Thrombosis and Bleeding After Implementation of an Intermediate-Dose Prophylactic Anticoagulation Protocol in ICU Patients With COVID-19: A Multicenter Screening Study

Thrombosis and bleeding after implementation of an intermediate-dose prophylactic anticoagulation protocol in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19): a multicenter screening study Background: Venous thromboembolism (VTE) is common among critically ill patients with COVID-19. Information regarding VTE prevalence and bleeding complications after implementation of intermediate-dose prophylactic anticoagulation in such patients is, however, limited. Methods: We performed a prospective, observational study in 6 ICUs in 2 university-affiliated teaching hospitals in Sweden. After implementation of an intermediate-dose prophylactic anticoagulation protocol, we performed ultrasound screening for proximal lower-extremity deep vein thrombosis (DVT) and collected routine computed tomography pulmonary angiography exam results. Results: A total of 100 COVID-19 patients were included from June 21, 2020, through February 18, 2021. During a median follow-up of 120 (IQR, 89-134) days, we found VTE in 37 patients with the majority (78.4%) being diagnosed after ICU arrival. Overall, 20 patients had proximal lower-extremity DVT with 95% being detected on ultrasound screening; 22 patients had pulmonary vascular thrombosis; and 4 patients had venous thrombosis at other sites. A total of 6 patients had both proximal lower-extremity DVT and pulmonary vascular thrombosis. On univariate logistic regression analysis of 14 baseline characteristics, only pre-existing heart failure was associated with VTE (OR 4.67, 95% CI 1.13-19.34). Major and non-major bleeding occurred in 10 and 18 patients, respectively. Conclusions: In our cohort of ICU patients with COVID-19, we observed a high prevalence of VTE and bleeding complications after implementation of intermediate-dose anticoagulation. In approximately half of patients, VTE was identified on screening ultrasound.

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Intermediate vs Standard-dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to ICU: Ninety-day Results from the INSPIRATION Trial

Thrombosis and Haemostasis ◽

10.1055/a-1485-2372 ◽

2021 ◽

Author(s):

Behnood Bikdeli ◽

Azita H Talasaz ◽

Farid Rashidi ◽

Hooman Bakhshandeh ◽

Farnaz Rafiee ◽

...

Keyword(s):

Hospital Discharge ◽

Major Bleeding ◽

Arterial Thrombosis ◽

Dose Group ◽

Standard Dose ◽

Controlled Trial ◽

Bleeding Events ◽

Major Bleeding Events ◽

Prophylactic Anticoagulation ◽

Intermediate Dose

Background: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

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Prevalence of the Use of Central Venous Access Devices Within and Outside of the Intensive Care Unit: Results of a Survey Among Hospitals in the Prevention Epicenter Program of the Centers for Disease Control and Prevention

Infection Control and Hospital Epidemiology ◽

10.1086/502163 ◽

2003 ◽

Vol 24 (12) ◽

pp. 942-945 ◽

Cited By ~ 92

Author(s):

Michael Climo ◽

Dan Diekema ◽

David K. Warren ◽

Loreen A. Herwaldt ◽

Trish M. Perl ◽

...

Keyword(s):

Central Venous Access ◽

Bloodstream Infections ◽

Venous Catheter ◽

Venous Access ◽

Teaching Hospitals ◽

Central Venous ◽

Prevalence Survey ◽

Icu Patients ◽

Medical Centers ◽

Control And Prevention

AbstractObjective:To determine the prevalence of central venous catheter (CVC) use among patients both within and outside the ICU setting.Design:A 1-day prevalence survey of CVC use among adult inpatients at six medical centers participating in the Prevention Epicenter Program of the CDC. Using a standardized form, observers at each Epicenter performed a hospital-wide survey, collecting data on CVC use.Setting:Inpatient wards and ICUs of six large urban teaching hospitals.Results:At the six medical centers, 2,459 patients were surveyed; 29% had CVCs. Among the hospitals, from 43% to 80% (mean, 59.3%) of ICU patients and from 7% to 39% (mean, 23.7%) of non-ICU patients had CVCs. Despite the lower rate of CVC use on non-ICU wards, the actual number of CVCs outside the ICUs exceeded that of the ICUs. Most catheters were inserted in the subclavian (55%) or jugular (22%) site, with femoral (6%) and peripheral (15%) sites less commonly used. The jugular (33.0% vs 16.6%; P < .001) and femoral (13.8% vs 2.7%; P < .001) sites were more frequently used in ICU patients, whereas peripherally inserted (19.9% vs 5.9%; P < .001) and subclavian (60.7% vs 47.3%; P < .001) catheters were more commonly used in non-ICU patients.Conclusions:Current surveillance and infection control efforts to reduce morbidity and mortality associated with bloodstream infections concentrate on the high-risk ICU patients with CVCs. Our survey demonstrated that two-thirds of identified CVCs were not in ICU patients and suggests that more efforts should be directed to patients with CVCs who are outside the ICU.

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Optimization of Combined CT Pulmonary Angiography with Lower Extremity CT Venography

American Journal of Roentgenology ◽

10.2214/ajr.174.1.1740067 ◽

2000 ◽

Vol 174 (1) ◽

pp. 67-69 ◽

Cited By ~ 78

Author(s):

David F. Yankelevitz ◽

Gordon Gamsu ◽

Ami Shah ◽

Jurgen Rademaker ◽

Dorith Shaham ◽

...

Keyword(s):

Lower Extremity ◽

Pulmonary Angiography ◽

Ct Pulmonary Angiography ◽

Ct Venography

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Limb salvage surgery in pediatric and AYA patients with osteosarcoma: The incidence of venous thrombosis (VT).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e22505 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e22505-e22505

Author(s):

Sarah Jane McKillop ◽

Quincy S. Chu ◽

Karen E. Mulder ◽

Mary E Bauman ◽

Ashley Crosty

Keyword(s):

Lower Extremity ◽

Venous Thrombosis ◽

Limb Salvage ◽

Surgical Resection ◽

Local Control ◽

Salvage Surgery ◽

Adolescent And Young Adult ◽

Limb Salvage Surgery ◽

Increased Risk ◽

Prophylactic Anticoagulation

e22505 Background: Pediatric, adolescent and young adult (AYA) patients with a diagnosis of osteosarcoma require surgical resection for local control in addition to adjuvant chemotherapy. Limb salvage surgery (LSS) has long been established as the standard of care. Pediatric and AYA patients with sarcoma are know to have an increased risk of VTE however thromboprophylaxis is not routinely used in the pediatric oncology patients. Here we review our experience over a 5 year period with patients up to 21 years diagnosed with osteosarcoma of the lower extremity treated with LSS, amputation or rotationplasty as local control and the development of VTE. Methods: A retrospective chart review was completed of patients up to 21 years of age treated for osteosarcoma of the lower extremity between January 2011 and December 2016 at our institutions. Those that underwent surgical resection of the tumor were included. Data regarding age, type of surgical procedure, the presence of a venous thrombosis, the time from diagnosis and surgery to detection of VTE and the use of anticoagulants was collected Results: 18 patients were identified: median age 14 year (6-21), 8 patients had LSS, 4 underwent rotationplasty and 6 had an amputation. Seven VTE were identified, 5 occurred in patients receiving LSS, 2 in a patient post rotationplasty and 0 in the amputation group. 6 of the 7 VTE occurred within the upper venous system, associated with the central venous line. Conclusions: In pediatric AYA patients being treated for lower limb osteosarcoma, the incidence of VTE was significantly increased for those undergoing LSS (63%) and rotationplasty (50%) compared to those receiving amputation (0%). While the population reviewed is small, based on these findings, prophylactic anticoagulation for patients with osteosarcoma, especially those patients undergoing LSS and rotationplasty should be considered beyond the immediate perioperative period. Larger prospective studies are needed to determine the risk of VTE and risks and benefits of prophylactic anticoagulation in this patient population.

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Pediatric Pulmonary Embolism: Diagnostic and Management Challenges

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135116663698 ◽

2016 ◽

Vol 9 (1) ◽

pp. 110-113 ◽

Cited By ~ 1

Author(s):

Christian Lilje ◽

Aman Chauhan ◽

Jason P. Turner ◽

Thomas H. Carson ◽

Maria C. Velez ◽

...

Keyword(s):

Pulmonary Embolism ◽

Functional Assessment ◽

Rare Case ◽

Three Dimensional ◽

Massive Pulmonary Embolism ◽

Pulmonary Angiography ◽

Computed Tomography Pulmonary Angiography ◽

Dimensional Reconstruction ◽

Surgical Embolectomy ◽

Prophylactic Anticoagulation

A rare case of massive pulmonary embolism is presented in an oligosymptomatic teenager with predisposing factors. Computed tomography pulmonary angiography supported by three-dimensional reconstruction was diagnostic. The embolus qualified as massive by conventional anatomical guidelines, but as low risk by more recent functional criteria. Functional assessment has complemented morphologic assessment for risk stratification in adult patients. Such evidence is scarce in pediatrics. The patient underwent surgical embolectomy, followed by prophylactic anticoagulation, without further events. Diagnostic and management challenges are discussed.

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First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS)

Health Technology Assessment ◽

10.3310/hta7110 ◽

2003 ◽

Vol 7 (11) ◽

Cited By ~ 199

Author(s):

N.J. Wald ◽

C. Rodeck ◽

A.K. Hackshaw ◽

J. Walters ◽

L. Chitty ◽

...

Keyword(s):

Down's Syndrome ◽

Down’S Syndrome ◽

Ultrasound Screening ◽

Antenatal Screening ◽

Second Trimester ◽

Screening Study

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Spontaneous retroperitoneal hematoma: a rare bleeding occurrence in COVID-19

Oxford Medical Case Reports ◽

10.1093/omcr/omab081 ◽

2021 ◽

Vol 2021 (9) ◽

Author(s):

Whei Chuern Yeoh ◽

Kee Tat Lee ◽

Nadiah Hanim Zainul ◽

Sharifah Baizura Syed Alwi ◽

Lee Lee Low

Keyword(s):

Rare Complication ◽

Psoas Muscle ◽

Antiplatelet Agents ◽

Retroperitoneal Hematoma ◽

Bleeding Complications ◽

Close Monitoring ◽

Increase Risk ◽

Thrombotic Complications ◽

High Index Of Suspicion ◽

Prophylactic Anticoagulation

ABSTRACT Emerging evidence suggest that COVID-19 is associated with hypercoagulability, predisposing patients to increase risk of thromboembolism. Anticoagulation is not without its risks of bleeding and decision to initiate anticoagulation should be carefully considered with close monitoring. Spontaneous retroperitoneal hematoma is a rare complication, and there are only a few documented reports implicating anticoagulant or antiplatelet agents as a potential cause. We report a 57-year-old gentleman with COVID-19 pneumonia who developed hypotension on Day 10 of illness while on prophylactic anticoagulation. Computed tomography scan of abdomen revealed a large right retroperitoneal and psoas muscle hematoma and he underwent surgical exploration to evacuate the hematoma. His condition improved and was discharged well. Although prophylactic anticoagulation may reduce thrombotic complications in severely ill COVID-19 patients, a high index of suspicion for rare bleeding complications should be maintained if patients become hemodynamically unstable. Early diagnosis and appropriate intervention may improve outcome and prevent mortality.

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Streptokinase and Urokinase in the Treatment of Pulmonary Thromboemboli

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647911 ◽

1976 ◽

Vol 35 (01) ◽

pp. 057-069 ◽

Cited By ~ 18

Author(s):

William R Bell

Keyword(s):

Pulmonary Embolism ◽

Thrombolytic Therapy ◽

Phase I ◽

Phase Ii ◽

Clinical History ◽

Pulmonary Angiography ◽

Lung Perfusion ◽

Bleeding Complications ◽

Significant Difference ◽

Cardiopulmonary Hemodynamics

SummaryIn Phase I of this study of 160 patients with pulmonary embolism, it was demonstrated that 12 hours of urokinase accelerated the resolution of pulmonary thromboemboli compared to heparin alone. Phase II compared 12 hours of urokinase, 24 hours of urokinase and 24 hours of streptokinase in 167 patients. All patients had a clinical history and angiographic diagnosis of pulmonary embolism. Patients were randomly allocated to treatment. All physicians making patient observations were unaware of drug assignment.Resolution of the thromboembolism 24–30 hours after therapy had been instituted was determined by pulmonary angiography, lung perfusion scans and cardiopulmonary hemodynamics. Twenty-four hours of urokinase did not demonstrate greater clot resolution than 12 hours of urokinase. Twenty-four hours of urokinase resulted in greater improvement than streptokinase in lung perfusion scans, but not in angiograms. In patients with massive embolism, this difference was statistically significant. Hemodynamic differences varied.Bleeding complications and morbidity due to allergic reactions with streptokinase and urokinase were minimal. There was no statistically significant difference in mortality in the three treatment groups.From the Phase I and Phase II data it is reasonable to conclude that all three regimens of thrombolytic therapy are more effective than heparin alone in accelerating resolution of pulmonary emboli. Thrombolytic therapy offers the clinician an alternative to pulmonary embolectomy.

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A Review Of Computed Tomography Pulmonary Angiograms In Three Teaching Hospitals: The Rise Of Sub-Segmental Pulmonary Emboli and Their Management

Blood ◽

10.1182/blood.v122.21.932.932 ◽

2013 ◽

Vol 122 (21) ◽

pp. 932-932

Author(s):

Jennifer Goy ◽

Justin Y. Lee ◽

Oren Levine ◽

Salman Chaudhry ◽

Mark A. Crowther

Keyword(s):

Computed Tomography ◽

Pulmonary Embolism ◽

Chart Review ◽

Anticoagulation Therapy ◽

Teaching Hospitals ◽

Bleeding Complications ◽

Recurrent Thrombosis ◽

Alternative Diagnosis ◽

Life Threatening

Abstract Background The availability of Computed Tomography Pulmonary Angiography (CTPA) has led to an increase in the number of investigations for Pulmonary Embolism (PE). With more widespread use of these high resolution scans, the frequency of identification of isolated Small Sub-segmental Emboli (SSPE) is also expected to increase. Current clinical practice guidelines do not make any treatment distinctions for SSPE, though the benefits of anticoagulation for SSPE have not been established. Aims To review the frequency of Pulmonary Embolism and Sub-segmental Pulmonary Embolism identified through CTPA as well as their management Methods Retrospective review of 2213 patient charts who underwent CTPA in three Hamilton teaching hospitals from 2009-2011. In depth chart review of patients with SSPE was undertaken to determine the frequency with which patients who received anticoagulation therapy for SSPE. The frequency of bleeding complications and recurrent thrombosis were also investigated in this detailed SSPE chart review. Results Our patient population (mean age 65) consisted of 1099 medical inpatients (50%), 702 surgical inpatients (32%) and 412 (18%) emergency department patients. PE was identified in 26 % of scans (n=576). Of these, SSPEs were the only identified thrombus in 82 patients (4% of total scans and 14% of identified PEs). In 55 of these 82 SSPEs, in addition to the SSPE, an alternative diagnosis that might explain the PE symptoms was found. Fifty-two percent (n=43) of the patients with an SSPE received therapeutic anticoagulation. In these life threatening bleeding occurred in 2 patients. There was no documented recurrent thrombosis or thrombosis-related deaths in three month follow-up among the 39 patients who did not receive anti-coagulation for SSPE. Of the 1,608 CTPAs that did not identify PE, an alternative diagnosis to account for the patient’s symptoms was identified on CT in 1078 (67%) and no alternative cause was found in 531 (33%). Summary/Conclusions Our study demonstrated a much lower frequency of pulmonary embolism in comparison to approximate 50 % pre-test probability of a positive scan seen in studies which validated CTPA for the diagnosis of PE. Isolated SSPEs accounted for 14% of all PEs found in our study population – and were present in 4% of all patients undergoing CTPA. A substantial proportion of patients were anti-coagulated SSPE (52%) and two developed life-threatening bleeding complications. No recurrent VTE was documented in patients who were not anticoagulated for PE, though follow-up was limited to hospital records. Randomized controlled trial data is needed to further investigate the risks and benefits of anticoagulation in patients with SSPE. Disclosures: No relevant conflicts of interest to declare.

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