Management, control, and decision making in unexpected recurrent venous thromboembolism in COVID-19: a case report.

BACKGROUND: Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance. CASE REPORT: A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3). CONCLUSION: In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

Screening Protocol and Prevalence of Venous Thromboembolic Disease in Hospitalized Patients With COVID-19.

BACKGROUND: SARS-CoV-2 disease (COVID-19) induces endothelial damage and sustained hypoxia and facilitates immobilization as factors of hypercoagulability. OBJECTIVES: The objective of our study was to assess the prevalence of venous thromboembolic disease (VTD) in COVID-19 patients and the usefulness of VTD screening based on age-adjusted D-dimer and point-of-care ultrasound (POCUS). PATIENTS/METHODS: We conducted a single cohort, prospective observational study in 102 consecutive hospitalized patients. RESULTS: A total of 102 POCUS and 39 pulmonary computed tomography angiography (PCTA) were performed diagnosing 27 VTD (26.5%): 17 deep vein thrombosis (DVT) (16.6% positive POCUS) and 18 pulmonary embolism (PE) (46.2% positive PCTA). COVID-19 patients with VTD were older (P < .030), had higher D-dimer (P < .001), higher International Society on Thrombosis and Hemostasis score (P < .001), and higher mortality (P = .025). However, there were no differences in inflammatory laboratory parameters neither in the cytokine storm syndrome (CSS) development. The ROC curve for D-dimer showed an AUC of 0.91. We have evidenced that patients with D-dimer between 2000 and 6000 ng/mL could benefit from a screening strategy with POCUS given the high sensitivity and specificity of the test. Furthermore, patients with D-dimer ≥6000 ng/mL should undergo POCUS and PCTA to rule out DVT and PE, respectively. CONCLUSIONS: In our cohort, 26.5% of the patients presented VTD. Screening strategy based on age-adjusted D-dimer and POCUS proved high sensitivity and specificity. Future trials focused on screening strategies are necessary to early detect the presence of DVT and PE and determine thromboprophylaxis strategies in patients with COVID-19.

Pulmonary embolus in patients with COVID-19: an Australian perspective.

Pulmonary embolus (PE) is a known complication of coronavirus disease 2019 (COVID-19). The diagnosis of PE in our hospitalised patients with COVID-19 correlated with more severe disease and occurred despite the use of routine thromboprophylaxis. Higher D-dimers were seen on admission in patients who developed PE and rose at PE diagnosis, suggesting a role for D-dimer in risk stratification.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PURPOSE: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). METHODS: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). RESULTS: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. CONCLUSION: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. GOV ID: NCT04377035.

Clinical-radiological correlations in COVID-19-related venous thromboembolism: Preliminary results from a multidisciplinary study.

INTRODUCTION: Among the multiple complex pathophysiological mechanisms underlying COVID-19 pneumonia, immunothrombosis has been shown to play a key role. One of the most dangerous consequences of the prothrombotic imbalance is the increased incidence of micro- and macrothrombotic phenomena, especially deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: We investigated the correlation between radiological and clinical-biochemical characteristics in a cohort of hospitalised COVID-19 patients. RESULTS: PE was confirmed in 14/61 (23%) patients, five (35.7%) had DVT. The radiographic findings, quantified by Qanadli score calculated on CT angiography, correlated with the clinical score and biochemical markers. The ratio between the right and left ventricle diameter measured at CT angiography correlated with the length of hospital stay. CONCLUSION: In our cohort radiological parameters showed a significant correlation with clinical prognostic indices and scores, thus suggesting that a multidisciplinary approach is advisable in the evaluation of PE in COVID-19 patients.

High prevalence of occult thrombosis in cases of mild/moderate COVID-19.

BACKGROUND AND PURPOSE: An increasing number of reports have observed thrombosis in severe cases of COVID-19. The aim of this study was to evaluate the incidence of thromboembolism in mild/moderate cases of COVID-19. All of the patients had normal coagulation tests and none had any overt thrombotic complications. Our findings indicate that it is important to screen the thrombotic status of cases with mild/moderate COVID-19. METHODS: Between 11 June and 8 July 2020, 23 patients with mild/moderate COVID-19 pneumonia consented to having computed tomography pulmonary angiography (CPTA) and computed tomography venography (CTV) scans of the lungs and extremity veins. Doppler ultrasound (DUS) was also performed in all patients for screening. The incidence, clinical manifestations, laboratory examinations, imaging features, and prognosis, of patients with venous thromboembolism (VTE) were analyzed and compared with those of patients with COVID-19 pneumonia without VTE. RESULTS: Nineteen patients (82.6%) had VTE, mainly distal limb thrombosis. Only one of the VTE patients was positive when screened by DUS; the other VTE patients were negative by DUS. All of the mild/moderate patients with VTE were screened by CTPA + CTV. Blood tests for inflammatory, coagulation, and biochemical, parameters were all within the normal range, except for WBC and LDH. CONCLUSIONS: When using CTV screening for DVT, we found that the incidence of thrombosis in patients with mild/moderate COVID-19 markedly increased to 82.6% (19/23). Screening for thrombosis is therefore important in patients with COVID-19. CTV is more sensitive than DUS for the detection of thrombosis. More research is now needed to evaluate the significance of thrombosis in COVID-19 pneumonia.

Impact of COVID-19 on the Society for Vascular Surgery Vascular Quality Initiative Venous Procedure Registries (varicose vein and inferior vena cava filter).

In response to the pandemic, an abrupt pivot of Vascular Quality Initiative physician members away from standard clinical practice to a restrictive phase of emergent and urgent vascular procedures occurred. The Society for Vascular Surgery Patient Safety Organization queried both data managers and physicians in May 2020. Approximately three-fourths (74%) of physicians adopted restrictive operating policies for urgent and emergent cases only, whereas one-half proceeded with "time sensitive" elective cases as urgent. Data manager case entry was negatively affected by both low case volumes and staffing due to reassignment or furlough. Venous registry volumes were reduced fivefold in the first quarter of 2020 compared with a similar period in 2019. The consequences of delaying vascular procedures for ambulatory venous practice remain unknown with increased morbidity likely. Challenges to determine venous thromboembolism mortality impact exist given difficulty in verifying "in home and extended care facility" deaths. Further ramifications of a pandemic shutdown will likely be amplified if postponement of elective vascular care extends beyond a short window of time. It will be important to monitor disease progression and case severity as a result of policy shifts adopted locally in response to pandemic surges.

Pulmonary thromboembolism in coronavirus disease 2019 patients undergoing thromboprophylaxis.

ABSTRACT: We aimed to investigate the prevalence of pulmonary thromboembolism (PTE) and its association with clinical variables in a cohort of hospitalized coronavirus disease 2019 (COVID-19) patients receiving low-molecular-weight heparin (LMWH) at prophylactic dosage.In this retrospective observational study we included COVID-19 patients receiving prophylactic LMWH from admission but still referred for lower-limbs venous Doppler ultrasound (LL-US) and computed tomography pulmonary angiography (CTPA) for clinical PTE suspicion. A dedicated radiologist reviewed CTPA images to assess PTE presence/extension.From March 1 to April 30, 2020, 45 patients were included (34 men, median age 67 years, interquartile range [IQR] 60-76). Twenty-seven (60%) had PTE signs at CTPA, 17/27 (63%) with bilateral involvement, none with main branch PTE. In 33/45 patients (73%) patients LL-US was performed before CTPA, with 3 patients having superficial vein thrombosis (9%, none with CTPA-confirmed PTE) and 1 patient having deep vein thrombosis (3%, with CTPA-confirmed PTE). Thirty-three patients (73%) had at least one comorbidity, mainly hypertension (23/45, 51%) and cardiovascular disease (15/45, 33%). Before CTPA, 5 patients had high D-dimer (11.21 µg/mL, IQR 9.10-13.02), 19 high fibrinogen (550 mg/dL, IQR 476-590), 26 high interleukin-6 (79 pg/mL, IQR 31-282), and 11 high C-reactive protein (9.60 mg/dL, IQR 6.75-10.65), C-reactive protein being the only laboratory parameter significantly differing between patients with and without PTE (P = .002)High PTE incidence (60%) in COVID-19 hospitalized patients under prophylactic LMWH could substantiate further tailoring of anticoagulation therapy.

Extensive Arterial Thrombus Following Discharge after a Covid-19 Infection.

The novel coronavirus pandemic is associated with coagulopathy and an increased risk of thromboembolic events. A case of an extensive arterial thrombus in the left leg of a patient that occurred after discharge from Covid-19 pneumonia is described. Some patients may be under continued risk of thromboembolism after discharge and the value of extended thromboprophylaxis should be investigated.

Computed tomography characterization and outcome evaluation of COVID-19 pneumonia complicated by venous thromboembolism.

BACKGROUND: COVID-19 is frequently complicated by venous thromboembolism (VTE). Computed tomography (CT) of the chest-primarily usually conducted as low-dose, non-contrast enhanced CT-plays an important role in the diagnosis and follow-up of COVID-19 pneumonia. Performed as contrast-enhanced CT pulmonary angiography, it can reliably detect or rule-out pulmonary embolism (PE). Several imaging characteristics of COVID-19 pneumonia have been described for chest CT, but no study evaluated CT findings in the context of VTE/PE. PURPOSE: In our retrospective study, we analyzed clinical, laboratory and CT imaging characteristics of 50 consecutive patients with RT-PCR proven COVID-19 pneumonia who underwent contrast-enhanced chest CT at two tertiary care medical centers. MATERIAL AND METHODS: All patients with RT-PCR proven COVID-19 pneumonia and contrast-enhanced chest CT performed at two tertiary care hospitals between March 1st and April 20th 2020 were retrospectively identified. Patient characteristics (age, gender, comorbidities), symptoms, date of symptom onset, RT-PCR results, imaging results of CT and leg ultrasound, laboratory findings (C-reactive protein, differential blood count, troponine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), fibrinogen, interleukin-6, D-dimer, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase muscle-brain (CKmb) and lactate,) and patient outcome (positive: discharge or treatment on normal ward; negative: treatment on intensive care unit (ICU), need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), or death) were analyzed. Follow-up was performed until May 10th. Patients were assigned to two groups according to two endpoints: venous thromboembolism (VTE) or no VTE. For statistical analysis, univariate logistic regression models were calculated. RESULTS: This study includes 50 patients. In 14 out of 50 patients (28%), pulmonary embolism was detected at contrast-enhanced chest CT. The majority of PE was detected on CTs performed on day 11-20 after symptom onset. Two patients (14%) with PE simultaneously had evidence of deep vein thrombosis. 15 patients (30%) had a negative outcome (need for intensive care, mechanical ventilation, extracorporeal membrane oxygenation, or death), and 35 patients (70%) had a positive outcome (transfer to regular ward, or discharge). Patients suffering VTE had a statistically significant higher risk of an unfavorable outcome (p = 0.028). In univariate analysis, two imaging characteristics on chest CT were associated with VTE: crazy paving pattern (p = 0.024) and air bronchogram (n = 0.021). Also, elevated levels of NT-pro BNP (p = 0.043), CK (p = 0.023) and D-dimers (p = 0.035) were significantly correlated with VTE. CONCLUSION: COVID-19 pneumonia is frequently complicated by pulmonary embolism (incidence of 28% in our cohort), remarkably with lacking evidence of deep vein thrombosis in nearly all thus affected patients of our cohort. As patients suffering VTE had an adverse outcome, we call for a high level of alertness for PE and advocate a lower threshold for contrast-enhanced CT in COVID-19 pneumonia. According to our observations, this might be particularly justified in the second week of disease and if a crazy paving pattern and / or air bronchogram is present on previous non-enhanced CT.

Lung and kidney perfusion deficits diagnosed by dual-energy computed tomography in patients with COVID-19-related systemic microangiopathy.

OBJECTIVES: There is increasing evidence that thrombotic events occur in patients with coronavirus disease (COVID-19). We evaluated lung and kidney perfusion abnormalities in patients with COVID-19 by dual-energy computed tomography (DECT) and investigated the role of perfusion abnormalities on disease severity as a sign of microvascular obstruction. METHODS: Thirty-one patients with COVID-19 who underwent pulmonary DECT angiography and were suspected of having pulmonary thromboembolism were included. Pulmonary and kidney images were reviewed. Patient characteristics and laboratory findings were compared between those with and without lung perfusion deficits (PDs). RESULTS: DECT images showed PDs in eight patients (25.8%), which were not overlapping with areas of ground-glass opacity or consolidation. Among these patients, two had pulmonary thromboembolism confirmed by CT angiography. Patients with PDs had a longer hospital stay (p = 0.14), higher intensive care unit admission rates (p = 0.02), and more severe disease (p = 0.01). In the PD group, serum ferritin, aspartate aminotransferase, fibrinogen, D-dimer, C-reactive protein, and troponin levels were significantly higher, whereas albumin level was lower (p < 0.05). D-dimer levels ≥ 0.485 µg/L predicted PD with 100% specificity and 87% sensitivity. Renal iodine maps showed heterogeneous enhancement consistent with perfusion abnormalities in 13 patients (50%) with lower sodium levels (p = 0.03). CONCLUSIONS: We found that a large proportion of patients with mild-to-moderate COVID-19 had PDs in their lungs and kidneys, which may be suggestive of the presence of systemic microangiopathy with micro-thrombosis. These findings help in understanding the physiology of hypoxemia and may have implications in the management of patients with COVID-19, such as early indications of thromboprophylaxis or anticoagulants and optimizing oxygenation strategies. KEY POINTS: • Pulmonary perfusion abnormalities in COVID-19 patients, associated with disease severity, can be detected by pulmonary DECT. • A cutoff value of 0.485 µg/L for D-dimer plasma levels predicted lung perfusion deficits with 100% specificity and 87% sensitivity (AUROC, 0.957). • Perfusion abnormalities in the kidney are suggestive of a subclinical systemic microvascular obstruction in these patients.

High prevalence of early asymptomatic venous thromboembolism in anticoagulated COVID-19 patients hospitalized in general wards.

Coronavirus disease 2019 (COVID-19) is associated with coagulation activation and high incidence of venous thromboembolism (VTE) in severe patients despite routine thromboprophylaxis. Conflicting results exist regarding the epidemiology of VTE for unselected anticoagulated COVID-19 patients hospitalized in general wards. The aim of this study was to evaluate the prevalence of asymptomatic deep venous thrombosis (DVT) in unselected patients with COVID-19 recently hospitalized in general wards. We performed a systematic complete doppler ultrasound (CDU) at a median 4 days after admission in 42 consecutive COVID-19 patients hospitalized in general wards of our university hospital, irrespective of D-Dimer level, and retrospectively collected clinical, biological and outcome data from electronic charts. Thromboprophylaxis was systematically applied following a French national proposal. In our population, the prevalence of asymptomatic DVT was 19% (8/42 patients), with distal thrombosis in 7/8 cases and bilateral DVT in 4/8 cases. Symptomatic pulmonary embolism was detected in 4 (9.5%) patients, associated to DVT in one case. Compared to patients without DVT, patients with DVT were older and experienced poorer outcomes. In conclusion, prevalence of asymptomatic DVT is high in the first days of hospitalization of unselected COVID-19 patients in general wards and may be related to poor prognosis. Individualized assessment of thromboprophylaxis and early systematic screening for DVT is warranted in this context.

Incidence of venous thromboembolism in hospitalized patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. OBJECTIVES: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID-19. METHODS: Single-center cohort study of 198 hospitalized patients with COVID-19. RESULTS: Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10-22), 33% (95% CI, 23-43) and 42% (95% CI 30-54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8-16), 21% (95% CI, 14-30) and 25% (95% CI 16-36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02-5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17-37), 47% (95% CI, 34-58), and 59% (95% CI, 42-72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4-15), 9.2% (95% CI, 2.6-21), and 9.2% (2.6-21) at 7, 14, and 21 days). CONCLUSIONS: The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.

BACKGROUND: Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. METHODS: We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). RESULTS: We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. CONCLUSIONS: The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.

COVID-19 pneumonia with hemoptysis: Acute segmental pulmonary emboli associated with novel coronavirus infection.

Recent retrospective studies from Wuhan, China suggest Novel Coronavirus Disease 2019 (COVID-19) may be associated with a hypercoagulable state and increased risk for venous thromboembolism. The overlap in the signs and symptoms of COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) and COVID-19 with concurrent pulmonary embolism creates a diagnostic challenge for emergency medicine physicians in patients already at risk for renal impairment. However, identifying features atypical for COVID-19 alone may play a role in the judicious use of Computed Tomography Angiography among these patients. Hemoptysis is seen in roughly 13% of pulmonary embolism cases and infrequently reported among COVID-19 infections. Additionally, the presence of right heart strain on electrocardiography (EKG) is a well described clinical presentations of pulmonary embolism not reported commonly with COVID-19 infections.