Thrombosis, cancer, and COVID-19

Abstract

Cancer and coronavirus disease 2019 (COVID-19) have unusual similarities: they both result in a markedly elevated risk of thrombosis, exceptionally high D-dimer levels, and the failure of anticoagulation therapy in some cases. Cancer patients are more vulnerable to COVID-19 infection and have a higher mortality rate. Science has uncovered much about SARS-CoV-2, and made extraordinary and unprecedented progress on the development of various treatment strategies and COVID-19 vaccines. In this review, we discuss known data on cancer-associated thrombosis (CAT), SARS-CoV-2 infection, and COVID-19 vaccines and discuss considerations for managing CAT in patients with COVID-19. Cancer patients should be given priority for COVID-19 vaccination; however, they may demonstrate a weaker immune response to COVID-19 vaccines than the general population. Currently, the Centers for Disease Control and Prevention recommends an additional dose and booster shot of the COVID-19 vaccine after the primary series in patients undergoing active cancer treatment for solid tumors or hematological cancers, recipients of stem cell transplant within the last 2 years, those taking immunosuppressive medications, and those undergoing active treatment with high-dose corticosteroids or other drugs that suppress the immune response. The mainstay of thrombosis treatment in patients with cancer and COVID-19 is anticoagulation therapy.

Keywords: Anticoagulation; COVID-19; COVID-19 vaccines; Cancer; Thrombosis.

Fig. 1

Pathophysiology of coagulopathy in COVID-19. SARS-CoV-2 enters host cells by interacting its spike protein with the entry receptor ACE2 in the presence of TMPRSS2 (left). The proposed mechanisms for COVID-19 associated coagulopathy include (1) direct virus-mediated cell damage; (2) dysregulation of the RAAS due to downregulation of ACE2 related to viral entry, which leads to decreased cleavage of angiotensin I and angiotensin II. ACE2 cleaves angiotensin II (AngII) to angiotensin 1-7 (Ang1-7). Invasion of the endothelial cells by SARS-CoV-2 causes internalization of the ACE2 receptor, promoting an imbalance of Ang1-7 and AngII, in favor of the latter, resulting in suppression of Ang1-7-mediated vasodilation and accumulation of AngII, which binds to angiotensin II receptor type 1 (AT1), with potential to exacerbate pulmonary vasoconstriction and induction of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) expression on platelets and the endothelium; (3) endothelial cell damage and immunothrombosis or thromboinflammation; and (4) dysregulation of the immune response and hyperinflammation caused by inhibition of interferon signaling by the virus, T cell lymphodepletion, and the production of proinflammatory cytokines, particularly IL-6 and TNF⍺

Fig. 2

Neutrophil Extracellular Traps (NETs)