Continuation of therapeutic anticoagulation before and during hospitalization is associated with reduced mortality in COVID-19 ICU patients

Background: Literature has well established COVID-19 associated coagulopathy with resulting thrombotic complications including microthrombi as an underlying mechanism leading to severe respiratory disease. Therapeutic anticoagulation (TAC) for COVID-19 patients has therefore been widely trialed to combat COVID-19’s coagulopathic effects. However, literature has yet to define which population of patients TAC benefits; the most current randomized controlled trials (RCTs) reveal TAC to be possibly beneficial to moderately-ill hospitalized COVID-19 patients, whereas benefits did not outweigh risks in critically-ill ICU patients. Importantly, these studies excluded patients who received prehospital TAC. We examined outcomes in critically ill COVID-19 ICU patients who received TAC vs prophylactic anticoagulation (PAC) and specifically whether prehospital TAC effected outcomes. Methods: Retrospective cohort study of 132 COVID-19 ICU patients admitted March-June, 2020. Initial clinical practice provided PAC, as literature demonstrating COVID-19 associated coagulopathy and increased thromboembolic complications emerged, a TAC protocol was initiated. Results: 130 patients were included in the study, 95 of whom received TAC and 35 PAC. There was 50.8% overall mortality, with lower mortality in the TAC vs PAC group (46.3% vs 62.9%, p=0.094). There were few thromboembolic and hemorrhagic complications, with no significant difference between TAC and PAC patients. Of 24 patients anticoagulated prior to and during hospitalization, only 1 (4.2%) died, whereas the mortality was 60.6% among patients therapeutically anticoagulated during hospitalization only (p<0.001). Multivariable analysis revealed patients who received prehospital and in hospital TAC had a 92% lower risk of death (p=0.008) compared to in hospital only TAC and PAC patients. Conclusions: Overall, therapeutic anticoagulation did not result in mortality benefit to COVID-19 ICU patients compared to prophylactic anticoagulation. However, a sub-population of patients who received TAC both prior to and during hospitalization had a 12-fold lower risk of death. This suggests a protective effect of TAC when it is continued before and during hospitalization. RCTs are needed to specifically examine this subset of COVID-19 patients.

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Anticoagulation Treatment for Patients with Coronavirus disease 2019 (COVID-19) and its clinical effectiveness in 2020: A meta-analysis study

10.21203/rs.3.rs-551086/v1 ◽

2021 ◽

Author(s):

Jingyi Ge ◽

Yingmin Ma ◽

Zhipeng Wu ◽

Jiawei Jin ◽

Xiao Sun

Keyword(s):

Deep Vein Thrombosis ◽

Lower Risk ◽

Cochrane Library ◽

Vein Thrombosis ◽

Therapeutic Anticoagulation ◽

Significant Difference ◽

Current Outbreak ◽

Prophylactic Anticoagulation ◽

And Control ◽

Deep Vein

Abstract Objective To better inform efforts to treat and control the current outbreak with effective anticoagulant treatment strategies for coronavirus disease 2019 (Covid-19) patients. Methods We searched Cochrane Library, Pubmed, EMBASE, MEDLINE, SCIEXPANDED, Web of Science, Google Scholar, CNKI (Chinese Database), WanFang (Chinese Database), CBM (Chinese Database), VIP (Chinese Database) for studies published from November 1st 2019 to October 1, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2. Publication bias was assessed using funnel plot. Results Fourteen studies involving 7,681 patients were included. We meta-analyzed the bleeding, deep vein thrombosis and pulmonary embolism risk between no anticoagulation and prophylactic anticoagulation, and found no significant difference. The same trend occurred in the comparison between with and without anticoagulation. However, when compared with no anticoagulation, both prophylactic anticoagulation (OR = 0.80, 95%CI: 0.69–0.93) and therapeutic anticoagulation (OR = 0.91, 95%CI: 0.80–1.05) had lower risk of mortality. Furthermore, the risk of overall bleeding among patients with therapeutic anticoagulation was 3.11 times (95% CI: 2.29–4.24) than that of patients with prophylactic anticoagulation, on the contrary, therapeutic anticoagulation had lower risk of deep vein thrombosis than prophylactic anticoagulation (OR = 0.34, 95%CI: 0.19–0.63). Conclusions Among Covid-19 patients, preventive and therapeutic anticoagulation were more beneficial than no anticoagulation for reducing mortality risk. The result will inform healthcare providers and public health policy makers in their efforts to treat and control the current outbreak.

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A Prospective Pilot Trial to Assess the Efficacy of Argatroban (Argatra®) in Critically Ill Patients with Heparin Resistance †

Journal of Clinical Medicine ◽

10.3390/jcm9040963 ◽

2020 ◽

Vol 9 (4) ◽

pp. 963 ◽

Cited By ~ 2

Author(s):

Mirjam Bachler ◽

Tobias Hell ◽

Johannes Bösch ◽

Benedikt Treml ◽

Bettina Schenk ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Treatment Success ◽

Pilot Trial ◽

Treatment Phase ◽

Thromboembolic Complications ◽

Treatment Groups ◽

Heparin Resistance ◽

Significant Difference ◽

Prophylactic Anticoagulation

The current study aims to evaluate whether prophylactic anticoagulation using argatroban or an increased dose of unfractionated heparin (UFH) is effective in achieving the targeted activated partial thromboplastin time (aPTT) of more than 45 s in critically ill heparin-resistant (HR) patients. Patients were randomized either to continue receiving an increased dose of UFH, or to be treated with argatroban. The endpoints were defined as achieving an aPTT target of more than 45 s at 7 h and 24 h. This clinical trial was registered on clinicaltrials.gov (NCT01734252) and on EudraCT (2012-000487-23). A total of 42 patients, 20 patients in the heparin and 22 in the argatroban group, were included. Of the patients with continued heparin treatment 55% achieved the target aPTT at 7 h, while only 40% of this group maintained the target aPTT after 24 h. Of the argatroban group 59% reached the target aPTT at 7 h, while at 24 h 86% of these patients maintained the targeted aPTT. Treatment success at 7 h did not differ between the groups (p = 0.1000), whereas at 24 h argatroban showed significantly greater efficacy (p = 0.0021) than did heparin. Argatroban also worked better in maintaining adequate anticoagulation in the further course of the study. There was no significant difference in the occurrence of bleeding or thromboembolic complications between the treatment groups. In the case of heparin-resistant critically ill patients, argatroban showed greater efficacy than did an increased dose of heparin in achieving adequate anticoagulation at 24 h and in maintaining the targeted aPTT goal throughout the treatment phase.

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486Are the results of the CASTLE-AF trial reproducible in the real life? Clinical outcomes after catheter ablation for atrial fibrillation with heart failure in a nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz747.0135 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Bisson ◽

F Mondout ◽

J Herbert ◽

N Clementy ◽

B Pierre ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cohort Study ◽

Catheter Ablation ◽

Lower Risk ◽

Multivariable Analysis ◽

Af Ablation ◽

Risk Of Death ◽

Systèmes D’Information ◽

Event Rates

Abstract Background Catheter ablation for atrial fibrillation (AF) is a validated therapy for patients with symptomatic AF to prevent recurrences. The CASTLE AF trial indicated that ablation for AF in patients with heart failure (HF) was associated with a lower rate of death from any cause or hospitalization for worsening HF than was medical therapy. The purpose of our study was to compare the incidence of these events in AF patients with HF after AF catheter ablation versus those not treated with AF ablation at a nationwide level in centers possibly less well experienced. Methods This French longitudinal cohort study was based on the national hospitalization PMSI (Programme de Médicalisation des Systèmes d'Information) database covering hospital care from the entire population. We included all patients, over 18 years old, with AF and HF from January 2010 to December 2015. Crude event rates were ascertained and hazard ratios (HR) were estimated using Cox proportional hazards risk model. Propensity-matched Cox regression was also used to compare event rates according to AF ablation usage status. Results Among the 261,449 patients identified with AF and HF, 1,270 patients were treated with AF ablation (24% female, mean age 63±10 yo) and 260,179 did not have AF ablation (45% female, mean age 79±11 yo). During follow-up (417±502 days), there were 56,981 hospitalizations with a primary diagnosis of HF and 81,393 deaths were recorded. Incidence of hospitalization for HF was significantly lower in patients with AF ablation than in those with no ablation (13.74% vs 51.11% person per year respectively, p<0.0001). Incidence of death was also significantly lower in patients with AF ablation than in those with no ablation (6.07% vs 27.42% person per year respectively, p<0.0001). These associations were confirmed in a multivariable analysis after adjustment on age and other comorbidities (HR 0.33, 95% CI 0.28–0.39, p<0.0001 for HF and HR 0.38, 95% CI 0.31–0.48, p<0.0001 for all-cause death). After 1:1 propensity score matching, AF ablation was also associated with a lower risk of hospitalization for HF (HR 0.38, 95% CI 0.31–0.47, p<0.0001) and a lower risk of death (HR 0.54, 95% CI 0.42–0.70, p<0.0001). Conclusion In the nationwide analysis of unselected AF patients with HF seen in hospitals, AF ablation was independently associated with a lower risk of hospitalization for HF and death. This provides “real world” data consistent with those observed in recent trials with lower numbers of highly selected patients

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Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study

Open Heart ◽

10.1136/openhrt-2021-001785 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001785

Author(s):

Kamal Matli ◽

Nibal Chamoun ◽

Aya Fares ◽

Victor Zibara ◽

Soad Al-Osta ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Hospital Mortality ◽

Primary Outcome ◽

Icu Admission ◽

Therapeutic Anticoagulation ◽

Hospitalised Patients ◽

Significant Difference ◽

Prophylactic Anticoagulation ◽

Improved Outcome

BackgroundCOVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.MethodsA retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.Results242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.ConclusionThe use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

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Prevalence of Venous Thromboembolism in Critically-ill COVID-19 Patients: Systematic Review and Meta-analysis

10.1101/2020.08.24.20175745 ◽

2020 ◽

Author(s):

Mouhand F.H. Mohamed ◽

Shaikha D. Al-Shokri ◽

Khaled M. Shunnar ◽

Sara F. Mohamed ◽

Mostafa S. Najim ◽

...

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Critically Ill ◽

Meta Analysis ◽

Ongoing Debate ◽

Systematic Screening ◽

Randomized Controlled ◽

Therapeutic Anticoagulation ◽

High Prevalence ◽

Prophylactic Anticoagulation

Background: Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis. Methods: We performed a systematic review and proportion meta-analysis following PRISMA guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 22/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, we compared the odds of VTE in patients on prophylactic compared to therapeutic anticoagulation. Results: The review comprised of 24 studies and over 2500 patients. The pooled proportion of VTE prevalence was 0.31 (95% CI 0.24, 0.39 I2 94%), of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63 I2 91%), of deep-venous-thrombosis was 0.23 (95% CI 0.14, 0.32 I2 96%), of pulmonary embolism was 0.14 (95% CI 0.09, 0.20 I2 90%). In a subgroup of studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared to therapeutic anticoagulation (OR 5.45; 95% CI 1.90, 15.57 I2 0%). Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages seem to reduce VTE burden in this patient's cohort compared to standard prophylactic anticoagulation; ongoing randomized controlled trials will further confirm this.

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Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Thrombosis Research ◽

10.1016/j.thromres.2020.04.013 ◽

2020 ◽

Vol 191 ◽

pp. 145-147 ◽

Cited By ~ 1078

Author(s):

F.A. Klok ◽

M.J.H.A. Kruip ◽

N.J.M. van der Meer ◽

M.S. Arbous ◽

D.A.M.P.J. Gommers ◽

...

Keyword(s):

Critically Ill ◽

Icu Patients ◽

Thrombotic Complications

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Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis

Thrombosis Research ◽

10.1016/j.thromres.2020.04.041 ◽

2020 ◽

Vol 191 ◽

pp. 148-150 ◽

Cited By ~ 392

Author(s):

F.A. Klok ◽

M.J.H.A. Kruip ◽

N.J.M. van der Meer ◽

M.S. Arbous ◽

D. Gommers ◽

...

Keyword(s):

Critically Ill ◽

Cumulative Incidence ◽

Icu Patients ◽

Thrombotic Complications

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Risk of Subsequent Thrombosis in Patients with Isolated Heparin-Induced Thrombocytopenia

Blood ◽

10.1182/blood-2018-99-117629 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3566-3566

Author(s):

Heather R Wolfe ◽

Yu-Min Shen

Keyword(s):

Optical Density ◽

Thrombotic Event ◽

Serotonin Release ◽

Short Term ◽

Heparin Induced Thrombocytopenia ◽

Significant Difference ◽

Thrombotic Complications ◽

Release Assay ◽

Prophylactic Anticoagulation

Abstract Background: Heparin-Induced Thrombocytopenia (HIT) is one of the most important and commonly encountered immune-mediated drug reactions which can lead to significant morbidity and mortality. In up to 25% of patients, thrombosis can be the presenting finding of HIT. Isolated HIT occurs in patients without clinically evident thrombosis at the time of diagnosis. The management of HIT focuses on reducing the risk of thrombotic complications. In addition to prompt discontinuation of heparin products, anticoagulation is recommended. The risk of thrombosis is thought to remain high for up to 4 weeks due to persistent circulating PF4-heparin antibodies. Prior studies have shown that in patients with isolated HIT, the subsequent 30-day risk of thrombosis is up to 53%. Guidelines recommend 3 months of anticoagulation for patients with HIT-associated thrombosis. The optimal duration of anticoagulation in isolated HIT is unknown. Many experts recommend prophylactic anticoagulation for up to 4 weeks after diagnosis. However in the era of direct thrombin inhibitors, the need for prophylactic anticoagulation and risk of thrombosis beyond normalization of platelet count remains to be determined. The aim of this study was to determine the incidence of subsequent thrombosis in patients with isolated HIT. Methods: In this retrospective review, we identified patients with a documented positive HIT (heparin-PF4 antibody) enzyme immunoassay (ELISA) at our affiliated hospitals between January 2006 and December 2016. Laboratory data from these patients were reviewed. Patients who met criteria for HIT, defined as HIT ELISA optical density ≥ 2 or positive serotonin release assay were included in the analysis. From this cohort of patients with confirmed HIT, clinical data was extracted from the electronic medical record, including anticoagulation management and documented thrombotic events within 3 months of HIT diagnosis. Patients with evidence of thrombosis at the time of diagnosis were excluded in the final analysis as our focus was on patients with isolated HIT. The incidence of subsequent thrombosis was compared in patients who received anticoagulation versus those who did not receive anticoagulation. Results: A total of 403 charts were reviewed from patients with a documented positive HIT ELISA, defined as an optical density of > 0.4. Of the 403 patients, 49.5% (n = 107) met criteria for HIT, with an optical density > 2 or positive serotonin release assay. In patients with HIT, 48.6% (n = 52) did not have evidence of thrombosis at the time of diagnosis. Of these patients with isolated HIT, 14 patients (26.9%) received no prophylactic anticoagulation, 8 patients (15.4%) received prophylactic anticoagulation for at least 4 weeks but less than 3 months, and 30 patients (57.7%) were anticoagulated for 3 months or longer. The total incidence of subsequent thrombosis in isolated HIT was 7.7%. In the cohort of patients that did not receive prophylactic anticoagulation, two patients (14.3%) developed a thrombotic event in the 3 months following the HIT diagnosis. No documented thrombotic complications occurred in the eight patients that received prophylactic anticoagulation for at least 4 weeks but less than 3 months. Three patients (10%) who received long-term anticoagulation (≥3 months) developed a subsequent thrombotic event. There was no significant difference in the incidence of subsequent thrombosis in patients who did not receive prophylactic anticoagulation versus patients who received short-term prophylactic anticoagulation (p=0.141). In addition, there was no significant difference in the incidence of subsequent thrombosis in patients who did not receive prophylactic anticoagulation versus those who received long-term anticoagulation (p=0.701). Conclusions: The optimal duration of anticoagulation in patients with isolated HIT is unknown. Our incidence of thrombosis following the diagnosis of HIT was lower than previously described. Patients who did not receive prophylactic anticoagulation did not have a significantly higher incidence of thrombosis compared to patients who received short-term prophylactic or long-term anticoagulation. The study was limited by the retrospective nature and small sample size. Further studies are needed to better understand the ideal length of anticoagulation to prevent thrombotic complications without leading to unnecessary increased risk of bleeding. Disclosures No relevant conflicts of interest to declare.

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Epidemiological and clinical characteristics of sepsis-associated encephalopathy in the ICU: a retrospective observational study

10.21203/rs.2.14475/v1 ◽

2019 ◽

Author(s):

Dao-Ming Tong ◽

Ye-Ting Zhou ◽

Shao=Dan Wang ◽

Guang-Sheng Wang ◽

Yuan-Wei Wang ◽

...

Keyword(s):

Critically Ill ◽

Sofa Score ◽

Clinical Characteristics ◽

Clinical Predictors ◽

Organ Function ◽

Icu Patients ◽

Risk Of Death ◽

Critically Ill Adults ◽

Ill Adults ◽

Function Assessment

Abstract Background Sepsis has an annual incidence of 30 million new cases around worldwide. However, the epidemiological and clinical characteristics in patients with sepsis-associated encephalopathy (SAE) remain understudy.Methods We prospectively enrolled patients with acute critically ill from ICU during 2 years period (2014-2015). The epidemiological and clinical characteristics for critically ill adults with SAE in ICU were analyzed by related statistics.Results Of the 1349 ICU patients with acute critically ill, 748 were enrolled. Among these, the prevalence of sepsis was 48.4% (362/748), with fatality at initial 30 days was 62.4%. The prevalence of SAE accounted for 97.2% of sepsis (352/362), with fatality at initial 30 days was 65.1%. We found that the two strong clinical predictors for SAE were systemic inflammatory response syndrome (SIRS) ≥2 (OR, 3.2; 95% CI, 0.304- 0.673) and sequential (sepsis-related) organ function assessment (SOFA) score ≥6 (GCS<13)(OR, 3.0; 95% CI, 0.304-0.673); the sensitivity was 67.3% and specificity was 55.3% for SIRS≥2, while the sensitivity was 99.1% and specificity was 99.0% for SOFA score≥6. Cox logistic adjusted analysis revealed that lower mean arterial pressure (OR, 1.504; 95% CI, 1.001-1.707),higher SOFA score (OR, 1.783; 95% CI, 1.145- 1.923), and no using antibiotics treatment in initial 3 hours (OR, 0.683; 95% CI, 0.492-0.947) were the powerful predictors of the risk of death among ICU patients with SAE.Conclusion SAE is a best frequent epidemiological type of sepsis in ICU, with an high hospital fatality. No using antibiotics treatment within initial 3 hours was related to the worse survival SAE.

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IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19

Molecular Medicine ◽

10.1186/s10020-020-00230-x ◽

2020 ◽

Vol 26 (1) ◽

Cited By ~ 1

Author(s):

Yu Chen ◽

Jinglan Wang ◽

Chenxi Liu ◽

Longxiang Su ◽

Dong Zhang ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Clinical Symptoms ◽

Enzyme Linked Immunosorbent Assay ◽

Monocyte Chemoattractant Protein 1 ◽

Risk Of Death ◽

Inflammatory Protein ◽

Laboratory Test Results ◽

Significant Difference ◽

Inducible Protein

Abstract Background COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients’ outcome. Methods This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.

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