A Review of Pathophysiology, Clinical Features, and Management Options of COVID-19 Associated Coagulopathy

Abstract

There is increasing evidence that novel coronavirus disease 2019 (COVID-19) leads to a significant coagulopathy, a phenomenon termed “COVID-19 associated coagulopathy”. COVID-19 has been associated with increased rates of both venous and arterial thromboembolic events, a source of significant morbidity and mortality in this disease. Further evidence suggests a link between the inflammatory response and coagulopathy associated with COVID-19. This presents a unique set of challenges for diagnosis, prevention, and treatment of thrombotic complications. In this review, we summarize and discuss the current literature on laboratory coagulation disruptions associated with COVID-19 and the clinical effects of thromboembolic events including pulmonary embolism (PE), deep vein thrombosis (DVT), peripheral arterial thrombosis, and acute ischemic stroke in COVID-19. Endothelial injury and augmented innate immune response are implicated in the development of diffuse macro- and microvascular thrombosis in COVID-19. The pathophysiology of COVID-19 associated coagulopathy is an important determinant of appropriate treatment and monitoring of these complications. We highlight the importance of diagnosis and management of dysregulated coagulation in COVID-19 in order to improve outcomes in COVID-19 patients with thromboembolic complications.

Venous thromboembolism after arthroscopic rotator cuff repair in a patient with a negative presurgical SARS-CoV-2 test who developed symptomatic COVID-19 three days after surgery

“…Large systematic reviews have analyzed the rate of VTE in COVID-19 patients, with reported rates ranging from 12%-17% for DVT and 8%-14% for PE. 3,5,10 Surprisingly, a large majority of PEs were not associated with a DVT, and it is thought the rate of undiagnosed clots is even higher than reported. Also, as expected, the rates of DVT and PE are higher in critically ill or ICU patients.…”

“…Routine incubation time for symptoms to emerge for COVID-19 has ranged from 2-14 days. 3 We recommend self-isolation prior to surgery for all patients, but in reality, this can be difficult to effectively implement. It is unrealistic to expect that all patients will comply with strict preoperative isolation protocols or be able to mitigate the risk of exposure from other sources, which are simply out of their control.…”

“…7 This unusual, but robust, response has been found to result in high VTE rates in severely ill patients. 3,5 We still have yet to understand the effect on baseline risk for developing a DVT or PE in less severe infections. Certainly, other factors such as immobilization and deconditioning from the illness can additionally predispose patients to venous stasis and subsequent thrombosis as well.…”

“…1,6,8,9 However, with the recent pandemic of the SARS-CoV-2 virus that causes COVID-19 infections, there has been significant concern over the high rate of VTE observed in infected patients. 3,5,7 The virus seems to stimulate a strong microvascular endothelial cell response that leads to thrombosis and clot formation. 7 As we have resumed normal elective surgeries, we have nationally implemented routine preprocedural SARS-CoV-2 screening in patients.…”

COVID-19 and cytokine storm syndrome: are there lessons from macrophage activation syndrome?

“…First, COVID-19 has other clinical features that are not seen in CSS such as MAS, such as marked coagulopathy with endothelial injury and microthrombosis. 50 Indeed, some patients with severe COVID-19 show evidence of catastrophic microvascular injury with complement activation, 51 which could suggest a phenotype similar to thrombotic microangiopathy. 52 More broadly, the model of cytokine storm implies that the inflammatory response (and cytokines in particular) are deleterious to the host, and fails to distinguish between an appropriate vs dysregulated immune response.…”