COVID-19 and thrombotic microangiopathies

Abstract

Severe COVID-19 can manifest as multiorgan dysfunction with pulmonary involvement being the most common and prominent. As more reports emerge in the literature, it appears that an exaggerated immune response in the form of unfettered complement activation and a cytokine storm may be a key driver of the widespread organ injury seen in this disease. In addition, these patients are also known to be hypercoagulable with a high rate of thrombosis and a higher-than-expected failure rate of anticoagulation. While macrovascular thrombosis is common in these individuals, the frequent finding of extensive microvascular thromboses in several series and case reports, raises the possibility of thrombotic microangiopathy (TMA) as being a contributing factor in the thrombotic and multi-organ complications of the disease. If this is correct, rapidly identifying a TMA and treating the underlying pathophysiology may allow for better outcomes in these critically ill patients. To further explore this, we reviewed the published literature on COVID-19, looking for reports describing TMA-like presentations. We summarize our findings here along with a discussion about presentation, pathophysiology, and a suggested treatment algorithm.

Keywords: C5 inhibition; COVID-19; SARS-CoV-2; Thrombosis; Thrombotic microangiopathy; Vascular injury.

Fig. 1

Potential mechanisms of the development of TMAs in COVID-19 patients (MAC – Membrane attack complex, UL-VWF – Ultra large von-Willebrand factor).

Fig. 2

Suggested algorithm for the management of TMAs in COVID-19 patients. * It is better to avoid the use of rituximab upfront together with corticosteroids to avoid superadded immunosuppression. ** Corticosteroids have proven efficacy in decreasing the mortality in selected groups of COVID-19 patients [45]. So, might be helpful in the setting of TMA as well. *** TPE is currently being tested in multiple studies for the treatment of severe COVID-19 related illnesses. It also has some efficacy in complement mediated TMA. (TPE – Therapeutic plasma exchange, TTP – Thrombotic thrombocytopenic purpura).