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INTRODUCTION: Bleeding and thrombotic events (BTE) are frequent during extracorporeal membrane oxygenation (ECMO). They occur at varying timepoints and may be affected by temporal changes in coagulation and fibrinolysis. We aimed to assess various coagulation and fibrinolytic markers over time and their relationship with BTE. METHODS: A single-centre prospective study was performed in 17 patients with severe respiratory failure receiving veno-venous ECMO. Blood samples were collected before and during ECMO, and around circuit decannulation. RESULTS: Prior to ECMO, D-Dimer, Plasmin-Antiplasmin complexes (PAP), Plasminogen-Activator Inhibitor-1 (PAI-1) and fibrinogen were elevated. There was an increase in D-Dimer and Prothrombin Fragments 1+2 (PF1+2) (729 to 1305pmol/L, p = .034) by day 1 and PAP increased by day 2 from baseline levels (median 1022 to 1797 µg/L, p = .023). There was a strong positive correlation in PAP, PF1+2 and thrombin-antithrombin complexes (TAT) to D-Dimer. BTE were frequent - 18% had major extracranial haemorrhage and 24% had intracranial haemorrhage. Over time, there was a progressive elevation PAP in patients developing subsequent extracranial haemorrhage, whereas D-Dimer, PAP and PF1+2 increased after intracranial haemorrhage. CONCLUSIONS: There were early changes in coagulation activity during ECMO by PF1+2 followed by subsequent fibrinolysis by PAP. Changes in PAP, PF1+2 and TAT were associated with major haemorrhage.
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Background: Several studies have found increased risks of thrombosis with thrombocytopenia syndrome (TTS) following the ChAdOx1 vaccination. However, case ascertainment is often incomplete in large electronic health record (EHR)-based studies. Objectives: To assess for an association between clinically validated TTS and COVID-19 vaccination. Methods: We used the self-controlled case series method to assess the risks of clinically validated acute TTS after a first COVID-19 vaccine dose (BNT162b2 or ChAdOx1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case ascertainment was performed uninformed of vaccination status via a retrospective clinical review of hospital EHR systems, including active ascertainment of thrombocytopenia. Results: One hundred seventy individuals were admitted to the hospital for a TTS event at the study sites between January 1 and March 31, 2021. A significant increased risk (relative incidence [RI], 5.67; 95% confidence interval [CI], 1.02-31.38) of TTS 4 to 27 days after ChAdOx1 was observed in the youngest age group (18- to 39-year-olds). No other period had a significant increase, although for ChAdOx1 for all ages combined the RI was >1 in the 4- to 27- and 28- to 41-day periods (RI, 1.52; 95% CI, 0.88-2.63; and (RI, 1.70; 95% CI, 0.73-3.8, respectively). There was no significant increased risk of TTS after BNT162b2 in any period. Increased risks of TTS following a positive SARS-CoV-2 test occurred across all age groups and exposure periods. Conclusions: We demonstrate an increased risk of TTS in the 4 to 27 days following COVID-19 vaccination, particularly for ChAdOx1. These risks were lower than following SARS-CoV-2 infection. An alternative vaccine may be preferable in younger age groups in whom the risk of postvaccine TTS is greatest.
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Síndrome Antifosfolípido , Tromboembolia Venosa , Administración Oral , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/tratamiento farmacológico , Humanos , Factores de Riesgo , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiologíaRESUMEN
OBJECTIVES: Extracorporeal membrane oxygenation is a lifesaving therapy for patients with severe acute respiratory distress syndrome refractory to conventional mechanical ventilation. It is frequently complicated by both thrombosis and hemorrhage. A markedly prothrombotic state associated with high rates of venous thromboembolism has been described in patients with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) infection. These rates have currently not been described during extracorporeal membrane oxygenation in comparison to other viral pneumonias. DESIGN: Retrospective observational study. SETTING: Single high-volume tertiary critical care department at a university hospital. PATIENTS: Patients 16 years old or greater receiving venovenous extracorporeal membrane oxygenation between March 1, 2020, and May 31, 2020, with coronavirus disease 2019 were compared with a cohort of patients with influenza pneumonia between June 1, 2012, and May 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The rates of venous thromboembolism and hemorrhage were compared in patients with coronavirus disease 2019 against a historic population of patients with influenza pneumonia who required extracorporeal membrane oxygenation. There were 51 patients who received extracorporeal membrane oxygenation due to coronavirus disease 2019 and 80 patients with influenza. At cannulation for extracorporeal membrane oxygenation, 37% of patients with coronavirus disease 2019 compared with 8% of patients with influenza had filling defects on CT pulmonary angiography (p = 0.0001). Catheter-associated deep vein thrombosis shown on ultrasound Doppler after decannulation was present in 53% with coronavirus disease 2019 versus 25% with influenza (p = 0.01). The rates of intracranial hemorrhage at the time of cannulation were 16% with coronavirus disease 2019 and 14% with influenza (p = 0.8). Elevated d-dimer levels were seen in both conditions and were significantly higher in those with pulmonary thromboembolism than those without in coronavirus disease 2019 (p = 0.02). Fibrinogen and C-reactive protein levels were significantly higher in those with coronavirus disease 2019 than influenza (p < 0.01). CONCLUSIONS: Significant rates of pulmonary thromboembolism and of catheter-associated deep vein thrombosis were seen in both viral infections but were greater in those requiring the use of extracorporeal membrane oxygenation in coronavirus disease 2019 than for influenza.
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COVID-19/terapia , Oxigenación por Membrana Extracorpórea , Gripe Humana/terapia , Hemorragias Intracraneales/complicaciones , Embolia Pulmonar/complicaciones , Tromboembolia Venosa/complicaciones , Trombosis de la Vena/complicaciones , Adulto , Proteína C-Reactiva/metabolismo , Angiografía por Tomografía Computarizada , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Humanos , Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Virus de la Influenza B , Londres/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2 , Medicina Estatal , Centros de Atención Terciaria , Ultrasonografía DopplerAsunto(s)
Síndrome Antifosfolípido/complicaciones , Paraproteinemias/complicaciones , Trombosis/etiología , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paraproteinemias/diagnóstico , Paraproteinemias/inmunología , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Trombosis/diagnóstico , Trombosis/inmunología , Factores de TiempoRESUMEN
OBJECTIVE: Thrombophilia is a prothrombotic condition that increases the risk of venous thromboembolism. It is unclear whether the presence of thrombophilia alters the clinical outcomes after deep venous stenting. The aim of the present study was to examine the relationship between thrombophilia and outcomes after stenting for post-thrombotic syndrome. METHODS: Consecutive patients (2012-2017) receiving a nitinol venous stent for chronic post-thrombotic venous occlusive disease with a minimum of 18 months of follow-up in one center using the same anticoagulation protocol were included. The clinical history and thrombophilia testing results were reviewed. The outcomes were stent patency, which was assessed using duplex ultrasonography at 24 hours, 2 and 6 weeks, 3 months, 6 months, and annually thereafter; and reinterventions, which were performed when the stent diameter was <50% or occluded. RESULTS: Of the 136 patients who had undergone intervention, 55 (40%) had had a provoked deep vein thrombosis (DVT) and 81 (60%) had had an unprovoked DVT and had therefore undergone thrombophilia testing. Of the 81 patients, 38 (47%) had had either inherited (n = 19; 50%) or acquired (n = 19; 50%) thrombophilia. Of the 136 patients who had undergone stenting, 68 had required reintervention (50%) during follow-up to maintain stent patency. Of the 55 patients with a provoked DVT, 29 (53%) had required reintervention. Of the 81 patients with an unprovoked DVT, 39 (48%) had required reintervention (P = .420). Of the 38 patients with unprovoked DVT and thrombophilia, 17 (45%) had required reintervention. Of the 43 patients with unprovoked DVT and no thrombophilia, 22 (51%) had required reintervention (P = .766). The cumulative patency rate was 80% for patients with provoked DVT and 88% for those with unprovoked DVT (P = .193). The presence of thrombophilia was not associated with patency loss (92% cumulative patency for patients with thrombophilia and 84% for patients without thrombophilia; P = .307). CONCLUSIONS: Using our anticoagulation protocol, patients with and without thrombophilia had similar clinical outcomes after deep venous stenting and should not be excluded from iliofemoral venous stenting. We found no significant differences in outcomes in conjunction with appropriate postoperative anticoagulation therapy.
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Vena Femoral/cirugía , Vena Ilíaca/cirugía , Síndrome Postrombótico/complicaciones , Síndrome Postrombótico/cirugía , Stents , Trombofilia/complicaciones , Adulto , Aleaciones , Anticoagulantes/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Grado de Desobstrucción VascularAsunto(s)
COVID-19/terapia , Cuidados Críticos , Hospitalización , Embolia Pulmonar/epidemiología , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/epidemiología , COVID-19/diagnóstico , COVID-19/mortalidad , Inglaterra , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidad , Embolia Pulmonar/terapia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/terapia , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/mortalidad , Trombosis de la Vena/terapiaAsunto(s)
Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Tromboembolia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Cuidados Críticos , Dalteparina/uso terapéutico , Oxigenación por Membrana Extracorpórea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Estudios Retrospectivos , SARS-CoV-2 , Atención Terciaria de Salud , Tromboembolia/diagnóstico por imagen , Tromboembolia/tratamiento farmacológico , Tromboembolia/terapia , Ultrasonografía Doppler , Reino Unido/epidemiología , Adulto JovenAsunto(s)
Anticoagulantes/uso terapéutico , Trastornos Mieloproliferativos/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Centros de Atención Terciaria , Resultado del Tratamiento , Reino Unido , Adulto JovenRESUMEN
A study is presented which assesses the diagnostic impact of incorporating Taipan snake venom time (TSVT) with ecarin time confirmatory test into an existing dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) repertoire when testing nonanticoagulated patients for lupus anticoagulants. A total of 387 plasma samples from nonanticoagulated patients being investigated for antiphospholipid antibodies were tested for lupus anticoagulant by dRVVT and dilute APTT with confirmatory and mixing tests, and TSVT with ecarin time, with commercially available reagents. All were analyzed on a Sysmex CS2000i automated analyzer. Lupus anticoagulant was not detected by dRVVT, dilute APTT or TSVT screening in 265 of 387 (68.5%) samples. A lupus anticoagulant was detected in 60 (15.5%) samples in dRVVT and/or dilute APTT analysis, but gave normal TSVT ratios. Thirty-nine (10.1%) were positive by TSVT and ecarin time and one or both of dRVVT and dilute APTT testing, whereas a further 23 (5.9%) were only positive in TSVT/ecarin time testing. Most of the lupus anticoagulants manifested in dRVVT and/or APTT analysis, as might be anticipated for this reagent pairing. The samples positive by TSVT/ecarin time only, as has been previously demonstrated, emphasize that the many variables that impact lupus anticoagulant testing mean that even a well established dRVVT and APTT pairing cannot deliver diagnostic certainty. Interference by direct factor Xa inhibitors in dRVVT testing could pave the way for wider adoption of TSVT screening as we gain more evidence of its diagnostic performance.
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Síndrome Antifosfolípido/diagnóstico , Endopeptidasas/química , Inhibidor de Coagulación del Lupus/sangre , Venenos de Víboras/química , Animales , Síndrome Antifosfolípido/sangre , Automatización de Laboratorios , Biomarcadores/sangre , Inhibidores del Factor Xa/química , Reacciones Falso Positivas , Humanos , Tiempo de Tromboplastina Parcial , Tiempo de ProtrombinaAsunto(s)
Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Activación de Complemento/genética , Glicoproteínas/sangre , Lectinas/sangre , Lectina de Unión a Manosa/sangre , Adulto , Anciano , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/genética , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/patología , Complemento C3a/genética , Complemento C3a/inmunología , Factor B del Complemento/genética , Factor B del Complemento/inmunología , Femenino , Expresión Génica , Glicoproteínas/genética , Glicoproteínas/inmunología , Humanos , Lectinas/genética , Lectinas/inmunología , Masculino , Lectina de Unión a Manosa/genética , Lectina de Unión a Manosa/inmunología , Persona de Mediana Edad , FicolinasRESUMEN
The antiphospholipid syndrome (APS) is the association of thrombosis and recurrent pregnancy loss and/or pregnancy morbidity with persistent antiphospholipid antibodies (aPL). Increased complement activation has been implicated in the pathogenesis of APS in animal models. It was our objective to evaluate complement activation in patients with aPL or primary antiphospholipid syndrome (PAPS). We measured complement activation products, fragments Bb and C3a-desArg by ELISA in 186 aPL/PAPS patients and 30 healthy controls. All patients with aPL had significantly increased levels of complement activation products. Fragment Bb levels (mean, 95% CI); (thrombotic APS 0.54 units/ml, 0.31-0.83, obstetric APS 0.60 units/ml,0.39-1.02, isolated aPL 0.48 units/ml, 0.29-0.85, overall 0.39 units/ml, 0.33-0.47) and C3a-desArg levels (mean, 95% CI): (thrombotic APS 261 ng/ml, 219-311, obstetric APS 308 ng/ml, 243-391, isolated aPL 258 ng/ml, 193-337, overall 225 ng/ml, 202-251) were significantly higher compared to controls (fragment Bb 0.06 units/ml, 0.03-0.11, C3a-desArg 69 ng/ml, 50-92). There were correlations between Fragment Bb and C3a-desArg levels in all patients with aPL. Receiver operator characteristic (ROC) analysis showed increased fragment Bb and C3a-desArg levels had strong associations with the presence of persistent lupus anticoagulant (area under ROC: Bb 0.89, and C3a-desArg 0.90), dual and triple aPL positivity (Bb 0.71-0.82, C3a-desArg 0.71-0.80) but not with high titre anti-cardiolipin antibodies (Bb 0.62, C3a-desArg 0.65), or anti ß2-glycoprotein 1 antibodies (Bb 0.66, C3a-desArg 0.67). Complement activation is present in all patient groups within this large cohort of patients aPL. This suggests it may have a major role in the pathogenesis of APS and merits further study.
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Síndrome Antifosfolípido/inmunología , Activación de Complemento , Complemento C3a/metabolismo , Factor B del Complemento/metabolismo , Adulto , Anciano , Animales , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Complemento C3a/inmunología , Factor B del Complemento/inmunología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
Coagulopathy occurs in most patients with (APML) and is life-threatening; therefore prompt diagnosis and recognition of any coagulation defect is imperative. Unfortunately haemorrhage remains a major cause of early death, preventing some from reaching treatment. The coagulopathy is caused directly or indirectly by the leukaemic cells through expression of activators of coagulation and fibrinolysis, proteases and cytokine generation, compounded by failure of platelet production due to marrow invasion. At presentation the predominant feature is usually hyperfibrinolysis. Since the introduction of all-trans retinoic acid (ATRA), patient outcome has dramatically improved; yet, haemorrhagic complications remain the most frequent cause of mortality. Thrombotic complications occur but are less well recognized and potentially underreported. Supportive measures and prompt initiation of ATRA currently represent the mainstay of treatment of the coagulopathy in patients with suspected APML, but unanswered questions remain as to the optimal approach to further decrease the associated haemorrhagic and thrombotic risks. In particular, it is unclear how to best predict and monitor the coagulopathy; whether there is a role for the early use of antifibrinolytics; the most appropriate trigger for giving fibrinogen replacement and the value of low-dose anticoagulation to suppress coagulation activation once fibrinolysis has been suppressed.
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Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/terapia , Leucemia Promielocítica Aguda/complicaciones , Trastornos de la Coagulación Sanguínea/diagnóstico , HumanosRESUMEN
OBJECTIVE: The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma. SUBJECTS AND METHODS: Twenty-four patients (13 women, 11 men; mean age, 67.1 years; range, 44-83 years) with bone marrow biopsy-proven multiple myeloma were included in the study. All patients underwent PET/CT and whole-body MRI within 10 days of each other. Eight patients underwent more than one follow-up PET/CT and whole-body MRI examination, for a total of 34 pairs of images. Activity was defined as lesions with a maximum standardized uptake value greater than 2.5 at PET and as evidence of marrow packing at whole-body MRI. PET and whole-body MRI results were correlated with findings at bone marrow aspiration biopsy. RESULTS: PET had a sensitivity of 59%, specificity of 75%, positive predictive value of 81%, and negative predictive value of 50% (p = 0.08). Whole-body MRI had a sensitivity of 68%, specificity of 83%, positive predictive value of 88%, and negative predictive value of 59% (p = 0.01). In 62% of cases, PET and whole-body MRI findings were concordant. When PET and whole-body MRI findings were concordant and positive, no false-positive results were found, yielding a specificity and a positive predictive value of 100% (p = 0.04). CONCLUSION: Whole-body MRI performed better than PET in the assessment of disease activity, having a higher sensitivity and specificity. The positive predictive value of whole-body MRI in the assessment of active disease was high at 88%. When used in combination and with concordant findings, PET and whole-body MRI were found to have a specificity and positive predictive value of 100%, which may be of value to clinicians assessing the effectiveness of aggressive and expensive treatment regimens.