scholarly journals Novel Coronavirus Infection (COVID-19) Related Thrombotic and Bleeding Complications in Critically Ill Patients: Experience from an Academic Medical Center

2021 ◽  
Vol 10 (23) ◽  
pp. 5652
Author(s):  
Thejus Jayakrishnan ◽  
Aaron Haag ◽  
Shane Mealy ◽  
Corbyn Minich ◽  
Abraham Attah ◽  
...  

Introduction: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill. Methods: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU. Secondary outcomes included mortality vis-a-vis the type of anticoagulation. Results: The cohort included 144 consecutive COVID-19 patients with a median age of 64 years (IQR 54.5–75). The majority were male (85 (59.0%)) and Caucasian (90 (62.5%)) with a median BMI of 30.5 kg/m2 (IQR 25.7–36.1). The median APACHE score at admission to the ICU was 12.5 (IQR 9.5–22). The coagulation parameters at admission were a d-dimer level of 109.2 mg/mL, a platelet count of 217.5 k/mcl, and an INR of 1.4. The anticoagulation strategy at admission included prophylactic anticoagulation for 97 (67.4%) patients and therapeutic anticoagulation for 35 (24.3%) patients, while 12 (8.3%) patients received no anticoagulation. A total of 29 patients (20.1%) suffered from thrombotic or major bleeding complications. These included 17 thrombus events (11.8%)—8 while on prophylactic anticoagulation (7 regular dose and 1 intermediate dose) and 9 while on therapeutic anticoagulation (p-value = 0.02)—and 19 major bleeding events (13.2%) (4 on no anticoagulation, 7 on prophylactic (6 regular dose and 1 intermediate dose), and 8 on therapeutic anticoagulation (p-value = 0.02)). A higher thrombosis risk among patients who received remdesivir (18.8% vs. 5.3% (p-value = 0.01)) and convalescent serum (17.3% vs. 5.8% (p-value = 0.03%)) was noted, but no association with baseline characteristics (age, sex, race, comorbidity), coagulation parameters, or treatments (steroids, mechanical ventilation) could be identified. There were 10 pulmonary embolism cases (6.9%). A total of 99 (68.8%) patients were intubated, and 66 patients (45.8%) died. Mortality was higher, but not statistically significant, in patients with thrombotic or bleeding complications—58.6% vs. 42.6% (p-value = 0.12)—and higher in the bleeding (21.2%) vs. thrombus group (12.1%), p-value = 0.06. It did not significantly differ according to the type of anticoagulation used or the coagulation parameters. Conclusions: This study describes a high incidence of thrombotic and bleeding complications among critically ill COVID-19 patients. The findings of thrombotic events in patients on anticoagulation and major bleeding events in patients on no or prophylactic anticoagulation pose a challenging clinical dilemma in the issue of anticoagulation for COVID-19 patients. The questions raised by this study and previous literature on this subject demonstrate that the role of anticoagulation in COVID-19 patients is worthy of further investigation.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sirui Zhang ◽  
Yupei Li ◽  
Guina Liu ◽  
Baihai Su

Abstract Background Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal anticoagulant strategy has not yet been defined. The objective of this meta-analysis was to investigate the effect of intermediate-to-therapeutic versus prophylactic anticoagulation for thromboprophylaxis on the primary outcome of in-hospital mortality and other patient-centered secondary outcomes in COVID-19 patients. Methods MEDLINE, EMBASE, and Cochrane databases were searched from inception to August 10th 2021. Cohort studies and randomized clinical trials that assessed the efficacy and safety of intermediate-to-therapeutic versus prophylactic anticoagulation in hospitalized COVID-19 patients were included. Baseline characteristics and relevant data of each study were extracted in a pre-designed standardized data-collection form. The primary outcome was all-cause in-hospital mortality and the secondary outcomes were incidence of thrombotic events and incidence of any bleeding and major bleeding. Pooled analysis with random effects models yielded relative risk with 95 % CIs. Results This meta-analysis included 42 studies with 28,055 in-hospital COVID-19 patients totally. Our pooled analysis demonstrated that intermediate-to-therapeutic anticoagulation was not associated with lower in-hospital mortality (RR=1.12, 95 %CI 0.99-1.25, p=0.06, I2=77 %) and lower incidence of thrombotic events (RR=1.30, 95 %CI 0.79-2.15, p=0.30, I2=88 %), but increased the risk of any bleeding events (RR=2.16, 95 %CI 1.79-2.60, p<0.01, I2=31 %) and major bleeding events significantly (RR=2.10, 95 %CI 1.77-2.51, p<0.01, I2=11 %) versus prophylactic anticoagulation. Moreover, intermediate-to-therapeutic anticoagulation decreased the incidence of thrombotic events (RR=0.71, 95 %CI 0.56-0.89, p=0.003, I2=0 %) among critically ill COVID-19 patients admitted to intensive care units (ICU), with increased bleeding risk (RR=1.66, 95 %CI 1.37-2.00, p<0.01, I2=0 %) and unchanged in-hospital mortality (RR=0.94, 95 %CI 0.79-1.10, p=0.42, I2=30 %) in such patients. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from very low to moderate. Conclusions We recommend the use of prophylactic anticoagulation against intermediate-to-therapeutic anticoagulation among unselected hospitalized COVID-19 patients considering insignificant survival benefits but higher risk of bleeding in the escalated thromboprophylaxis strategy. For critically ill COVID-19 patients, the benefits of intermediate-to-therapeutic anticoagulation in reducing thrombotic events should be weighed cautiously because of its association with higher risk of bleeding. Trial registration The protocol was registered at PROSPERO on August 17th 2021 (CRD42021273780). Graphical abstract


2018 ◽  
Vol 21 (6) ◽  
pp. 529-536 ◽  
Author(s):  
Michelle Pavlick ◽  
Cynthia RL Webster ◽  
Dominique G Penninck

Objectives Liver biopsy is necessary for a diagnosis of liver disease; however, post-biopsy bleeding is a concern. The aim of this study was to describe the extent of bleeding and the occurrence of complications after percutaneous ultrasound-guided liver biopsy (PUGLB) in cats. Methods The medical records of 30 cats that had a PUGLB were retrospectively reviewed. Using human guidelines, bleeding was classified as minor or major when the absolute change in packed cell volume (ΔPCV) was <0 and >−6% or ≤-6%, respectively. Complications were defined as physiologic compromise necessitating an intervention, or death. The relationship between ΔPCV and the occurrence of complications and the signalment, initial PCV, coagulation parameters, serum liver enzymes and bilirubin, number of biopsies, histological diagnosis, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration were assessed using Fisher’s exact test, ANOVA and Pearson’s correlation coefficient, with a P value <0.05 considered significant. Results All cats had a decrease in PCV after biopsy. The mean ΔPCV was −6.9% ± 4.1%. Minor and major bleeding occurred in 13/30 (43.3%) and 17/30 (56.7%) cats, respectively, and non-lethal bleeding complications occurred in 5/30 (16.7%). Cats with complications had a lower pre-biopsy PCV ( P <0.003). Major bleeding was more likely with a diagnosis of hepatic lipidosis ( P = 0.03). There was no correlation between ΔPCV or complications and signalment, coagulation parameters, serum parameters, number of biopsies, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration. Conclusions and relevance PUGLB is a relatively safe procedure in cats, although many cats have a subclinical decrease in PCV. As conventional coagulation tests did not predict complications or the magnitude of ΔPCV, there is a need for more sensitive indicators of bleeding risk in cats undergoing PUGLB.


TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e376-e382
Author(s):  
Eric Wenzler ◽  
Monaz H. Engineer ◽  
Maidah Yaqoob ◽  
Scott T. Benken

Abstract Introduction Despite the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), rates of thromboembolic disease, and subsequent morbidity and mortality remain unacceptably high in patients with severe novel coronavirus disease 2019 (COVID-19) disease. Direct oral anticoagulants (DOACs), such as apixaban, have numerous purported benefits although the safety and efficacy of their use in intensive care unit (ICU) patients with severe COVID-19 has yet to be evaluated. Materials and Methods Single-center, retrospective cohort study of 21 ICU patients with severe COVID-19 respiratory disease treated with apixaban for atrial fibrillation (AFib), venous thromboembolism (VTE), catheter-induced thrombosis, and/or COVID-19-induced coagulopathy. The primary objective was to evaluate the incidence of bleeding events and secondary objectives included thromboembolic events, coagulation parameters, and mortality. Results Ninety percent of patients were non-White, 43% were obese, 90% had acute respiratory distress syndrome, and 76% required mechanical ventilation. Nearly half of (47.6%) also experienced renal dysfunction and required renal replacement therapy. Eighty-six percent of patients received prophylaxis or treatment with UFH or LMWH within the 24-hour period prior to apixaban initiation. Patients were initiated on apixaban for the treatment of suspected or confirmed VTE (67%) or AFib (33%). All coagulation parameters remained abnormal but stable throughout the 10-day monitoring period. No patients experienced any major bleeding events or thrombosis throughout the study period. There were four deaths during the follow-up period, all deemed unrelated to coagulopathy or bleeding. Conclusion Apixaban appeared safe and efficacious in ICU patients with severe COVID-19 disease. These data encourage future trials seeking to optimize anticoagulation strategies in patients with severe COVID-19.


Author(s):  
Isadore Budnick ◽  
Jessica Davis ◽  
Anirudh Sundararaghavan ◽  
Samuel Konkol ◽  
Chelsea Lau ◽  
...  

Background: Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients. Objective: We aimed to determine if treatment with cryoprecipitate (CRYO) for low FIB levels were associated with bleeding complications or survival. Patients / Methods: 237 cirrhosis patients admitted to an intensive care unit at a tertiary care liver transplant center with initial FIB levels less than 150 mg/dL were retrospectively assessed for CRYO transfusion, bleeding events, and survival outcomes. Results: The mean MELD score was 27.2 (95% CI 26.0 - 28.3) and CLIF-C Acute on Chronic Liver Failure (ACLF) score was 53.4 (51.9 - 54.8). Ninety-nine (41.8%) were admitted for acute bleeding and the remainder were admitted for non-bleeding illnesses. FIB level on admission correlated strongly with disease severity. After adjusting for disease severity, FIB on admission was not an independent predictor of 30-day survival (HR 0.99, 95% CI 0.99 - 1.01, p = 0.68). CRYO transfusion increased FIB levels but had no independent effect on mortality or bleeding complications (HR 1.10, 95% CI 0.72 - 1.70, p = 0.65). Conclusions: In cirrhosis patients with critical illness, low FIB levels on presentation reflect severity of illness but are not independently associated with 30-day mortality. Treatment of low FIB with CRYO also does not affect survival or bleeding complications suggesting FIB is an additional marker of severity of illness but is not itself a direct factor in the pathophysiology of bleeding in critically ill cirrhosis patients.


Author(s):  
Behnood Bikdeli ◽  
Azita H Talasaz ◽  
Farid Rashidi ◽  
Hooman Bakhshandeh ◽  
Farnaz Rafiee ◽  
...  

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.


Author(s):  
Alexandra Jayne Nelson ◽  
Brian W Johnston ◽  
Alicia Achiaa Charlotte Waite ◽  
Gedeon Lemma ◽  
Ingeborg Dorothea Welters

Background. Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes for general critical care patients with AF. Our aim was to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for AF. Methodology. A systematic literature search was conducted using MEDLINE, EMBASE, CENTRAL and PubMed databases. Studies reporting anticoagulation strategies for AF in adults admitted to a general critical care setting were assessed for inclusion. Results. Four studies were selected for data extraction. A total of 44087 patients were identified with AF, of which 17.8-49.4% received anticoagulation. The reported incidence of thromboembolic events was 0-1.4% for anticoagulated patients, and 0-1.3% in non-anticoagulated patients. Major bleeding events were reported in three studies and occurred in 7.2-8.6% of the anticoagulated patients and up to 7.1% of the non-anticoagulated patients. Conclusions. There was an increased incidence of major bleeding events in anticoagulated patients with AF in critical care compared to non-anticoagulated patients. There was no significant difference in the incidence of reported thromboembolic events within studies, between patients who did and did not receive anticoagulation. However, the outcomes reported within studies were not standardised, therefore, the generalisability of our results to the general critical care population remains unclear. Further data is required to facilitate an evidence-based assessment of the risks and benefits of anticoagulation for critically ill patients with AF.


2020 ◽  
Vol 58 ◽  
pp. 34-40
Author(s):  
Yosuf W. Subat ◽  
Hamza Rayes ◽  
Andrew C. Hanson ◽  
Madeline Q. Johnson ◽  
Phillip J. Schulte ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 708-708
Author(s):  
Manuel Monreal ◽  
José Nieto ◽  
Ana de Tuesta ◽  
Pablo Marchena ◽  
Gregorio Tiberio ◽  
...  

Abstract Introduction Patients who have experienced a recent major bleeding episode are usually excluded from clinical trials of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials of VTE treatment may not be optimal for these patients. The Registro Informatizado de la Enfermedad TromboEmbólica (RIETE), initiated in March 2001, is a multicenter, observational registry gathering data on VTE treatment practices and clinical outcomes in patients with objectively confirmed, symptomatic, acute VTE. The aim of this analysis was to study outcomes in patients with VTE who had experienced major bleeding <30 days prior to VTE diagnosis. Methods Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patients are excluded if they are participating in a therapeutic clinical trial or not available for 3-months follow-up. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3-months are recorded. Results Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding prior to VTE diagnosis: 69 (40.6%) gastrointestinal tract; 60 (35.3%) intracranial; 41 (24.1%) other. More patients with recent major bleeding had cancer compared with those without recent major bleeding (26.4% vs 20.4%, respectively; p=0.05). More patients who experienced recent major bleeding had undergone surgery <2 months prior to enrollment or had immobility ≥4 days. The incidences of recurrent PE and minor, major, and fatal bleeding complications were also higher in patients who had experienced recent major bleeding (table 1). Patients with recent major bleeding and cancer had an increased incidence of major bleeding compared to those without cancer (20.0% vs. 2.4%, respectively; OR 10.0; 95% CI 2.3–50.0; p<0.001); 11.0% of patients who had recent major bleeding prior to VTE diagnosis and cancer experienced fatal PE compared with none in patients who had recent major bleeding but without cancer (OR 4.1; 95% CI 4.98–17; p<0.05). Conclusion Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes, in terms of bleeding complications, fatal PE and overall mortality compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to VTE diagnosis, those with cancer had a poorer clinical outcome than those without cancer. Table 1. Clinical outcome of enrolled patients 3-month outcome Recent major bleeding No recent major bleeding OR (95% CI) p value n (%) n=170 n=6191 Fatal bleeding 7 (4.1) 41 (0.6) 6.4 (2.6-15) <0.001 Major bleeding 12 (7.1) 146 (2.3) 3.1 (1.6-5.9) 0.001 Minor bleeding 12 (7.1) 172 (2.8) 2.6 (1.4-5.0) <0.005 Fatal (initial) PE 1 (0.6) 14 (0.2) 2.6 (0.2-19) NS Fatal (recurrent) PE 4 (2.4) 33 (0.5) 4.5 (1.3-14) <0.05 Recurrent VTE 8 (4.7) 184 (2.9) 1.6 (0.7-3.4) NS Overall mortality 25 (15.0) 479 (7.7) 2.1 (1.3-3.2) <0.005


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