Severe COVID-19 seems to interact with the von Willebrand Factor (VWF)-ADAMTS13 axis in unknown ways to increase the risk of thrombotic disease, according to a recent letter to the editor published in the Journal of Thrombosis and Haemostasis.
COVID-19 puts people at increased risk for thrombotic disease that does not respond to therapeutic anticoagulation. Some studies have found elevated levels of VWF activity, VWF antigen, and Factor VIII levels. A recent study found that the VWF-ADAMTS13 axis may be correlated with disease activity in COVID-19.
In their letter, Satish Maharaj, MD, of the James Graham Brown Cancer Center in Louisville, Kentucky, and colleagues described the case of a 69-year-old African American female patient with a history of immune thrombocytopenic purpura (TTP). She was first diagnosed in 2003 and received multiple treatments, including fondaparinux.
In 2020, she was treated for TTP relapse and tested negative for COVID-19 with no symptoms of the disease. She responded to initial treatment but then began to decline and relapsed 5 weeks later. She was treated with plasmapheresis and steroids but was readmitted 3 weeks later. Her ADAMTS13 level was 2.1% at this readmission. After further treatment she asked to be discharged but returned 2 days later with acute hypoxic respiratory failure and tested positive for COVID-19.
ADAMTS13 activity was at 2.9% and her VWF antigen and Factor VIII activity were elevated, but her platelet count increased with COVID-19 treatment. However, she continued to test positive for COVID-19, was intubated 2 weeks after diagnosis, and died 6 weeks after diagnosis.
The authors noted that in this case and other studies, the VWF-ADAMTS13 axis seems to have a role in thrombotic disease with COVID-19. However, the studies did not explain in vivo hematologic effects of COVID-19. The authors suspected that COVID-19 affects several pathways to interact with the axis to modify the TTP/thrombotic microangiopathy (TMA) response.
“These interactions mitigate some effects that would lead to platelet consumption and result in fulminant TMA, but still drive a hypercoagulable state,” the authors concluded. Future studies should define how COVID-19 leads to hypercoagulability.
Maharaj S, Xue R, Rojan A. Thrombotic thrombocytopenic purpura (TTP) response following COVID-19 infection: implications for the ADAMTS13-von Willebrand factor axis. J Thromb Haemost. Published online December 31, 2020. doi:10.1111/jth.15230