SUMMARY: The SARS-CoV-2 Coronavirus (COVID-19) induced pandemic first identified in December 2019 in Wuhan, China, has contributed to significant mortality and morbidity in the US, and the numbers of infected cases continue to increase worldwide. As of May 1, 2022, over 81.4 million total cases have been reported in the US and 993,000 individuals have died from COVID-19. Majority of the patients present with treatment-resistant pyrexia and respiratory insufficiency, with some of these patients progressing to a more severe systemic disease and multiple organ dysfunction.
One of the most important and significant poor prognostic features in patients with COVID-19 is the development of coagulopathy, which is associated with an increased risk of death. The coagulation changes seen suggest the presence of a hypercoagulable state that can potentially increase the risk of thromboembolic complications. The coagulation abnormalities mimic other systemic coagulopathies associated with severe infections, such as Disseminated Intravascular Coagulation (DIC) or Thrombotic MicroAngiopathy (TMA), but the features are distinct in that, with DIC associated with sepsis, thrombocytopenia is usually more profound, and D-dimer concentrations do not reach the high values as seen among patients with COVID-19. COVID-19 infection related coagulopathy can also be associated with increased Lactate DeHydrogenase (LDH), and in some patient’s strikingly high ferritin levels, reminiscent of findings in TMA.
Severe COVID-19 infection is characterized by high concentrations of proinflammatory cytokines and chemokines such as Tumor Necrosis Factor-α (TNF-α) and interleukins including IL-1 and IL-6. IL-6 can induce tissue factor expression on mononuclear cells, initiating coagulation activation and thrombin generation, whereas TNF-α and IL-1 suppress endogenous anticoagulant pathways. COVID-19 infection also has a direct effect on endothelial cells, resulting in an exaggerated inflammatory response, down regulation of Angiotensin Converting Enzyme 2 receptors, and activation of the coagulation system. The relative incidence of pulmonary embolism is higher with COVID-19 infection and has been attributed to immunothrombosis (thrombosis in the pulmonary vessels from local inflammation). The increased risk of bleeding has been attributed to endothelial dysfunction, coagulopathy, or DIC. Previously published studies on the risk of venous thromboembolism after COVID-19 infection have shown conflicting results.
The researchers conducted this analysis using self-controlled case series and matched cohort study methods, and the objective of this study was to quantify the risk of deep vein thrombosis and pulmonary embolism, as well as bleeding after covid-19. Using Swedish national health databases, the researchers identified 1,057,174 individuals who tested positive for SARS-CoV-2 between February 2020 and May 2021. The incidence of first deep venous thrombosis (DVT), pulmonary embolism (PE), and bleeding during the subsequent 180 days was recorded, regardless of disease severity. A cohort of 4,076,342 individuals who did not have COVID-19 served as matched controls. The mean age was 40.2 years, 49% were males and 51% were females.
After statistical adjustments, the risks for DVT, PE, and bleeding were significantly higher in the 30 days following diagnosis of COVID-19 compared to the matched control group (risk ratios 5, 33 and 2; meaning 5 times, 33 times, 2 times more respectively). These risks remained significantly elevated for three, six, and two months after COVID-19, respectively. Further, there was a higher risk of events in patients with comorbidities, patients with more severe covid-19, and during the first pandemic wave, compared with the second and third waves.
It was concluded that the finding from this study support thromboprophylaxis to avoid thrombotic events, especially for high risk patients, and strengthens the importance of vaccination against covid-19. The authors added that it remains unclear whether the period of thromboprophylaxis after covid-19 should be extended, and additional clinical research would be beneficial.
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. Katsoularis I, Fonseca-Rodríguez, Farrington P, et al. BMJ 2022; 377 doi: https://doi.org/10.1136/bmj-2021-069590 (Published 06 April 2022)
