Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia

Abstract

Background Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. Methods This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. Results In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). Conclusion Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

Pulmonary embolism in COVID-19, risk factors and association with inflammatory biomarkers

“…In contrast, Ronaldo and colleagues found an increase in VTE in individuals on steroids in their study. [25] The limitations of our study as a retrospective observational design are evident. We only looked at VTE and not COVID-19 related arterial thrombotic events such as myocardial infarctions or strokes.…”

“…In contrast, Ronaldo and colleagues found an increase in VTE in individuals on steroids in their study. [25]…”

Persistent Hypoxemia and Biomarkers in Severe COVID-19 Pneumonia Patients Treated with Methylprednisolone

“…Chronicity of corticosteroids is also associated with elevated levels of procoagulant factors. (22,35) Cushing's syndrome is a disease of excess endogenous glucocorticoids and it's associated with elevated levels of Factor VIII, Factor IX, and von Willebrand Factor (vWF). (36, 37) One in-vitro study suggested that exogenous corticosteroids increase synthesis of vWF and plasminogen-activator-1 (PAI-1).…”