Venous Thromboembolism Prophylaxis (VTEp) in COVID-19 adult medical inpatients

What's New

02-06-22 please note guideline updated:

'' Following emerging evidence the majority of patients with COVID infection follow the same VTEP protocol as other hospitalised patients. This guideline details the few exceptions to this rule (patient in ITU, patients at extremes of weight and patients with low eGFR)''

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COVID-19 infection is associated with inflammation, disseminated intravascular coagulation (DIC), hypoxaemia and immobility, all of which increase the risk of development of thromboembolic complications

There is an increased prevalence of venous thromboembolism (VTE) in COVID positive patients, particularly those with more severe disease and those who require intensive care, even after their discharge from hospital

Patients who suffered from VTE in the context of COVID had a higher mortality than COVID patients without VTE.

Clinicians should be aware of this increased risk and have a low threshold for investigating for VTE in these patients

Previously, therapeutic levels of anticoagulation have been used as prophylaxis due to emerging concern that prophylactic dose was not sufficient. However with larger published clinical trials, the evidence for therapeutic or prophylactic dose anticoagulation on clinical outcomes reports inconsistent findings. The largest trials which collectively included 1,113 patients with critical or severe COVID-19 report that therapeutic anticoagulation did not improve survival or organ support free days compared with prophylactic anticoagulation. In patients with moderate disease, who did not require critical care, the evidence is conflicting and therefore it is no longer recommended to offer therapeutic anticoagulation to all patients with COVID-19 infection.

For all patients, assess bleeding risk using standard risk assessment tool as soon as possible after admission (within 14 hours)

Dosing recommendations

Prescribe enoxaparin 40mg once daily for all patients with COVID-19 infection, whether on oxygen or not, or using respiratory support or not, UNLESS being treated for suspected or proven venous thromboembolism.

Patient group	Enoxaparin dose (prophylaxis)	Anti-Xa monitoring?
Body weight between 50 and 120kg and eGFR at least 30mL/min	40mg ONCE a day	No
Above 120kg bodyweight	40mg TWICE a day	Yes
Under 50kg bodyweight	20mg ONCE a day	Yes
eGFR below 30mL/min	20mg ONCE a day OR heparin 5000 units ONCE a day	Yes (enoxaparin) No (heparin)
eGFR below 30mL/min AND bodyweight above 100kg	Heparin 5000 units THREE times a day	Not applicable for heparin

Note: for specific individual patients who have a severe COVID-19 pneumonia (who may be unvaccinated or severely immunosuppressed, have bilateral changes on CXR, significant oxygen requirement, elevated D-Dimer or raised inflammatory markers), experienced clinicians MAY decide to provide VTEp at a treatment dose (this is an unlicensed indication). These patients should have anti-Xa monitoring. The table below provides dosing and monitoring information.

Treatment dose LMWH should no longer be offered to all patients with COVID-19 infection

Patient Group	Enoxaparin dose (treatment)	Anti-Xa monitoring?
Body weight up to 120kg AND eGFR at least 30mL/min	1.5mg/kg ONCE a day rounded to the nearest 10mg	No
Above 120kg bodyweight	Maximum 180mg ONCE a day	Yes
eGFR below 30ml/min	1mg/kg rounded to nearest 10mg ONCE a day	Yes
If obese, symptomatic PE, active cancer, recurrent PE or proximal (vena iliaca) thrombosis	1mg/kg rounded to nearest 10mg TWICE a day to a maximum of 120mg per dose	Yes

Anti-Xa monitoring

Take the sample 4 hours after the 3rd dose to ensure levels at steady state. Send blood sample in a green (citrate) tube to the blood sciences laboratory.

Reference ranges differ depending on dose. Repeat level if the dose or renal function changes. Discuss levels out with the target range with Haematology.

Dosing schedule	Anti-Xa Range
Prophylaxis	0.1 to 0.4 units/mL
Treatment dose 1.5mg/kg daily	0.5 to 1.2 units/mL
Treatment dose 1mg/kg TWICE a day	1.0 to 2.0 units/mL

Pregnancy

Seek advice from the obstetrics team on VTEp in a pregnant patient with COVID-19 infection.

Other scenarios

Patients in ICU may be treated on alternative dosing – the most common being 40mg twice daily enoxaparin. Although there is no clinical research to support this dose, there is a lot of local experience with this.

If a patient steps down from ICU on an alternative dosing (ASSUMING NOT BEING TREATED FOR VTE) they should continue on ICU dosing (e.g. enoxaparin 40mg twice daily) for a minimum of 7 days and could then be stepped down to standard prophylactic dosing for the remainder of their inpatient stay.

Patients already on anti-coagulation at admission

Continue on current therapeutic dose of anticoagulation without change (addition or amendment) unless contraindicated by a change in clinical circumstance e.g. new renal impairment, initiation of drug with significant interaction.

Consider switching to regimen outlined in this guidance if their clinical condition is deteriorating.

Duration of treatment

VTE prophylaxis should be started within 14 hours of admission and continued for the duration of the hospital stay.

Extended thromboprophylaxis on discharge from hospital for high risk patients

High risk patients are defined as those who are COVID positive and have required advanced respiratory support, critical care treatment or one or more of the standard VTE risks as documented on the venous thromboembolism prophylaxis assessment protocol.

High risk patients should be considered for extended prophylaxis i.e. for a minimum of 7 days unless there is a contraindication.

If a high risk patient is discharged before day 7, an individual decision can be made to continue enoxaparin on discharge if the patient is educated to do so and no bleeding or falls risks are identified.

Contra-Indications to enoxaparin

Platelets < 30 x 10⁹/L. (If 30 to 50 x 10⁹/L and clinical concerns please discuss with haematology)
Patient receiving anticoagulation for another indication e.g. systemic anticoagulation for PE or DVT.
Patient considered to be at a high risk of bleeding e.g. recent intracranial haemorrhage, untreated inherited/acquired bleeding disorders.
Trauma with high bleeding risk.
Significant active bleeding (discuss with consultant if minor oozing or bleeding)
Heparin induced thrombocytopenia.
Acute stroke (risk of haemorrhagic transformation; discuss with stroke team).
Within 12 hours of procedures e.g. tracheostomy, lumbar puncture.
Persistent hypertension ≥ 230/120mmHg
Liver failure and International normalized ratio (INR) ≥ 2.0

Mechanical thromboprophylaxis

Thromboembolic deterrent stocking (TEDs) should be prescribed and used alone in patients with bleeding or platelet count <30 x 10⁹/L unless there are contra-indications (oedema, cellulitis, ulcers, dermatitis, peripheral vascular disease, acute stroke in the previous 14 days)

Management of confirmed VTE in COVID 19 patients

Treat as for any provoked VTE with a minimum of 3 months full dose anticoagulation as per standard guidelines.

Line associated VTE should be treated with full dose anticoagulation for 6 weeks after the line has been removed.

Notes and references

COVID-19 positive patients can develop abnormal coagulation and thrombocytopenia, but this is not common, and bleeding symptoms are rare.

Prolonged PT/APTT are not a contra-indication to thromboprophylaxis as long as fibrinogen is ≥ 1.0g/L. Consider discussing with haematology if significantly deranged.

If platelets fall by more than 50% from baseline, consider heparin induced thrombocytopaenia (HIT) and discuss urgently with consultant haematologist. This is more likely from day 5 of therapy.

References

Date accessed: 01/04/2022 https://www.brit-thoracic.org.uk/document-library/quality-improvement/covid-19/bts-guidance-on-venous-thromboembolic-disease-in-patients-with-covid-19/

Prevention and Management of venous thromboembolism in Covid -19. Sign Guidelines. https://www.sign.ac.uk/our-guidelines/prevention-and-management-of-venous-thromboembolism-in-covid-19/

COVID-19 rapid guideline: reducing the risk of venous thromboembolism in over 16s with COVID-19 (NG186). https://www.nice.org.uk/guidance/ng186

COVID-19 rapid guideline: managing COVID-19 (NG191 published 23 March 2021, updated 30 March 2022). https://www.nice.org.uk/guidance/ng191

Glossary

Abbreviation	Meaning
BiPAP	Bilevel positive airway pressure
CPAP	Continuous positive airway pressure
CXR	Chest X-ray
DIC	Disseminated intravascular coagulation
DVT	Deep vein thrombosis
eGFR	Estimate glomerular filtration rate
HFNO	High flow nasal oxygen
HIT	Heparin induced thrombocytopaenia
ICU	Intensive Care Unit
INR	International normalised ratio
LMWH	Low-molecular-weight heparin
mHDU	Medical High Dependency Unit
PE	Pulmonary Embolism
PT/APTT	Prothrombin time/Activated partial thromboplastin time
TEDs	Thromboembolic deterrent stocking
VTE	Venous thrombo-embolism
VTEp	Venous Thromboembolism Prophylaxis

Editorial Information

Last reviewed: 31 May 2022

Next review: 31 August 2022

Author(s): COVID-19 working group

Version: 2

Approved By: Awaiting approval of TAM Subgroup of the ADTC

Reviewer Name(s): Alison Macdonald, Antimicrobial Pharmacist, Wendy Beadles, Infectious Diseases Consultant

Document Id: COVID090

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