Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort studyBMJ 2022; 377 doi: https://doi.org/10.1136/bmj-2021-069590 (Published 06 April 2022) Cite this as: BMJ 2022;377:e069590
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Re: Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
The study by Kotsoularis et al. documented increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE) and bleeding after COVID-19 which coincided with something that as practitioners we had seen in our practice as well. One of the biggest strengths of this study was that it is from the Sweden national database that is publicly funded making this a great epidemiological design to avoid publication bias. The study had a large sample with follow up of patients over a period of 60 and 90 days proving ample time for monitoring of complications. Furthermore, the study also included a buffer period following up these patients before they tested positive for COVID. The study design using four matched controls for one patient accounting for confounding in this study and adding to the strength of the study.
Having a large sample is believed to ideal for research but it tends to make us run into an issue with statistics. When numerous cases are included in the statistics, analysis power is substantially increased. This implies an exaggerated tendency to reject null hypotheses with clinically negligible differences. What is insignificant becomes significant. Thus, a potential statistically significant difference in the ANB angle of 0.1° between the groups cited in the previous example would obviously produce no clinical difference in the effects of wearing an appliance .
In the results it showed 2x an increase in COVID-19 positive patients with PE compared to DVT in the same patient population which prompted a question that did patients have symptoms of PE that triggered them to come in to the ED or were all patients with COVID-19 getting CT angiogram with contrast resulting in over diagnosis of PE. We also were wondering did patients get lower extremity venous ultrasounds along with the CTA chest to rule out Lower extremity Deep vein thrombosis. Also, there was no mention of other hypercoagulopathy modifiers such as smoking, oral contraceptive use, obesity. Of note, vaccination status of the patients was not reported.
In addition, this study was from patients in Sweden and compared to other countries Sweden had the one of the least amount of COVID cases so using the results of this study for practitioners in other countries where COVID-19 rates in the first and second waves are higher will be a little delicate. Sweden had lax controls compared to other countries since they were pursuing herd immunity. Their COVID-19 strategy left large segments of the society open instead of imposing a lockdown to combat the spread of the coronavirus .
Furthermore, the study concluded that there was an increase in DVT and PE after COVID-19 for 2, 3 and up to 6 months so we were wondering did the study look at anticoagulation on discharge for prophylaxis against DVT and PE in patients with COVID-19 especially patients with COVID-19 and multiple comorbidities.
Thank you for your time.
Dr. Yusra Medik
Dr. Amanda Chajkowski
Dr. Gabby Gerbino
Dr. Nawal Aamir
Dr. Angela Adelizzi
Dr. Vinod Nookala
1. Faber, Jorge, and Lilian Martins Fonseca. “How Sample Size Influences Research Outcomes.” Dental Press Journal of Orthodontics, Dental Press International, 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296634/.
2. Pashakhanlou, Arash Heydarian. “Sweden's Coronavirus Strategy: The Public Health Agency and the Sites of Controversy.” World Medical & Health Policy, John Wiley and Sons Inc., 3 June 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242624/.
Competing interests: No competing interests
The study by Kotsoularis et al. clearly suggests "that COVID-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after COVID-19”. (1)
We fully agree with this report. In addition, a recently published study provides evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial, even among subjects who were not hospitalized during the acute phase of the disease. (2)
In our experience, we observed that after complete clinical recovery from COVID-19, restoration of wellbeing, and normalization of molecular swab, 20% of patients had substantially elevated levels of D-dimer, which returned progressively to normal after about two weeks of treatment with prophylactic doses of enoxaparin. (3) This has led us to ask whether the persistence of elevated D-dimer beyond the clinical recovery could be a signal to understand mechanisms leading to the frequent long-term consequences of SARS-CoV-2 infection.
In addition, we observed elevation of D-dimer after mRNA vaccinations (both Pfizer and Moderna) in some subjects, probably at risk of clotting. D-dimer levels were assessed the day before vaccination and after 5-7 days (unpublished data), with clinical spectrum ranging from no symptoms to severe, requiring hospitalization. (4)
Therefore, we believe that D-dimer might be considered a simple, reliable, and inexpensive test to track and follow the patients recovered from COVID-19 who should continue a treatment with low molecular weight heparin or other blood thinners after clinical recovery.
1) Katsoularis I, Fonseca-Rodriguez O, Farrington P, et al. Risk of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19: nationwide self-controlled cases series and matched cohort study. BMJ 2022;377: e069590
2) Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med 28, 583-590 (2022). https://doi.org/10.1038/s41591-022-01689-3
3) Fazio S, Tufano A, de Simone G. Sustained high D-dimer in outpatients who have recovered from mild to moderate coronavirus disease (COVID-19). Semin Thromb Hemost. 2022 Feb; 48(1):115-117. doi: 10.1055/s-0041-1729857. Epub 2021 May 7. PMID: 33962473.
4) Fazio S, Vaccariello M, Affuso F. A case of adverse reaction to booster dose of COVID-19: could D-dimer elevation suggest increased clotting risk? Health Vol. 14 No. 2, February 2022. DOI: 10.4236/health.2022.142015.
Competing interests: No competing interests