Amplified venous thromboembolism risk due to COVID-19 in patients with malignant tumors

In a recent review published in thrombosis researchinvestigators explore the mechanisms involved in coronavirus disease 2019 (COVID-19) coagulopathy and consequences, risk of thromboembolic complications, and consequences of management strategies for severe acute respiratory syndrome coronavirus 2 (SARS) in cancer patients. -CoV-2) reported the importance of infection.

Cancer patients are at increased risk of COVID-19 severity and associated adverse outcomes, either due to the neoplasm itself (such as lung cancer or hypercoagulable hematologic malignancies) or immunological suppression as a result of anti-tumor therapy. reported in multiple studies. Severe SARS-CoV-2 infections can be complicated by clotting disorders such as COVID-19, which can lead to venous thromboembolism.

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In the current review, researchers describe COVID-19 coagulopathy pathways and their relevance in cancer patients for venous thromboembolic complications.

Mechanisms of COVID-19 coagulopathy

Severe COVID-19 is causing significant morbidity, including multiple organ failure, respiratory failure and death. Age, obesity, and comorbidities such as hypertension, lung disease, and diabetes are established risk factors for COVID-19 severity. In addition, immunocompromised individuals, such as those who have received organ transplants, those who are taking immunosuppressive drugs, and those with hematologic malignancies who are receiving antitumor drugs, are highly susceptible to severe SARS-CoV-2 infection. It is easy to catch.

Patients with severe COVID-19 develop hemostatic abnormalities such as venous thromboembolism. The risk is 12 times higher in cancer patients than in healthy individuals. SARS-CoV-2-related coagulopathy is associated with a significant increase. D-dimer Levels with more severe elevations than in cancer patients. In addition, serologic levels of fibrinogen, factor VIII, and tissue-type plasminogen activator (t-PA) cytokine storm [especially interleukin (IL)-6] COVID-19 is associated with abnormal coagulation and increased tissue viscoelasticity.

Elevated plasmin levels may activate metalloproteinase molecules that modify the extracellular matrix essential for capillary leakage and pulmonary edema. Platelet counts and anticoagulants such as protein C and antithrombin decrease in severe COVID-19. In addition, SARS-CoV-2 infection is associated with intravascular neutrophil extracellular trap (NET) formation (NETosis) induced by complement activation and IL-8.

NETs promote thrombus formation by activating the intrinsic coagulation pathway, providing a platform for procoagulants such as erythrocytes, platelets, and vWF (von Willebrand factor). Thus, NETosis markers such as citrullinated histone H3 and myeloperoxidase (MPO)-deoxyribonucleic acid (DNA) complexes are elevated in severe SARS-CoV-2 infection. NET-forming neutrophils coexist with platelets in pulmonary microthrombi of COVID-19 patients, and NETs are abundantly found in coronary thrombi of patients with COVID-19-related myocardial infarction (MI).

Perturbation of endothelial cells after vWF release provides an ideal surface for intravascular thrombus formation in SARS-CoV-2 infection. ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) can be overwhelmed by its cleaving ability, resulting in thrombotic microangiopathy in blood vessels of multiple organs in COVID-19. SARS-CoV-2-infected coagulopathy with vessel wall thickening, stenosis, and microthrombus formation causes a hypercoagulable state and increases the risk of thromboembolic complications. This is augmented by the indwelling wire and immobilization of her SARS-CoV-2-positive patient in hospital.

Relevance of SARS-CoV-2-associated coagulopathy in cancer

Cancer patients with low lymphocyte counts, especially those who recently underwent major surgery or chemotherapy, had a 2-fold and 1.2-fold increased risk of COVID-19-related death among patients with haematological malignancies and other cancers. has been reported. Studies have shown that cancer patients have greater coagulation and inflammatory responses to COVID-19 than non-cancer patients.

Patients with mild and severe COVID-19 have been documented to have a six-fold and three-fold increased risk of developing pulmonary embolism and venous thrombosis, respectively, with the most prominent risk factor being the presence of active neoplasm. increase. Venous thromboembolism is reported to be higher (10%) in patients who have recently received antineoplastic therapy than in those who have not (6%).

High-dose thromboprophylaxis is marginally less safe with increasing evidence that it is safer. Effectiveness Comparison with conventional medication prophylaxis in hospitalized SARS-CoV-2 infected cancer patients. However, clinical studies do not support high-dose antithrombotic prophylaxis for his severely ill COVID-19 patients due to the high risk of bleeding. This finding may also be extended to patients with malignancies who are at high risk of bleeding.

Antithromboprophylaxis is not recommended for unhospitalized malignant patients infected with SARS-CoV-2. However, the risk-benefit ratio may tilt towards conventional dose thromboprophylaxis for outpatients during active SARS-CoV-2 infection, which needs to be confirmed in further clinical studies. Patients with hematologic malignancies have been shown to have lower anti-SARS-CoV-2 antibody titers and significantly lower seroconversion rates than healthy individuals. Although the COVID-19 vaccine is considered safe for cancer patients, there are concerns about messenger ribonucleic acid (mRNA) penetration and retention of mRNA vaccination in tumor cells.

Overall, the results of the review showed that COVID-19 may amplify the risk of venous thrombosis in active cancer patients, especially those taking immunomodulatory drugs. Strategies to optimize the protection of cancer patients against COVID-19 are therefore essential. Management strategies (such as high-dose antithromboprophylaxis) to improve his COVID-19 outcome in malignant patients are lacking and require further investigations focused on safety and efficacy.