key: cord-0990579-z8ead35v authors: García-Ceberino, Pedro M.; Faro-Míguez, Naya; Beltrán-Ávila, Francisco Javier; Fernández-Reyes, Daniel; Gallardo-Muñoz, Inmaculada; Guirao-Arrabal, Emilio title: Point of care ultrasoud (POCUS) in diagnosis of proximal deep vein thrombosis among COVID-19 hospitalized patients with a high rate of low molecular weight heparin prophylaxis date: 2021-02-27 journal: Med Clin (Barc) DOI: 10.1016/j.medcli.2021.01.012 sha: 5b7d3d0d1aa8060899e9904bfd0763d98b0f9f64 doc_id: 990579 cord_uid: z8ead35v Background: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are both complications linked with COVID-19. Lower limb point-of-care clinical ultrasound (POCUS) could detect occult clots, helping decide whom to treat with anticoagulation. Objectives: To determine proximal DVT prevalence with POCUS screening among hospitalized COVID-19 patients. Patients/Methods: Lower limb POCUS was performed in all patients admitted either to the ward or intensive care unit (ICU) between April 22th and 30th 2020. Clinical and laboratory features, prescriptions, thrombotic complications and outcomes were assessed. Results: 87 patients were screened, of which 26 (29.8%) either had been discharged from ICU (19.5%) or were still in critical condition (10.3%). DVT was found in 4 patients (3 femoral, 1 popliteal), of which 1 had not received low molecular weight heparin (LMWH) prophylaxis. 21 CT pulmonary angiograms were performed, being positive for PE in 5 cases (23.8%); only 2 of these patients suffered DVT. Conclusions: Screening lower extremities with POCUS did not find a high rate of DVT among patients receiving LMWH-prophylaxis. However, there was a noteworthy amount of PE without DVT. Results: 87 patients were screened, of which 26 (29.8%) either had been discharged from ICU (19.5%) or were still in critical condition (10.3%). DVT was found in 4 patients (3 femoral, 1 popliteal), of which 1 had not received low molecular weight heparin (LMWH) prophylaxis. 21 CT pulmonary angiograms were performed, being positive for PE in 5 cases (23.8%); only 2 of these patients suffered DVT. Screening lower extremities with POCUS did not find a high rate of DVT among patients receiving LMWH-prophylaxis. However, there was a noteworthy amount of PE without DVT. Antecedentes: La trombosis venosa profunda (TVP) y la embolia pulmonar (EP) son complicaciones relacionadas con la COVID-19. La ecografía clínica en el punto de atención de las extremidades inferiores (POCUS) podría detectar coágulos ocultos, ayudando a decidir a quién tratar con anticoagulación. Conclusiones: El cribado de las extremidades inferiores con POCUS no encontró una tasa elevada de TVP entre los pacientes que recibían profilaxis con HBPM. Sin embargo, hubo una cantidad notable de EP sin TVP. Palabras clave: COVID-19; Trombosis venosa profunda; Heparina de bajo peso molecular; Embolia pulmonar; Ecografía. Coronavirus disease-2019 (COVID-19) pneumonia may increase events such as venous thrombosis (VT) 1,2 . Different research has been conducted to prove an increase of deep vein thrombosis (DVT) and pulmonary embolism (PE) prevalence in those patients admitted to the hospital, despite proper prophylaxis. Additionally, there seems to be a gap between deep venous thrombosis (DVT) and pulmonary embolism (PE), being the former higher 3, 4 . It has been hypothesized that this difference is due to local inflammation, known as endotheliitis, which lead to the formation of thrombi without distal embolism 5 . Following the hypothesis, COVID-19 disease is associated with elevated Ddimer values. In fact, higher levels of D-dimer lead to a poorer prognosis 6 . Moreover, there is a special concern in determining which D-dimer level could predict thrombotic phenomena 7 . Screening lower extremities with an ultrasound exam is an option to detect clots. The use of point-of-care ultrasound (POCUS) by properly trained physicians is highly accurate and an alternative option, especially when the critical situation of many patients dramatically limits feasibility of performing CT pulmonary angiogram (CTPA) to diagnose PE. To determine proximal deep vein thrombosis prevalence with POCUS screening among hospitalized COVID-19 patients. We performed an observational retrospective study conducted at a hospital in Granada, Spain. The inclusion criteria were: patients older than 18 years with a confirmed diagnosis of COVID-19 pneumonia who were hospitalized either in the general ward or ICU. Diagnosis of COVID-19 pneumonia was defined as a positive reverse transcription polymerase chain reaction (RT-PCR) test in either nasopharyngeal swab or sputum sample along with radiological findings consistent with pneumonia. No exclusion criteria were made on the basis of median hospital stay, clinical or analytical features. Patients' data were collected through their electronic health record (EHR). These consisted of baseline characteristics (mainly those predisposing for VT), analytical features (maximum values of D-dimer, C protein reactive (CPR) and ferritin), clinical factors related either to COVID-19 (time length from symptoms onset to admission, disease severity and complications, use of immunosuppressive therapy [IST], use of LMWH prophylaxis schedule or other anticoagulant therapy) or to VT and its diagnosis. Clinical severity was categorized as mild, moderate, severe and critical, depending on the category achieved during the admission, according the Handbook of COVID-19 of Zhejiang University School of Medicine. Lower extremity ultrasound (US) was performed in all patients admitted to our hospital due to COVID-19 between April 22th and 30th 2020 by Internal Medicine specialists trained in POCUS alongside with a radiologist who carried out the exams in all ICU patients and some ward patients in case of discordant findings. The ultrasound device used was a Sonosite X-Porte with a linear probe. The exams were performed at bedside, using a 2-point technique consisting of assessing compressibility of common femoral vein (CFV) and popliteal vein (PV) in search for clots. Additionally, we reviewed the CTPA performed according to physician criteria among our patient series in order to rule out PE. Categorical variables were presented as frequency and percentage. Continuous quantitative variables were presented whether as mean and its standard deviation (SD) in the case of normal distribution or as median and interquartile range (IQR) otherwise. For comparison, either the Student's t test or the Mann-Whitney U test were performed according to the normality of the variable. * IBM SPSS statistics software version 20.0 (IBM, Chicago, IL, USA) was used for all calculations. Borrado: A two-tailed alpha error of less than 0.05 was considered statistically significant. Our patients' baseline features are summarized at Table 1 . Eighty-seven (87) patients were included. At least one baseline risk factor for thrombosis was found in 14.9% of patients, apart from immobilization. Precisely 17.2% were on anticoagulant therapy prior to admission. At the time the screening was conducted, 9 (10.3%) were still in critical condition being at the ICU, and 17 patients (19.5%) had previously been there. As seen in Table 2 , DVT was found in 4 (4.6%) asymptomatic patients: 3 femoral and 1 popliteal location. Among these cases, 3 of them took place despite the use of any kind of prophylaxis strategy or anticoagulant dose. All of them had VT risk factors apart from COVID-19. Median time from the onset of symptoms and hospital admission to US screening resulted in 19.2 (+/-11.3) and 24.6 (+/-13.1) days each. CTPA was performed according to physician criteria in 21 patients in order to rule out PE, being detected in 5 cases (23.8%). There were 2 (40%) patients with PE who had concomitant DVT in lower limbs. All patients with PE were classified either as clinically severe or critical (40% and 60%) previously to the finding. Among the 26 ICU patients, 3 (11.6%) of them suffered PE. Globally, prevalence obtained for VT (DVT and PE) in our study was 8.1%. Separately, prevalence in critical care unit reached 15.4%, while at ward the rate was 4.9%. The main characteristics of those patients (VT) are shown in Table 3 . Within them, we found a higher rate of patients admitted to ICU (57% in VT group vs 27.5% in non-VT group). Patients in the VT group were found to have higher maximum D-dimer values: median 11.18 (IQR 7.38-22.00) mg/L vs. 3.37 (IQR 1.20-12.62) mg/L in the non-VT group. * No other differences were observed in the rest of the analytical parameters. Borrado p=0.034. Heparin prophylactic doses were titrated according to centre protocols. Most subjects (62.1%) received LMWH standard doses; 3500 international units (IU) of bemiparin daily. A group of patients (13.8%) received intermediate doses (5000 IU bemiparin daily). Up to 19 patients (21.8%) received anticoagulant LMWH doses because of previous indications and only 3 (3.4%) did not receive any LMWH scheme at all. Seven (7, 8%) bleeding events were found among our patients, yet only two of them were major haemorrhages. While DVT prevalence in a general inpatient setting has been a controversial topic, some series point out that DVT prevalence might be increased in the course of COVID-19 1-4 . Moreover, it appears to be clear that DVT prevalence will be higher when LMWH-prophylaxis is obviated 2 or distal DVT is considered 8 . The results in our study seem to reveal that proximal DVT prevalence in admitted patients with COVID-19 (4.6%) is similar to that found previously in other series, provided LMWH-prophylaxis is prescribed [8] [9] [10] . The prevalence of PE events in patients infected with SARS-COV-2 has been suggested to be increased, showing a gap between PE and DVT prevalence 3,4,7,9 . Our results (5.7% PE in all patients) show a similar trend, nonetheless only 21 CTPA (24.1%) were performed globally. Among our 5 patients who had PE, only 2 of them were detected to have DVT at the same time. Being known that COVID-19 disease is associated with elevated D-dimer values among hospitalized patients, our results show higher levels in the VT group, seeming to be at great use to predict thrombotic phenomena among COVID-19 patients 7, 8 . Antithrombotic prophylaxis among COVID-19 hospitalized patients is widely recommended. Up to 96.6% of our patients received some kind of antithrombotic scheme. Among the 3 patients who did not, 2 thrombotic events were found. The use of higher doses of HBPM are yet to be established 10 . In our study DVT screening was performed long after COVID-19 symptoms onset (24.6 days) and patients' admission (19.3 days). Therefore, chances of missing events that could be developed in the latest days of admission were considerably reduced. POCUS is a helpful tool detecting DVT in COVID-19 patients. Our series found a DVT prevalence of 4.6%. However, the absence of DTV did not exclude the presence of PE. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19 Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence Incidence of venous thromboembolism in hospitalized patients with COVID-19 Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to D-Dimer Levels Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated Ddimer levels Incidence of thrombotic complications in critically ill ICU patients with COVID-19 Pulmonary Embolism or Pulmonary Thrombosis in COVID-19? Is the Recommendation to Use High-Dose Heparin for Thromboprophylaxis Justified?