Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning

Saeed Mirsadraee, MD, PhD, FRCR, FRCPE; Diana A. Gorog, MD, PhD, FRCP; Ciara F. Mahon, BCh, BAO, MSc, MRCP; Bhavin Rawal, MBBS, FRCR; Thomas R. Semple, FRCR; Edward D. Nicol, MD, FRCP, FRCR; Deepa R. J. Arachchillage, MD, MRCP, FRCPath; Anand Devaraj, MD, FRCR; Susanna Price, PhD, FRCP; Sujal R. Desai, MD, FRCR, FRCP; Carole A. Ridge, FFRRCSI; Suveer Singh, MD, PHD; Simon P. G. Padley, MBBS, FRCR

Disclosures

Crit Care Med. 2021;49(5):804-815. 

In This Article

Results

Patient Cohort

Seventy-two patients with COVID-19 were admitted to our ICU for advanced respiratory support during the study period (March 19, 2020, to June 23, 2020). The baseline clinical characteristics are shown in Table 1. Baseline biochemical and hematological data are shown in Table 2 and Table 3.

Twenty-four patients (33%) had one CECT, 31 (43%) had two, 12 (17%) had three, and 5 (7%) had four scans. Sixty-one patients (85%) had at least one unenhanced CT of head. Systemic or pulmonary arterial thrombus or systemic venous thrombosis was diagnosed on the first CECT in 34 of 45 patients (76%) and on subsequent CECT in the remaining 11 patients. Thrombus was detected on CECT in 53% of patients within the first 3 days of arrival to ICU. Thrombus was detected on CECT in 38 patients (53%) within the first 3 days of arrival to ICU. The median time from the onset of disease and hospital admission to the diagnosis of thrombosis was 15 days (3–48 d) and 9 days (0–36 d). The time from hospital admission to first CT scan in patients with and without thrombus was 7.8 ± 6.8 and 7.1 ± 5.9 days, respectively (p = 0.701). The time from intubation and ventilation to first CT scan in patients with and without thrombus was 6 ± 6.3 and 6.1 ± 5.3 days, respectively (p = 0.896). Ninety-three percent of pulmonary thromboses (31/34) were identified on the first CECT with the remainder identified on follow-up CECT, requested due to poor clinical response. The mean time interval between the onset of symptoms and from admission to our ICU and the final status (discharged alive or death) was 41 days (± 20 d) and 32 days (± 18 d), respectively. Fifty-five patients (76%) survived and were discharged, 17 (24%) died as at 23 June 2020 (Table 4).

The biomarkers, outcomes, and the LOS in patients receiving ECMO are summarized in Supplementary Table 1 (https://links.lww.com/CCM/G184) and Supplementary Table 2 (https://links.lww.com/CCM/G185). The hematological and biochemical profiles of these patients at admission to ICU were similar, with the exception of fibrinogen that was higher and CRP that was lower in patients on ECMO. The prevalence of venous and arterial thrombotic complications was not significantly different among patients on ECMO compared with those patients who did not require ECMO (63% vs 54%; p = 0.695).

Thrombotic Complications

Examples of thrombotic complications are shown in Figure 1. Apart from one patient with evidence of intracranial hemorrhage, all received UFH if the patient was on ECMO. The prevalence of thrombotic complications was 54 in 42 of 72 patients (58%). Venous thrombosis was observed in 15 patients (21%) of whom 11 (73%) had thrombus in the iliac or femoral veins, and portal vein in one patient. There was evidence of head and neck vein thrombosis in four patients (27%). Thrombus was associated with a venous catheter in six patients.

Figure 1.

Examples of thrombotic complications in patients with coronavirus disease 2019 admitted to ICU. A, Large thrombus in the left lower lobe pulmonary artery (thick arrow) with wedge shape reduced lung attenuation indicating reduced perfusion (small arrows). B, Segmental thrombus (thick arrow) in the right lower lobe with visible reduced lung perfusion (small arrows). C, New watershed ischemic lesions (small arrows). D, Multiple splenic infarctions (small arrows). E, Thrombus in the right iliac vein (arrow) with cannula in the opposite side vein.

Pulmonary artery thromboembolism was observed in 34 patients (47%), 12 (35%) of whom had thrombi in the main pulmonary artery and/or the proximal branches, while in the remaining 22 (65%) patients, thrombi were only visualized in the segmental and subsegmental pulmonary artery branches. Of the 34 patients with pulmonary artery thrombosis, 27 (77%) did not have radiological evidence of peripheral deep venous thrombosis. Of 15 patients with deep venous thrombosis, seven (47%) had no CT evidence of pulmonary artery thrombosis.

Arterial thrombosis and/or systemic embolism were observed in five patients (7%). Aortic macrothrombosis was present in two patients. Embolic ischemic changes were observed in five patients (splenic infarction, n = 2; bowel ischemia, n = 1; ischemic stroke, n = 2; and renal ischemia, n = 1). All patients with arterial thrombosis also had pulmonary thrombosis, but none had peripheral venous thrombosis. Intracerebral hemorrhage was present in two patients. There was no difference in the mean length of ICU stay in patients with and without thrombotic complications (32 ± 18 vs 31 ± 15 d, respectively [p > 0.53]; Table 4). Patients with thrombotic complications were more likely to die, and patients without thrombotic complications were more likely to be discharged alive (p = 0.022; Table 4). There was no significant difference in LOS in patients with or without ECMO (p = 0.546) and in those with or without thrombosis (p = 0.53) (Table 4; and Supplementary Table 2, https://links.lww.com/CCM/G185). From 20 cases on ECMO and imaging evidence of thrombotic complications, thrombosis was detected in 14 patients (70%) on the admission CT scan, immediately before or after the ECMO initiation. In six patients, the mean time from ECMO to the detection of thrombosis was 9 days (+4 d; 3–14 d). This indicates that in a significant number of cases, the thrombosis was likely present prior to ECMO initiation. In the other 30%, thrombosis occurred later and despite full anticoagulation.

Relation of Clinical Characteristics and Biomarkers to Thrombotic Complications

Specific demographics (i.e., male gender, non-Caucasian ethnicity, history of hypertension, and diabetes) were not associated with a higher risk of thrombotic complications (Table 1). The following biomarkers on ICU admission were interrogated for their relationship to subsequent thrombotic complications: D-dimer (with or without age-adjustment), aPTT, international normalized ratio, platelet count, WBC count, lymphocyte count, hs-CRP, and fibrinogen (Table 2 and Table 3). None of these variables alone, or in univariate analysis, or in combination as part of multivariate analysis, was predictive of thrombotic complications.

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