Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 636
Filter
Add filters

Document Type
Year range
1.
BMJ ; 376: e068407, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1612964

ABSTRACT

OBJECTIVE: To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). DESIGN: INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. SETTING: 11 hospitals in Iran. PARTICIPANTS: Adults aged ≥18 years with covid-19 admitted to the ICU. INTERVENTION: Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. MAIN OUTCOME MEASURES: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. RESULTS: Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). CONCLUSIONS: In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04486508.


Subject(s)
Anticoagulants/therapeutic use , Atorvastatin/therapeutic use , COVID-19/complications , Critical Care/methods , Venous Thromboembolism/epidemiology , Adolescent , Adult , Aged , COVID-19/mortality , Critical Care/statistics & numerical data , Double-Blind Method , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Heparin/therapeutic use , Humans , Intensive Care Units , Iran/epidemiology , Male , Middle Aged , Odds Ratio , SARS-CoV-2 , Treatment Outcome , Venous Thromboembolism/prevention & control , Venous Thromboembolism/virology , Young Adult
2.
Medicine (Baltimore) ; 100(47): e27861, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1604977

ABSTRACT

BACKGROUND: To better inform efforts to treat and control the current outbreak with effective anticoagulant treatment strategies for coronavirus disease 2019 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 1, 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 7681 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 (odd ratio [OR] = 0.80, 95% confidence interval [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 coronavirus disease 2019 patients, preventive and therapeutic anticoagulation were more beneficial than no anticoagulation for reducing mortality rate. The result will inform healthcare providers and public health policy makers in efforts to treat and control the current outbreak.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/drug therapy , Hemorrhage , Humans , SARS-CoV-2 , Treatment Outcome , Venous Thrombosis
5.
Anaesthesist ; 70(8): 662-670, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1575534

ABSTRACT

BACKGROUND: In the context of sepsis and septic shock, coagulopathy often occurs due to the close relationship between coagulation and inflammation. Sepsis-induced coagulopathy (SIC) is the most severe and potentially fatal form. Anticoagulants used in prophylactic or therapeutic doses are discussed to potentially exert beneficial effects in patients with sepsis and/or SIC; however, due to the lack of evidence recent guidelines are limited to recommendations for drug prophylaxis of venous thromboembolism (VTE), while treatment of SIC has not been addressed. METHODS: In order to determine the status quo of VTE prophylaxis as well as treatment of SIC in German intensive care units (ICU), we conducted a Germany-wide online survey among heads of ICUs from October 2019 to May 2020. In April 2020, the survey was supplemented by an additional block of questions on VTE prophylaxis and SIC treatment in coronavirus disease 2019 (COVID-19) patients. RESULTS: A total of 67 senior doctors took part in the survey. The majority (n = 50; 74.6%) of the responses were from ICU under the direction of an anesthesiologist and/or a department of anesthesiology. Most of the participants worked either at a university hospital (n = 31; 47.8%) or an academic teaching hospital (n = 27; 40.3%). The survey results show a pronounced heterogeneity in clinical practice with respect to the prophylaxis of VTE as well as SIC treatment. In an exemplary case of pneumogenic sepsis, low molecular weight heparins (LMWH) were by far the most frequently mentioned group of medications (n = 51; 76.1% of the responding ITS). In the majority of cases (n = 43; 64.2%), anti-FXa activity is not monitored with the use of LMWH in prophylaxis doses. Unfractionated heparin (UFH) was listed as a strategy for VTE prophylaxis in 37.3% of the responses (n = 25). In an exemplary case of abdominal sepsis 54.5% of the participants (n = 36; multiple answers possible) stated the use of UFH or LMWH and UFH with dosage controlled by PTT is used on two participating ICUs. The anti-FXa activity under prophylactic anticoagulation with LMWH is monitored in 7 participating clinics (10.6%) in abdominal sepsis. Systematic screening for sepsis-associated coagulation disorders does not take place in most hospitals and patterns in the use of anticoagulants show significant variability between ICUs. In the case of COVID-19 patients, it is particularly noticeable that in three quarters of the participating ICUs the practice of drug-based VTE prophylaxis and SIC treatment does not differ from that of non-COVID-19 patients. CONCLUSION: The heterogeneity of answers collected in the survey suggests that a systematic approach to this topic via clinical trials is urgently needed to underline individualized patient care with the necessary evidence.


Subject(s)
Anticoagulants , Blood Coagulation Disorders , Heparin, Low-Molecular-Weight/therapeutic use , Sepsis , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19 , Germany , Heparin/therapeutic use , Humans , Intensive Care Units , Sepsis/complications
8.
Viruses ; 13(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572662

ABSTRACT

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.


Subject(s)
COVID-19 , Heparin , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Enoxaparin , Fondaparinux , Hemorrhage , Heparin, Low-Molecular-Weight , Humans , Inpatients , Intensive Care Units , Pandemics , SARS-CoV-2 , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
10.
Nutrients ; 13(12)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542693

ABSTRACT

Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities in many areas of medicine. Due to its low toxicity, high efficiency, high availability, and relative simplicity of acquisition, it is the object of inexhaustible interest of scientists. This review summarizes scientific reports concerning the possible application of bromelain in treating cardiovascular diseases, blood coagulation and fibrinolysis disorders, infectious diseases, inflammation-associated diseases, and many types of cancer. However, for the proper application of such multi-action activities of bromelain, further exploration of the mechanism of its action is needed. It is supposed that the anti-viral, anti-inflammatory, cardioprotective and anti-coagulatory activity of bromelain may become a complementary therapy for COVID-19 and post-COVID-19 patients. During the irrepressible spread of novel variants of the SARS-CoV-2 virus, such beneficial properties of this biomolecule might help prevent escalation and the progression of the COVID-19 disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Bromelains/therapeutic use , COVID-19/drug therapy , Cardiotonic Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Neoplasms/drug therapy , Plant Proteins/therapeutic use , SARS-CoV-2 , Ananas/enzymology , Anti-Inflammatory Agents/chemistry , Anticoagulants/chemistry , Bromelains/chemistry , Cardiotonic Agents/chemistry , Fibrinolysis/drug effects , Humans , Plant Proteins/chemistry
11.
Minerva Anestesiol ; 87(11): 1239-1254, 2021 11.
Article in English | MEDLINE | ID: covidwho-1527106

ABSTRACT

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a common and potentially fatal complication in the Intensive Care Unit (ICU). Critically ill patients have some special characteristics that increase the risk for VTE and complicate risk stratification and diagnosis. Given the positive effect of thromboprophylaxis on main outcomes, its use is mandatory in these patients, which is documented by various studies and recommended by all published guidelines. However, anticoagulation management is not an easy issue in clinical practice, as the critical patient may be at high risk for thrombosis or, conversely, at increased risk of bleeding or may balance between thrombotic and bleeding risk. Thrombotic and bleeding risk scoring should be evaluated daily in order to select the appropriate form of thromboprophylaxis. The selection depends on the degree of bleeding risk and the subgroup of ICU patients involved, such as patients with sepsis, acute brain injury, major trauma or COVID-2019. If there is no bleeding risk or other contraindication, the patient should receive pharmacologic thromboprophylaxis with unfractionated heparin or low molecular weight heparins, weighing the advantages of each agent. If the patient is at high risk of bleeding or there is a contraindication to pharmacologic prophylaxis, he should receive mechanical thromboprophylaxis mainly with intermittent pneumatic compression or graduated compression stockings. Thromboprophylaxis compliance with the guidelines is a prerequisite for moving from theory to practice. Direct oral anticoagulants have been studied in ICU patients and have no place at present in VTE prophylaxis requiring further research.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Anticoagulants/therapeutic use , Critical Illness , Heparin , Humans , Male , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/prevention & control
13.
Clin Appl Thromb Hemost ; 27: 10760296211053315, 2021.
Article in English | MEDLINE | ID: covidwho-1523220

ABSTRACT

High rates of thromboembolic events have been described in intensive care unit (ICU) patients. Data regarding thromboembolic events in all hospitalized patients has been less frequently reported, raising concerns that thromboembolic events in non-ICU may be underrecognized. In addition, optimal anticoagulation type and dose is still unsettled at this time. This is a retrospective cohort study of 159 hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia during a 9-month period to determine an association between the frequency of thromboembolic rates and hospitalized patients with COVID-19. Secondary outcomes sought to investigate association of thromboembolic events with relation to place of admission, risk factors, anticoagulation, mortality, hospital length of stay, and discharge disposition. Among the cohort of 159 hospitalized patients who met criteria, 16 (10%) were diagnosed with a thromboembolic event. There were a total of 18 thromboembolic events with 12 venous and 6 arterial. Admission to the ICU was not associated with a higher frequency of thromboembolic events compared with non-ICU patients (37.5% vs 62.5%), p = .71. Patients with a thromboembolic event had a significantly higher mortality compared with those with no thromboembolic event (37.5% vs 13.3%), p = .012. Patients hospitalized with COVID-19 have increased rates of thromboembolic events, both venous and arterial, which contribute to a significant increase in mortality. However, the frequency of thromboembolism in patients admitted to the ICU was similar to events in non-ICU patients. We hope to increase awareness of the increased risk of hypercoagulability in all hospitalized patients with COVID-19 including non-ICU patients.


Subject(s)
COVID-19/complications , Thromboembolism/etiology , Aged , Anticoagulants/therapeutic use , Female , Hospitalization , Humans , Incidence , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Thromboembolism/drug therapy
15.
Int J Mol Sci ; 22(21)2021 Nov 07.
Article in English | MEDLINE | ID: covidwho-1512380

ABSTRACT

Heparin and its derivatives are saving thousands of human lives annually, by successfully preventing and treating thromboembolic events. Although the mode of action during anticoagulation is well studied, their influence on cell behavior is not fully understood as is the risk of bleeding and other side effects. New applications in regenerative medicine have evolved supporting production of cell-based therapeutics or as a substrate for creating functionalized matrices in biotechnology. The currently resurgent interest in heparins is related to the expected combined anti-inflammatory, anti-thrombotic and anti-viral action against COVID-19. Based on a concise summary of key biochemical and clinical data, this review summarizes the impact for manufacturing and application of cell therapeutics and highlights the need for discriminating the different heparins.


Subject(s)
Anticoagulants/chemistry , Cell- and Tissue-Based Therapy/methods , Heparin/analogs & derivatives , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Cell Adhesion , Hemorrhage/etiology , Heparin/adverse effects , Heparin/therapeutic use , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Regenerative Medicine , Thromboembolism/drug therapy
17.
Clin Appl Thromb Hemost ; 27: 10760296211048808, 2021.
Article in English | MEDLINE | ID: covidwho-1495924

ABSTRACT

We aimed to investigate association between mean platelet volume (MVP), platelet distribution width (PDW) and red cell distribution width (RDW) and mortality in patients with COVID-19 and find out in which patients the use of acetylsalicylic acid (ASA) affects the prognosis due to the effect of MPV on thromboxan A2. A total of 5142 patients were divided into those followed in the intensive care unit (ICU) and those followed in the ward. Patient medical records were examined retrospectively. ROC analysis showed that the area under curve (AUC) values were 0.714, 0.750, 0.843 for MPV, RDW and D-Dimer, the cutoff value was 10.45fl, 43.65fl, 500.2 ng/mL respectively. (all P < .001). Survival analysis showed that patients with MPV >10.45 f/l and D-Dimer >500.2 ng/mL, treatment with ASA had lower in-hospital and 180-day mortality than patients without ASA in ICU patients (HR = 0.773; 95% CI = 0.595-0.992; P = .048, HR = 0.763; 95% CI = 0.590-0.987; P = .036). Administration of low-dose ASA in addition to anti-coagulant according to MPV and D-dimer levels reduces mortality.


Subject(s)
Blood Platelets , COVID-19/blood , Erythrocyte Indices , Erythrocytes , Mean Platelet Volume , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Platelets/drug effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Predictive Value of Tests , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome
18.
J Hematol Oncol ; 14(1): 172, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1477441

ABSTRACT

BACKGROUND: Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking. METHODS: On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding. RESULTS: A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68-0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68-0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66-0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79-0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76-0.83)]. CONCLUSIONS: Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/epidemiology , Thromboembolism/drug therapy , Thromboembolism/virology , Warfarin/therapeutic use , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/pharmacology , COVID-19/blood , COVID-19/drug therapy , COVID-19/virology , Cohort Studies , England/epidemiology , Humans , Middle Aged , SARS-CoV-2/isolation & purification , Thromboembolism/blood , Thromboembolism/epidemiology , Treatment Outcome , Young Adult
19.
BMJ ; 375: n2400, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1470506

ABSTRACT

OBJECTIVE: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. DESIGN: Randomised controlled, adaptive, open label clinical trial. SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. PARTICIPANTS: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). INTERVENTIONS: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. MAIN OUTCOME MEASURES: The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. RESULTS: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). CONCLUSIONS: In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/mortality , COVID-19/therapy , Heparin/therapeutic use , Hospitalization/statistics & numerical data , Respiration, Artificial , Biomarkers/blood , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index
SELECTION OF CITATIONS
SEARCH DETAIL
...