A Spanish study published in the Journal of Thrombosis and Thrombolysis reported a high rate of pulmonary embolism (PE) in non-critically ill hospitalised patients with coronavirus disease 2019 (COVID-19) despite use of standard thromboprophylaxis.
B. Mestre-Gómez, Internal Medicine Department, Infanta Leonor University Hospital, Madrid, Spain, and colleagues said “we found 29 patients with proven PE and COVID-19 pneumonia out of 91 CTPA (computed tomography pulmonary angiography tests) performed among the 452 patients admitted in the study period. That represents an incidence of 6.4% in a medical ward and one third of positive CTPA despite prophylactic doses of LMWH (low-molecular-weight heparin).”
They added that an increase in D-dimer levels is a good predicting factor of PE, with a best cut-off point of > 5,000 µg/dL.
The single cohort, longitudinal study focused on patients admitted with COVID-19 diagnosis to the internal medicine department of a secondary hospital in Madrid between March 30 and April 12, 2020. Investigators retrospectively reviewed 452 electronic medical records, analyzing the cumulative incidence of PE, and associated risk factors. Included were 91 patients who underwent a multidetector CTPA during conventional hospitalization.
Of the 91 CT scans performed, 29 patients (31.9%) were diagnosed with acute PE, while the cumulative incidence over the entire cohort was 6.4% (29/452 patients). Among these PE patients, 23 were classified as COVID-19 infection via RT-PCR positive tests, and 6 had positive CT scans and negative RT-PCR.
In the PE group, 72% (21/29) of patients were male and the median age was 65 years (IQ 1–3: 56–73), while median body mass index was 28.8 kg/m2 (IQ 1–3:26.8–31.8). Median plasma D-dimer peak was 14,480 µg/dL (IQ 1–3: 5,540–33,170 µg/dL), median platelet counts were 137 × 103 (IQ 1–3: 248–260 × 103), median C-reactive protein 110.6 mg/dL (Q1-3: 40–193) and median ferritin 829 ng/mL (Q1-3: 387–1272). There was no associated coagulopathy, with a prothrombin time of 12.5 seconds (Q1-Q3: 11.9–13.5). Most of the PE patients received LMWH (79.3%; 23/29) at prophylactic doses at the time of diagnosis of PE.
Regarding radiological findings, 51.7% of PE cases were bilateral (15/29 patients) and 48.3% unilateral. Most PEs were in a peripheral location in segmental and sub-segmental arteries (68.9%, 20/29 patients) and 31.0% (9/29 patients) in a central location (main and lobar arteries).
When comparing PE and non-PE patients, D-dimer peak was found to be significantly elevated in the PE group (median 14,480 µg/dL, IQR 5,540–33,170) compared to patients without PE (7,230 µg/dL, IQR 2,100- 16,415, p = 0.03). According to the authors, a multivariate analysis of patients who underwent a CTPA indicated that plasma D-dimer peak was an independent predictor of PE with a best cut off point of > 5,000 µg/dL (OR 3.77; IC95% (1.18–12.16), p = 0.03).
Statistically significant differences were also found between the two groups for history of dyslipidemia [10.7%, (3/29) in PE patients versus 40.3% (25/62) in non-PE patients, p = 0.003], as well as for history of autoimmune disease [10.7% (3/29) versus 0% (0/62), p = 0.03)].
“Interestingly, we found the history of dyslipidemia as a protector factor for PE in the multivariate analysis. Patients who did not have this cardiovascular risk in their medical records, had a nine-fold increased risk for PE compared to those with dyslipidemia (OR 9.06; IC95% (1.88–43.60). A possible explanation could be that patients previously treated with statins had a potential benefit either by their immunomodulatory action or by preventing cardiovascular damage,” the authors said, adding “ongoing trials with statins will offer evidence in this area.”
Meanwhile, there were no statistical differences in either mortality or admission to the intensive care unit (ICU) between the PE and non-PE arms in this cohort of non-critically ill COVID 19 patients.
“In our study the absence of classic risk factor for venous thromboembolism (advanced age, history of thrombosis, thrombophilia, cancer and ICU admission) and the peripherical localization of PE suggest microthrombosis in situ. Wells index seems not to be accurate to predict PE in such a challenging context,” the authors said.
“There was no difference in severity of pneumonia by CURB-65 score, also [no statistical] difference in inflammation parameters (high in both groups), treatment or need of non-invasive ventilation, although figures are higher for non PE group. Importantly, the actual presence of PE on CT was not associated with mortality in this small sample,” the authors noted.
They indicated that the main limitations of the study are its observational and retrospective nature, as well as small sample size. Another limitation was the practical absence of screening of deep vein thrombosis in legs. “Randomized controlled trials on venous thromboembolism prevention will help to optimize therapeutic strategies,” the authors noted.