It's increasingly clear that critically ill patients with COVID-19 can develop a pro-thrombotic form of DIC which places them at a dramatically increased risk of thrombosis. Thrombotic events may include pulmonary micro-vascular thrombosis (reported in some autopsies) or macro-vascular thrombosis (e.g., deep vein thrombosis). To date, an evidentiary vacuum has left it highly controversial as to when patients should receive therapeutic anticoagulation.
Cui et al: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia
This is a single-center retrospective study describing 81 patients with COVID-19 requiring ICU admission.1 All patients were evaluated for lower extremity deep vein thrombosis using ultrasonography.
Baseline demographic data is sparse (table below). For example, it's unclear how many patients were intubated. Based on the very high discharge rate (85%), it's likely that this was a cohort of patients with relatively mild disease (when compared to other ICU cohorts).
25% of patients developed DVT. DVT correlated with indicators of disease severity and DIC (e.g., older age, lower lymphocyte count, and prolonged APTT). The strongest correlation was with D-dimer:
The authors subsequently tested various D-dimer cutoff values for the ability to predict DVT occurrence. The best cutoff was 1,500 ng/ml (with a sensitivity of 85% and a specificity of 89%).
This study has numerous weaknesses:
- It's unclear how frequently DVT studies were performed. If testing was performed only once, or very infrequently – then this could miss DVTs.
- Patients didn't receive prophylactic anticoagulation to prevent DVT. This likely increased the observed rate of DVT.
- This cohort of patients appears less ill than most ICU cohorts, which could decrease the rate of DVT (when compared to sicker cohorts of patients).
- The occurrence of pulmonary emboli wasn't systematically reported or investigated. It's likely that some patients without DVT did have a PE, thus under-estimating the burden of venous thromboembolic disease.
- The rate of venous thromboembolic disease in patients with severe COVID is substantial.
- D-dimer appears to be the best single predictor of patients who will develop venous thromboembolic disease.
- In this patient cohort, a D-dimer >1,500 ng/ml had an 85% sensitivity and 89% specificity for predicting which patients would develop DVT. This supports the concept of empiric anticoagulation for patients with markedly elevated D-dimers (especially in situations where frequent CT angiography is impossible due to logistic restraints).
- Numerous methodological limitations in this study prevent it from being definitive (e.g., lack of screening for pulmonary emboli may have led to under-diagnosis of venous thromboembolic disease).
- Until additional data is available, when to initiate full anticoagulation will remain controversial. For now, these decisions may be judged on a patient-by-patient basis, considering both risks of thrombosis and hemorrhage. Among patients without risk factors for hemorrhage, empiric anticoagulation may be reasonable for patients with D-dimer levels above ~1,500 ng/ml.
related
- DIC section in COVID-19 IBCC chapter
- Thrombosis & Hemoglobin in COVID-19 (Salim Reaie, RebelEM)
Image Credit: Photo by Mael Balland on Unsplash
references
- 1.Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. April 2020. doi:10.1111/jth.14830
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From community hospital in Chicago: Perfectly relevant info for this morning. My patient has DDimer= 1440, This helps with decision-making. Thank you Scott and team for interpreting and sharing!
*Josh
Klok, F. A., Kruip, M. J. H. A., van der Meer, N. J. M., Arbous, M. S., Gommers, D. A. M. P. J., Kant, K. M., et al. (2020). Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research, 1–11.
Study of 184 ICU patients with proven COVID-19 pneumonia. They found à 27% incidence of VTE.
From a COVID ward in north Italy: in the past weeks we noticed a great number of patients with really high d-d levels, frequently ranging around 2000-6000. Even in milder pneumonia cases and in the recovery phase (normalized CRP) the d-d is elevated. There is no evidence and we still don’t understand the meaning of such elevated d-d levels. In Italy someone advocate therapeutic or half-therapeutic doses. We still don’t know a lot of things, they are difficult patients. Thanks
Have you guys started anticoagulants
If yes prophylaxis or therapeutic
I am really interested d-d levels
We have many COVID patients with AKI/ARF, rising Cr., etc, Could you comment on interpretation of D dimer when in context of renal impairment?
Thanks,
Ken
Article seems not to report thromboprophylaxis regime they used. I understood from elsewhere that they did not use anything, but I actually do not know. In this light besides that there is a risk we cannot quantify it and I am not sure if we are allowed to argue that in a setting where you do use thromboprophylaxis with eg LMWH we should increase the dose at a certain level of d-dimers. We are going to pay for it with more bleeding… I do not want to say it is not an issue: incidence is high with (changing regimes of… Read more »
Does anyone happen to know if the assays used reported FEUs or DDUs?
Not sure about this one…full anticoagulation is a significant decision with a lot of potential complications and additional exposure of contagion to staff, based on almost no evidence. There are many other prothrombotic states (septic shock) in ICU where we don’t take this approach based on labs…why would COVID somehow be different? Why not just slightly increase dose of prophylaxis? Is there another infectious disease process that we anticoagulate for when we reach a certain dimer or other lab threshold? I just have a lot of questions about this and a lot of the other stuff we’re doing for COVID.… Read more »
I took care of a very sick business partner from the Seattle WA area in my Harrisburg, PA home 12-03-19 to 12-10-19 I took him to the ER because I was really afraid he was gravely ill. They ran a ton of tests. Very expensive tests – and 2 hours later sent him on his way with the diagnosis of Non-Specific Virus. I asked him to send me his test results as we are now in the midst of the Covid 19 Pandemic that they swear got here in Jan/Feb 2020 – his blood results have classic markers of this… Read more »
It’s interesting that the Klok et al paper “Incidence of thrombotic complications in critically ill ICU patients with COVID-19” (https://www.thrombosisresearch.com/article/S0049-3848(20)30120-1/pdf) finds (1) a similarly high rate of VTE – 31%, even without screening, (2) doesn’t report D dimers and (3) still doesn’t support full dose anticoagulation routinely. Not sure the Chinese studies are generalisable to our populations given they don’t routinely given prophylactic heparin. Does feel a bit gung-ho to fully anticoagulate without clinical evidence of VTE. I’m particularly worried by the language of Tang et al (https://www.ncbi.nlm.nih.gov/pubmed/32220112) when they claim to “anticoagulate” patients with markedly elevated D dimers –… Read more »
Hi: had a middleaged COVID patient today who was just slow to improve. His SAO2 remained around 93% on air with pulse rate of around 105 and improving classic COVID CXR and improving CRP. Otherwise well and on prophylactic anticoagulation. Decided to request CTPA and to my surprise he had bilateral central and segmental PE’s. I have a ward full of COVID patients with mild hypoxia. Not sure now who not to scan !