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1.
Clin Neurol Neurosurg ; 215: 107212, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763637

ABSTRACT

OBJECTIVE: To determine the level of compliance of The American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) for initiation of venous thromboembolism (VTE) prophylaxis after non-operative traumatic brain injury (TBI) and the explanation for the deviations. METHODS: A retrospective review from May 2018 to February 2020 in a Level II trauma center for patients with TBI and length of stay of more than 24 h. We performed an analysis of overall and subgroup compliance with guidelines. The ACS TQIP criteria for low and moderate-risk for hemorrhagic progression were used for subgroup classification. RESULTS: Of 393 patients, 239 (60.8%) patients received chemoprophylaxis in a mean of 64 (SD: +/-42) hours since admission. "Compliance" was achieved in 52.2% of patients. In subgroup analysis, 51.4% of patients in "low-risk" and 55.1% in "moderate-risk" were "compliant." The most common rationale for non-compliance in "low-risk" was a stay less than 48 h in 35.9% of patients. However, in "moderate-risk," the most common non-compliance was starting prophylaxis before the recommended 72 h from admission in 37% of cases. CONCLUSIONS: Guidelines streamline clinical practice to optimize outcomes, but there are scenarios in which deviation of the recommendations may be indicated based on clinical judgment. We show that a stay of less than 48 h was the most common rationale for not starting prophylaxis in "low-risk" patients. However, in the "moderate-risk" subgroup, the most common reason was starting chemoprophylaxis before the recommended time frame, which we called a "paradoxical" non-compliance.


Subject(s)
Brain Injuries, Traumatic , Venous Thromboembolism , Anticoagulants/therapeutic use , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Chemoprevention , Humans , Retrospective Studies , Trauma Centers , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
2.
Cardiovasc Hematol Agents Med Chem ; 20(2): 114-124, 2022.
Article in English | MEDLINE | ID: covidwho-1760080

ABSTRACT

Direct (New-generation) Oral Anticoagulants (DOACs) have emerged as effective agents which are used in place of vitamin-K antagonists in treatment and prophylaxis of Venous Thromboembolism (VTE), atrial fibrillation and other thrombotic diseases. Among them, the FIIa- direct thrombin inhibitor dabigatran and FXa inhibitors (rivaroxaban, apixaban, edoxaban) are the most broadly used. Anticoagulant dosing may differ under special considerations. The patients' physiological reserves, organ functional status and failures should be taken into account in clinical decision-making processes. The advantages and drawbacks of each specific agent should be weighed with special regard to metabolism, pharmacokinetics and pharmacodynamics, along with the efficiency of the agents in different indications. This article aims to review the most recent literature to highlight the usage and efficacy of the agents in different clinical conditions.


Subject(s)
Atrial Fibrillation , Venous Thromboembolism , Administration, Oral , Anticoagulants/pharmacology , Atrial Fibrillation/drug therapy , Dabigatran , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
3.
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
4.
Clin Appl Thromb Hemost ; 28: 10760296221086286, 2022.
Article in English | MEDLINE | ID: covidwho-1753040

ABSTRACT

BACKGROUND: Thrombotic events can increase the COVID-19 associated disease mortality. The administration of prophylactic anticoagulants had been shown to decrease the incidence of thrombosis, mortality, and ICU admission rates in COVID-19 patients. AIMS: The present study investigates the rate of thrombosis with early anticoagulation prophylaxis, the various risk factors for thrombotic events, and the overall survival rate in hospitalized COVID-19 cases. METHODS: In this prospective observational study, 425 patients aged ≥14 years were included in the study who were hospitalized with COVID-19 related symptoms from March to October 2020 at two tertiary care hospitals in the Kingdom of Saudi Arabia. Venous thromboembolism (VTE) score was evaluated, and VTE prophylaxis was administered according to the hospital guidelines. Patients' demographics, comorbidities, disease presentation, and sequential hematological profiles were also recorded. Samples were collected at different time points to determine the hematological profiles. RESULTS: Out of 425 with positive COVID-19 subjects, eight (1.9%) patients developed thrombosis during admission, with pulmonary embolism being the most common type. VTE prophylaxis was administered to 394 (92.7%) patients. These anticoagulants included enoxaparin (86.3%), heparin (12.7%), warfarin (0.8%) and apixaban (0.3%). Comorbid conditions were recorded in 253 (59.5%) patients. ICU admission rate was 28% (n = 119), with a median time to transfer to ICU of 1 day (r: 0-33 days). A trend of high VTE score (5.0) with ICU admission and mortality (P = <.001) was observed. The observed mortality rate for our cohort was 5.9% (25 events out of 425); however, for patients admitted in ICU, it was 16% (19 events out of 119 admissions). CONCLUSION: We are reporting a low incidence of thrombosis in COVID-19 patients. We have demonstrated that the early administration of prophylactic anticoagulants might reduce the risk of thrombotic events and the associated mortality. We observed a higher VTE score and thrombosis in patients admitted to the ICU.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Adolescent , Humans , Incidence , Saudi Arabia/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
5.
Clin Appl Thromb Hemost ; 28: 10760296221074353, 2022.
Article in English | MEDLINE | ID: covidwho-1650421

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Although initial reports concentrated on severe respiratory illness, emerging literature has indicated a substantially elevated risk of thromboembolic events in patients with COVID-19 disease. Pro-inflammatory cytokine release has been linked to endothelial dysfunction and activation of coagulation pathways, as evident by elevated D-dimer levels and deranged coagulation parameters. Both macrovascular and microvascular thromboses have been described in observational cohort and post-mortem studies. Concurrently, preliminary data have suggested the role of therapeutic anticoagulation in preventing major thromboembolic complications in moderately but not critically ill patients. However, pending results from randomized controlled trials, clear guidance is lacking regarding the intensity and duration of anticoagulation in such patients. Herein, we review the existing evidence on incidence and pathophysiology of COVID-19 related thromboembolic complications and guide anticoagulation therapy based on current literature and societal consensus statements.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Thrombosis/etiology , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Biomarkers/blood , Blood Coagulation , COVID-19/blood , COVID-19/drug therapy , Critical Illness , Heart Disease Risk Factors , Hospitalization , Humans , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Thrombosis/epidemiology , Thrombosis/prevention & control , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
6.
Blood Adv ; 6(2): 664-671, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1648275

ABSTRACT

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation. CONCLUSIONS: This recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.


Subject(s)
COVID-19 , Hematology , Venous Thromboembolism , Aftercare , Anticoagulants/adverse effects , Evidence-Based Medicine , Humans , Patient Discharge , SARS-CoV-2 , United States , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
7.
Clin Respir J ; 16(3): 182-189, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1642633

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a newly recognized illness that has spread rapidly all over the world. More and more reports highlight the risk of venous thromboembolism (VTE) in COVID-19. Our study aims to identify in-hospital VTE risk and bleeding risk in COVID-19 patients. METHODS: We retrospectively studied 138 consecutively enrolled patients with COVID-19 and identified in-hospital VTE and bleeding risk by Padua Prediction Score and Improve bleed risk assessment model. The clinical data and features were analyzed in VTE patients. RESULTS: Our findings identified that 23 (16.7%) patients with COVID-19 were at high risk for VTE according to Padua prediction score and 9 (6.5%) patients were at high risk of bleeding for VTE prophylaxis according to Improve prediction score. Fifteen critically ill patients faced double high risk from thrombosis (Padua score more than 4 points in all 15 [100%] patients) and hemorrhage (Improve score more than 7 points in 9 [60.0%] patients). Thrombotic events were identified in four patients (2.9%) of all COVID-19 patients. All of them were diagnosed with deep vein thrombosis by ultrasound 3 to 18 days after admission. Three (75.0%) were critically ill patients, which means that the incidence of VTE among critically ill patients was 20%. One major hemorrhage happened in critically ill patients during VTE treatment. CONCLUSION: Critically ill patients with COVID-19 suffered both a high risk of thrombosis and bleeding risks. More effective VTE prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Hemorrhage/epidemiology , Hemorrhage/etiology , Humans , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
8.
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
9.
Arch Cardiol Mex ; 91(Suplemento COVID): 047-054, 2021 Dec 20.
Article in Spanish | MEDLINE | ID: covidwho-1609046

ABSTRACT

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.


La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.


Subject(s)
Anticoagulants/therapeutic use , COVID-19 , Thrombosis , Venous Thromboembolism , COVID-19/complications , Consensus , Hemostasis , Humans , Latin America , Thrombosis/prevention & control , Thrombosis/therapy , Venous Thromboembolism/prevention & control , Venous Thromboembolism/therapy
10.
BMC Pulm Med ; 22(1): 6, 2022 Jan 06.
Article in English | MEDLINE | ID: covidwho-1605048

ABSTRACT

BACKGROUND: Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. METHODS: This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. RESULTS: In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). CONCLUSION: Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.


Subject(s)
COVID-19/mortality , Heparin/pharmacology , Methylprednisolone/pharmacology , Venous Thromboembolism/prevention & control , Anticoagulants/pharmacology , COVID-19/complications , Follow-Up Studies , Glucocorticoids/pharmacology , Hospital Mortality/trends , Humans , Incidence , Retrospective Studies , SARS-CoV-2 , Survival Rate/trends , Time Factors , United States/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
11.
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
12.
Lancet ; 399(10319): 50-59, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1569147

ABSTRACT

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.


Subject(s)
Aftercare , Blood Coagulation/drug effects , COVID-19/complications , Factor Xa Inhibitors/pharmacology , Factor Xa Inhibitors/therapeutic use , Rivaroxaban/pharmacology , Rivaroxaban/therapeutic use , Venous Thromboembolism/prevention & control , Adult , Aged , COVID-19/drug therapy , Female , Heparin/administration & dosage , Heparin/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Patient Discharge , Treatment Outcome
14.
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
15.
Viruses ; 13(11)2021 11 15.
Article in English | MEDLINE | ID: covidwho-1524170

ABSTRACT

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/etiology , Cohort Studies , Critical Illness , Female , Hemorrhage/epidemiology , Hospitalization , Humans , Male , Prognosis , Risk Factors , Venous Thromboembolism/complications , Venous Thromboembolism/prevention & control
16.
Nat Med ; 27(4): 601-615, 2021 04.
Article in English | MEDLINE | ID: covidwho-1517636

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Acute Disease , COVID-19/epidemiology , COVID-19/ethnology , COVID-19/therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Humans , Patient Advocacy , Syndrome , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
18.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
19.
J Thromb Thrombolysis ; 53(3): 586-593, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1491307

ABSTRACT

This study aims to review the available literature pertinent to vascular complications in COVID-19. A systematic search was performed using PubMed and Google Scholar to identify all relevant studies based on our study objective. Multiple studies have reported widespread systemic inflammation and procoagulant/hypercoagulable state in COVID-19, including thrombotic microangiopathy, endothelial dysfunction, bleeding disorder, and thrombosis. However, large specialised studies on vascular complications are lacking despite current evidence indicating dysfunctional coagulation pathways. Furthermore, there are no clear and definitive recommendations regarding thromboprophylaxis or full therapeutic anticoagulation in COVID-19. Several studies have reported hypercoagulability and vascular complications as important predictors of patient outcome in COVID-19. Therefore, it is important to understand the pathogenesis, epidemiology, management, and outcomes of patients who develop venous or arterial thrombosis and those with a pre-existing thrombotic disease who contract COVID-19 for risk stratification, thromboprophylaxis, optimal antithrombotic therapy during active infection and long-term anticoagulation following discharge or recovery.


Subject(s)
COVID-19 , Cardiovascular Diseases , Thrombophilia , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , Blood Coagulation , COVID-19/complications , Cardiovascular Diseases/drug therapy , Humans , Thrombophilia/complications , Thrombosis/chemically induced , Venous Thromboembolism/prevention & control
20.
Viruses ; 13(11)2021 10 22.
Article in English | MEDLINE | ID: covidwho-1481019

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control , Anticoagulants/administration & dosage , Delphi Technique , Duration of Therapy , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Venous Thromboembolism/complications , Venous Thromboembolism/diagnosis
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