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2.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(3. Vyp. 2): 33-37, 2021.
Artículo en Ruso | MEDLINE | ID: mdl-33908230

RESUMEN

OBJECTIVE: To assess the safety and efficacy of Revelisa in patients with ischemic stroke in real-world clinical practice. MATERIAL AND METHODS: The interim analysis of an open-label, prospective, multicenter, non-interventional study IVT-AIS-R included 223 patients (50.2% women and 49.8% men, mean age 66.6 (13.5) years) with ischemic stroke who were admitted to the study sites since July 2019 and who, in the absence of contraindications, underwent thrombolytic therapy (TLT) with Revelisa within the first 4.5 hours from the onset of stroke. Data were collected as a continuous sample. According to the reperfusion therapy protocol for ischemic stroke, all patients included in the study underwent clinical examination, investigations and laboratory tests before TLT and within the first days after it. Symptomatic hemorrhagic transformation was determined in accordance with the ECASS 3 criteria. RESULTS: Most of the patients (96%) had hypertension, 74% of patients had chronic heart failure, 57.4% had coronary artery disease, of which 8.5% were patients with a previous myocardial infarction. Various cardiac arrhythmias were observed in 33.2% of cases, 21.5% of patients had type 2 diabetes, 18.4% had a history of previous acute cerebrovascular accidents. Hemorrhagic transformation (HT) of a cerebral lesion developed in 7.1% of cases, with the frequency of symptomatic HT being 3.1% (7 patients). The hospital mortality rate was 13.9%. The median NIHSS score was 4 points (p<0.0001) on day 7 versus baseline. The proportion of patients with good functional recovery (the modified Rankin scale score 0-2) at discharge was 48.2%. CONCLUSION: The data obtained with the use of Revelisa in patients with ischemic stroke in real-world clinical practice allow drawing conclusions about a comparable safety and efficacy profile to that in previously published registry studies of alteplase.


Asunto(s)
Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Resultado del Tratamiento
3.
Nat Commun ; 12(1): 2286, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33863882

RESUMEN

We recently discovered that Mfsd2b, which is the S1P exporter found in blood cells. Here, we report that Mfsd2b is critical for the release of all S1P species in both resting and activated platelets. We show that resting platelets store S1P in the cytoplasm. After activation, this S1P pool is delivered to the plasma membrane, where Mfsd2b is predominantly localized for export. Employing knockout mice of Mfsd2b, we reveal that platelets contribute a minor amount of plasma S1P. Nevertheless, Mfsd2b deletion in whole body or platelets impairs platelet morphology and functions. In particular, Mfsd2b knockout mice show significantly reduced thrombus formation. We show that loss of Mfsd2b affects intrinsic platelet functions as part of remarkable sphingolipid accumulation. These findings indicate that accumulation of sphingolipids including S1P by deletion of Mfsd2b strongly impairs platelet functions, which suggests that the transporter may be a target for the prevention of thrombotic disorders.


Asunto(s)
Plaquetas/metabolismo , Lisofosfolípidos/metabolismo , Proteínas de la Membrana/metabolismo , Esfingosina/análogos & derivados , Trombosis de la Vena/patología , Animales , Plaquetas/citología , Plaquetas/efectos de los fármacos , Citoplasma/metabolismo , Modelos Animales de Enfermedad , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , Pruebas de Función Plaquetaria , Esfingosina/metabolismo , Trombosis de la Vena/sangre , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/tratamiento farmacológico
4.
Sci Rep ; 11(1): 8497, 2021 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-33875764

RESUMEN

The burden of COVID-19 has been noted to be disproportionately greater in minority women, a population that is nevertheless still understudied in COVID-19 research. We conducted an observational study to examine COVID-19-associated mortality and cardiovascular disease outcomes after testing (henceforth index) among a racially diverse adult women veteran population. We assembled a retrospective cohort from a Veterans Affairs (VA) national COVID-19 shared data repository, collected between February and August 2020. A case was defined as a woman veteran who tested positive for SARS-COV-2, and a control as a woman veteran who tested negative. We used Kaplan-Meier curves and the Cox proportional hazards model to examine the distribution of time to death and the effects of baseline predictors on mortality risk. We used generalized linear models to examine 60-day cardiovascular disease outcomes. Covariates studied included age, body mass index (BMI), and active smoking status at index, and pre-existing conditions of diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and a history of treatment with antiplatelet or anti-thrombotic drug at any time in the 2 years prior to the index date. Women veterans who tested positive for SARS-CoV-2 had 4 times higher mortality risk than women veterans who tested negative (Hazard Ratio 3.8, 95% Confidence Interval CI 2.92 to 4.89) but had lower risk of cardiovascular events (Odds Ratio OR 0.78, 95% CI 0.66 to 0.92) and developing new heart disease conditions within 60 days (OR 0.67, 95% CI 0.58 to 0.77). Older age, obesity (BMI > 30), and prior CVD and COPD conditions were positively associated with increased mortality in 60 days. Despite a higher infection rate among minority women veterans, there was no significant race difference in mortality, cardiovascular events, or onset of heart disease. SARS-CoV-2 infection increased short-term mortality risk among women veterans similarly across race groups. However, there was no evidence of increased cardiovascular disease incidence in 60 days. A longer follow-up of women veterans who tested positive is warranted.


Asunto(s)
/patología , Enfermedades Cardiovasculares/diagnóstico , Adulto , Índice de Masa Corporal , /mortalidad , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Fumar
5.
Blood Coagul Fibrinolysis ; 32(3): 167-171, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33827111

RESUMEN

Coronavirus disease 2019 infection produce a prothrombotic state. This is initiated through multiple pathways and is finally aggravated by cross talks with cytokine storm and neutrophil, platelet, complement activation. All these combine towards the second week of illness to produce thrombosis in the lung capillaries surrounding the alveolus producing characteristic pulmonary dysfunction (PaO2/FiO2 > 300, normal or minimally increased lung compliance and very high d-dimer levels) and a high rate of peripheral venous thrombosis. International and many national guidelines have approached this state in different ways but all emphasized the need for management and prevention of widespread thrombosis. It is felt more aggressive and graded thrombosis prevention and management should be initiated early in the treatment. d-Dimer, neutrophil count, SaO2, fibrinogen levels should be used to control the hypercoagulability. Drugs like statins which have anti-inflammatory action as well as ability to reduce fibrinogen and other clotting factors should be used in the beginning along with antiplatelet drugs and progressively complement activation and neutrophil extracellular traps inhibitors, oral mucopolysaccharides, full-scale anticoagulation along with judicial use of fibrinolysis supporting drugs should be added. In the present review, we have evaluated the various studies and argued the rationality that the anticoagulation in this condition should be initiated early during the infection and should be increased in a graded manner depending on clinical and laboratory progression of the condition until a strong specific antiviral drug for coronavirus disease 2019 infection is available.


Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , /fisiopatología , Trombofilia/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Antivirales/uso terapéutico , Plaquetas/efectos de los fármacos , Trampas Extracelulares/efectos de los fármacos , Fibrinolíticos/uso terapéutico , Glicosaminoglicanos/farmacología , Glicosaminoglicanos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inflamación/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Pulmón/virología , Inhibidores de Agregación Plaquetaria/uso terapéutico
7.
Physiology (Bethesda) ; 36(3): 160-173, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33904788

RESUMEN

Beyond blood pressure control, angiotensin receptor blockers reduce common injury mechanisms, decreasing excessive inflammation and protecting endothelial and mitochondrial function, insulin sensitivity, the coagulation cascade, immune responses, cerebrovascular flow, and cognition, properties useful to treat inflammatory, age-related, neurodegenerative, and metabolic disorders of many organs including brain and lung.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antivirales/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , /efectos de los fármacos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Animales , Antiinflamatorios/uso terapéutico , Antihipertensivos/uso terapéutico , Antivirales/efectos adversos , /fisiopatología , Fibrinolíticos/uso terapéutico , Humanos , /patogenicidad
8.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33804911

RESUMEN

BACKGROUND: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. METHODS: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. RESULTS: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110δ inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. CONCLUSION: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.


Asunto(s)
Plaquetas/efectos de los fármacos , Fibrinolíticos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Purinas/farmacología , Quinazolinonas/farmacología , Trombosis/tratamiento farmacológico , Animales , Plaquetas/metabolismo , Plaquetas/fisiología , Calcio/metabolismo , Células Cultivadas , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Adhesividad Plaquetaria , Inhibidores de Proteínas Quinasas/uso terapéutico , Purinas/uso terapéutico , Quinazolinonas/uso terapéutico
9.
Neurosciences (Riyadh) ; 26(2): 179-185, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33814371

RESUMEN

OBJECTIVES: To assess low dose altepase outcome and safety in comparison with a standard-dose regimen for acute ischemic stroke treatment in Egyptian patients. MATERIALS: An observational prospective cohort non-randomized single blinded study was carried out during the period from November 2017 to December 2018. Eighty Egyptian acute ischemic stroke patients, all eligible for intravenous alteplase, were subdivided into 2 groups (40 patients in each group). Patients were thrombolysed at a dose of 0.6 mg/kg in the first group and 0.9 mg/kg in the second group. Both groups were compared in regard to safety and outcome. Safety was expressed by the rate of symptomatic intracranial hemorrhage (SICH) and 3 months mortality, while outcome was expressed by favorable outcomes at three months (modified Rankin Scale [mRS] of 0 to 2). RESULTS: In the first group, 69.2% (n=27) achieved favorable outcomes at 90 days compared with 64.1% (n=25) in the second group (p=0.631). Ninety-day mortality was 5% (n=2) in the first group versus 2.5% (n=1) in the second group (p=0.556). Symptomatic intracranial hemorrhage was noted in 3 patients in the second group and zero patients in the first group (p=0.077). CONCLUSION: Low-dose alteplase could be a practical alternative for Egyptian populations with acute ischemic stroke especially in 3 to 4.5 hours window.


Asunto(s)
Fibrinolíticos/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Administración Intravenosa , Anciano , Relación Dosis-Respuesta a Droga , Egipto , Femenino , Fibrinolíticos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo , Activador de Tejido Plasminógeno/administración & dosificación , Resultado del Tratamiento
10.
Neurosciences (Riyadh) ; 26(2): 199-206, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33814374

RESUMEN

OBJECTIVES: To present the experience on stroke thrombolysis of a tertiary care center in Riyadh, KSA. METHODS: Cross-sectional, observational study of patients thrombolyzed between January 2012 and December 2018. RESULTS: Thrombolysis was performed in 148 patients (mean age: 58.2±14.5 years), 94 (63.5%) of them were men. The median onset-to-door time was 81 minutes, and 25% of the patients arrived within 1 hour. The median National Institute of Health Stroke Scale score upon admission was 13. Hypertension (68.9%), diabetes (56.1%), and dyslipidemia (40.5%) were the most common risk factors for stroke. The most common mechanism of stroke was cardioembolism (43.2%), which was associated with a more severe presentation (p=0.031). Intravenous thrombolysis alone was given to 98 patients (66.2%); the rest received intravenous tissue plasminogen activator plus endovascular therapy or endovascular therapy alone. The median door-to-needle (DTN) time was 70.5 min, with a significant improvement from 2012 (111.6 minutes) to 2018 (69.9 minutes) (p<0.001). Among the patients, 53 (35.8%) showed a good outcome (with a modified Rankin score of 0-2) whereas 14 (9.5%) died. Symptomatic intracranial hemorrhage (sICH) was seen in 8.1%. All vascular risk factors were more common in patients aged >60 years, except smoking, which was more common in the younger age group (p=0.007). CONCLUSION: In our cohort, the utilization of thrombolysis and the DTN time improved over time. One-thirds of the patients received endovascular treatment. Moreover, the frequency of the vascular risk factors was high. Compared with the published findings, our results showed that cardioembolic strokes were the most frequent and had severe presentation and were likely the cause of the slight increase in mortality and sICH.


Asunto(s)
Procedimientos Endovasculares , Fibrinolíticos/uso terapéutico , Trombolisis Mecánica/métodos , Accidente Cerebrovascular/terapia , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Arabia Saudita , Accidente Cerebrovascular/tratamiento farmacológico , Centros de Atención Terciaria , Resultado del Tratamiento , Adulto Joven
11.
BMJ Case Rep ; 14(3)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33727290

RESUMEN

We present a case of a giant ovarian cyst in a 20-year-old woman who presented atypically at our Emergency Department with left-sided back pain followed by acute left leg swelling. Blood tests showed significantly raised C-Reactive Protein and D-Dimer. CT-Abdomen-Pelvis demonstrated a large mass in the region of the right ovary with suspicious heterogeneous filling defects in the left external iliac vein, confirmed as a left-sided deep-vein thrombosis on ultrasound Doppler. MRI revealed the lesion to be cystic and the deep venous thrombosis was treated with twice-daily Clexane. Prior to removal of the cyst, an Inferior Vena Cava Filter was placed to reduce thromboembolic risk. The cyst was resected without complication and the postoperative period was uneventful. This case occurred while face-to-face services were limited by COVID-19 and illustrates the need for robust systemic measures to safeguard patients against the emergency sequelae of insidious gynaecological pathology.


Asunto(s)
Dolor de Espalda/etiología , Diagnóstico por Imagen/métodos , Quistes Ováricos/complicaciones , Quistes Ováricos/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiología , Adulto , Diagnóstico Diferencial , Enoxaparina/uso terapéutico , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Pierna , Imagen por Resonancia Magnética , Quistes Ováricos/cirugía , Ovario/diagnóstico por imagen , Ovario/cirugía , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler , Trombosis de la Vena/tratamiento farmacológico , Adulto Joven
12.
Medicine (Baltimore) ; 100(9): e24698, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33655934

RESUMEN

RATIONALE: Capsular warning syndrome (CWS) is a term to describe stereotyped lacunar transient ischemic attacks (TIAs). Patients with CWS are at high risk of developing completed stroke. However, the exact pathophysiology of CWS is still unclear, and there is no conclusive clinical strategy for CWS patients. PATIENT SYMPTOMS: Two cases of middle-aged men with hypertension, hyperlipidemia, and diabetes mellitus presented with fluctuating right-sided weakness, numbness, and dysarthria. DIAGNOSES: These two patients were diagnosed with CWS. INTERVENTIONS: Recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (0.9 mg/kg) was administered first and treated with aspirin (100 mg) and clopidogrel (75 mg) after 24 h of rt-PA for 21 days following by aspirin (100 mg) alone. OUTCOMES: Both cases got favorable clinical outcomes of somatic symptoms. In addition, diffusion-weighted imaging (DWI or DW-MRI) showed that ischemic injury disappeared in case 1 while maintained within a reasonable range in case 2. LESSONS: Early recognition and rt-PA/dual antiplatelet treatment may be an effective strategy for patients with CWS.


Asunto(s)
Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Fibrinolíticos/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Imagen de Difusión por Resonancia Magnética , Terapia Antiplaquetaria Doble , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Accidente Cerebrovascular/prevención & control , Síndrome , Terapia Trombolítica , Resultado del Tratamiento
14.
Lancet Neurol ; 20(4): 294-303, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33743239

RESUMEN

BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.


Asunto(s)
Fibrinolíticos/uso terapéutico , Hemorragias Intracraneales/etiología , /tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/diagnóstico por imagen , Ataque Isquémico Transitorio/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia , Riesgo
16.
Eur J Pharmacol ; 898: 173988, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33667455

RESUMEN

There is a need for therapeutic approaches to prevent and mitigate the effects of Coronavirus Disease (2019) (COVID-19). The histone deacetylase (HDAC) inhibitor valproic acid, which has been available for the therapy of epilepsy for many years, is a drug that could be repurposed for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This article will review the reasons to consider valproic acid as a potential therapeutic to prevent severe COVID-19. Valproic acid could reduce angiotensin-converting enzyme 2 and transmembrane serine protease 2 expression, required for SARS-CoV-2 viral entry, and modulate the immune cellular and cytokine response to infection, thereby reducing end-organ damage. The combined anti-thrombotic, anti-platelet, and anti-inflammatory effects of valproic acid suggest it could be a promising therapeutic target for COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Fibrinolíticos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ácido Valproico/uso terapéutico , Animales , Reposicionamiento de Medicamentos , Humanos
18.
J Am Coll Cardiol ; 77(15): 1903-1921, 2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33741176

RESUMEN

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs.


Asunto(s)
/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Tromboembolia/prevención & control , /complicaciones , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia/virología
19.
Med Hypotheses ; 149: 110537, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33647606

RESUMEN

As the COVID-19 pandemic continues, researchers seek to identify efficacious treatments. Current approaches to COVID-19 therapeutics focus on antiviral agents, convalescent plasma, monoclonal antibodies, immunomodulators and more traditional therapies such as steroids [1-6]. Reversing disturbances in coagulation has also been identified as a priority area for candidate therapies, such as through the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 adaptive clinical trial (ACTIV-4) which is currently evaluating aspirin, heparins and apixaban [7]. Since there is a clear relationship between mechanisms of coagulation and the immune response, it is possible that reversing disturbances in coagulation may diminish the dysregulated immune response observed in COVID-19. The basis for this hypothesis is described below and is followed by discussion of a proposed candidate therapy - activated protein C. By treating COVID-19 patients using a novel approach, which does not focus on immune-based or antiviral treatments, but instead which addresses both the anti-thrombotic and inflammatory consequences of infection, the hope is that new therapeutic targets can be considered and new candidate therapies, such as activated protein C, may be evaluated.


Asunto(s)
/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Proteína C/uso terapéutico , Animales , Antivirales/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Humanos , Inflamación/tratamiento farmacológico , Modelos Teóricos , Proteínas Recombinantes/uso terapéutico , Sepsis/inmunología , Sepsis/terapia
20.
Eur Rev Med Pharmacol Sci ; 25(4): 2123-2130, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33660832

RESUMEN

OBJECTIVE: Diffuse thrombosis represents one of the most predominant causes of death by COVID-19 and SARS-CoV-2 infection seems to increase the risk of developing venous thromboembolic diseases (VTE). Aim of this study is to analyze the relationship between validated predictive scores for VTE such as IMPROVE and IMPROVEDD and: (1) Intensification of Care (IoC, admission to Pulmonology Department or Intensive Care Unit) (2) in-hospital mortality rate 3) 30-days mortality rate. PATIENTS AND METHODS: We retrospectively evaluated 51 adult patients with laboratory diagnosis of SARS-CoV-2 infection and calculated IMPROVE and IMPROVEDD scores. All patients underwent venous color-Doppler ultrasound of the lower limbs to assess the presence of superficial vein thrombosis (SVT) and/or deep vein thrombosis (DVT). Patients with normal values of D-dimer did not receive heparin therapy (LMWH); patients with ≥ 4 ULN values of D-dimer or with a diagnosis of DVT were treated with therapeutic LMWH dosage, while the remaining patients were treated with prophylactic LMWH dosages. RESULTS: We found strong relations between IMPROVE score and the need for IoC and with the in-hospital mortality rate and between the IMPROVEDD score and the need for IoC. We defined that an IMPROVE score greater than 4 points was significantly associated to in-hospital mortality rate (p = 0.05), while an IMPROVEDD score greater than 3 points was associated with the need for IoC (p = 0.04). Multivariate logistic analysis showed how IMPROVE score was significantly associated to in-hospital and 30-days mortality rates. CONCLUSIONS: IMPROVE score can be considered an independent predictor of in-hospital and 30-days mortality.


Asunto(s)
/complicaciones , Fibrinolíticos/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Trombosis de la Vena/prevención & control , Adulto , /diagnóstico por imagen , Cuidados Críticos/estadística & datos numéricos , Supervivencia sin Enfermedad , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinolíticos/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Humanos , Italia , Modelos Logísticos , Extremidad Inferior/diagnóstico por imagen , Análisis Multivariante , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Ultrasonografía Doppler Dúplex , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiología , Trombosis de la Vena/mortalidad
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