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Patients with coronavirus disease 2019 (COVID-19) pneumonia are prone to intrapulmonary thrombosis owing to excessive inflammation and platelet activation. Myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with ring sideroblasts and thrombocytosis (RS-T) is a rare disease in MDS/MPN overlap entities. Patients with MDS/MPN RS-T are known to be at a high risk of thrombosis, and platelet count control with drug therapy does not necessarily reduce this risk. Here, we report the autopsy case of an older male patient with MDS/MPN RS-T and severe COVID-19 pneumonia complicated by intrapulmonary thrombosis. His platelet count had been controlled in the normal range after treatment with hydroxyurea and 5-aza-2'-deoxycytidine. On admission day, he rapidly developed respiratory distress and tested positive on a polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). After admission, he received supplemental oxygen and was administered remdesivir and dexamethasone; however, his respiratory and circulatory status did not improve. The patient died on day 4 of illness. Autopsy findings revealed massive thrombi within blood vessels and diffuse alveolar damage in both lungs, which were determined to be the cause of death. In patients with MDS/MPN RS-T combined with COVID-19 pneumonia, clinicians may need to pay close attention to the risk of pulmonary thrombosis.
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Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 µM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.
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Eugenol , Embolia Pulmonar , Humanos , Ratones , Animales , Eugenol/farmacología , Eugenol/uso terapéutico , Eugenol/metabolismo , Fosfolipasa C gamma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Modelos Animales de Enfermedad , Activación Plaquetaria , Agregación Plaquetaria , Plaquetas/metabolismo , Fosforilación , Proteína Quinasa C/metabolismo , Tromboxano A2/metabolismo , Colágeno/metabolismo , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/metabolismo , Fosfolipasas A2 Citosólicas/metabolismoRESUMEN
Chlamydia psittaci pneumonia frequently leads to various extrapulmonary complications; however, reports of C. psittaci-pneumonia complicated by pulmonary thrombosis are uncommon. We report a case of severe C. psittaci pneumonia in a patient with a history of poultry contact and clinical manifestations including hyperpyrexia, dyspnea, and respiratory failure, which necessitated tracheal intubation for assisted ventilation. C. psittaci in bronchoalveolar lavage fluid was detected with metagenomic next-generation sequencing. Following targeted antibiotic therapy, the fever subsided, although dyspnea persisted without significant improvement, and chest pain developed. Compared to previous measurements, the D-dimer level increased, and CT pulmonary angiography revealed thromboses in the pulmonary artery trunk and left pulmonary artery. The symptoms improved after anticoagulant treatment, and the patient was discharged subsequently. This study suggests that C. psittaci infection may be associated with the formation of pulmonary thrombosis. Additional clinical data are required to support this inference. Following targeted antibiotic therapy, if persistent dyspnea, chest pain, and increased D-dimer level are present, pulmonary thrombosis should be considered, and pulmonary artery angiography can confirm the diagnosis.
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IMPORTANCE: The early use of tranexamic acid (TXA) has demonstrated benefit among some trauma patients in hemorrhagic shock. The association between TXA administration and thromboembolic events (including deep vein thrombosis (DVT), pulmonary embolism (PE) and pulmonary thrombosis (PT)) remains unclear. We aimed to characterize the risk of venous thromboembolism (VTE) subtypes among trauma patients receiving TXA and to determine whether TXA is associated with VTE risk and mortality. METHODS: We analyzed a prospective, observational, multicenter cohort data from the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study group. The study was conducted across 17 US level I trauma centers between January 1, 2018, and December 31,2020. We studied trauma patients ages 18-40 years, admitted for at least 48 h with a minimum of 1 VTE risk factor and followed until hospital discharge or 30 days. We compared TXA recipients to non-recipients for VTE and mortality using inverse probability weighted Cox models. The primary outcome was the presence of documented venous thromboembolism (VTE). The secondary outcome was mortality. VTE was defined as DVT, PE, or PT. RESULTS: Among the 7,331 trauma patients analyzed, 466 (6.4%) received TXA. Patients in the TXA group were more severely injured than patients in the non-TXA group (ISS 16+: 69.1% vs. 48.5%, p < 0.001) and a higher percentage underwent a major surgical procedure (85.8% vs. 73.6%, p < 0.001). Among TXA recipients, 12.5% developed VTE (1.3% PT, 2.4% PE, 8.8% DVT) with 5.6% mortality. In the non-TXA group, 4.6% developed VTE (1.1% PT, 0.5% PE, 3.0% DVT) with 1.7% mortality. In analyses adjusting for patient demographic and clinical characteristics, TXA administration was not significantly associated with VTE (aHR 1.00, 95%CI: 0.69-1.46, p = 0.99) but was significantly associated with increased mortality (aHR 2.01, 95%CI: 1.46-2.77, p < 0.001). CONCLUSION: TXA was not clearly identified as an independent risk factor for VTE in adjusted analyses, but the risk of VTE among trauma patients receiving TXA remains high (12.5%). This supports the judicious use of TXA in resuscitation, with consideration of early initiation of DVT prophylaxis in this high-risk group.
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Embolia Pulmonar , Ácido Tranexámico , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Estudios Prospectivos , Embolia Pulmonar/prevención & control , Ácido Tranexámico/efectos adversos , Centros Traumatológicos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/prevención & control , Adolescente , Adulto Joven , AdultoRESUMEN
Behçet's disease is a systematic, inflammatory disorder affecting vessels of all sizes. It affects both venous and arterial systems. Vascular involvement carries a high risk of morbidity and mortality. Knowing that Behçet's disease is the most common vasculitides that causes pulmonary artery aneurysms, with a mortality rate of around 25%, makes early detection crucial. Thrombosis in Behçet's disease is mainly caused by an inflammatory process rather than a thrombophilic state, thus vascular thrombosis control is achieved with immunosuppressant medications rather than anticoagulants. An exception to the use of anticoagulants in Behçet's disease appears to be due to cerebral venous thrombosis. The occurrence of multiple site thrombosis and aneurysm simultaneously makes the management very challenging, as we will highlight in our case. We present a case of a 31-year-old female patient with many prior hospitalizations due to cerebral venous thrombosis, bilateral pulmonary thrombi, right ventricular thrombus, and right pulmonary artery aneurysm. The patient was diagnosed with Behçet's disease according to the Behçet's Syndrome International Study Group criteria and then managed with the prophylactic low molecular weight heparin, cyclophosphamide, and prednisolone, resulting in significant improvement in the patient's symptoms. Presentation with cerebral venous thrombosis, pulmonary thrombosis, and aneurysm simultaneously is very rare in Behçet's disease. This made this case distinct and challenging in achieving good control of thrombosis and aneurysm simultaneously, which needs close monitoring and a multidisciplinary team to deal with the case.
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The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.
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COVID-19 , Trombosis , Trombosis de la Vena , Humanos , COVID-19/complicaciones , Trombosis de la Vena/complicaciones , Coagulación Sanguínea , Trombosis/etiología , Trombosis/inducido químicamente , Anticoagulantes/efectos adversosRESUMEN
BACKGROUND: Trauma patients are at high risk of Venous thromboembolism (VTE), but compared to well-established deep venous thrombosis (DVT), data specifically evaluating post-traumatic pulmonary embolism (PE) are scarce. The aim of this study is to assess whether PE represents a distinct clinical entity with injury pattern, risk factors, and prophylaxis strategy different from DVT, among severe poly-trauma patients. PATIENTS AND METHODS: We retrospectively enrolled patients admitted to our level I trauma center from January 2011 to December 2021 who were diagnosed with severe multiple traumatic injuries and identified thromboembolic events among them. We regarded four groups as None (without thromboembolic events), DVT only, PE only, and PE with DVT. Demographics, injury characteristics, clinical outcomes, and treatments were collected and analyzed in individual groups. Patients were also classified according to the occurring time of PE, and indicative symptoms and radiological findings were compared between early PE (≤ 3 days) and late PE (> 3 days). Logistic regression analyses were conducted to explore independent risk factors for different VTE patterns. RESULTS: Among 3498 selected severe multiple traumatic patients, there were 398 episodes of DVT only, 19 of PE only, and 63 of PE with DVT. Injury variables associated with PE only included shock on admission and severe chest trauma. Severe pelvic fracture and mechanical ventilator days (MVD) ≥ 3 were the independent risk factors for PE with DVT. There were no significant differences in the indicative symptoms and location of pulmonary thrombi between the early and late PE groups. Obesity and severe lower extremity injury might have an impact on the incidence of early PE, while patients with a severe head injury and higher ISS are particularly at risk for developing late PE. CONCLUSION: Occurring early, lacking association with DVT, and possessing distinct risk factors warrant PE in severe poly-trauma patients special attention, especially for its prophylaxis strategy.
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Traumatismo Múltiple , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Estudios Retrospectivos , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Tromboembolia Venosa/prevención & control , Centros Traumatológicos , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/epidemiología , Factores de RiesgoRESUMEN
Neonatal venous thrombosis is a rare condition that can be iatrogenic or occur due to viral infections or genetic mutations. Thromboembolic complications are also commonly observed as a result of SARS-CoV-2 infections. They can affect pediatric patients, especially the ones suffering from multisystem inflammatory syndrome in children (MIS-C) or multisystem inflammatory syndrome in neonates (MIS-N). The question remains whether the maternal SARS-CoV-2 infection during pregnancy can lead to thromboembolic complications in fetuses and neonates. We report on a patient born with an embolism in the arterial duct, left pulmonary artery, and pulmonary trunk, who presented several characteristic features of MIS-N, suspecting that the cause might have been the maternal SARS-CoV2 infection in late pregnancy. Multiple genetic and laboratory tests were performed. The neonate presented only with a positive result of IgG antibodies against SARS-CoV-2. He was treated with low molecular weight heparin. Subsequent echocardiographic tests showed that the embolism dissolved. More research is necessary to evaluate the possible neonatal complications of maternal SARS-CoV-2 infection.
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COVID-19 , Conducto Arterial , Complicaciones Infecciosas del Embarazo , Trombosis de la Vena , Masculino , Recién Nacido , Femenino , Embarazo , Humanos , Niño , ARN Viral , COVID-19/complicaciones , SARS-CoV-2 , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/etiología , Parto , VitaminasRESUMEN
Background and Aim: We aimed to develop a clinical prediction model for pulmonary thrombosis (PT) diagnosis in hospitalized COVID-19 patients. Methods: Non-intensive care unit hospitalized COVID-19 patients who underwent a computed tomography pulmonary angiogram (CTPA) for suspected PT were included in the study. Demographic, clinical, analytical, and radiological variables as potential factors associated with the presence of PT were selected. Multivariable Cox regression analysis to develop a score for estimating the pre-test probability of PT was performed. The score was internally validated by bootstrap analysis. Results: Among the 271 patients who underwent a CTPA, 132 patients (48.7%) had PT. Heart rate >100 bpm (OR = 4.63 [95% CI: 2.30-9.34]; P < 0.001), respiratory rate >22 bpm (OR = 5.21 [95% CI: 2.00-13.54]; P < 0.001), RALE score ≥4 (OR = 3.24 [95% CI: 1.66-6.32]; P < 0.001), C-reactive protein (CRP) >100 mg/L (OR = 2.10 [95% CI: 0.95-4.63]; P = 0.067), and D-dimer >3.000 ng/mL (OR = 6.86 [95% CI: 3.54-13.28]; P < 0.001) at the time of suspected PT were independent predictors of thrombosis. Using these variables, we constructed a nomogram (CRP, Heart rate, D-dimer, RALE score, and respiratory rate [CHEDDAR score]) for estimating the pre-test probability of PT. The score showed a high predictive accuracy (area under the receiver-operating characteristics curve = 0.877; 95% CI: 0.83-0.92). A score lower than 182 points on the nomogram confers a low probability for PT with a negative predictive value of 92%. Conclusions: CHEDDAR score can be used to estimate the pre-test probability of PT in hospitalized COVID-19 patients outside the intensive care unit. Relevance for Patients: Developing a new clinical prediction model for PT diagnosis in COVID-19 may help in the triage of patients, and limit unnecessary exposure to radiation and the risk of nephrotoxicity due to iodinated contrast.
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Pulmonary thrombosis (PT) is a frequent complication of COVID-19. However, the risk factors, predictive scores, and precise diagnostic guidelines on indications for CT pulmonary angiography (CTPA) are still lacking. This study aimed to analyze the clinical and laboratory characteristics associated with PT in patients with COVID-19. We conducted a cohort study of consecutively hospitalized adult patients with COVID-19 who underwent CTPA at the University Hospital for Infectious Diseases in Zagreb, Croatia between 1 April and 31 December 2021. Of 2078 hospitalized patients, 575 (27.6%) underwent CTPA. PT was diagnosed in 178 (30.9%) patients (69.6% males, median age of 61, IQR 50-69 years). The PT group had a higher CRP, LDH, D-dimer, platelets, and CHOD score. PT was more frequent in patients requiring ≥15 L O2/min (25.0% vs. 39.7%). In multivariable analysis, only D-dimer ≥ 1.0 mg/L (OR 1.78, 95%CI 1.12-2.75) and O2 ≥ 15 L (OR 1.89, 95%CI 1.26-2.84) were associated with PT. PT was not associated with in-hospital mortality. In conclusion, our data confirmed a high incidence of PT in hospitalized patients with COVID-19, however, no correlation with traditional risk factors and mortality was found. CTPA should be performed in patients requiring high-flow supplemental oxygen or those with increased D-dimer levels.
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Purpose: The SARS-CoV-2 disease predisposes infected individuals to thrombosis, the underlying mechanisms of which are not fully understood. The balance between pro-coagulant factors and natural coagulation inhibitors in critically ill patients with Covid-19 is fundamental to the prevention and treatment of complications. The aim of the present study was to investigate the pulmonary injury patterns in Covid-19 having higher mortality in the presence of deep vein thrombosis in comparison to patients without venous thrombosis and determine the Gamma variant. Methods: A retrospective study was conducted involving the evaluation of 200 medical records of patients with Covid-19 and a clinical suspicion of deep vein thrombosis (DVT) at the intensive care unit of a public hospital. The sample was divided into two groups of patients were formed - those positive and those negative for DVT. Statistical analysis involved the use of Fisher's exact test, the paired t-test and chi-square test. Results: Patients with DVT had more severe lung injuries (greater than 70%) compared to those without DVT (p = 0.003). Lesions affecting 50% to 70% of the lung area occurred in little more half of the group with DVT and just under half in the group without DVT (p = 0.5). Pulmonary lesions affecting less than 50% of the lung occurred more in patients without DVT (p = 0.0001). The Gamma variant increased prevalence of the both DVT and mortality (p=0.0001). Conclusion: Deep vein thrombosis is an aggravating factor of mortality in patients with SARS-CoV-2, and the Gamma variant is an aggravating factor of both thrombotic events and mortality.
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COVID-19 , Lesión Pulmonar , Trombosis de la Vena , Humanos , SARS-CoV-2 , Lesión Pulmonar/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Trombosis de la Vena/complicacionesRESUMEN
Cold agglutinin disease is a rare cause of arterial thrombosis leading to stroke, commonly encountered against a background of mycoplasma pneumonia infections. A 22-year-old patient presented with acute-onset left hemiplegia preceded by a short history of fever and cough. Magnetic resonance imaging (MRI) showed a right middle cerebral artery infarct. Serially repeated hemoglobin levels showed a progressive drop and peripheral smear showed evidence of hemolysis. Blood drawn for investigations would rapidly clot, suggesting a possibility of cold agglutinin-induced hemolysis. The patient was then worked up for all the possible causes of hemolytic anemia including secondary causes which were all negative except for significant immunoglobulin M mycoplasma levels with elevated cold antibody titers. The patient was then initiated on pulse steroids with azithromycin and doxycycline and hemoglobin levels stabilized. The patient also developed pulmonary thromboembolism which was managed with anticoagulation. The patient made a steady improvement, was discharged, and is on follow-up. Here, we present a unique case of mycoplasma associated cold agglutinin disease causing arterial thrombosis.
Résumé La maladie à l'agglutinine froide est une cause rare de thrombose artérielle conduisant à un accident vasculaire cérébral, couramment rencontré dans un contexte d'infections à la pneumonie des mycoplasmes. Un patient de 22 ans a présenté une hémiplégie gauche aiguë précédée d'une courte histoire de fièvre et de toux. L'imagerie par résonance magnétique (IRM) a montré une infarctus de l'artère cérébrale moyenne droite. Les niveaux d'hémoglobine répétés en série ont montré une baisse progressive et le frottis périphérique a montré des preuves d'hémolyse. Le sang prélevé pour les investigations allait rapidement, suggérant une possibilité d'hémolyse induite par l'agglutinine froide. Le patient a ensuite été élaboré pour toutes les causes possibles de l'anémie hémolytique, y compris des causes secondaires qui étaient toutes négatives, sauf pour des niveaux d'immunoglobuline M de Mycoplasma significatifs avec des titres élevés d'anticorps froid. Le patient a ensuite été initié sur des stéroïdes d'impulsion avec de l'azithromycine et des niveaux de doxycycline et d'hémoglobine stabilisés. Le patient a également développé une thromboembolie pulmonaire qui a été gérée avec l'anticoagulation. Le patient a fait une amélioration constante, a été libéré et est sur le suivi. Ici, nous présentons un cas unique de maladie d'agglutinine à froid associée aux mycoplasmes provoquant une thrombose artérielle. Mots-clés: Maladie d'agglutinine à froid, accident vasculaire cérébral, thrombose pulmonaire.
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Anemia Hemolítica Autoinmune , Anemia Hemolítica , Trombosis , Adulto , Anemia Hemolítica/complicaciones , Anemia Hemolítica Autoinmune/complicaciones , Anticoagulantes , Azitromicina , Doxiciclina , Hemoglobinas , Hemólisis , Humanos , Inmunoglobulina M , Trombosis/complicaciones , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Adulto JovenRESUMEN
Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease associated with systemic changes in immune response, which might be associated with coronavirus disease 2019 (COVID-19) severity. The aim of this study was to investigate the impact of NAFLD on COVID-19 severity and outcomes. Methods: A prospective observational study included consecutively hospitalized adult patients, hospitalized between March and June 2021, with severe COVID-19. Patients were screened for fatty liver by ultrasound and subsequently diagnosed with NAFLD. Patients were daily followed until discharge, and demographic, clinical, and laboratory data were collected and correlated to clinical outcomes. Results: Of the 216 patients included, 120 (55.5%) had NAFLD. The NAFLD group had higher C-reactive protein (interquartile range [IQR]) (84.7 [38.6-129.8] mg/L vs 66.9 [32.2-97.3] mg/L; Pâ =â .0340), interleukin-6 (49.19 [22.66-92.04] ng/L vs 13.22 [5.29-39.75] ng/L; Pâ <â .0001), aspartate aminotransferase (58 [40-81] IU/L vs 46 [29-82] IU/L; Pâ =â .0123), alanine aminotransferase (51 [32-73] IU/L vs 40 [23-69] IU/L; Pâ =â .0345), and lactate dehydrogenase (391 [285-483] IU/L vs 324 [247-411] IU/L; Pâ =â .0027). The patients with NAFLD had higher disease severity assessed by 7-category ordinal scale, more frequently required high-flow nasal cannula or noninvasive ventilation (26, 21.66%, vs 10, 10.42%; Pâ =â .0289), had longer duration of hospitalization (IQR) (10 [8-15] days vs 9 [6-12] days; Pâ =â .0018), and more frequently had pulmonary thromboembolism (26.66% vs 13.54%; Pâ =â .0191). On multivariable analyses, NAFLD was negatively associated with time to recovery (hazard ratio, 0.64; 95% CI, 0.48 to 0.86) and was identified as a risk factor for pulmonary thrombosis (odds ratio, 2.15; 95% CI, 1.04 to 4.46). Conclusions: NAFLD is associated with higher COVID-19 severity, more adverse outcomes, and more frequent pulmonary thrombosis.
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BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by a necrotizing vasculitis with tissue and peripheral blood eosinophilia affecting small and medium-sized arteries, capillaries, and veins. Venous thromboembolic events are uncommon in EGPA. Moreover, there are only a few reported cases of EGPA complicated by pulmonary embolism or infarction. CASE PRESENTATION: We report the case of a 43-year-old woman with eosinophilic granulomatosis with polyangiitis and acute respiratory and heart failure due to bilateral pulmonary artery thrombosis and left femoral vein thrombosis 12 years after disease onset. She also had cardiac involvement (myocarditis, pericardial effusion, and diastolic dysfunction), gastrointestinal symptoms, and peripheral neuropathy. The condition was refractory to treatment with systemic corticosteroids, intravenous cyclophosphamide, and mepolizumab, but the thrombosis and associated acute cardiac failure, as well as the cardiac and gastrointestinal symptoms and multiple polyneuropathy, improved after a switch to rituximab. However, the heart failure did not improve sufficiently and the patient continued to need inhaled oxygen at 1 L/min and asthma exacerbations occurred. We then swapped the patient's mepolizumab treatment for dupilumab. Not only did she have no further asthma attacks after switching to dupilumab, but also her vasculitis symptoms improved. Oxygen therapy was discontinued as the heart failure improved 5 months after starting the dupilumab. CONCLUSIONS: This may be the first case report of the successful treatment by rituximab of pulmonary thromboembolism associated with EGPA. In addition, in this patient, treatment with dupilumab was effective not only for the asthma symptoms but also for the symptoms of vasculitis and heart failure.
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Platelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from Tetradium ruticarpum, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK]), Ro106-9920 (an inhibitor of proteasomes), and RUT concentration-dependently (1-6 µM) inhibited platelet aggregation and P-selectin expression. RUT was found to have a similar effect to that of BAY11-7082; however, it exhibits more effectiveness than Ro106-9920. RUT suppresses the NF-κB pathway as it inhibits IKK, IκBα, and p65 phosphorylation and reverses IκBα degradation in activated platelets. This study also investigated the role of p38 and NF-κB in cell signaling events and found that SB203580 (an inhibitor of p38) markedly reduced p38, IKK, and p65 phosphorylation and reversed IκBα degradation as well as p65 activation in a confocal microscope, whereas BAY11-7082 had no effects in p38 phosphorylation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay shows that RUT and BAY11-7082 did not exhibit free radical scavenging activity. In the in vivo study, compared with BAY11-7082, RUT more effectively reduced mortality in adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism without affecting the bleeding time. In conclusion, a distinctive pathway of p38-mediated NF-κB activation may involve RUT-mediated antiplatelet activation, and RUT could act as a strong prophylactic or therapeutic drug for cardiovascular diseases.
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Fibrinolíticos/farmacología , Alcaloides Indólicos/farmacología , FN-kappa B/metabolismo , Nitrilos/farmacología , Quinazolinas/farmacología , Sulfonas/farmacología , Trombosis/tratamiento farmacológico , Trombosis/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Modelos Animales de Enfermedad , Fibrinolíticos/uso terapéutico , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/uso terapéutico , Radicales Libres/antagonistas & inhibidores , Humanos , Quinasa I-kappa B/antagonistas & inhibidores , Imidazoles/farmacología , Imidazoles/uso terapéutico , Alcaloides Indólicos/uso terapéutico , Masculino , Ratones Endogámicos ICR , FN-kappa B/antagonistas & inhibidores , Nitrilos/uso terapéutico , Selectina-P/metabolismo , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/metabolismo , Piridinas/farmacología , Piridinas/uso terapéutico , Quinazolinas/uso terapéutico , Sulfonas/uso terapéutico , Factor de Transcripción ReIA/metabolismoRESUMEN
We report a case of pulmonary thrombosis in a teenager during a hypercoagulable state associated with COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). A condition rare in children and adolescents, pulmonary thrombosis underdiagnosis likely increases morbidity and mortality. A pulmonary thrombosis diagnosis requires a high level of suspicion and relies on the combination of clinical presentation, D-dimer elevation, and computed tomography (CT) pulmonary angiography or ventilation/perfusion scans, imaging techniques that are difficult to perform. Electrical impedance tomography (EIT) has gained attention, as it provides real-time ventilation distribution analysis. In addition, lung pulsatility images can be obtained through this technique using electrocardiogram gating to filter out ventilation. In this case report, the reduced EIT pulsatility corresponded to the perfusion defect found on the CT scan, information that was obtained at the bedside without radiation or contrast exposure.
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COVID-19 , Trombosis de la Vena , Adolescente , Niño , Impedancia Eléctrica , Humanos , Pulmón , Ventilación Pulmonar , SARS-CoV-2 , Tomografía , Tomografía Computarizada por Rayos XRESUMEN
Pulmonary thromboembolism (PTE) is the third leading cause of death in cardiovascular diseases. PTE is believed to be caused by thrombi detached from deep veins of lower extremities. The thrombi travel with systemic circulation to the lung and block pulmonary arteries, leading to sudden disruption of hemodynamics and blood gas exchange. However, this concept has recently been challenged by accumulating evidence demonstrating that de novo thrombosis may be formed in pulmonary arteries without deep venous thrombosis. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH), a subtype of pulmonary hypertension, could have different pathogenesis than traditional PTE. Therefore, this article summarized and compared the risk factors, the common and specific pathogenic mechanisms underlying PTE, in situ pulmonary artery thrombosis, and CTEPH at molecular and cellular levels, and suggested the therapeutic strategies to these diseases, aiming to facilitate understanding of pathogenesis, differential diagnosis, and precision therapeutics of the three pulmonary artery thrombotic diseases.
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BACKGROUND: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism. METHODS: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants. RESULTS: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 µg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 µg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer. CONCLUSION: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.
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Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE). Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92-1.00; p = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04-0.84; p = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15-33.7; p = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients (n = 79) and COVID-19 negative hospitalized control patients (n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development. Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.
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Epidemiological evidence shows that smoking causes a thrombophilic milieu that may play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD) as well as pulmonary thromboembolism. The increased nicotine level induces a prothrombotic status and abnormal blood coagulation in smokers. Since several anticoagulants increase bleeding risk, alternative therapies need to be identified to protect against thrombosis without affecting hemostasis. Astragalin is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities of antioxidant and anti-inflammation. The current study investigated that astragalin attenuated smoking-induced pulmonary thrombosis and alveolar inflammation. In addition, it was explored that molecular links between thrombosis and inflammation entailed protease-activated receptor (PAR) activation and oxidative stress-responsive mitogen-activated protein kinase (MAPK)-signaling. BALB/c mice were orally administrated with 10-20 mg/kg astragalin and exposed to cigarette smoke for 8 weeks. For the in vitro study, 10 U/mL thrombin was added to alveolar epithelial A549 cells in the presence of 1-20 µM astragalin. The cigarette smoking-induced the expression of PAR-1 and PAR-2 in lung tissues, which was attenuated by the administration of ≥10 mg/kg astragalin. The oral supplementation of ≥10 mg/kg astragalin to cigarette smoke-challenged mice attenuated the protein induction of urokinase plasminogen activator, plasminogen activator inhibitor-1and tissue factor, and instead enhanced the induction of tissue plasminogen activator in lung tissues. The astragalin treatment alleviated cigarette smoke-induced lung emphysema and pulmonary thrombosis. Astragalin caused lymphocytosis and neutrophilia in bronchoalveolar lavage fluid due to cigarette smoke but curtailed infiltration of neutrophils and macrophages in airways. Furthermore, this compound retarded thrombin-induced activation of PAR proteins and expression of inflammatory mediators in alveolar cells. Treating astragalin interrupted PAR proteins-activated reactive oxygen species production and MAPK signaling leading to alveolar inflammation. Accordingly, astragalin may interrupt the smoking-induced oxidative stress-MAPK signaling-inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism.