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1.
World Neurosurg ; 157: e357-e363, 2022 01.
Article in English | MEDLINE | ID: covidwho-1757929

ABSTRACT

BACKGROUND: Prior studies demonstrated reduced risk for venous thromboembolism (VTE) in neurosurgical patients secondary to prophylaxis with both heparin and low-molecular-weight heparin. The ability to monitor low-molecular-weight heparin by obtaining anti-factor Xa (anti-Xa) serum levels provides an opportunity to evaluate safety and efficacy. The aim of this study was to describe characteristics of patients who have anti-Xa levels outside of the goal range (0.2-0.4/0.5 IU/mL) and investigate incidence of major bleeding and VTE. METHODS: A single-center, retrospective, observational study was conducted on neurosurgical patients receiving enoxaparin for VTE prophylaxis between August 2019 and December 2020. Significance testing was conducted via Fisher exact test and independent samples t test. RESULTS: The study included 85 patients. Patients were less likely to have an anti-Xa level in the goal range if they were male, had a higher weight, or were morbidly obese. Three neuroendovascular patients (3.5%) experienced a major bleed. Serum anti-Xa levels were significantly higher in patients who experienced major bleeds compared with patients who did not (0.45 ± 0.16 IU/mL vs. 0.28 ± 0.09 IU/mL, P = 0.003). Patients with a supraprophylactic anti-Xa level (>0.5 IU/mL) were more likely to experience a major bleed (P = 0.005). One VTE event occurred: the patient experienced a pulmonary embolism with anti-Xa level at goal. CONCLUSIONS: Anti-Xa-guided enoxaparin dosing for VTE prophylaxis in neurosurgical patients may help prevent major bleeding. These data suggest that a higher anti-Xa level may predispose patients to major bleeding. Further evaluation is needed to identify the goal anti-Xa level for VTE prophylaxis in this population.


Subject(s)
Enoxaparin/blood , Factor Xa Inhibitors/blood , Hemorrhage/blood , Neurosurgical Procedures/trends , Pre-Exposure Prophylaxis/trends , Adult , Aged , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/blood , Drug Monitoring/methods , Enoxaparin/administration & dosage , Enoxaparin/adverse effects , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/prevention & control , Humans , Male , Middle Aged , Obesity, Morbid/blood , Obesity, Morbid/surgery , Pre-Exposure Prophylaxis/methods , Retrospective Studies , Sex Factors , Venous Thromboembolism/blood , Venous Thromboembolism/prevention & control
2.
Biomolecules ; 11(11)2021 10 27.
Article in English | MEDLINE | ID: covidwho-1488477

ABSTRACT

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of "clinically" relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, "IV-effects" of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 µg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.


Subject(s)
Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Hemorrhage/prevention & control , S-Nitrosoglutathione/administration & dosage , Stroke/complications , Thrombolytic Therapy/adverse effects , Animals , Behavior, Animal , Blood Pressure , Blood-Brain Barrier , COVID-19/epidemiology , Hemorrhage/complications , Hypoxia , Infusions, Intravenous , Laser-Doppler Flowmetry , Male , Mice , Mice, Inbred C57BL , Microcirculation , Nebulizers and Vaporizers , Neuroprotective Agents/pharmacology , Perfusion , Reperfusion Injury/drug therapy , Risk , Stress, Mechanical
3.
Molecules ; 25(21)2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-1389462

ABSTRACT

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1ß induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Plant Extracts/therapeutic use , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Air Sacs/drug effects , Air Sacs/virology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19 , Chromatography, High Pressure Liquid/methods , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Disease Models, Animal , Fever/drug therapy , Fever/etiology , Hemorrhage/prevention & control , Humans , Interleukin-6/metabolism , Kidney/drug effects , Necrosis/pathology , Necrosis/prevention & control , Pandemics , Phytotherapy , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Respiratory Mucosa/transplantation , Transcriptional Activation/drug effects , Tumor Necrosis Factor-alpha/metabolism , Zebrafish
6.
J Thromb Thrombolysis ; 52(1): 354-362, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1201643

ABSTRACT

American Society of Hematology conducts an annual meeting, where investigators from around the globe presented ground-breaking research in the fields of malignant and non-malignant hematology. We provide a summary of non-malignant hematology abstracts from the 2020 meeting. Topics included range from those related to thrombosis, including thrombotic complications of COVID-19, bleeding and novel therapies such as gene therapies. Readers are encouraged to access meeting materials for a more detailed coverage of the event.


Subject(s)
Biomedical Research , Hematology , Animals , Anticoagulants/therapeutic use , Antifibrinolytic Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/drug therapy , Congresses as Topic , Genetic Therapy , Hematologic Diseases/blood , Hematologic Diseases/genetics , Hematologic Diseases/therapy , Hemorrhage/etiology , Hemorrhage/prevention & control , Humans , Thrombosis/blood , Thrombosis/etiology , Thrombosis/prevention & control
7.
Semin Thromb Hemost ; 47(4): 372-391, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1182900

ABSTRACT

We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40-0.62; I 2: 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15-0.60; I 2: 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60-4.00; I 2: 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients.


Subject(s)
Anticoagulants , COVID-19/drug therapy , COVID-19/mortality , Hemorrhage , Hospital Mortality , SARS-CoV-2 , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Disease-Free Survival , Hemorrhage/mortality , Hemorrhage/prevention & control , Hospitalization , Humans , Survival Rate
8.
J Thromb Thrombolysis ; 52(1): 18-21, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1107856

ABSTRACT

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.


Subject(s)
Anticoagulants/adverse effects , Blood Coagulation/drug effects , COVID-19/complications , Hemorrhage/chemically induced , Thrombosis/prevention & control , Aged , Anticoagulants/administration & dosage , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Critical Illness , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Hemorrhage/diagnosis , Hemorrhage/prevention & control , Humans , Inflammation Mediators/blood , Male , Middle Aged , Respiration, Artificial , Retrospective Studies , Risk Assessment , Risk Factors , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology , Time Factors , Treatment Outcome
10.
Blood Coagul Fibrinolysis ; 32(3): 200-203, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1072463

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a new medical challenge for all individuals, especially for those with underlying disorders, such as congenital bleeding disorders (CBDs). Therefore, the pandemic might significantly change the behaviour of patients with CBDs and results in some challenges. In the present study, we assessed the main challenges of COVID-19 infection to patients with CBDs. Data were collected from medical files and interviews of patients with CBDs who had COVID-19 infection. Follow-ups were performed on patients who had active severe acute respiratory syndrome coronavirus 2 infection between April and October 2020. All patients were interviewed by an expert in order to collect the pertinent data. Some questions were about patients' preventive behaviors and feelings prior to infection, and some were about the consequences of infection on patients' replacement therapy and bleeding management. Among 25 patients, infection and death of loved ones (n: 7, 28%), and their own (n: 5, 20%) or family members' (n: 1, 4%) infection, and the resulting economic burden (n: 2, 8%) were main concerns. Six patients experienced depression during the pandemic. The pandemic caused all severely affected patients but one (n: 11, 92%) to abandon replacement therapy. However, two received on-demand therapy after exacerbation of their bleeding. Only one (25%) of four patients on prophylaxis received in-home therapy, whereas the others (75%) abandoned prophylaxis. It seems that COVID-19 infection has great consequences on the lives of patients with CBDs, causing some to take dangerous actions, such as abandonment of their treatment. Healthcare systems, and healthcare providers, should have an appropriate strategy for management of patients with CBDs that prevents infection and provides timely replacement therapy.


Subject(s)
Blood Coagulation Disorders, Inherited/complications , COVID-19/complications , Adolescent , Adult , Blood Coagulation Disorders, Inherited/therapy , COVID-19/blood , COVID-19/physiopathology , COVID-19/psychology , Databases, Factual , Depression/complications , Female , Follow-Up Studies , Hemorrhage/prevention & control , Humans , Male , Middle Aged , Surveys and Questionnaires
12.
Trials ; 21(1): 920, 2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-917939

ABSTRACT

OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. TRIAL DESIGN: Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. PARTICIPANTS: Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. DATA COLLECTION: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient's age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. INTERVENTION AND COMPARATOR: Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. MAIN OUTCOMES: The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RANDOMIZATION: RedCap→ randomization - 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. BLINDING (MASKING): No blinding - Open label format NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Total number of patients 90 (45 per group) TRIAL STATUS: Trial version 2.0 - ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 TRIAL REGISTRATION: Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Acute Kidney Injury , Coronavirus Infections , Drug Monitoring/methods , Heparin , Pandemics , Pneumonia, Viral , Renal Dialysis , Thrombosis/prevention & control , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Adult , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Blood Coagulation/drug effects , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Female , Fibrin Fibrinogen Degradation Products/analysis , Hemoglobins/analysis , Hemorrhage/etiology , Hemorrhage/prevention & control , Heparin/administration & dosage , Heparin/adverse effects , Humans , Male , Outcome Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Renal Dialysis/adverse effects , Renal Dialysis/methods , Risk Adjustment/methods , Thrombocytopenia/etiology , Thrombocytopenia/prevention & control , Thrombosis/complications
13.
Clin Appl Thromb Hemost ; 26: 1076029620961450, 2020.
Article in English | MEDLINE | ID: covidwho-901722

ABSTRACT

Two of the more common potential complications after arthroplasty are venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolus (PE), and excess bleeding. Appropriate chemoprophylaxis choices are essential to prevent some of these adverse events and from exacerbating others. Risk stratification to prescribe safe and effective medications in the prevention of postoperative VTE has shown benefit in this regard. The Department of Orthopaedic Surgery at Syosset Hospital/Northwell Health, which performs over 1200 arthroplasties annually, has validated and is using the 2013 version of the Caprini Risk Assessment Model (RAM) to stratify each patient for risk of postoperative VTE. This tool results in a culling of information, past and present, personal and familial, that provides a truly thorough evaluation of the patient's risk for postoperative VTE. The Caprini score then guides the medication choices for thromboprophylaxis. The Caprini score is only valuable if the data is properly collected, and we have learned numerous lessons after applying it for 18 months. Risk stratification requires practice and experience to achieve expertise in perioperative patient evaluation. Having access to pertinent patient information, while gaining proficiency in completing the Caprini RAM, is vital to its efficacy. Ongoing, real time analyses of patient outcomes, with subsequent change in process, is key to improving patient care.


Subject(s)
Arthroplasty, Replacement/adverse effects , Postoperative Complications/prevention & control , Risk Assessment/methods , Venous Thromboembolism/prevention & control , Aged , Arthroplasty, Replacement/methods , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Female , Hemorrhage/etiology , Hemorrhage/prevention & control , Humans , Male , Middle Aged , Postoperative Complications/etiology , Premedication , Venous Thromboembolism/etiology
14.
J Am Coll Cardiol ; 76(16): 1815-1826, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-849705

ABSTRACT

BACKGROUND: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. OBJECTIVES: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. METHODS: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. RESULTS: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. CONCLUSIONS: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.


Subject(s)
Anticoagulants , Autopsy/statistics & numerical data , Coronavirus Infections , Hospitalization/statistics & numerical data , Pandemics , Pneumonia, Viral , Post-Exposure Prophylaxis , Thromboembolism , Aged , Anticoagulants/classification , Anticoagulants/therapeutic use , Betacoronavirus/isolation & purification , Blood Coagulation , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Hospital Mortality , Humans , Male , New York City/epidemiology , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Post-Exposure Prophylaxis/methods , Post-Exposure Prophylaxis/statistics & numerical data , Risk Adjustment/methods , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/mortality , Thromboembolism/prevention & control , Thromboembolism/virology
15.
Am J Emerg Med ; 41: 261.e1-261.e3, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-688657

ABSTRACT

OBJECTIVE: No guidelines exist for the management of massive pulmonary embolism (PE) in COVID-19. We present a COVID-19 patient with refractory acute respiratory syndrome (ARDS), and life-threatening PE who underwent successful thrombolysis. CASE PRESENTATION: A previously healthy 47 year old male was admitted to our hospital due to severe COVID-19 pneumonia [confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR)]. He had rapidly evolving ARDS [partial arterial pressure of oxygen to fractional inspired concentration of oxygen ratio: 175], and sepsis. Laboratory results showed lymphocytopenia, and increased D-dimer levels (7.7 µg/ml; normal: 0-0.5 µg/ml). The patient was treated in the intensive care unit. On day-1, ARDS-net/prone positioning ventilation, and empiric anti-COVID treatment integrating prophylactic anticoagulation was administered. On hospital day-2, the patient developed shock with worsening oxygenation. Point-of-care-ultrasound depicted a large thrombus migrating from the right atrium to the pulmonary circulation. Intravenous alteplase (100 mg over 2 h) was administered as rescue therapy. The patient made an uneventful recovery, and was discharged to home isolation (day-20) on oral rivaroxaban. CONCLUSION: Thrombolysis may have a critical therapeutic role for massive PE in COVID-19; however the risk of potential bleeding should not be underestimated. Point-of-care ultrasound has a pivotal role in the management of refractory ARDS in COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/therapeutic use , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Critical Care , Fibrinolytic Agents/adverse effects , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Humans , Male , Middle Aged , Point-of-Care Testing , Pulmonary Embolism/diagnostic imaging , SARS-CoV-2 , Tissue Plasminogen Activator/adverse effects , Ultrasonography
18.
Semin Thromb Hemost ; 46(7): 819-822, 2020 10.
Article in English | MEDLINE | ID: covidwho-593025
19.
J Thromb Haemost ; 18(8): 1859-1865, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-381991
20.
Thromb Haemost ; 120(6): 937-948, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-101973

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected. Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases. Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders. Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19. This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed. With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Venous Thromboembolism/prevention & control , Venous Thromboembolism/therapy , Anticoagulants/therapeutic use , Betacoronavirus , Blood Coagulation Disorders/drug therapy , COVID-19 , China/epidemiology , Consensus , Coronavirus Infections/blood , Coronavirus Infections/therapy , Critical Illness , Europe/epidemiology , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/prevention & control , Humans , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Pulmonary Embolism/complications , Pulmonary Embolism/prevention & control , Registries , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome , Venous Thromboembolism/complications , Venous Thrombosis/complications , Venous Thrombosis/prevention & control
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