be done once or twice daily; in case of altered parameters at first time, twice daily
monitoring should be done. Altered parameters include platelet count <100 × 109/L, fibrinogen <2 g/L, and raised D-dimer (although a
specific cutoff for D-dimer cannot be defined, a three to four-fold elevation is considered a markedly raised value)
Other investigations include protein C, protein S, AT, tissue factor pathway inhibitor
(TFPI), and coagulation factors.
The above test may not be readily available; thromboelastography ad rotational thromboelastometry can help evaluate clot-formation and
dissolution thereby helping to guide treatment strategies.
For risk stratification, electrocardiogram, echocardiography and lung ultrasound should also be performed.
Duplex study, CT angiography, and MRI brain should also be considered importat for the assessment of the thromboembolic complications.2

7. Radiological findings of thromboembolic complications
in patients with COVID19
Reference: 1. Robba C, Battaglini D, Ball L, et al. Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome:
A Critical Review. J Clin Med. 2021;10(1):140. Published 2021 Jan 3. 2. Omar S, Habib R, Motawea A. Radiological findings of COVID-19-related thromboembolic
complications The Egyptian Journal of Radiology and Nuclear Medicine. 2021 Jan;52(1).
A study by Omar and colleagues on
imaging findings of patients with
COVID19 (n = 1245) demonstrated that
thromboembolic manifestations were
diagnosed in 10% patients; 45.2%
presented with pulmonary embolism,
25.8% presented with cerebrovascular
manifestations, 13.7% presented with
limb affection; 15.3% presented with
gastrointestinal thromboembolic
complications.
0
5
10
15
20
25
30
35
40
45
50
Gastrointenstinal
thrombo-embolism
Peripheral vascular
embolism
Cerebro-vascular
embolism
Pulmonary
embolism
Percent
(%)
Sites of thrombo embolism
45.2
25.8
13.7
15.3

8. Need for anticoagulation in COVID19 patients
References: 1. Komiyama M, Hasegawa K. Anticoagulant Therapy for Patients with Coronavirus Disease 2019: Urgent Need for Enhanced Awareness. Eur Cardiol. 2020 Aug 7;15:e58. .
Anticoagulation therapy is associated with lower in-hospital mortality in critically-ill patients
on mechanical ventilation.
The International Society on Thrombosis and Haemostasis (ISTH) recommends (interim
guidance) the use of low-molecular- weight heparin for hospitalised patients with COVID-19
with markedly elevated D-dimer levels or high fibrinogen levels.
Coagulopathy in
COVID19 patients
has a poor
prognosis. For patients with cerebral infarction or myocardial infarction, anti-platelet agents are
administered.
Non-vitamin K antagonist oral anticoagulants (NOACs) are advisable in patients
whose condition is favourable.

9. Benefit of anticoagulation
Reference; Rentsch CT, Beckman JA, Tomlinson L, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease
2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ. 2021;372:n311.
A certain number of COVID19 deaths are due to venous thromboembolism and arterial thromboses.
Recommendation by the America Society of Hematology, International Society on Thrombosis and Haemostasis(ISTH),
CHEST guideline and expert panel suggest 'Prophylactic Anticoagulation for patients admitted with COVID19 to
prevent risk of thromboembolism'.
A observational cohort study by Rentsch and colleagues examined the benefit of early
initiation of anticoagulation on 30 day mortality in COVID19 patients.
Early initiation of prophylactic anticoagulation in COVID19 hospitalized patients was
associated with lower risk of 30 day mortality

10. Benefit of anticoagulation (Cont'd)
Results: Patients receiving prophylactic
anticoagulation therapy had lower incidence of
(14.3%) of cumulative incidence of mortality at
30 day as compared to those receiving no
anticoagulation (18.7%)
A 27% decreased risk of death over the first 30
days was observed with prophylactic
anticoagulation (Figure1).
Figure 1: Inverse probability weighting showing lower risk of 30 day mortality in prophylactic
anticoagulation group versus no anticoagulation group.
Reference; Rentsch CT, Beckman JA, Tomlinson L, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019
mortality in patients admitted to hospital in the United States: cohort study. BMJ. 2021;372:n311.
Centers for Disease Control and Prevention (CDC), International Society on Thrombosis and Haemostasis interim guidance (ISTH-IG), American Society of Hematology (ASH), American College of Chest Physicians (ACCP), Scientific and Standardization Committee of ISTH
(SCC-ISTH), Anticoagulation Forum (ACF), and American College of Cardiology (ACC); Extracorporeal membrane oxygenation (ECMO); Continuous renal replacement therapy (CRRT); Pulmonary embolism (PE), Deep vein thrombosis (DVT)

11. CDC and societal recommendations regarding
therapeutic anticoagulation
Consider when a clinically suspected thromboembolic event is present or highly suspected despite imaging confirmation.
Reference: Flaczyk A, Rosovsky RP, Reed CT, Bankhead-Kendall BK, Bittner EA, Chang MG. Comparison of published guidelines for management of coagulopathy
and thrombosis in critically ill patients with COVID 19: implications for clinical practice and future investigations. Crit Care. 2020 Sep 16;24(1):559.
Centers for Disease Control and Prevention (CDC), International Society on Thrombosis and Haemostasis interim guidance (ISTH-IG), American Society of Hematology (ASH), American College of Chest Physicians (ACCP), Scientific and Standardization Committee of ISTH
(SCC-ISTH), Anticoagulation Forum (ACF), and American College of Cardiology (ACC)
ACF
ACC Recommendation
Consider increasing the intensity of anticoagulation regimen (i.e., from standard to intermediate intensity, from intermediate to
therapeutic intensity) or change anticoagulants in patients who have recurrent thrombosis of catheters and extracorporeal circuits
(i.e., ECMO, CRRT) on prophylactic anticoagulation regimens.
ASH
Patient with PE or proximal DVT.
ACCP
'Direct oral anticoagulants (DOAC) have advantages including lack of monitoring that are
ideal for outpatient management'.
Consider when a clinically suspected thromboembolic event is present or highly suspected despite imaging confirmation. Insufficient
data to recommend for or against the increase of anticoagulation intensity outside the context of a clinical trial. Mentions patients who
have thrombosis of catheters or extracorporeal filters should be treated accordingly to standard institutional protocols for patients
without COVID-19.
CDC

12. Recommendation for the use of anticoagulation in
COVID19 patients for VTE
LMWH or UFH (standard dosing). Insufficient data to recommend for or against the increase of
anticoagulation intensity outside of a clinical trial.
Reference: Flaczyk A, Rosovsky RP, Reed CT, Bankhead-Kendall BK, Bittner EA, Chang MG. Comparison of published guidelines for management of coagulopathy
and thrombosis in critically ill patients with COVID 19: implications for clinical practice and future investigations. Crit Care. 2020 Sep 16;24(1):559.
Centers for Disease Control and Prevention (CDC), International Society on Thrombosis and Haemostasis interim guidance (ISTH-IG), American Society of Hematology (ASH), American College of Chest Physicians (ACCP), Scientific and Standardization Committee of ISTH (SCC-ISTH), Anticoagulation Forum (ACF), and
American College of Cardiology (ACC), Low molecular weight heparin (LMWH), Unfractionated heparin (UFH).
CDC
VTE prophylaxis regimen and preferred medications Therapeutic anticoagulation regimens and preferred medications
Standard regimens for non-COVID-19 patients.
LMWH (standard dosing)
ISTH-IG Not mentioned
Suggests an increased intensity of venous thromboprophylaxis be considered for critically ill patients#
(i.e., LMWH 40 mg SC twice daily, LMWH 0.5 mg/kg subcutaneous twice daily, heparin 7500 SC three
times daily, or low-intensity heparin infusion) that they state is based largely on expert opinion.
ACF
LMWH over UFH whenever possible to avoid additional laboratory monitoring, exposure, and personal
protective equipment. In patients with AKI or creatinine clearance < 15–30 mL/min, UFH is recommended
over LMWH.
LMWH over UFH (standard dosing) to reduce exposure unless risk of bleeding outweighs risk of
thrombosis.
ASH
LMWH or UFH over direct oral anticoagulants due to reduced drug-drug interactions and shorter half-life.
LMWH (standard dosing)
ACCP
LMWH or fondaparinux over UFH. UFH preferred in patients at high bleeding risk and in renal failure or
needing imminent procedures. Recommend increasing dose of LMWH by 25–30% in patients with
recurrent VTE despite therapeutic LMWH anticoagulation.
LMWH or UFH. Intermediate intensity LMWH can be considered in high risk critically ill patients
(50% of responders) and may be considered in non-critically ill hospitalized patients (30% of
respondents). Mentions that there are several advantages of LMWH over UFH including once vs
twice or more injections and less heparin-induced thrombocytopenia. Regimens may be modified
based on extremes of body weight (50% increase in dose if obese), severe thrombocytopenia*, or
worsening renal function.
ACF
Not mentioned
Enoxaparin 40 mg daily or similar LMWH regimen (i.e., dalteparin 5000 u daily) can be administered
with consideration of SC heparin (5000 u twice to three times per day) in patients with renal
dysfunction (i.e., creatinine clearance < 30 mL/min). Once daily regimens of LMWH may be
advantageous over UFH to reduce missed doses associated with worse outcomes, reduce healthcare
worker exposure, and conserve personal protective equipment. There is insufficient data to consider
routine therapeutic or intermediate dose parenteral anticoagulation with UFH or LMWH. Only a
minority of the panel considered intermediate intensity (31.6%; i.e., enoxaparin 1 mg/kg/day,
enoxaparin 40 mg BID, UFH with target PTT 50–70) to therapeutic anticoagulation (5.2%) reasonable.
ACC
Medication regimen likely to change depending on comorbidities (i.e., renal or hepatic dysfunction,
gastrointestinal function, thrombocytopenia). Parenteral anticoagulation (i.e., UFH) may be preferred in many
ill patients given it may be withheld temporarily and has no known drug-drug interactions with COVID-19
therapies. LMWH may be preferred in patients who are unlikely to need procedures as there are concerns with
UFH regarding the time to achieve therapeutic PTT and increased exposure to healthcare workers. DOACs have
advantages including lack of monitoring that is ideal for outpatient management but may have risks in settings
of organ dysfunction related to clinical deterioration and lack of timely reversal at some centers.

13. Reference: 1. Cuker A, Tseng EK, Nieuwlaat R, et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv. 2021 Feb 9;5(3):872-888.
2. COVID19 treatment guidelines. Adapted from https://www.covid19treatmentguidelines.nih.gov/whats-new/ , accessed on 28th April, 2021.
AmericanSocietyof Hematology(ASH), Venousthromboembolism(VTE).
The ASH guideline panel suggests using
prophylactic-intensity over intermediate-
intensity or therapeutic-intensity
anticoagulation for patients with COVID-19
related critical illness who do not have
suspected or confirmed VTE.1
Hospitalized non-pregnant adults with COVID-19
should receive prophylactic dose anticoagulation
(AIII). Anticoagulant oranti-platelet therapy
should not be used to prevent arterial thrombosis
outside of the usual standard of care for patients
without COVID-19 (AIII).2
ASH guideline NIH guideline

14. Reference: Mondal, S., Quintili, A.L., Karamchandani, K. et al. Thromboembolic disease in COVID-19 patients: A brief narrative review. j intensive care 8, 70 (2020).
aPTT = activated partial thromboplastin time;unfractionated (UFH)
Algorithm for the diagnosis management of
anticoagulation in patients hospitalized with COVID-19
Patient with Covid-19
Obtain baseline prothrombin time, d dimer, fibrinogen, platelet count
Low/acceptable
Assess Bleeding risk
Encourage mobilization+ initiate thromboprophylaxis with UFH/LMWH
*consider higher dosing for patients at higher risk (obese, active
malignancy, immobility, surgery/spontaneous echo contrast on US)
Encourage mobilization+ Sequential Compression device(SCD)
when not ambulating + Hold thromboprophylaxis
Active routine screening for venous/arterial thrombosis (cutaneous, pulmonary, deep venous, stroke, line thrombosis, acute coronary syndrome): Clinico-radicological surveillance
Trend d Dimer
Consider therapeutic anticoagulation (AC) with either UFH/LMWH titraded to aPIT/anti-Xa levels. Reassess bleeding risk routinely
(Insufficient evidence to recommend initiation of therapeutic AC based on d-dimer cutoffs only)
Transition to Vitamin K antagonist/UFH/Direct oral anticoagulant on discharge (*Beware of drug interactions with antivirals/antiplatelets)
insufficient data on long term outcomes in patienys (3-6 months in the absence of risk factors beyond COVID-19.modifications needed in the setting of sdditional risk factors)
Screen positive or very high clinical suspicion of occult microthrombosis
High
There is insufficient information on the anticoagulation management of patients with COVID19 and healthcare providers should consider prophylactic versus therapeutic
anticoagulation based on a combination of patient specific Criteria including laboratory results, imaging, clinical suspicion and careful balance of thrombotic and bleeding risks.

15. Reference: 1. Adapted from https://www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Coronavirus/FINAL%20Guidance%20on%20safe%20switching%20of%20warfarin%20to%20DOAC%20COVID-
19%20Mar%202020.pdf?ver=2020-03-26-180945-627, accessed on 3rd May, 2021. 2. Patel R, Czuprynska J, Roberts LN, et al. Switching warfarin patients to a direct oral anticoagulant during the Coronavirus Disease-19
pandemic. Thromb Res. 2021 Jan;197:192-194
Switching from warfarin to DOACs
Guidance on DOAC Prescribing for Non-Valvular AF and DVT/PE
DOAC Apixaban Edoxaban Rivaroxaban Dabigatran
How to change from warfarin Stop warfarin. Start DOAC when INR ≤2.5 - See additional guidance overleaf (from EHRA guidance:
https://academic.oup.com/eurheartj/article/39/16/1330/4942493?guestAccessKey=e7e62356-8aa6-472a-aeb1-eb5b58315d49)
Baseline checks Renal function (CrCl)- serum creatinine (Cr) and bodyweight, full blood count (FBC), liver function tests (LFTs). Use results from last 3 months if stable. If for AF: CHA2DS2VASC and HASBLED scores.
Dosing in Nonvalvular AF Prescribe Apixaban 5mg twice daily Prescribe Edoxaban 60mg once daily Prescribe Rivaroxaban 20mg once daily Prescribe Dabigatran 150mg twice daily
(lifelong unless risk:benefit of
anticoagulation therapy changes)
Reduce dose to 2.5mg twice daily if at least two of
the following characteristics: age ≥ 80 years, body
weight ≤ 60 kg, or serum creatinine ≥ 133 micromol/l
or if exclusive criteria of CrCl 15 - 29 ml/min.
Reduce dose to 30mg once daily if: Body weight <
50ml/min, or co-prescribed with ciclosporin,
dronedarone, erythromycin or ketoconazole.
Reduce dose to 15mg once daily if CrCl< 50mL/min
in NVAF patients only.
if aged 50mL/min, low risk of bleeding (weight 80 years or
prescribed verapamil. Consider 110mg twice daily based
on individual assessment of thrombotic risk and the risk
of bleeding in patients aged between 75 and 80 years or
with CrCl
Dosing in patients with DVT / PE
(loading doses are not required if
patient has been stabilised on warfarin)
Dose is 5mg twice daily (use with caution if CrCl
<30ml/min). Check intended duration of therapy. For
long term prevention of recurrence 2.5mg twice daily
(after 6 months’ treatment dose).
Dosing as above. Check intended duration of
therapy.
Dose is 20mg daily (consider 15mg dose if
CrCl<50ml/min and bleeding risk outweighs VTE
risk). Check intended duration of therapy. For long
term prevention of recurrence 10mg daily could be
considered.
Dosing as above. Check intended duration of therapy.
Duration of therapy for DVT/PE For a provoked DVT/PE: 3 months treatment if provoking factors have been addressed.
For unprovoked DVT/PE or recurrent DVT/PE: At least 6 months treatment dose followed by prophylaxis dosing as indicated/advised.
Contraindications CrCl <15ml/min CrCl <15ml/min CrCl <15ml/min CrCl <30ml/min
Cautions
See also individual SPCSs
CrCl <95ml/min CrCl <30ml/min. Take with or after food (15mg and
20mg doses).
Do not use in a standard medication compliance aids (MCA)
Interactions Ketoconazole, itraconazole, voriconazole,
posaconazole, ritonavir - not recommended (See
SPC for full details) Rifampicin, phenytoin,
carbamazepine, phenobarbital, St. John's Wort – use
with caution. Do not use apixaban with patients on
strong enzyme inducers for acute VTE treatment
Rifampicin, phenytoin, carbamazepine, phenobarbital
or St. John's Wort – use with caution Ciclosporin,
dronedarone, erythromycin, ketoconazole – reduce
dose as above. (See BNF and SPC for edoxaban for
further information)
Ketoconazole, itraconazole, voriconazole,
posaconazole, ritonavir, dronedarone – not
recommended (See SPC for full details) Rifampicin,
phenytoin, carbamazepine, phenobarbital, St. John's
Wort – Should be avoided.
Ketoconazole, ciclosporin, itraconazole, tacrolimus,
dronedarone - contraindicated (See SPC for full details)
Rifampicin, St John’s Wort, carbamazepine, phenytoin –
should be avoided. Amiodarone, quinidine, ticagrelor,
posaconazole – use with caution. Verapamil (use
reduced dose). Antidepressants: SSRIs and SNRIs-
increased bleeding risk
Guidance for the Safe Switching of Warfarin to Direct Oral Anticoagulants (DOACs) for Patients with Non-Valvular AF and Venous Thromboembolism (DVT / PE) - 26 March 2020

16. Reference1:Iturbe-Hernandez T, GarcÃa de Guadiana R L, Gil Ortega I, et al. Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL
protocol. Drugs Context. 2020 Sep 18;9:2020-8-3.
Oral anticoagulation in COVID19 patients
As per a scoping review, among patients with COVID-19 infection, there is 3% and 20% incidence of
stroke and venous thromboembolism.
Despite anticoagulation with low-molecular-weight heparin (LMWH) which lowers the the risk of death in
severe COVID19 patients with coagulopathy, many patients with acute respiratory distress syndrome
(ARDS) still develop severe thrombotic complications.
The recommendation to use DOACs is dependent on their drug-drug interaction which leads to the
increase or decrease of the their drug concentrations.

17. Reference: Canonico ME, Siciliano R, Scudiero F, Sanna GD, Parodi G. The tug-of-war between coagulopathy and anticoagulant agents in patients with COVID-19.
Eur Heart J Cardiovasc Pharmacother. 2020;6(4):262-264. doi:10.1093/ehjcvp/pvaa048
Dabigatran has low potential for drug-drug interaction
Dabigatran shows 'no expected interaction, with Remdesivir, Favipiravir, Ribavarin, Tocilizumab and Interferon-β'.
Figure: Drug interaction potential of anticoagulants with experimental COVID19 drugs

18. Reference 1.Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M. COVID-19 and the liver. J Hepatol. 2020;73(5):1231-1240. 2. Iturbe-Hernandez T, GarcÃa de Guadiana R L, Gil Ortega I, et al. Dabigatran,
the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL protocol. Drugs Context. 2020 Sep 18;9:2020-8-3. 3. Canonico ME, Siciliano R, Scudiero F,
Sanna GD, Parodi G. The tug-of-war between coagulopathy and anticoagulant agents in patients with COVID-19. Eur Heart J Cardiovasc Pharmacother. 2020;6(4):262-264.
Safety of Dabigatran
Dabigatran has low hepatoxicity and can be used with
concomitantly with COVID19 drugs such as Remdesivir and
Tocilizumab (which may possibly increase hepatotoxicity).2,3
Figure 1: Comparative incidence of hospitalization due to liver injury among
different anticoagulation.
2-11%
patients with COVID19
have underlying
chronic liver disease.1
14-53%
patients with COVID19
develop hepatic
dysfunction.1

19. Reference: 1. Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous
thromboembolism with Dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72.
Dabigatran vs Heparin in patients with
acute venous thromboembolism
Dabigatran is non-inferior to
warfarin for the prevention of
recurrent or fatal venous
thromboembolism(P<0.001).1
Figure 1: Comparative primary outcome for efficacy seen in the Dabigatran and warfarin
groups from baseline upto 6 months.
In 2.3% patients
treated with
Dabigatran and 2.2%
treated with
warfarin, the primary
outcome for efficacy
was observed (hazard
ratio, 1.08; 95% CI,
0.64–1.80)1

20. Reference: 1. Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous
thromboembolism with Dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72.
Dabigatran vs Heparin in patients with
acute venous thromboembolism
Dabigatran has lesser
incidence of major or
clinically relevant bleeding
and any bleeding as
compared to the warfarin
group (Figure1).1
Figure 1: Cumulative risks of a first event of major bleeding (data lines) and of any bleeding
among patients randomly assigned to Dabigatran or warfarin.
Major bleeding event
was observed in 1.2%
patients in the
Dabigatran
group and 1.7% in
the warfarin group
(hazard ratio, 0.69;
95% CI, 0.36–1.32 )1

21. Reference: 1. Ezekowitz MD, Eikelboom J, Oldgren J, et al. Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation. Europace. 2016;18(7):973-978.
Long-term efficacy of Dabigatran
Ezelowitz and colleagues conducted a pre-
planned analysis to describe the longest
continuous randomized experience of any
target-specific oral anticoagulant. Follow-up
was done upto 6.7 years.
Figure 1: Cumulative risk of stroke or pulmonary embolism Figure 2: Cumulative risk of all-cause mortality
Dabigatran at a dosage of 110mg and
150mg was compared to warfarin.
The rates of myocardial infarction (P =
0.75), vascular mortality (P = 0.63) and
all-cause mortality (P = 0.54, Figure 2)
were similar for both doses of
dabigatran.

22. Reference: 1. Adapted from https://www.isth.org/news/553619/ISTH-Endorses-Recommendations-for-COVID-19-Vaccinations-of-Patients-on-Anticoagulants.htm, accessed on 1st May, 2021
Vaccination
There is a risk of bruising
at the injection site, but it
may not have any
serious effects related to
anticoagulation.
According to the
International Society
on Thrombosis and
Haemostasis (ISTH)
'Individuals receiving direct oral anticoagulant (Apixaban, Dabigatran,
Edoxaban & Rivaroxaban) or warfarin in therapeutic INR range or on full
dose heparin or fondaparinux injections can all receive the COVID-19
vaccination'.
Prolonged pressure
(at least 5 minutes)
should be applied to the
injection site to reduce
bruising.
Patients on warfarin
with supra-therapeutic
INR should wait until
their INR is <4.0.
Vaccinations are
encouraged and
should not be avoided
on the basis of being
on anticoagulation.

23. Summary
Weak immune mechanism along with with cytokine surge due to COVID-19 infection is one of the major
reported causes of death.
01
The resultant high levels of inflammation due to the cytokine storm is associated with coagulopathic
complications.
02
Prophylactic anticoagulation is suggested patients admitted with COVID19 to prevent risk of thromboembolism'.
03
Dabigatran is non-inferior to warfarin and has lesser incidence of bleeding events.
04
Dabigatran has low hepatoxicity and can be used with concomitantly with COVID19 drugs such as
Remdesivir and Tocilizumab.
03

26. Contact me for any heart related queries
Dr.Pankaj Jariwala, Cardiologist @ YASHODA HOSPITALS,
SOMAJIGUDA
Cell – 9393178738
Email -docpjariwala@yahoo.co.in