Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 858
Filter
1.
J Am Soc Nephrol ; 33(2): 442-453, 2022 02.
Article in English | MEDLINE | ID: covidwho-2141040

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.


Subject(s)
Atrial Fibrillation/complications , Atrial Fibrillation/therapy , Renal Insufficiency, Chronic/complications , Adult , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/therapeutic use , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Cohort Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Multivariate Analysis , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index , Warfarin/therapeutic use
2.
J Thromb Haemost ; 20(11): 2457-2464, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2137109

ABSTRACT

Pulmonary embolism response teams (PERTs) have emerged as a multidisciplinary, multispecialty team of experts in the care of highly complex symptomatic acute pulmonary embolism (PE), with a centralized unique activation process, providing rapid multimodality assessment and risk stratification, formulating the best individualized diagnostic and therapeutic approach, streamlining the care in challenging clinical case scenarios (e.g., intermediate-high risk and high-risk PE), and facilitating the implementation of the recommended therapeutic strategies on time. PERTs are currently changing how complex acute PE cases are approached. The structure, organization, and function of a given PERT may vary from hospital to hospital, depending on local expertise, specific resources, and infrastructure for a given academic hospital center. Current emerging data demonstrate the value of PERTs in improving time to PE diagnosis; shorter time to initiation of anticoagulation reducing hospital length of stay; increasing use of advanced therapies without an increase in bleeding; and in some reports, decreasing mortality. Importantly, PERTs are positively impacting outcomes by changing the paradigm of care for acute PE through global adoption by the health-care community.


Subject(s)
Pulmonary Embolism , Humans , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapy , Hemorrhage , Acute Disease , Anticoagulants/therapeutic use
3.
Infection ; 50(6): 1453-1463, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2129441

ABSTRACT

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).


Subject(s)
Anticoagulants , COVID-19 , Humans , Anticoagulants/therapeutic use , Network Meta-Analysis , COVID-19/drug therapy
6.
Clin Appl Thromb Hemost ; 28: 10760296221137848, 2022.
Article in English | MEDLINE | ID: covidwho-2117653

ABSTRACT

The aim was to describe inpatients with COVID-19 empirically prescribed heparinoid anticoagulants and compare resource utilization between prophylactic/low-dose and therapeutic/high-dose groups. Methods: This retrospective observational study used real-world data from 880 US hospitals in the PINC AI™ Healthcare Database during 4/1/2020-11/30/2020. Descriptive analysis was used to characterize patients. Multivariable regression was used to evaluate intensive care unit (ICU) admissions, length of stay (LOS), mortality, and costs by anticoagulation dose group, adjusting for cohort characteristics. Among 122,508 inpatients, 29,225 (23.9%) received therapeutic/high-dose, and 93,283 (76.1%) received prophylactic/low-dose anticoagulation. The high-dose group had more comorbidities and worse laboratory values compared with low-dose. Respectively, ICU admission rates were 36.7% and 19.1% and LOS median (Q1, Q3) was 8 (5, 15) and 5 (3, 9) days. In separate adjusted models, high-dose anticoagulation was associated with a 45% increase in odds of ICU admission, 26% increase in odds of in-hospital mortality, 21% longer average LOS, and 28% greater average total cost compared with low-dose (each P < 0.001). Prophylactic/low-dose anticoagulation treatment was associated with decreased healthcare resource utilization (HRU) in hospitalized patients with COVID-19.


Subject(s)
COVID-19 , Heparinoids , Humans , Anticoagulants/therapeutic use , COVID-19/drug therapy , Hospitalization , Intensive Care Units , Retrospective Studies , Patient Acceptance of Health Care
7.
J Ayub Med Coll Abbottabad ; 34(3): 557-562, 2022.
Article in English | MEDLINE | ID: covidwho-2115707

ABSTRACT

BACKGROUND: Coronavirus disease 19 (COVID-19) is a viral disease caused by SARS-CoV-2. There is an increased incidence of a thromboembolic phenomenon in patients with COVID-19 infection. Pulmonary embolism is the most common thrombotic presentation in COVID-19 patients. Extra-pulmonary thrombosis is an unusual thrombotic complication of COVID-19 disease. METHODS: This study was conducted at The Aga Khan University Hospital from June-July'2021. Patients clinical and laboratory findings, treatment, and outcomes were recorded. RESULTS: We report three cases with the diagnosis of COVID-19 pneumonia associated with extra-pulmonary thrombosis from June to July 2021. The mean age of the patients were 66.3 and two of them (66.6%) were male. The diagnosis of COVID-19 was confirmed by real-time reverse transcriptase-polymerase chain reaction analysis in all the three patients. Extra-pulmonary thrombosis was identified in the celiac artery and splenic veins in case 1, left common iliac artery in case 2, and left ventricular apical thrombus in case 3. All the patients were treated with anticoagulation. In total, two patients were discharged home after total recovery, while the third patient died. CONCLUSIONS: The take-home message is that COVID-19 infection is a pro-thrombotic condition that can provoke arterial and venous thrombosis. Extra-pulmonary thrombosis is increasingly identified with COVID-19 infection. It is important to remember that the patient might have no potential risk factor for thromboses, as COVID-19 infection per se is a risk to induce thrombosis.


Subject(s)
COVID-19 , Thrombosis , Venous Thrombosis , Humans , Male , Female , COVID-19/complications , SARS-CoV-2 , Anticoagulants/therapeutic use , Venous Thrombosis/etiology , Thrombosis/etiology
8.
J Med Microbiol ; 71(11)2022 Nov.
Article in English | MEDLINE | ID: covidwho-2107718

ABSTRACT

Introduction. Coronavirus disease 2019 (COVID-19) identified in December 2019 in Wuhan, China, is associated with high mortality rates worldwide.Hypothesis/Gap Statement. Thrombotic problems, such as coagulopathy, are common in COVID-19 patients. Despite anticoagulation, thrombosis is more common in patients in the intensive care unit and patients with more severe disease. Although the exact mechanisms of coagulopathy in COVID-19 patients are still unclear, studies showed that overactivation of the renin-angiotensin system (RAS), cytokine storm, endothelial damage, formation of neutrophil extracellular traps (NETs), and also extracellular vesicles (EVs) in response to COVID-19 induced inflammation can lead to systemic coagulation and thrombosis.Aim. The management of COVID-19 patients requires the use of basic and readily available laboratory markers, both on admission and during hospitalization. Because it is critical to understand the pathophysiology of COVID-19 induced coagulopathy and treatment strategies, in this review we attempt to explain the underlying mechanism of COVID-19 coagulopathy, its diagnosis, and the associated successful treatment strategies.Conclusion. The exact mechanisms behind COVID-19-related coagulopathy are still unclear, but several studies revealed some mechanisms. More research is needed to determine the best anticoagulant regimen and to study other therapeutic options.


Subject(s)
COVID-19 , Thrombosis , Humans , COVID-19/complications , SARS-CoV-2 , Thrombosis/drug therapy , Anticoagulants/therapeutic use , China
9.
Respir Res ; 23(1): 296, 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2098345

ABSTRACT

BACKGROUND: Anticoagulant treatment is recommended for at least three months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related acute pulmonary embolism (PE), but the persistent pulmonary clot burden after that time is unknown. METHODS: Lung perfusion was assessed by ventilation-perfusion (V/Q) SPECT/CT in 20 consecutive patients with SARS-CoV-2-associated acute PE after a minimum of three months anticoagulation therapy in a retrospective observational study. RESULTS: Remaining perfusion defects after a median treatment period of six months were observed in only two patients. All patients (13 men, seven women, mean age 55.6 ± 14.5 years) were on non-vitamin K direct oral anticoagulants (DOACs). No recurrent venous thromboembolism or anticoagulant-related bleeding complications were observed. Among patients with partial clinical recovery, high-risk PE and persistent pulmonary infiltrates were significantly more frequent (p < 0.001, respectively). INTERPRETATION: Temporary DOAC treatment seems to be safe and efficacious for resolving pulmonary clot burden in SARS-CoV-2-associated acute PE. Partial clinical recovery is more likely caused by prolonged SARS-CoV-2-related parenchymal lung damage rather than by persistent pulmonary perfusion defects.


Subject(s)
COVID-19 , Pulmonary Embolism , Male , Humans , Female , Adult , Middle Aged , Aged , SARS-CoV-2 , COVID-19/complications , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Lung/diagnostic imaging , Single Photon Emission Computed Tomography Computed Tomography , Anticoagulants/therapeutic use , Acute Disease , Perfusion
10.
Blood ; 140(8): 809-814, 2022 08 25.
Article in English | MEDLINE | ID: covidwho-2083050

ABSTRACT

Coronavirus disease-19 (COVID-19) includes a thromboinflammatory syndrome that may manifest with microvascular and macrovascular thrombosis. Patients with COVID-19 have a higher incidence of venous thromboembolism than other hospitalized patients. Three randomized control trials suggesting benefit of therapeutic heparin in hospitalized noncritically ill patients with COVID-19 have led to conditional guideline recommendations for this treatment. By contrast, prophylactic-dose heparin is recommended for critically ill patients. Unprecedented collaboration and rapidly funded research have improved care of hospitalized patients with COVID-19.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Blood Coagulation , COVID-19/complications , Heparin/pharmacology , Heparin/therapeutic use , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
11.
Int J Mol Sci ; 23(20)2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2082320

ABSTRACT

Recent research has contributed significantly to our understanding of the pathogenesis of acute disseminated intravascular coagulation. COVID-19 can be considered as a new underlying condition of disseminated intravascular coagulation. In this narrative review, current evidence is presented regarding biomarker differences between sepsis-induced and COVID-19-associated coagulopathies, supporting the importance of acquired antithrombin deficiency in the early differential diagnosis of septic coagulopathy and its potential impact on treatment with endogenous anticoagulants. Establishing new scoring systems for septic coagulopathy in combination with endogenous anticoagulant biomarker activities may allow for the identification of those in the heterogeneous population of sepsis patients who are more likely to benefit from targeted specific treatment interventions.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Disseminated Intravascular Coagulation , Sepsis , Humans , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Antithrombins/therapeutic use , COVID-19/complications , Anticoagulants/therapeutic use , Anticoagulants/pharmacology , Blood Coagulation Disorders/complications , Sepsis/complications , Antithrombin III , Biomarkers
12.
Ulus Travma Acil Cerrahi Derg ; 28(10): 1468-1474, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2081059

ABSTRACT

BACKGROUND: There has been an increased incidence of rectus sheath hematoma (RSH) due to chronic cough attacks and anti-coagulant therapy due to the COVID-19 pandemic. The present study aims to determine, in which parameters differ before and during the diagnosis of RSH in COVID-19 patients and what may be expected during diagnosis and follow-up. METHODS: Thirty-five patients diagnosed with RSH were evaluated retrospectively between March 2016 and March 2021. The COVID-19 group comprised 11 patients. Various information including patient history and time of discharge/death were retrieved and compared between the experimental groups. RESULTS: The rates of hypotension on admission (p=0.011) and the rates of defense and rebound (p=0.030) were higher in the patients with COVID-19 than in those without. Although there was no difference in terms of bleeding width, there was a greater decrease in the hemoglobin levels (p=0.009) in the COVID-19 patients and the need for erythrocyte suspension (p=0.040) increased significantly in that group. CONCLUSION: The present study constitutes the first evaluation of RSH in COVID-19 patients. The clinical situation is serious due to high rates of hypotension, defense or rebound, and decreases in hemoglobin levels in COVID-19 patients. This makes the clinical management of RSH more difficult, resulting in longer hospitalization. Despite these difficulties, COVID-19 infection does not increase morbidity or mortality.


Subject(s)
COVID-19 , Hypotension , Muscular Diseases , Anticoagulants/therapeutic use , COVID-19 Testing , Follow-Up Studies , Gastrointestinal Hemorrhage , Hematoma/diagnosis , Hematoma/etiology , Hematoma/therapy , Hemoglobins , Humans , Hypotension/complications , Hypotension/drug therapy , Muscular Diseases/complications , Muscular Diseases/drug therapy , Pandemics , Rectus Abdominis , Retrospective Studies
13.
Ann Saudi Med ; 42(5): 305-308, 2022.
Article in English | MEDLINE | ID: covidwho-2080739

ABSTRACT

BACKGROUND: COVID-19 infection affects the quality of the medical services globally. The pandemic required changes to medical services in several institutions. We established a virtual clinic for anticoagulation management during the pandemic using the Whatsapp application. OBJECTIVES: Compare anticoagulation management quality in virtual versus in-person clinics. DESIGN: A retrospective crossover study SETTINGS: Specialized cardiac care center PATIENTS AND METHODS: The study included patients who presented to Prince Sultan Cardiac Center in Riyadh for anticoagulation management during the pandemic from March 2020 to January 2021. We compared time in therapeutic range (TTR) in the same patients during virtual and in-person clinics. All international normalized ratio (INR) measures during the virtual clinic visits and prior ten INR measures from the in-person clinic were recorded. Patients who had no prior follow-up in the in-person clinic were excluded. MAIN OUTCOME MEASURE: TTR calculated using the Rosendaal method. SAMPLE SIZE: 192 patients RESULTS: The mean age was 58.6 (16.6) years and 116 (60.4%) were males. Patients were diagnosed with atrial fibrillation (n=101, 52.6%), mechanical mitral valve (n=88, 45.8%), mechanical aortic valve (n=79, 41%), left ventricular thrombus (n=5, 2.6%) and venous thromboembolism (n=8, 4.2%). Riyadh residents represented 56.7% of the study population (n=93). The median (IQR) percent TTR was 54.6 (27.3) in the in-person clinic versus 50.0 (33.3) (P=.07). CONCLUSION: Virtual clinic results were comparable to in-person clinics for anticoagulation management during the COVID-19 pandemic. LIMITATIONS: Number of INR measures during the virtual clinic visits, retrospective nature and single-center experience. CONFLICT OF INTEREST: None.


Subject(s)
COVID-19 , Warfarin , Anticoagulants/therapeutic use , Cross-Over Studies , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Warfarin/therapeutic use
14.
Medicine (Baltimore) ; 101(37): e30367, 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2077953

ABSTRACT

In patients with coronavirus disease 2019 (COVID-19), anticoagulation was suggested as a mitigating strategy. However, little research has been conducted on the adverse consequences of anticoagulant medication. This study aimed to investigate the adverse effect of low molecular weight heparin (LMWH) on hemoglobin fall in COVID-19 treatment. The electronic medical records of COVID-19 patients with pneumonia were collected (including clinical characteristics, vaccination status, complete blood count, coagulation profile, inflammatory cytokines, serum biochemical indicators, and computerized tomography imaging score). Whether they received LMWH, patients were divided into the LMWH group and the control group. Count data were represented as frequency distribution, and a 2-tailed test was used to compare the 2 groups. Spearman rank correlation was used to evaluate the interrelation between changes in hemoglobin and LMWH. The confounding factors were excluded by logistic regression analysis. A total of 179 COVID-19 pneumonia patients were enrolled (81 in the LMWH group and 98 in the control group). The change in hemoglobin was -6.0g/L (IQR -10.8 to 1.0) in the LMWH group and -2.0g/L (IQR -7.0 to 4.0) in the control group (P < .001, between-group difference, -5.0 g/L; 95% confidence interval, -7.0 to -3.0, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). The results of multivariate regression analysis showed that after adjusting for confounding factors, LMWH use was not associated with a decrease in hemoglobin (P > .05). In nonsevere COVID-19 patients with pneumonia, the preventive use of LMWH did not lower hemoglobin.


Subject(s)
COVID-19 , Pneumonia , Anticoagulants/therapeutic use , COVID-19/drug therapy , Cytokines , Hemoglobins , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pneumonia/drug therapy
15.
Sci Rep ; 12(1): 17408, 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2077099

ABSTRACT

Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.


Subject(s)
Acute Kidney Injury , COVID-19 , Thrombosis , Humans , Nadroparin/adverse effects , Critical Illness , Prospective Studies , COVID-19/complications , Anticoagulants/therapeutic use , Thrombosis/prevention & control
16.
Int J Mol Sci ; 23(20)2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2071505

ABSTRACT

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/drug therapy , Molecular Docking Simulation , Coronavirus 3C Proteases , Molecular Dynamics Simulation , Fondaparinux , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Dabigatran , Ticagrelor , Eptifibatide , Gentian Violet , Protease Inhibitors/chemistry , Viral Nonstructural Proteins/metabolism , Heparin/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry
17.
Clin Exp Rheumatol ; 40(8): 1461-1471, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2067772

ABSTRACT

This review highlights publications on different aspects of Behçet's syndrome (BS) that appeared in 2021 and provides a critical view. These publications include works on the epidemiology of BS across different continents, newly developed instruments to assess damage in BS, studies highlighting the immunopathogenesis, genetics and epigenetic factors, histopathology of the pathergy lesion, clinical and imaging aspects of vascular involvement, and safety and efficacy of therapeutic agents including tocilizumab, apremilast and direct oral anticoagulants.


Subject(s)
Behcet Syndrome , Anticoagulants/therapeutic use , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Behcet Syndrome/epidemiology , Humans
18.
Clin Lymphoma Myeloma Leuk ; 22 Suppl 2: S322, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2062037

ABSTRACT

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.


Subject(s)
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
19.
BMJ Open ; 12(9): e063855, 2022 09 26.
Article in English | MEDLINE | ID: covidwho-2053218

ABSTRACT

INTRODUCTION: The use of fibrinolytic therapy has been proposed in severe acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, anticoagulation has received special attention due to the frequent findings of microthrombi and fibrin deposits in the lungs and other organs. Therefore, the use of fibrinolysis has been regarded as a potential rescue therapy in these patients. In this prospective meta-analysis, we plan to synthesise evidence from ongoing clinical trials and thus assess whether fibrinolytic therapy can improve the ventilation/perfusion ratio in patients with severe COVID-19-caused ARDS as compared with standard of care. METHODS AND ANALYSIS: This protocol was registered in PROSPERO. All randomised controlled trials and prospective observational trials that compare fibrinolytic therapy with standard of care in adult patients with COVID-19 and define their primary or secondary outcome as improvement in oxygenation and/or gas exchange, or mortality will be considered eligible. Safety outcomes will include bleeding event rate and requirement for transfusion. Our search on 25 January 2022 identified five eligible ongoing clinical trials. A formal search of MEDLINE (via PubMed), Embase, CENTRAL will be performed every month to identify published results and to search for further trials that meet our eligibility criteria. DISSEMINATION: This could be the first qualitative and quantitative synthesis summarising evidence of the efficacy and safety of fibrinolytic therapy in critically ill patients with COVID-19. We plan to publish our results in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021285281.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Anticoagulants/therapeutic use , Critical Illness/therapy , Fibrin , Humans , Meta-Analysis as Topic , Observational Studies as Topic , Pandemics , Prospective Studies , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Thrombolytic Therapy , Treatment Outcome
20.
Semin Thromb Hemost ; 48(7): 850-857, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2050627

ABSTRACT

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.


Subject(s)
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
SELECTION OF CITATIONS
SEARCH DETAIL