965:  Predicting factors for pulmonary embolism in non-critically ill COVID-19 patients - D Dimer > 5000

A Spanish study published in the Journal of Thrombosis and Thrombolysis has reported a high rate of pulmonary embolism (PE) in non-critically ill hospitalized patients with COVID-19 despite the use of standard thromboprophylaxis. B. Mestre-Gómez, Internal Medicine Department, Infanta Leonor University Hospital, Madrid, Spain, and colleagues stated that they had found 29 patients with established PE and COVID-19 pneumonia out of 91 CTPA (computed tomography pulmonary angiography tests) performed among 452 patients admitted over the study period. This points to an incidence of 6.4% in a medical ward and one-third of positive CTPA despite prophylactic doses of LMWH (low-molecular-weight heparin).

Investigators further stated that an increase in D-dimer levels is a potential predictor of PE, with a best cut-off point of >5,000 µg/dL.

The single cohort, longitudinal study assessed patients admitted with COVID-19 diagnosis to the internal medicine department of a secondary hospital in Madrid from March 30 through April 12, 2020. A retrospective review of 452 electronic medical records was done, to assess the cumulative incidence of PE, and associated risk factors. Ninety one patients who underwent a multidetector CTPA during conventional hospitalization were included in the study.

Of the 91 CT scans, 29 patients (31.9%) were diagnosed with acute PE, while the cumulative incidence over the entire cohort was 6.4% (29/452 patients). Among the PE patients, 23 were found to have COVID-19 infection via RT-PCR positive tests, and 6 had positive CT scans and negative RT-PCR.

Among the PE patients, 72% (21/29) 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 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 appeared to be no associated coagulopathy, with a prothrombin time of 12.5 seconds (Q1-Q3: 11.9–13.5). Most of the PE patients were given LMWH (79.3%; 23/29) at prophylactic doses at the time of diagnosis of PE.

Nearly 51.7% of PE cases were bilateral (15/29 patients) and 48.3% unilateral. Most PEs were noted 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).

It was noted that D-dimer peak was significantly elevated in the PE patients (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).

A multivariate analysis of patients subjected to a CTPA suggested that plasma D-dimer peak independently predicted PE with a best cut off point of > 5,000 µg/dL (OR 3.77; IC95% (1.18–12.16), p = 0.03).

There were statistically significant differences between the two groups for history of dyslipidemia [10.7%, (3/29) in PE patients vs. 40.3% (25/62) in non-PE patients, p = 0.003], and for history of autoimmune disease [10.7% (3/29) vs. 0% (0/62), p = 0.03)].

Investigators stated that the history of dyslipidemia appeared to be a protector factor for PE in the multivariate analysis. Patients who did not have this cardiovascular risk in their records, were found to have a nine times increased risk for PE compared to those with dyslipidemia (OR 9.06; IC95% (1.88–43.60). It seems possible that patients previously treated with statins had a potential benefit either by their immunomodulatory action or by preventing cardiovascular damage.

No statistical differences were noted in either mortality or admission to the intensive care unit (ICU) between the PE and non-PE groups in this cohort of non-critically ill COVID 19 patients.

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 does not seem to be accurate to predict PE in such a challenging context, according to the authors.

Additionally, there was no difference in severity of pneumonia by CURB-65 score. Furthermore, no statistical difference was evident in inflammation parameters (high in both groups), treatment or need of non-invasive ventilation; however, the figures are higher for non PE group.

The actual presence of PE on CT was not found to be linked with mortality in this small sample.

[SOURCE: DG Alerts; Journal of Thrombosis and Thrombolysis]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA