Should anticoagulation / venous thromboembolism (VTE) / deep venous thrombosis (DVT) prophylaxis be routine in ventilated patients with COVID-19?

Posted on April 1, 2020 by Ellison Richmond

Summary

  • BCCDC guidelines state:
    • “Rates of VTE in hospitalized patients with COVID-19 are expected to be similar patients with inflammatory disorders or sepsis.”
    • “Currently, the standard VTE prophylaxis regimen is enoxaparin 40 mg SC daily. In specific populations (e.g. orthopedic trauma and spinal cord injury patients), enoxaparin 30 mg SC twice daily is often used.”
  • Studies of COVID-19 patients have found some coagulopathic lab findings associated with mortality.

I.   Guidelines

  • BCCDC has released guidelines on ‘Unproven Therapies for COVID-19’ (1). Current recommendation is “Suggest enoxaparin 30 mg SC bid as the preferred dose for VTE prophylaxis in hospitalized patients with COVID-19. This dose was selected to reduce clinician suspicion of incident VTE and potentially save health care resources with patient transport and minimize risk of COVID-19 transmission to staff and others.”
    • “Rates of VTE in hospitalized patients with COVID-19 are expected to be similar patients with inflammatory disorders or sepsis. All hospitalized patients with COVID-19 should receive pharmacologic VTE prophylaxis, unless contraindicated. Based on observational data, thrombocytopenia and coagulopathy are not expected from COVID-19 while D-dimer levels are typically elevated in 50% of COVID-19 patients”
    • “Currently, the standard VTE prophylaxis regimen is enoxaparin 40 mg SC daily. In specific populations (e.g. orthopedic trauma and spinal cord injury patients), enoxaparin 30 mg SC twice daily is often used. The potential benefits with a higher daily dose of prophylactic anticoagulation include a reduced clinical suspicion for incident venous thromboembolism and, in turn, a lesser need for confirmatory radiologic procedures. This would result in reduced use of healthcare resources with patient transport and also lessen the risk of staff exposure and equipment contamination with COVID-19. “
  • Thrombosis UK has an online document updated weekly titled “Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19” (https://thrombosisuk.org/covid-19-thrombosis.php) (2)
    • “Pharmacological thromboprophylaxis should be given to all immobilised and severely ill patients with COVID-19 patients unless otherwise contraindicated
    • “For CrCl > 30: Give LMWH or fondaparinux s.c. according to license
    • “For CrCl < 30 or AKI: Unfractionated heparin 5000 units SC BD or TDS or dose-reduced LMWH
    • “All completely immobilised patients would benefit from intermittent pneumatic compression in addition to pharmacological thromboprophylaxis.
    • “Mechanical thromboprophylaxis should be used alone if platelets <30,000 or bleeding
    • “Consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure.
    • “Consider switching to LMWH in patients taking direct oral anticoagulants (DOACs) or vitamin K antagonist (e.g warfarin) for stroke prevention in atrial fibrillation or previous VTE.
    • “Abnormal coagulation results do not require correction in patients who are not bleeding.
    • [There are guidelines regarding minor and major bleeding]
    • “For patients with major bleeding give empirical FFP and red cells followed by blood products determined by repeat coagulation screens, using PT/INR >1.5 or APTT > 1.5 as an indication to give FFP 15-25mg/Kg. For fibrinogen <1.5g/l give cryoprecipitate or fibrinogen concentrate, if platelets <50x 109/l give a pool of platelets. If the patient does not have DIC then also give tranexamic acid 1gm IV.
    • “Manage bleeding with blood product replacement as per managing major bleeding as above: i.e. if PT/INR or APTT ratios are greater than 1.5 then give FFP 15-25mg/Kg; if fibrinogen is <1.5g/l then give a source of fibrinogen- either cryoprecipitate or fibrinogen concentrate; if platelet are < 50x 109/l then give platelets
    • “Do not use tranexamic acid in COVID-associated DIC”

II.   Effect of anticoagulation on COVID-19 patients

  • Of 449 Chinese patients with severe COVID-19, there was no difference on 28-day mortality between heparin users and non-users, but there was reduced associated mortality amongst patients with a sepsis-induced coagulopathy (SIC) score of 4 or more (40.0% vs 64.2%, P=0.029), or D‐dimer over 6 fold of upper limit of normal (32.8% vs 52.4%, p=0.017). (3)
  • A brief guideline synopsis of management of critically-ill adults with COVID-19 by the Surviving Sepsis Campaign does not specifically mention anticoagulation. It does have guidelines regarding ventilatory support including starting with high-flow nasal cannula, pulmonary vasodilatory support, and comments regarding corticosteroids and empiric antimicrobials. (4)

III.   Effect of COVID-19 on coagulation

  • The Thrombosis UK guideline writes: “Patients with severe COVID-19 are immobile, have an acute inflammatory state leading to a hypercoagulable state. There is also the possibility of endothelial cell activation/damage due to binding of the virus to ACE2 receptor. The optimal thromboprophylaxis in COVID patients is unknown. Drug-drug interactions between antiviral treatments and direct oral anticoagulants, and the difficulty in maintaining stable INRs in patients taking vitamin K antagonists while unwell, mean that patients on these drugs should be switched/bridged to low molecular weight heparins (LMWHs) or unfractionated heparins (UFH) with or without mechanical prophylaxis while unwell.”
  • In a study of 138 consecutive COVID-19 patients in China, non-survivors showed higher D-dimer and fibrin degradation product FDP levels, longer prothombin time PTT, activated partial thromboplastin time aPTT, and higher rates of disseminated intravascular coagulation DIC compared to survivors. (5)
  • Of 191 COVID-19 patients in China, d-dimer greater than 1 ug/mL was associated with in-hospital death (OR 18.42 95% CI 2.64-128.55) alongside older age, and higher SOFA score. (6)
  • As referenced in BCCDC guidelines above, observation of 1099 COVID-19 patients showed D-dimer elevated of 0.5 mg/L or more in 46% and thrombocytopenia (plts <150,000/mm^3) in 36% of patients. (7)
  • A double case report of COVID-19 pneumonia shows complication by acute pulmonary embolism with associated CT imagery for both cases. (8)

IV.   Additional notes on anticoagulated patients

  • The  International Society on Thrombosis and Haemostasis has a FAQ from 16 March 2020 regarding anticoagulated outpatient management. They note that anticoagulated patients are not considered high-risk for COVID-19, though some patients with cardiac conditions are. They make other recommendations regarding minimizing exposure risk  and working with home quarantine. Finally, they note that COVID-19 infection may impact INR. (9)

Questions? Comments? Does this need to be updated? Do you have valuable points to add ? Please email ask.reakt@ubc.ca.

References

  1.  BC Centre for Disease Control COVID Guidelines Committee. Unproven Therapies for COVID-19. 30 March 2020, accessed online 1 April 2020. http://www.bccdc.ca/Health-Professionals-Site/Documents/Guidelines_Unproven_Therapies_COVID-19.pdf. 
  2. Hunt B, Retter A, McClintock C. Thrombosis UK. Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19. [Internet]. Thrombosisuk.org. 2020 [cited 2020 Apr 1]. Available from: https://thrombosisuk.org/covid-19-thrombosis.php
  3. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. Journal of thrombosis and haemostasis : JTH [Internet]. 2020 [cited 2020 Apr 2];10.1111/jth.14817. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32220112
  4. Poston JT, Patel BK, Davis AM. Management of Critically Ill Adults With COVID-19. JAMA [Internet]. 2020 Mar 26 [cited 2020 Apr 1]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2763879
  5. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis [Internet]. 2020 Apr [cited 2020 Apr 1];18(4):844–7. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jth.14768
  6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet [Internet]. 2020 Mar [cited 2020 Apr 2];395(10229):1054–62. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext
  7. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine [Internet]. 2020 Feb 28 [cited 2020 Apr 1]; Available from: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2002032?articleTools=true
  8. COVID-19 Complicated by Acute Pulmonary Embolism | Radiology: Cardiothoracic Imaging [Internet]. Radiology: Cardiothoracic Imaging. 2020 [cited 2020 Apr 1]. Available from: https://pubs.rsna.org/doi/10.1148/ryct.2020200067
  9. World Thrombosis Day [Internet].  International Society on Thrombosis and Haemostasis, Inc.  Worldthrombosisday.org. 2020 [cited 2020 Apr 1]. Available from: https://www.worldthrombosisday.org/news/post/anticoagulation-forum-managing-anticoagulation-during-covid-19-pandemic-frequently-asked-questions/

Disclaimer

The above is intended to serve as a rapidly-created, accessible source of information curated by medical students and healthcare professionals. It is for educational purposes only and is not a complete reference resource. It is not professional medical advice, and is not a substitute for the discretion, judgment, and duties of healthcare professionals. You are solely responsible for evaluating the information above.