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1.
Am J Case Rep ; 23: e937739, 2022 Nov 01.
Статья в английский | MEDLINE | ID: covidwho-2100411

Реферат

BACKGROUND We present the report of the first case, to the best of our knowledge, of central retinal vein occlusion (CRVO) that occurred 3 days after anticoagulation discontinuation in a patient with a history of pulmonary embolism in the course of COVID-19. CASE REPORT A previously healthy 38-year-old man was hospitalized in April 2021 with severe COVID-19 pneumonia, complicated by segmental and subsegmental pulmonary embolism. The patient was treated with a concurrent combination of remdesivir, dexamethasone, therapeutic enoxaparin, ceftriaxone, passive oxygen therapy, and convalescent plasma therapy, which led to pulmonary improvement. The treatment with therapeutic enoxaparin (80 mg/0.8 mL twice a day) was continued for 1 month after discharge, followed by 15 mg of rivaroxaban twice a day for 3 weeks and 20 mg of rivaroxaban once a day for 11 weeks. Within 3 days after rivaroxaban discontinuation, the patient experienced a decrease in visual acuity in his right eye, to the level of 5/25. Nonischemic CRVO with cystoid macular edema was diagnosed and an intravitreal injection of ranibizumab was performed. Common identifiable factors contributing to CRVO were excluded, and the treatment with prophylactic enoxaparin was initiated. Two weeks later, macular edema decreased significantly and visual acuity improved to 20/20. The treatment with enoxaparin was discontinued. CONCLUSIONS Rebound hypercoagulability after discontinuation of rivaroxaban therapy can manifest as CRVO in a young patient with a history of COVID-19 pulmonary embolism. It was successfully treated with an intravitreal injection of ranibizumab.


Тема - темы
COVID-19 , Macular Edema , Pulmonary Embolism , Retinal Vein Occlusion , Male , Humans , Adult , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/diagnosis , Rivaroxaban/therapeutic use , Ranibizumab/therapeutic use , Enoxaparin/therapeutic use , Glucocorticoids/therapeutic use , Macular Edema/drug therapy , Macular Edema/etiology , Intravitreal Injections , Pulmonary Embolism/drug therapy , Pulmonary Embolism/complications , Tomography, Optical Coherence , Angiogenesis Inhibitors/therapeutic use , Treatment Outcome
2.
Clin Appl Thromb Hemost ; 28: 10760296221131802, 2022.
Статья в английский | MEDLINE | ID: covidwho-2089101

Реферат

OBJECTIVES: This study aimed to investigate in-hospital mortality rates in patients with coronavirus disease (COVID-19) according to enoxaparin and heparin use. METHODS: This retrospective cohort study included 962 patients admitted to two hospitals in Kuwait with a confirmed diagnosis of COVID-19. Cumulative all-cause mortality rate was the primary outcome. RESULTS: A total of 302 patients (males, 196 [64.9%]; mean age, 57.2 ± 14.6 years; mean body mass index, 29.8 ± 6.5 kg/m2) received anticoagulation therapy. Patients receiving anticoagulation treatment tended to have pneumonia (n = 275 [91.1%]) or acute respiratory distress syndrome (n = 106 [35.1%]), and high D-dimer levels (median [interquartile range]: 608 [523;707] ng/mL). The mortality rate in this group was high (n = 63 [20.9%]). Multivariable logistic regression, the Cox proportional hazards, and Kaplan-Meier models revealed that the use of therapeutic anticoagulation agents affected the risk of all-cause cumulative mortality. CONCLUSION: Age, hypertension, pneumonia, therapeutic anticoagulation, and methylprednisolone use were found to be strong predictors of in-hospital mortality. In elderly hypertensive COVID-19 patients on therapeutic anticoagulation were found to have 2.3 times higher risk of in-hospital mortality. All cause in-hospital mortality rate in the therapeutic anticoagulation group was up to 21%.


Тема - темы
COVID-19 , SARS-CoV-2 , Male , Humans , Aged , Adult , Middle Aged , Enoxaparin/therapeutic use , Heparin , COVID-19/drug therapy , Hospital Mortality , Retrospective Studies , Anticoagulants , Methylprednisolone
3.
Clin Lymphoma Myeloma Leuk ; 22 Suppl 2: S322, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2062037

Реферат

CONTEXT: Hypereosinophilic syndrome (HES) is characterized by persistent blood eosinophilia, organ damage, and the absence of an underlying cause. Heterogeneous presentations, etiologies, and prognosis are recognized. The landscape of targeted therapies has emphasized the importance of its etiology and pathogenesis. We present a boy with extreme, refractory eosinophilia and end-organ complications. The persistence, severity, and outcome suggested an aggressive myeloid neoplasm. PRESENTATION: A 6-year-old boy presented with fever and respiratory symptoms. A blood count revealed hyperleukocytosis of 200×109/L with 90% eosinophils, normal platelets, and anemia with no hemolysis as well as increased cobalamin levels. Flow cytometry on the blood showed no evidence of hematolymphoid neoplasm. Fluorescent in-situ hybridization on the blood was negative for FIP1L1/PDGFRA, PDGFRB, FGFR1, and CBFB. Renal and liver functions were normal, and no evidence of tumor lysis was present. Parasitic and infectious etiologies were ruled out. Levels of immunoglobulin and complement as well as acute phase reactants were normal. CT scan showed no occult infection or lymphadenopathy. INTERVENTIONS: He was started on glucocorticoids and hydroxyurea as well as imatinib and a trial of antihelmintics. Signs of end-organ damage included 1) CNS hemiparesis, dysarthria, and MRI-documented small-vessel and white matter abnormalities; 2) myocarditis by cardiac ultrasound; and 3) respiratory distress with interstitial infiltrates. Covid PCR test was positive, so he was given Remdesivir, after which PCR became negative. Increased D-dimers led to enoxaparin, intravenous immunoglobulin, and support. Bone marrow evaluation ruled out an abnormal T-cell population and occult acute lymphoblastic leukemia by flow cytometry and immunohistochemistry. Marrow biopsy showed dysmorphic megakaryocytes, so a myeloid neoplasm could not be excluded. Cytogenetics on the marrow showed a normal karyotype, and myeloid-directed next generation sequencing on the blood was negative for mutations. A lung biopsy showed increased eosinophils within vessels and pleural fibrosis but no interstitial fibrosis or vasculitis. Subcutaneous interferon alfa was given 3 times weekly with no response. The 4 drugs were well tolerated. The boy was followed over 9 months, requiring antibiotics, anticoagulation, and oxygen support. Eosinophilia remained high at 40,000-150,000×109/L. The patient expired from respiratory failure. CONCLUSIONS: HES may be life-threatening in the pediatric population. Diagnosis and therapy can be challenging.


Тема - темы
COVID-19 , Hypereosinophilic Syndrome , Myeloproliferative Disorders , Acute-Phase Proteins/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Child , Enoxaparin/therapeutic use , Fibrosis , Humans , Hydroxyurea/therapeutic use , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/drug therapy , Imatinib Mesylate/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interferon-alpha/therapeutic use , Male , Myeloproliferative Disorders/diagnosis , Oxygen/therapeutic use , Receptor, Platelet-Derived Growth Factor beta/genetics , Receptor, Platelet-Derived Growth Factor beta/therapeutic use , Vitamin B 12
4.
Semin Thromb Hemost ; 48(7): 850-857, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2050627

Реферат

Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008-0-012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH-anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.


Тема - темы
COVID-19 , Hemostatics , Humans , Heparin, Low-Molecular-Weight/therapeutic use , Enoxaparin/therapeutic use , COVID-19/drug therapy , Critical Illness , C-Reactive Protein , Anticoagulants/therapeutic use , Heparin/adverse effects , Viper Venoms , Antithrombins , Factor Xa Inhibitors
7.
Res Social Adm Pharm ; 18(12): 4048-4055, 2022 12.
Статья в английский | MEDLINE | ID: covidwho-1937139

Реферат

BACKGROUND: Many thrombotic complications are linked to coronavirus disease 2019 (COVID-19). Antithrombotic treatments are important for prophylaxis against these thrombotic events. OBJECTIVES: This study was designed to compare enoxaparin and rivaroxaban as prophylactic anticoagulants in moderate cases of COVID-19 in terms of efficacy, safety, and clinical outcomes. METHODS: The study involved 124 patients with moderate COVID-19 (pneumonia without hypoxia) divided into two groups. The first group (G1) comprised 66 patients who received enoxaparin subcutaneously at a dose of 0.5 mg/kg every 12 h until discharge from the hospital. The second group (G2) comprised 58 patients who received oral rivaroxaban at a dose of 10 mg once daily until discharge from the hospital. The outcomes evaluated in this study were as follows: intermediate care unit (IMCU) duration, the number of patients transferred from the IMCU to the intensive care unit (ICU), ICU duration, the total length of hospital stay, in-hospital mortality, and thrombotic and bleeding complications. RESULTS: No significant differences in IMCU duration (p = 0.39), ICU duration (p = 0.96), and total length of hospital stay (p = 0.73) were observed between the two groups. The percentage of patients requiring ICU admission after hospitalization was 21.2% in G1 and 22.4% in G2 (p = 0.87). The mortality rate was 12.1% in G1 and 10.3% in G2 (p = 0.76). The proportion of patients who had thrombotic complications was 9.1% in G1 and 12.1% in G2 (p = 0.59). The incidence of mild bleeding was 3% in G1 and 1.7% in G2 (p = 0.64). CONCLUSION: Either enoxaparin or rivaroxaban may be used as thromboprophylaxis agents in managing patients with moderate COVID-19. Either medication has no clear advantage over the other.


Тема - темы
COVID-19 , Venous Thromboembolism , Humans , Enoxaparin/therapeutic use , Enoxaparin/adverse effects , Anticoagulants/therapeutic use , Rivaroxaban/therapeutic use , Venous Thromboembolism/prevention & control
8.
J Vasc Surg Venous Lymphat Disord ; 10(4): 803-810, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1899994

Реферат

BACKGROUND: Deep vein thrombosis (DVT) has been reported to occur at different rates in patients with coronavirus disease 2019 (COVID-19). Limited data exist regarding comparisons with non-COVID-19 patients with similar characteristics. Our objective was to compare the rates of DVT in patients with and without COVID-19 and to determine the effect of DVT on the outcomes. METHODS: We performed a retrospective, observational cohort study at a single-institution, level 1 trauma center comparing patients with and without COVID-19. The 573 non-COVID-19 patients (age, 61 ± 17 years; 44.9% male) had been treated from March 20, 2019 to June 30, 2019, and the 213 COVID-19 patients (age, 61 ± 16 years; 61.0% male) had been treated during the same interval in 2020. Standard prophylactic anticoagulation therapy consisted of 5000 U of heparin three times daily for the medical patients without COVID-19 who were not in the intensive care unit (ICU). The ICU, surgical, and trauma patients without COVID-19 had received 40 mg of enoxaparin daily (not adjusted to weight). The patients with COVID-19 had also received enoxaparin 40 mg daily (also not adjusted to weight), regardless of whether treated in the ICU. The two primary outcomes were the rate of deep vein thrombosis (DVT) in the COVID-19 group vs that in the historic control and the effect of DVT on mortality. The subgroup analyses included patients with adult respiratory distress syndrome (ARDS), pulmonary embolism (PE), and intensive care unit patients (ICU). RESULTS: The rate of DVT and PE for the non-COVID-19 patients was 12.4% (71 of 573) and 3.3% (19 of 573) compared with 33.8% (72 of 213) and 7.0% (15 of 213) for the COVID-19 patients, respectively. Unprovoked PE had developed in 10 of 15 COVID-19 patients (66.7%) compared with 8 of 497 non-COVID-19 patients (1.6%). The 60 COVID-19 patients with ARDS had had an incidence of DVT of 46.7% (n = 28). In contrast, the incidence of DVT for the 153 non-COVID-19 patients with ARDS was 28.8% (n = 44; P = .01). The COVID-19 patients requiring the ICU had had an increased rate of DVT (39 of 90; 43.3%) compared with the non-COVID-19 patients (33 of 123; 33.3%; P = .01). The risk factors for mortality included age, DVT, multiple organ failure syndrome, and prolonged ventilatory support with the following odd ratios: 1.030 (95% confidence interval [CI], 1.002-1.058), 2.847 (95% CI, 1.356-5.5979), 4.438 (95% CI, 1.973-9.985), and 5.321 (95% CI, 1.973-14.082), respectively. CONCLUSIONS: The incidence of DVT for COVID-19 patients receiving standard-dose prophylactic anticoagulation that was not weight adjusted was high, especially for ICU patients. DVT is one of the factors contributing to increased mortality. These results suggest a reevaluation is necessary of the present standard-dose thromboprophylaxis for patients with COVID-19.


Тема - темы
COVID-19 , Pulmonary Embolism , Respiratory Distress Syndrome , Venous Thromboembolism , Venous Thrombosis , Adult , Aged , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Enoxaparin/therapeutic use , Female , Humans , Incidence , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/epidemiology , Pulmonary Embolism/prevention & control , Retrospective Studies , Venous Thromboembolism/drug therapy , Venous Thrombosis/etiology
9.
Int J Mol Sci ; 23(9)2022 Apr 27.
Статья в английский | MEDLINE | ID: covidwho-1809941

Реферат

Neutrophil Extracellular Traps (NETs) are a contributing factor of vascular thrombosis and alveolar damage in COVID-19 patients. As enoxaparin is currently used to inhibit vascular thrombosis, this study aimed to investigate whether enoxaparin also reduced inflammation and NETs in COVID-19 patients. Patients with COVID-19 infection were classified into three groups: mild, moderate, and severe (n = 10 for all groups). Plasma was collected from patients and healthy donors (n = 10). Neutrophils isolated from healthy controls were incubated with COVID-19 or healthy plasma, and with or without enoxaparin pretreatment in vitro. Neutrophils and plasma isolated from patients treated with enoxaparin were also investigated. The levels of inflammatory cytokines and NET products such as dsDNA, NE, MPO-DNA and Histone-DNA complexes in plasma and supernatants were measured using immunofluorescence staining and ELISA kits. The expression of inflammatory signaling genes by neutrophils (RELA, SYK, ERK and PKC) was measured using real-time qPCR. The levels of NET products were elevated in the plasma of COVID-19 patients, particularly in the severe group (p < 0.01). Moreover, plasma from the severe group enhanced NET formation (p < 0.01) from neutrophils in vitro. Enoxaparin pretreatment in vitro decreased plasma-induced NETs in a dose-dependent manner and down-regulated the expression of inflammatory genes (p < 0.05). Patients treated with prophylactic enoxaparin showed lower inflammatory cytokine levels and expression of inflammatory genes (p < 0.05). Increased NETs were associated with the severity of COVID-19 infection, particularly in patients with severe pneumonia, and could be used as biomarkers to assess disease severity. Enoxaparin pretreatment inhibited NETs and reduced the expression of inflammatory cytokines, and these effects mostly persisted in patients treated with prophylactic enoxaparin.


Тема - темы
COVID-19 , Extracellular Traps , Thrombosis , Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Cytokines/metabolism , DNA/metabolism , Enoxaparin/pharmacology , Enoxaparin/therapeutic use , Extracellular Traps/metabolism , Humans , Neutrophils/metabolism , Thrombosis/drug therapy , Thrombosis/metabolism
10.
Pol Merkur Lekarski ; 50(296): 118-123, 2022 Apr 19.
Статья в английский | MEDLINE | ID: covidwho-1790558

Реферат

COVID-19 patients, particularly those with severe pulmonary involvement, are at an increased thromboembolic risk related, among various causes, to the cytokine storm and excessive activation of the coagulation cascade and platelets. Different intensity of anticoagulation for them is proposed, mainly with low molecular weight heparins (LMWHs); in a confirmed pulmonary embolism (PE) the therapeutic dose of LMWH is routinely used. Some authors suggest that hemorrhagic complications in COVID-19 patients are rare. At the same time, one can find reports on internal bleeding, including retroperitoneal hematoma (RPH) and other abdominal hematomas. CASE REPORTS: The authors describe 5 cases (3 of those aged more than 80 years) with giant RPHs and with moderate/severe COVID-19 pneumonia, treated before RPH diagnosis with different enoxaparin doses. The therapeutic dose was given to the male with verified PE limited to the segmental/subsegmental pulmonary arteries and initially to the female in whom echocardiography was strongly suggestive of PE, yet this diagnosis was excluded on CT angiography. In one patient, the enoxaparin dose was escalated from 40 mg bd to 60 mg bd after the D-dimer increase. Two patients had bleeding complications despite the enoxaparin dose restricted to 40 mg/daily or bd. Two males had a coexistent psoas hematoma while in only one female there was a coexistent femoral hematoma. RPHs occurred between day 4 and 14 of hospitalization and all were treated conservatively. Three patients who died were particularly charged, so their deaths were not merely directly associated with RPH, which was closely analyzed in one autopsy performed. The authors underline that the choice of anticoagulation intensity in patients with COVID-19 pneumonia without venous thromboembolism seems sometimes difficult but recent publications indicate the low prophylactic enoxaparin dose as an optimal option. Anticoagulation dose escalation based only on the D-dimer level may not be appropriate for certain patients; moreover, the D-dimer increase is commonly observed during internal bleeding.


Тема - темы
COVID-19 , Pulmonary Embolism , Adult , Aged , Aged, 80 and over , Anticoagulants , COVID-19/complications , Enoxaparin/adverse effects , Enoxaparin/therapeutic use , Female , Hematoma/chemically induced , Hematoma/drug therapy , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle Aged , Pulmonary Embolism/drug therapy
11.
Biomed Pharmacother ; 149: 112920, 2022 May.
Статья в английский | MEDLINE | ID: covidwho-1767922

Реферат

Since the COVID-19 pandemic started, mesenchymal stromal cells (MSC) appeared as a therapeutic option to reduce the over-activated inflammatory response and promote recovery of lung damage. Most clinical studies use intravenous injection for MSC delivery, raising several concerns of thrombogenic risk due to MSC procoagulant activity (PCA) linked to the expression of tissue factor (TF/CD142). This is the first study that demonstrated procoagulant activity of TF+ human immature dental pulp stromal cells (hIDPSC, NestaCell® product) with the percentage of TF+ cells varied from 0.2% to 63.9% in plasma of healthy donors and COVID-19 heparin-treated patients. Thrombogenic risk of TF+ hIDPSCs was evaluated by rotational thromboelastometry (in vitro) and in critically ill COVID-19 patients (clinical trial). We showed that the thromboelastography is not enough to predict the risk of TF+ MSC therapies. Using TF-negative HUVEC cells, we demonstrated that TF is not a unique factor responsible for the cell's procoagulant activity. However, heparin treatment minimizes MSC procoagulant (in vitro). We also showed that the intravenous infusion of hIDPSCs with prophylactic enoxaparin administration in moderate to critically ill COVID-19 patients did not change the values of D-dimer, neither in the PT and PTT times. Our COVID-19 clinical study measured and selected the therapeutic cells with low TF (less than 25% of TF+ hIDPSCs). Our data indicate that the concomitant administration of enoxaparin and low TF-loaded is safe even for critically ill COVID-19 patients.


Тема - темы
COVID-19 , Thromboplastin , Cell- and Tissue-Based Therapy , Clinical Trials as Topic , Critical Illness , Enoxaparin/pharmacology , Enoxaparin/therapeutic use , Heparin , Humans , Pandemics , Thromboplastin/metabolism
12.
J Am Coll Cardiol ; 79(9): 917-928, 2022 03 08.
Статья в английский | MEDLINE | ID: covidwho-1706820

Реферат

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).


Тема - темы
Anticoagulants/therapeutic use , COVID-19/complications , Thromboembolism/prevention & control , Thrombosis/prevention & control , COVID-19/therapy , Critical Care , Enoxaparin/therapeutic use , Hospitalization , Humans , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thromboembolism/virology , Thrombosis/virology
13.
Am J Trop Med Hyg ; 105(6): 1472-1475, 2021 Oct 04.
Статья в английский | MEDLINE | ID: covidwho-1629955

Реферат

Human lives and nations' economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.


Тема - темы
COVID-19/drug therapy , Piperidines/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cytokine Release Syndrome/prevention & control , Cytokines/genetics , Cytokines/metabolism , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Female , Gene Expression Regulation/drug effects , Humans , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Piperidines/administration & dosage , Prednisone/administration & dosage , Prednisone/therapeutic use , Pyrimidines/administration & dosage
14.
Eur J Clin Invest ; 52(5): e13735, 2022 May.
Статья в английский | MEDLINE | ID: covidwho-1583578

Реферат

BACKGROUND: It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards METHODS: This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. versus 40 mg o.d. enoxaparin in COVID-19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding. RESULTS: The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5-11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm. CONCLUSIONS: No DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.


Тема - темы
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Anticoagulants , COVID-19/complications , Enoxaparin/therapeutic use , Hemorrhage/chemically induced , Humans , Pulmonary Embolism/epidemiology , Venous Thromboembolism/epidemiology
15.
J Med Virol ; 94(1): 291-297, 2022 01.
Статья в английский | MEDLINE | ID: covidwho-1544344

Реферат

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.


Тема - темы
COVID-19/drug therapy , COVID-19/mortality , Critical Care/statistics & numerical data , Severity of Illness Index , Aged , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/therapeutic use , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/pathology , Comorbidity , Drug Combinations , Enoxaparin/therapeutic use , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Pyrazines/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , Turkey/epidemiology
16.
N Engl J Med ; 385(7): 609-617, 2021 08 12.
Статья в английский | MEDLINE | ID: covidwho-1354155

Реферат

BACKGROUND: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation. METHODS: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery. RESULTS: Venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group. CONCLUSIONS: This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).


Тема - темы
Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , Arthroplasty, Replacement, Knee , Enoxaparin/therapeutic use , Factor XI/antagonists & inhibitors , Postoperative Complications/prevention & control , Venous Thromboembolism/prevention & control , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Dose-Response Relationship, Drug , Enoxaparin/adverse effects , Factor XI/metabolism , Female , Hemorrhage/chemically induced , Humans , Infusions, Intravenous , Injections, Subcutaneous , Male , Middle Aged , Partial Thromboplastin Time
17.
Clin Drug Investig ; 41(8): 723-732, 2021 Aug.
Статья в английский | MEDLINE | ID: covidwho-1333143

Реферат

BACKGROUND AND OBJECTIVE: Low-dose acetylsalicylic acid (ASA, aspirin) is a well-known and frequently studied drug for primary and secondary prevention of disease due to its anti-inflammatory and coagulopathic effects. COVID-19 complications are attributed to the role of thrombo-inflammation. Studies regarding the use of low-dose ASA in COVID-19 are limited. For this reason, we propose that the use of low-dose ASA may have protective effects in COVID-19-related thromboembolism and lung injury. This study was conducted to assess the efficacy of low-dose ASA compared with enoxaparin, an anticoagulant, for the prevention of thrombosis and mechanical ventilation. METHODS: We conducted a retrospective cohort study on COVID-19-confirmed hospitalized patients at the Mansoura University Quarantine Hospital, outpatients, and home-isolated patients from September to December 2020 in Mansoura governorate, Egypt. Binary logistic regression analysis was used to assess the effect of ASA compared with enoxaparin on thromboembolism, and mechanical ventilation needs. RESULTS: This study included 225 COVID-19 patients. Use of ASA-only (81-162 mg orally daily) was significantly associated with reduced thromboembolism (OR 0.163, p = 0.020), but both low-dose ASA and enoxaparin, and enoxaparin-only (0.5 mg/kg subcutaneously (SC) daily as prophylactic dose or 1 mg/kg SC every 12 hours as therapeutic dose) were more protective (odds ratio [OR] 0.010, OR 0.071, respectively, p < 0.001). Neither ASA-only nor enoxaparin-only were associated with a reduction in mechanical ventilation needs. Concomitant use of low-dose ASA and enoxaparin was associated with reduced mechanical ventilation (OR 0.032, 95% CI 0.004-0.226, p = 0.001). CONCLUSIONS: Low-dose ASA-only use may reduce the incidence of COVID-19-associated thromboembolism, but the reduction may be less than that of enoxaparin-only, and both ASA and enoxaparin. Concomitant use of ASA and enoxaparin demonstrates promising results with regard to the reduction of thrombotic events, and mechanical ventilation needs.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , Aspirin , Enoxaparin/therapeutic use , Humans , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Thrombosis/prevention & control
18.
Thromb Res ; 205: 120-127, 2021 09.
Статья в английский | MEDLINE | ID: covidwho-1324320

Реферат

BACKGROUND: In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing. OBJECTIVES: To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients. METHODS: This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration. RESULTS: A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment. CONCLUSION: In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels.


Тема - темы
COVID-19 , Enoxaparin , Anticoagulants , Critical Illness , Enoxaparin/therapeutic use , Humans , Retrospective Studies , SARS-CoV-2
19.
Am Heart J ; 238: 1-11, 2021 08.
Статья в английский | MEDLINE | ID: covidwho-1309127

Реферат

BACKGROUND: Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation. DESIGN: ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) vs standard of care with any approved venous thromboembolism prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following efficacy outcomes: incidence of venous thromboembolism , acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria. SUMMARY: The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels.


Тема - темы
Anticoagulants/therapeutic use , COVID-19/complications , Enoxaparin/therapeutic use , Rivaroxaban/therapeutic use , Thrombosis/prevention & control , Administration, Oral , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Brazil , COVID-19/blood , COVID-19/mortality , Drug Administration Schedule , Enoxaparin/administration & dosage , Enoxaparin/adverse effects , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/chemically induced , Hospitalization , Humans , Oxygen Inhalation Therapy , Rivaroxaban/administration & dosage , Rivaroxaban/adverse effects , Thrombosis/etiology , Time Factors
20.
Viruses ; 13(6)2021 06 01.
Статья в английский | MEDLINE | ID: covidwho-1259619

Реферат

In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.


Тема - темы
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , COVID-19/immunology , Clinical Laboratory Techniques , Dexamethasone/therapeutic use , Disseminated Intravascular Coagulation/drug therapy , Enoxaparin/therapeutic use , Female , Humans , Middle Aged , SARS-CoV-2/immunology , Vaccination
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