Our findings identified that 16.67% of patients with COVID-19 were at high risk for VTE according to Padua prediction score, and 6.52% of patients were at high risk of bleeding for VTE prophylaxis according to Improve prediction score. The prediction risk of VTE (6.5%), as well as the incidence of VTE (0.8%), was low in non-critically patients. However, critically ill patients faced double high risk from thrombosis (Padua score more than 4 points in 100% of critically ill patients) and hemorrhage (Improve score more than 7 points in 60.0% of critically ill patients). Furthermore, we identified a high incidence of VTE (20.0%) in critically ill patients with COVID-19,despite the use of universal, guideline-recommended thromboprophylaxis. Critically ill patients suffered a marked incidence of bleeding (26.7%), which suggested a complicated situation in VTE prophylaxis to COVID-19.
As described, there are several reasons for high risk of VTE in critically ill patients with COVID-19. On the one hand, critically ill population in our findings had three qualities in physiology, including: venous stasis due to sedation or bedridden, hypercoagulability caused by glucocorticoid and immunoglobulins, and endothelial damage from central venous catheterization and/or ECMO. On the other hand, a significant number of COVID-19 patients, especially critically ill ones, were the aged(1) who were easy to complicate with VTE high risk factors, such as heart failure, stroke, cancer and diabetes. In addition, critically ill patients had a higher level of D-dimer compared to non-critically one(5), which might be associated with hypercoagulability induced by coronavirus. All these factors increased the risk of developing potentially deadly blood clots.
The COVID-19 patients, especially critically ill ones, should pay attention to high risk of bleeding during thromboprophylaxis. Older Age is the high-risk factors of both thrombosis and hemorrhage(11, 12). Nearly 70% of patients in our study had age-related bleeding risk. Besides age, coexisting medical conditions, including tumors, renal or liver failure, hypertension, and diabetes, brought the risk of bleeding in our patients. Moreover, some Invasive treatment increased the bleeding risk, especially ECMO which widely used in critically ill patients(13).
Our findings confirmed four patients with VTE complications. That did not mean the rate of VTE complications occurring in COVID-19 patients was low. More likely, it was the consequence of effective thromboprophylaxis in patients classified as being at high risk of thrombosis. The high incidence of VTE in critically ill patients of COVID-19 despite the universal use of guideline-recommended VTE prophylaxis was similar to sepsis(14) but markedly higher than published reports in critically ill patients without sepsis(15, 16), suggesting that dysregulated hemostasis and coagulation in severe COVID-19.
Notably, both VTE complications and major bleeding events occurred in critically ill patients. Hence, routine thromboprophylaxis was provided to critically ill patients based on an individual assessment of their thrombosis and bleeding risks in our study. For critically ill patients with extremely high levels of D-dimer and FDP associated with pulmonary microthrombosis, heparin was recommended. For those at a very high risk of bleeding, mechanical prophylaxis was instituted(17). For those used ECMO, better control of the aPTT (through better control of either coagulopathy or anticoagulation) was essential(18).
This study has several limitations. First, a small population were included in this study. We hope that the findings presented here will encourage a larger cohort study. Second, among the 138 cases, some of the patients are still hospitalized at the time of manuscript submission. Therefore, it is difficult to assess the exact incidence of VTE and major bleeding events, and continued observations are needed. Third, this is a retrospective study. The data in this study permit a preliminary assessment of VTE and bleeding risk of patients with COVID-19. Further prospective studies need to determine the exact incidence of VTE among these patients and focus on thromboprophylaxis.
In conclusion, critically ill patients with COVID-19 suffered both high risk of thrombosis and bleeding risks. However, the prediction risk of VTE and major bleeding was low in non-critically patients. More effective VTE prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.