In a recent review published in Thrombosis Research, researchers reported the mechanisms involved in coronavirus disease 2019 (COVID-19) coagulopathy and the importance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections for cancer patients concerning outcomes, thromboembolic complication risks and consequences of management strategies.

Study: COVID-19 associated coagulopathy and thrombosis in cancer. Image Credit: MattLphotography/Shutterstock

Studies have reported that cancer patients are at an elevated risk of COVID-19 severity and associated hostile outcomes, either resulting from the neoplasm itself (resembling lung cancers and hematological malignancies with hypercoagulable states) or resulting from immunological suppression consequently of antineoplastic therapy. Severe SARS-CoV-2 infections may be complicated by coagulopathies resembling COVID-19, which can lead to venous thromboembolism.

In regards to the review

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

Mechanisms of COVID-19 coagulopathy

Severe COVID-19 has caused significant morbidity, including multiple organ dysfunction and respiratory insufficiency, and deaths. Age, obesity, and comorbidities resembling hypertension, pulmonary disorders, and diabetes are established risk aspects for COVID-19 severity. As well as, immunocompromised individuals resembling those that received organ transplants, those on immunosuppressive medications, and people with hematological malignancies receiving anti-neoplastic agents, are highly susceptible to severe SARS-CoV-2 infections.

Severe COVID-19 patients develop hemostatic abnormalities resembling venous thromboembolism, the danger for which is 12-fold higher amongst cancer patients than healthy individuals. SARS-CoV-2-associated coagulopathy is related to significantly increased D-dimer levels with more profound elevations than those amongst cancer patients. As well as, serological levels of fibrinogen, factor VIII, and tissue-type plasminogen activators (t-PA) are elevated, in response to the cytokine storm [especially interleukin (IL)-6] in COVID-19, with abnormal coagulation and increased tissue viscoelasticity.

Elevated plasmin levels could activate metalloproteinase molecules in modifying extracellular matrices essential for leakage from capillaries and pulmonary edema. Platelet counts and coagulation inhibitors resembling protein C and antithrombin are reduced in severe COVID-19. Further, SARS-CoV-2 infections are related to neutrophil extracellular trap (NET) formation (NETosis) in blood vessels, induced by complement activation and IL-8.

NETs promote the formation of thrombus by activating the intrinsic clotting pathway and supply a platform for erythrocytes, platelets, and procoagulants like vWF (von Willebrand factor). Due to this fact, NETosis markers resembling citrullinated histone H3 and myeloperoxidase (MPO)-deoxyribonucleic acid (DNA) complex are elevated in severe SARS-CoV-2 infections. NET-forming neutrophils co-populate with thrombocytes in COVID-19 patients’ pulmonary microthrombi, and NETs have been present in abundance in coronary vessel thrombi of COVID-19-associated myocardial infarction (MI) patients. 

Perturbations in endothelial cells after vWF release provide an excellent surface for thrombus formation intravascularly in SARS-CoV-2 infections. ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaving capability could also be overwhelmed, leading to thrombotic microangiopathies within the vessels of multiple organs in COVID-19. SARS-CoV-2 infection coagulopathy involving vessel wall thickening, stenosis, and microthrombi formation results in a hypercoagulable situation, enhancing thromboembolic complication risks, potentiated by in-dwelling lines and immobilization amongst hospitalized SARS-CoV-2-positive patients.

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

Cancer patients with low lymphocyte counts, particularly those that underwent major surgeries or chemotherapy recently, have been reported to have two-fold and 1.2-fold higher COVID-19-associated mortality risks amongst hematological malignancy and other cancer patients. Studies have reported that coagulation and inflammatory responses to COVID-19 in cancer patients are greater than in non-cancer patients.

It has been documented that mild and severe COVID-19 patients have six-fold and three-fold higher risks of developing pulmonary embolism and venous thrombosis, respectively, essentially the most outstanding risk factor for which was the presence of lively neoplasms. Venous thromboembolism has been reported to be higher (10%) amongst patients who received anti-neoplastic therapy in recent times in comparison with those that didn’t (six percent).

A growing body of evidence states that high-dose thrombosis prophylaxis has only marginally lesser safety and more efficacy compared to standard dosage prophylaxis amongst hospitalized SARS-CoV-2-infected cancer patients; nevertheless, clinical research doesn’t favor high-dose antithrombotic prophylaxis amongst severely sick COVID-19 patients, resulting from high bleeding risks. The finding might be prolonged to malignancy patients who even have elevated risks of bleeding.

Antithrombotic prophylaxis isn’t beneficial for non-hospitalized malignancy patients who acquire SARS-CoV-2 infections; nevertheless, the risk-benefit ratio may tip towards conventional dose thrombosis prophylaxis for outpatients during lively SARS-CoV-2 infections, but this must be confirmed in further clinical studies. Hematological malignancy patients have shown significantly lower seroconversion rates with low anti-SARS-CoV-2 antibody titers than healthy individuals. COVID-19 vaccines are considered protected for cancer patients, although there are concerns about messenger ribonucleic acid (mRNA) permeation and retention in tumor cells for mRNA vaccinations.

Overall, the review findings showed that COVID-19 could amplify the danger of venous thrombosis in lively cancer patients, particularly amongst those on immunomodulators. Due to this fact, strategies for optimized protection of cancer patients against COVID-19 are essential. Management strategies to enhance COVID-19 outcomes in malignancy patients (resembling high-dose antithrombotic prophylaxis) are lacking and require further investigation with a deal with safety and efficacy.