In March 2020, the COVID-19 pandemic reached Belgium and threw the entire medical world in turmoil. For Professor Cécile Oury (research director F.R.S.-FNRS, head of the laboratory of Cardiology, GIGA-Cardiovascular unit at Liège University), who had only just been appointed president of the BSTH less than two months prior, it was a challenging time.
“As we were all at home during the first lockdown in March, we began to think how we as BSTH could help the clinicians and the patients and how we could offer advice from both a scientific and technical point of view. Some of our members were also involved with Sciensano, the Belgian federal agency for health, and from Sciensano came the request if we could produce an algorithm concerning prevention of thrombosis in COVID patients, that could be used in hospitals throughout Belgium. We created a working group with haematologists, cardiologists, gynaecologists and clinical biologists from all university hospitals in Belgium and gathered information and data on thrombotic complications associated with COVID-19. This resulted in two algorithms (one concerning hospitalized COVID19 patients & patients after discharge and another concerning non-hospitalized patients).”
The BSTH recommendations for the management of coagulopathies associated with COVID-19 and the algorithms that were devised as a practical tool for clinicians were greeted with universal enthusiasm. “We heard that our algorithms were found to be very useful”, prof. Oury confirms. “And the same algorithms remain valid. In December 2020 we held a meeting to see what we could do to update the consensus guidelines. But basically, these did not need to be adapted.”
One year after the consensus guidelines were introduced, much more is known about COVID-19 and its association with blood-clotting issues and about their prevalence. Progress has also been made in identifying which groups of people are most at risk, and about the mechanisms behind the aggravated risk of blood clots.
Prof. Oury: “According to a recent meta-analysis1, the incidence rate of venous thromboembolism (VTE) in COVID-19 patients admitted to intensive care units reaches 28%, whereas this rate is about 7% in non-ICU settings. This appears to be lower than reported in initial studies. Risk factors for VTE in COVID-19 are the development of acute respiratory distress syndrome and older age. Since people with pre-existing medical conditions are more likely to get severely ill from COVID-19, they are also more likely to develop COVID-19 associated thrombotic complications.”
Prof. Oury sums up the medical conditions that come with a raised risk of becoming severely ill from COVID-19. “These conditions include cancer, chronic kidney disease, chronic lung disease, pulmonary hypertension, diabetes, Down syndrome, heart conditions (heart failure, coronary artery disease, cardiomyopathies, hypertension), HIV infection, immunocompromised state, liver disease, obesity, sickle cell disease and cerebrovascular disease. Smoking and substance use disorders are other at risk conditions.”
“Meanwhile, the mechanisms of blood clotting are not fully understood. Elevations of factor VIII, Von Willebrand factor, fibrinogen and D-dimers are common. Studies showed endotheliopathy due to virus invasion in endothelial cells or endothelial dysfunction elicited by exacerbated immune response and subsequent acute systemic inflammation.”
Insights continue to be gained surrounding the clinical treatment of thrombosis and COVID-19, and on the use of anticoagulants. Prof. Oury cautions: “Empirical use of escalated doses of anticoagulants should be avoided, since major bleeding complications can occur. The optimal thromboprophylaxis regimen for COVID-19 inpatients remains uncertain. Data from ongoing randomized clinical trials are awaited. For example, first data from the INSPIRATION clinical trial2 indicate that the use of intermediate-dose prophylactic anticoagulation in COVID-19 ICU patients did not result in less arterial or venous thrombosis, need for extracorporeal membrane oxygenation, or 30-day mortality than the use of standard-dose prophylactic anticoagulation.”
Prof. Oury eagerly awaits the results of the latest research into the correlation of COVID-19 and thrombotic events. She continues: “The role of thrombo-inflammation in COVID-19 pathophysiology is currently under investigation with the aim to identify new therapeutic strategies or drug targets. Since inflammation promotes thrombosis, and thrombosis enhances inflammation, anti-inflammatory strategies are likely to hamper thrombosis. Conversely, anti-inflammatory strategies are also included in RCT of various anti-thrombotic regimens, including heparin derivatives and antiplatelet agents that inhibit both thrombosis and inflammation. Some of these regimens may also have anti-viral effects.”
As an internationally renowned specialist in the field of platelet biology, trials surrounding antiplatelet therapies are of particular interest to prof. Oury. “Currently, there are over 80 randomized clinical trials ongoing investigating the combination of existing medicines such as antiplatelet regimens and anticoagulants as an antithrombotic therapy or as prophylaxis in different patient settings, either in ICU- or inpatient- or outpatient-settings. There are many reports showing that platelets may play a role in the pathophysiology of thrombotic complications associated with COVID-19. The balance between bleeding and antithrombotic effects is always a problem. I am really curious to see what the trials with antiplatelet agents will show. For example, if you take the P2Y12 inhibitors that are currently being tested, especially ticagrelor, we know that it has some remarkable anti-inflammatory properties in addition to its antiplatelet effect. This has already been shown in patients with pneumonia in intensive care units. So, I really wonder what this could mean in the treatment of COVID-19. My guess is that this research could open up new therapeutic pathways regarding prophylaxis.”