RESUMEN
La púrpura fulminante adquirida postinfecciosa es una entidad aguda y grave, poco frecuente, caracterizada por necrosis cutánea asociada a coagulopatía intravascular diseminada (CID), en ausencia de infección activa o alteraciones previas de la coagulación. Afecta fundamentalmente a la población pediátrica y, en el 90 % de los casos, está precedida por un proceso infeccioso. El mecanismo fisiopatológico es un déficit transitorio de proteína S mediado por autoanticuerpos que favorece un estado de hipercoagulabilidad. Se presenta el caso de un varón de 8 años previamente sano, con lesiones cutáneas purpúricas características de púrpura fulminante asociada a CID en ausencia de sepsis. Se constató deficiencia plasmática transitoria de proteína S. Requirió tratamiento sustitutivo con plasma fresco congelado y anticoagulación; la evolución fue favorable. La actividad de la proteína S permaneció disminuida durante 2 meses.
Acquired postinfectious purpura fulminans is a rare, acute, and severe disease characterized by skin necrosis associated with disseminated intravascular coagulation (DIC) in the absence of active infection or previous coagulation disorders. It mainly affects the pediatric population and, in 90% of cases, it is preceded by an infectious process. The pathophysiological mechanism is a transient autoantibodymediated protein S deficiency that favors a hypercoagulable state. Here we describe the case of a previously healthy 8-year-old boy with purpuric skin lesions typical of purpura fulminans associated with DIC in the absence of sepsis. A transient plasma protein S deficiency was confirmed. He required replacement therapy with fresh frozen plasma and anticoagulation; he had a favorable course. Protein S activity remained decreased for 2 months.
Asunto(s)
Humanos , Masculino , Niño , Púrpura Fulminante/diagnóstico , Púrpura Fulminante/etiología , Deficiencia de Proteína S/complicaciones , Deficiencia de Proteína S/diagnóstico , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiologíaRESUMEN
Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24â h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.
Asunto(s)
Coagulación Intravascular Diseminada , Insuficiencia Multiorgánica , Sepsis , Humanos , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/mortalidad , Sepsis/complicaciones , Sepsis/mortalidad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Mortalidad HospitalariaRESUMEN
Since July 2022, obstetrical disseminated intravascular coagulation (DIC) in Japan has been diagnosed based on the new criteria (tentative version), which assesses the main underlying disease, fibrinogen level, and fibrin/fibrinogen degradation products or D-dimer level. In June 2024, the tentative version underwent minor revision and the final version was released. The previous Japanese criteria assessed underlying disease, clinical symptoms, and various laboratory findings. This study aimed to prove the effectiveness, reliability, and validity of the new criteria (final version). We analyzed 212 women with singleton pregnancies who delivered after 22 gestational weeks and experienced blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean section. Those with missing laboratory findings before receiving blood transfusion at delivery were excluded. In the obstetrical DIC group, the frequency of fibrinogen levels < 150 mg/dL was significantly higher than in the control group (90% vs. 5%, p < 0.0001), as was the frequency of scores ≥ 8 according to the previous Japanese criteria (100% vs. 10%, p < 0.0001). Cronbach alpha was 0.757 and Spearman's rank-order correlation was 0.558 between the new and previous criteria. In conclusion, we proved the effectiveness, reliability, and validity of the Japanese new criteria (final version) to diagnose obstetrical DIC.
Asunto(s)
Coagulación Intravascular Diseminada , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/sangre , Femenino , Embarazo , Japón , Adulto , Reproducibilidad de los Resultados , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/sangre , Cesárea , Pueblos del Este de AsiaRESUMEN
A 43-year-old man with pancytopenia was diagnosed with acute promyelocytic leukemia (APL). On the first day of induction therapy with all-trans retinoic acid (ATRA) alone, he presented with high fever and was found to have coronavirus disease 2019 (COVID-19) infection by SARS-CoV2 antigen test. While it is generally recommended to delay treatment for APL patients with COVID-19 unless urgent APL treatment is required, this patient needed to continue treatment due to APL-induced disseminated intravascular coagulation (DIC). Considering the challenge of distinguishing between differentiation syndrome (DS) and COVID-19 exacerbation, the ATRA dosage was reduced to 50%. The patient was able to continue treatment without development of DS or exacerbation of DIC, leading to his recovery from COVID-19 and remission of APL.
Asunto(s)
COVID-19 , Leucemia Promielocítica Aguda , Inducción de Remisión , Tretinoina , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/complicaciones , Tretinoina/administración & dosificación , Tretinoina/uso terapéutico , Masculino , Adulto , COVID-19/complicaciones , Resultado del Tratamiento , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/etiologíaRESUMEN
BACKGROUND: D-dimer, a specific product of cross-linked fibrin degradation, is of great clinical value in the early diagnosis of thrombotic diseases and in monitoring the efficacy of thrombolysis; therefore, the accuracy of D-dimer test results is crucial. METHODS: This article reports a case of a patient with disseminated intravascular coagulation (DIC) who experienced a false decrease in D-dimer due to the hook effect. RESULTS: The three D-dimer test results for DIC patients were 1.09 mg/L, 0.93 mg/L, and 1.43 mg/L. After sample dilution, the results were: first time (1:128) 842.24 mg/L, second time (1:128) 1,505.28 mg/L, third time (1:32) 415.68 mg/L. There was a significant difference in the three test results before and after dilution, because the D-dimer concentration was too high, exceeding the detection range and causing the hook effect, which falsely lowered the D-dimer value. CONCLUSIONS: When the D-dimer value of DIC patients does not match the clinical situation, the possibility of the hook effect should be considered, and the false decrease can be ruled out by the sample dilution method. In this way, accurate clinical results can be obtained to avoid delaying the diagnosis and treatment of DIC patients.
Asunto(s)
Coagulación Intravascular Diseminada , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/diagnóstico , Masculino , Femenino , Reacciones Falso Positivas , Persona de Mediana Edad , Anciano , Reacciones Falso NegativasRESUMEN
HISTORY AND EXAMINATION: A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both sacroiliac (SI) joints. Patient was being admitted and evaluated, and during the course of evaluation, developed severe headache, which was severe in intensity and associated with nausea and projectile vomiting. Initial investigations: An X-ray of the bilateral SI joints revealed inflammation, and the antinuclear antibody (ANA) turned out to be 4+ with pancytopenia and raised lactate dehydrogenase (LDH), but the liver function tests were normal. Rest of the rheumatological profile was unremarkable. During the course of the evaluation, she developed a severe headache, which, on imaging, showed presence of cerebral edema with chronic subdural hematoma, and a concomitant coagulopathy workup revealed evidence of disseminated intravascular coagulation (DIC). DISCUSSION: Taking the whole picture into consideration, a malignant process in the body was suspected, and serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) were sent, all of which were raised. Validating the clinical clue was the bone marrow biopsy done for pancytopenia, which revealed malignant epithelial infiltration. A contrast-enhanced computed tomography (CECT) thorax and whole abdomen were done to find out the primary, which showed a neoplastic mass at the gastroesophageal junction along with bony metastases in the vertebrae and left adrenal. Tissue from the primary lesion was taken for histopathological examination (HPE) through upper gastrointestinal endoscopy. Although HPE revealed grade III poorly differentiated stomach adenocarcinoma, the patient had succumbed to the disease process by the time the diagnosis came to light. CONCLUSION: In short, this case perfectly illustrates how solid organ malignancies might be a mimicker of multisystem disorders, thereby delaying diagnosis and worsening the prognosis even further.
Asunto(s)
Coagulación Intravascular Diseminada , Pancitopenia , Humanos , Femenino , Pancitopenia/diagnóstico , Pancitopenia/etiología , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiología , Adulto Joven , AutoinmunidadRESUMEN
Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.
Asunto(s)
Lipoproteínas , Choque Séptico , Tromboplastina , Humanos , Choque Séptico/sangre , Choque Séptico/metabolismo , Tromboplastina/metabolismo , Masculino , Femenino , Lipoproteínas/sangre , Lipoproteínas/metabolismo , Persona de Mediana Edad , Anciano , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/etiología , Coagulación Intravascular Diseminada/sangre , Estudios de Casos y Controles , Adulto , Biomarcadores/sangreRESUMEN
Disseminated intravascular coagulation (DIC) is a pathologic state that follows systemic injury and other diseases. Often a complication of sepsis or trauma, DIC causes coagulopathy associated with paradoxical thrombosis and hemorrhage. DIC upregulates the thrombotic pathways while simultaneously downregulating the fibrinolytic pathways that cause excessive fibrin deposition, microcirculatory thrombosis, multiorgan dysfunction, and consumptive coagulopathy with excessive bleeding. Given these opposing disease phenotypes, DIC management is challenging and includes treating the underlying disease and managing the coagulopathy. Currently, no therapies are approved for DIC. We have developed clot-targeted therapeutics that inhibit clot polymerization and activate clot fibrinolysis to manage DIC. We hypothesize that delivering both an anticoagulant and a fibrinolytic agent directly to clots will inhibit active clot polymerization while also breaking up pre-existing clots; therefore, reversing consumptive coagulopathy and restoring hemostatic balance. To test this hypothesis, we single- and dual-loaded fibrin-specific nanogels (FSNs) with antithrombinIII (ATIII) and/or tissue plasminogen activator (tPA) and evaluated their clot preventing and clot lysing abilities in vitro and in a rodent model of DIC. In vivo, single-loaded ATIII-FSNs decreased fibrin deposits in DIC organs and reduced blood loss when DIC rodents were injured. We also observed that the addition of tPA in dual-loaded ATIII-tPA-FSNs intensified the antithrombotic and fibrinolytic mechanisms, which proved advantageous for clot lysis and restoring platelet counts. However, the addition of tPA may have hindered wound healing capabilities when an injury was introduced. Our data supports the benefits of delivering both anticoagulants and fibrinolytic agents directly to clots to reduce the fibrin load and restore hemostatic balance in DIC.
Asunto(s)
Coagulación Intravascular Diseminada , Activador de Tejido Plasminógeno , Activador de Tejido Plasminógeno/farmacología , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/química , Animales , Coagulación Intravascular Diseminada/tratamiento farmacológico , Nanogeles/química , Fibrinolíticos/farmacología , Fibrinolíticos/química , Fibrinolíticos/administración & dosificación , Humanos , Ratas , Fibrina/metabolismo , Fibrina/química , Antitrombinas/farmacología , Antitrombinas/química , Antitrombinas/administración & dosificación , Ratones , Masculino , Trombosis/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Coagulación Sanguínea/efectos de los fármacosAsunto(s)
Anticoagulantes , Coagulación Intravascular Diseminada , Oxigenación por Membrana Extracorpórea , Hemorragia , Heparina , Humanos , Heparina/administración & dosificación , Heparina/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/efectos adversos , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/prevención & control , Coagulación Intravascular Diseminada/tratamiento farmacológico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Hemorragia/prevención & controlRESUMEN
INTRODUCTION: Adult-onset Still disease (AOSD) is a rare inflammatory condition with a monophasic, intermittent, or chronic clinical course, and a subset may experience life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH). This study aims to characterize concurrent AOSD and HLH and identify variables independently associated with in-hospital death. METHODS: We performed a medical records review of AOSD with and without HLH from the 2016-2019 National Inpatient Sample database. We performed a multivariable logistic regression analysis for in-hospital death. Results were reported as adjusted odds ratios (OR adj ). RESULTS: There were 5495 hospitalizations with AOSD, of which 340 (6.2%) had HLH. Thirty (9.0%) of the combined AOSD and HLH group died in the hospital compared with 75 (1.5%) of those without HLH. Multivariable analysis in AOSD inpatients showed that disseminated intravascular coagulation (OR adj 6.13), hepatic failure (OR adj 7.16), infection (OR adj 3.72), respiratory failure (OR adj 6.89), and thrombotic microangiopathy (OR adj 14.05) were associated with higher odds of death. However, HLH itself was not an independent predictor of mortality in AOSD population. CONCLUSIONS: HLH occurred in a small minority of inpatients with AOSD. HLH itself was not an independent risk factor for in-hospital death. Disseminated intravascular coagulation, hepatic failure, infection, respiratory failure, and thrombotic microangiopathy were associated with higher odds of in-hospital death in AOSD. Better awareness of these life-threatening complications may improve hospital outcomes.
Asunto(s)
Mortalidad Hospitalaria , Linfohistiocitosis Hemofagocítica , Enfermedad de Still del Adulto , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/epidemiología , Linfohistiocitosis Hemofagocítica/mortalidad , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/epidemiología , Enfermedad de Still del Adulto/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estados Unidos/epidemiología , Coagulación Intravascular Diseminada/epidemiología , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiología , Fallo Hepático/etiología , Fallo Hepático/epidemiología , Fallo Hepático/diagnóstico , Factores de Riesgo , Anciano , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/diagnóstico , Estudios Retrospectivos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/epidemiología , Hospitalización/estadística & datos numéricos , Bases de Datos FactualesAsunto(s)
Coagulación Intravascular Diseminada , Fibrinólisis , Hemostasis , Humanos , Fibrinólisis/fisiología , Fibrinólisis/efectos de los fármacos , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/fisiopatología , Hemostasis/fisiologíaRESUMEN
Sepsis is a severe inflammatory disease characterized by cytokine storm, often accompanied by disseminated intravascular coagulation (DIC). PANoptosis is a novel form of cell death triggered by cytokine storms, characterized by a cascade reaction of pyroptosis, apoptosis, and necroptosis. It exists in septic platelets and is closely associated with the onset and progression of DIC. However, there remains an unmet need for drugs targeting PANoptosis. The anti-PANoptosis effect of myricetin was predicted using network pharmacology and confirmed through molecular docking. In vitro platelet activation models demonstrated that myricetin significantly attenuated platelet particle release, integrin activation, adhesion, spreading, clot retraction, and aggregation. Moreover, in a sepsis model, myricetin reduced inflammatory infiltration in lung tissue and platelet activation while improving DIC. Additionally, whole blood sequencing samples from sepsis patients and healthy individuals were analyzed to elucidate the up-regulation of the PANoptosis targets. Our findings demonstrate the inhibitory effect of myricetin on septic platelet PANoptosis, indicating its potential as a novel anti-cellular PANoptosis candidate and therapeutic agent for septic DIC. Furthermore, our study establishes a foundation for utilizing network pharmacology in the discovery of new drugs to treat various diseases.
Asunto(s)
Plaquetas , Coagulación Intravascular Diseminada , Flavonoides , Sepsis , Flavonoides/farmacología , Flavonoides/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/sangre , Humanos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/patología , Coagulación Intravascular Diseminada/sangre , Animales , Masculino , Simulación del Acoplamiento Molecular , Activación Plaquetaria/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones , Piroptosis/efectos de los fármacosRESUMEN
Hematological malignancies may require rapid-onset treatment because of their short doubling time, notably observed in acute leukemias and specific high-grade lymphomas. Furthermore, in targeted onco-hematological scenarios, chemotherapy is deemed necessary as an emergency measure when facing short-term, life-threatening complications associated with highly chemosensitive hematological malignancies. The risks inherent in the disease itself, or in the initiation of treatment, may then require admission to the intensive care unit (ICU) to optimize monitoring and initial management protocols. Hyperleukocytosis and leukostasis in acute leukemias, tumor lysis syndrome, and disseminated intravascular coagulation are the most frequent onco-hematological complications requiring the implementation of emergency chemotherapy in the ICU. Chemotherapy must also be started urgently in secondary hemophagocytic lymphohistiocytosis. Tumor-induced microangiopathic hemolytic anemia and plasma hyperviscosity due to malignant monoclonal gammopathy represent infrequent yet substantial indications for emergency chemotherapy. In all cases, the administration of emergency chemotherapy in the ICU requires close collaboration between intensivists and hematology specialists. In this review, we provide valuable insights that aid in the identification and treatment of patients requiring emergency chemotherapy in the ICU, offering diagnostic tools and guidance for their overall initial management.
Asunto(s)
Neoplasias Hematológicas , Unidades de Cuidados Intensivos , Humanos , Unidades de Cuidados Intensivos/organización & administración , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Síndrome de Lisis Tumoral/etiología , Síndrome de Lisis Tumoral/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/etiología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/complicacionesRESUMEN
D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications.
Asunto(s)
Biomarcadores , COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , COVID-19/sangre , COVID-19/diagnóstico , Biomarcadores/sangre , SARS-CoV-2 , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/sangre , Fibrinólisis , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/sangre , Pronóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/sangre , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/sangreRESUMEN
PURPOSE: Evaluate maternal and neonatal outcomes in peripartum coronavirus disease 2019 (COVID-19) positive women. METHODS: A retrospective cohort study was conducted, comparing outcomes between women with and without peripartum COVID-19. All singleton deliveries from June 2020 to January 2022 were included. Univariate analysis was followed by multivariate analysis. RESULTS: Of 26,827 singleton deliveries, 563 women had peripartum COVID-19, associated with preterm deliveries both near-term and remote from term [adjusted odds ratio (aOR) 1.6 and 2.0, respectively, p = 0.007 and 0.003]. Women with peripartum COVID-19 had a significantly higher rate of disseminated intravascular coagulation (DIC) (aOR 23.0, p < 0.001). Conversely, peripartum COVID-19 peripartum COVID-19 was negatively associated with premature rupture of membranes and prolonged maternal length of stay (aOR 0.7 and 0.5, respectively, p = 0.006 and <0.001). In cesarean delivery (CDs), patients with COVID-19 had higher rate of urgent CDs (75.5 vs. 56.1%, p < 0.001), higher rate of regional anesthesia (74.5 vs. 64.9%, p = 0.049), and longer anesthesia duration (86.1 vs. 53.4 min, p < 0.001). CD rate due to non-reassuring fetal heart rate (NRFHR) was significantly higher in women with COVID-19 (29.6 vs. 17.4%, p = 0.002). Conversely, CDs rate due to history of previous single CD was significantly higher in patients without COVID-19 diagnosis (13.6 vs. 4.1%, p = 0.006). Concerning neonatal outcomes, an association has been observed between COVID-19 and low one-minute APGAR score <5, as well as neonatal COVID-19 infection (aOR 61.8 and 1.7 respectively, p < 0.001 and p = 0.037). CONCLUSIONS: Peripartum COVID-19 is associated with preterm deliveries, urgent CDs and DIC, potentially aligning with the infection's pathophysiology and coagulation alterations.
Asunto(s)
COVID-19 , Cesárea , Coagulación Intravascular Diseminada , Periodo Periparto , Complicaciones Infecciosas del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , COVID-19/complicaciones , COVID-19/epidemiología , Estudios Retrospectivos , Adulto , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Resultado del Embarazo/epidemiología , Recién Nacido , Cesárea/estadística & datos numéricos , Coagulación Intravascular Diseminada/epidemiología , Coagulación Intravascular Diseminada/etiología , SARS-CoV-2 , Nacimiento Prematuro/epidemiología , Rotura Prematura de Membranas Fetales/epidemiología , Rotura Prematura de Membranas Fetales/virología , Tiempo de Internación/estadística & datos numéricosRESUMEN
A 52-year-old woman presented to our hospital with chief complaints of upper abdominal bloating and lower leg edema. Computed tomography (CT) revealed liver metastasis from a gallbladder tumor. This tumor was diagnosed as neuroendocrine carcinoma (NEC) on performing a biopsy. Physical examination revealed a moon face. Blood tests revealed hypokalemia and high levels of adrenocorticotropic hormone (ACTH) and cortisol. Dexamethasone suppression test revealed that cortisol secretion was not suppressed, and the patient was diagnosed with gallbladder NEC and ectopic ACTH syndrome (EAS). Metyrapone was administered to suppress cortisol production; however, she developed septic shock due to cellulitis in the lower leg and died on the 16th day of admission. A pathological autopsy was performed, which revealed disseminated intravascular coagulation and acute respiratory distress syndrome as the cause of death. Only a few cases of EAS due to NEC originating from the gallbladder have been reported. The patient reported here succumbed shortly after diagnosis, thereby highlighting the challenges in treating gallbladder NEC complicated by EAS.
Asunto(s)
Síndrome de ACTH Ectópico , Carcinoma Neuroendocrino , Neoplasias de la Vesícula Biliar , Humanos , Femenino , Neoplasias de la Vesícula Biliar/complicaciones , Persona de Mediana Edad , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/secundario , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/diagnóstico , Resultado Fatal , Sepsis/complicaciones , Sepsis/etiología , Coagulación Intravascular Diseminada/etiología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/complicaciones , Choque Séptico/etiología , Síndrome de Dificultad Respiratoria/etiologíaRESUMEN
BACKGROUND: Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis, respectively, undergo substantial activation after sepsis. SUMMARY: Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation," which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. KEY MESSAGES: Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.
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Activación de Complemento , Sepsis , Humanos , Sepsis/inmunología , Activación de Complemento/inmunología , Animales , Coagulación Sanguínea , Coagulación Intravascular Diseminada/inmunología , Coagulación Intravascular Diseminada/etiología , Inmunidad Innata , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/etiología , Fibrinólisis , Trastornos de la Coagulación Sanguínea/inmunología , Trastornos de la Coagulación Sanguínea/etiología , Trombosis/inmunología , Trombosis/etiologíaRESUMEN
RATIONALE: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation. PATIENTS CONCERNS: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced. DIAGNOSIS: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE. INTERVENTIONS: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications. OUTCOMES: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae. LESSONS: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.
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Embolia de Líquido Amniótico , Oxigenación por Membrana Extracorpórea , Humanos , Femenino , Embolia de Líquido Amniótico/terapia , Embolia de Líquido Amniótico/diagnóstico , Oxigenación por Membrana Extracorpórea/métodos , Adulto , Embarazo , Cesárea/efectos adversos , Transfusión Sanguínea/métodos , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/administración & dosificación , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/terapia , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificaciónRESUMEN
BACKGROUND: Antithrombin is a small plasma glycoprotein synthesized in the liver that belongs to the serpin family of serine protease inhibitors and inactivates several enzymes in the coagulation pathway. It plays a leading major factor on coagulation pathway, therefore administration of antithrombin is essential to treat serious clinical conditions such as disseminated intravascular coagulation (DIC). Despite the theoretical benefits of antithrombin supplementation, the optimal antithrombin activity for heparin efficacy and the benefits of antithrombin supplementation in various disease entities are not yet fully understood. METHODS: The strict administration guidelines on antithrombin III in cases of DIC by the National Health Insurance Service and the Ministry of Food and Drug Safety complied as follows: antithrombin levels below 20 mg/dL in adults; antithrombin activity below 70% of normal in adults; total administration period of antithrombin must be carefully limited to within maximum 3 days, and the total administration dose must be below 7,000 international unit (IU), (loading dose, 1,000 IU in 1 hour: maintenance dose, 500 IU every 6 hours for 3 days). RESULTS: We identified 76 eligible for analysis according to the above-mentioned criteria in our institution (male/female, 59/17). Forty-four were identified to the non-survivor group and 32 patients were recognized as the survivor group. The baseline parameters in the non-survivor and survivor groups were comparable with no significant differences in age (66.5±18.1 vs. 66.0±16.2 years, P=0.90), sex (32/12 vs. 27/5, P=0.35), hospital length of stay (31.1±34.5 vs. 31.2±26.1 days, P=0.99), sequential organ failure assessment (SOFA) (7.3±2.5 vs. 6.6±2.0, P=0.22), simplified acute physiology score II (SAPS II) (46.0±8.8 vs. 43.5±9.2, P=0.23), cause for DIC (P=0.95), and underlying disease (P=0.38). The levels of antithrombin III on the day just before the administration significantly lower in the non-survivor groups than in the survivor groups (50.1%±13.6% vs. 57.6%±12.5%, P=0.01). The hemoglobin level in the 2nd day and 7th day after antithrombin III administration was significantly different between the non-survivor and survivor groups (9.9±1.9 vs. 11.0±2.0 g/dL, P=0.01, and 9.4±1.8 vs. 10.5±1.6 g/dL, P=0.006). The antithrombin III levels on the day of administration [area under the curve (AUC) =0.672] demonstrated significantly better prediction of mortality than the A antithrombin III levels on 1st day (AUC =0.552), the 2nd day (AUC =0.624), and 7th day (AUC =0.593). CONCLUSIONS: Our study suggests that the antithrombin administration may be effective tools for DIC treatment, and may be more positively considered, especially in the cases of DIC, which is a frequent complication of septic shock, sepsis, and other critical disease entities and which is associated with a high level of mortality. Furthermore, our study also suggests that the total doses and periods of antithrombin administration, which recommended by national guidelines, may be insufficient, therefore prolongation of period and increase of total dose of antithrombin supplement might be necessary.
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Antitrombina III , Coagulación Intravascular Diseminada , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Coagulación Intravascular Diseminada/tratamiento farmacológico , Estudios Longitudinales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Disseminated intravascular coagulation (DIC) is considered to be the most common and lethal complication of sepsis. NLR-family pyrin domain-containing-3 (NLRP3) inflammasome plays an important role in host defense against microbial pathogens, and its deregulation may cause coagulation cascade and should be strictly managed. Here, we identified the deubiquitinase YOD1, which played a vital role in regulating coagulation in a NLRP3 inflammasome-dependent manner in sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA). YOD1 interacted with NLRP3 to remove K33-linked ubiquitination of NLRP3 based on its deubiquitinating enzyme activity and specifically inhibited expression of NLRP3 as well as activation of NLRP3 inflammasome. Deficiency of YOD1 expression enhanced NLRP3 inflammasome activation and coagulation both in vitro and in vivo. In addition, pharmacological inhibition of the NLRP3 effectively improved coagulation and alleviated organ injury in Yod1-/- mice infected with MRSA. Thus, our study reported that YOD1 is a key regulator of coagulation during MRSA infection, and provided YOD1 as a potential therapeutic target for the treatment of NLRP3 inflammasome-related diseases, especially MRSA sepsis-induced DIC.