Trastornos de la coagulación en cirrosis hepática: artículo de revisión / Coagulation disorders in liver cirrhosis: a review article

Los eventos fisiopatológicos de la cirrosis hepática alteran drásticamente los procesos de hemostasia primaria, secundaria y fibrinólisis. Antiguamente se conceptuaba que dichas alteraciones predisponían exclusivamente a un estado de hipocoagulabilidad, debido a la baja producción hepática de factores procoagulantes y a la trombocitopenia característica. Actualmente existe evidencia de mecanismos de compensación que llevan a un reequilibrio hemostático, que es inestable y fácilmente desregulado ante comorbilidades, complicaciones y progresión de la enfermedad, conduciendo a fenómenos prohemorrágicos o protrombóticos, como trombosis venosa portal, tromboembolismo venoso, etc. Para determinar eficazmente si un paciente cirrótico tiene riesgo de sangrado, no son de utilidad las pruebas de coagulación convencionales. El tratamiento dependerá del estado hipo o hipercoagulable del paciente. Para ello desarrollamos una revisión de los fenómenos hemostáticos en la cirrosis, con el fin de dar a conocer sus características, el método de diagnóstico más eficaz y los tratamientos disponibles.

The pathophysiological events of liver cirrhosis drastically alter the processes of primary and secondary hemostasis and fibrinolysis. Previously, it was conceptualized that these alterations exclusively predisposed to hypocoagulation, due to the low hepatic production of procoagulant factors and the characteristic thrombocytopenia. Currently, there is evidence of compensation mechanisms that lead to a hemostatic rebalancing, which is unstable and easily dysregulated in the presence of comorbidities, complications and progression of the disease, leading to prohemorrhagic or prothrombotic phenomena, such as portal vein thrombosis, venous thromboembolism, etc. To effectively determine whether a cirrhotic patient is at risk for bleeding, conventional coagulation tests are not helpful. Treatment will depend on the hypo or hypercoagulable state of the patient. In this manuscript, we review the hemostatic phenomena in cirrhosis, to reveal its characteristics, effective diagnostic methods and treatment.

Evaluating the effect of antidiabetic treatment on haemostatic and fibrinolytic parameters among type 2 diabetics in Ilorin, Nigeria

Background:Type 2 Diabetes Mellitus is a disease of epidemic proportions and many patients are at a great risk of premature mortality and complication of atherothrombotic disorders affecting coronary, cerebral and peripheral arterial trees. Increased Plasminogen Activator Inhibitor Type 1 inhibits fibrinolysis and predicts cardiovascular risk in those living with Type 2 Diabetes. This study aimed to determine the effect of antidiabetic treatment on haemostatic and fibrinolytic parameters among Type 2 Diabetic subjects in Ilorin.Methods:This was a comparative cross-sectional study involving 78 Type 2 diabetic patients, (39 treatment naïve, 39 treatment experienced). Full blood count was performed using Sysmex XP300 while Prothrombin time was determined using one stage test of Owren. Activated partial thromboplastin time was determined by method of Proctor and Rapaport. Fibrinogen and Plasminogen Activator Inhibitor type-1 were assayed using AssayMax Human Fibrinogen ELISAand AssayMax Human PAI-1 ELISAkit. Data Analysis was done using SPSS version 25.0.Results:Mean PAI-1 levels were significantly higher in treatment naïve diabetics when compared to treatment experienced diabetics (2.44 ±2.57 vs 2.51±1.47 ng/ml p=0.002) as were fibrinogen levels (434.65±366.15 vs 482.24± 299.64mg /dl; p = 0.048). PAI -1 levels were lowest among diabetics treated with Metformin + DPP4 inhibitors, while fibrinogen levels were lowest among those treated with Metformin + sulfonylurea combination.Conclusion:Oral hypoglycaemic treatment, combination therapy in particular, improves fibrinolysis in type 2 diabetics thereby reducing the risk of cardiovascular disease in type 2 diabetes mellitus patients

Successful systemic fibrinolysis in a patient with Covid-19: Case report / Fibrinólisis sistémica exitosa en un paciente con Covid- 19: Reporte de Caso

Abstract The new coronavirus 2019-nCov or SARS-Cov-2 is responsible for the most important pandemic in the 21st century: the coronavirus disease (COVID-19). The 2019-nCov infection elicits a hyper-coagulable state, conditioning a worse outcome in these patients. The pathophysiology of the exaggerated coagulation activation in these patients is still unknown, and probably involves several mechanisms, different from those involved in sepsis-associated coagulopathy. This article discusses the case of a patient with no remarkable medical history, who after 7 days of fever, diarrhea and epigastric pain was diagnosed with COVID-19 bilateral pneumonia, further aggravated by severe Acute Respiratory Distress Syndrome. In this context, the patient experienced a massive acute pulmonary thromboembolism accompanied by an acute thrombus in the heart's right ventricle, leading to hemodynamic instability. For the first time in our center in these patients, systemic fibrinolysis was successfully performed, with resolution of the intracavitary thrombus and the acute hemodynamic shock.

Resumen El nuevo coronavirus 2019-nCov o SARS-Cov-2 es responsable de la pandemia más importante del siglo XXI: la enfermedad del coronavirus (COVID-19). La infección por 2019-nCov produce un estado de hipercoagulabilidad, que promueve peores desenlaces en estos pacientes. La fisiopatología de la exagerada activación de la coagulación en estos pacientes aún se desconoce y posiblemente involucre varios mecanismos, diferentes a los participan en la coagulopatía asociada a sepsis. El presente artículo presenta el caso de un paciente sin antecedentes médicos y quien luego de 7 días de fiebre, diarrea y dolor epigástrico, fue diagnosticado con neumonía bilateral por COVID-19, agravada por la presencia de Síndrome de Dificultad Respiratoria Aguda. En este contexto, el paciente desarrolla un tromboembolismo pulmonar agudo masivo, acompañado de un trombo agudo en el ventrículo derecho, produciéndole inestabilidad hemodinámica. Por primera vez en nuestro centro, se realizó exitosamente una fibrinólisis sistémica, con resolución del trombo intracavitario y del shock hemodinámico agudo.

Acurácia da redução do segmento-ST pós-trombólise como preditor de reperfusão adequada em estratégia fármaco-invasiva / Accuracy of post-thrombolysis ST-segment reduction as an adequate reperfusion predictor in the pharmaco-invasive aproach

Resumo Fundamento A intervenção coronária percutânea primária é considerada o "padrão-ouro" para reperfusão coronária. Entretanto, quando não disponível, a estratégia fármaco-invasiva é método alternativo, e o eletrocardiograma (ECG) tem sido utilizado para identificar sucesso na reperfusão. Objetivos Nosso estudo teve como objetivo examinar alterações no segmento-ST pós-lise e seu poder de prever a recanalização, usando os escores angiográficos TIMI e blush miocárdio (MBG) como critério de reperfusão ideal. Métodos Foram estudados 2.215 pacientes com infarto agudo do miocárdio com supra-ST submetidos à fibrinólise [(Tenecteplase)-TNK] e encaminhados para angiografia coronária em até 24 h pós-fibrinólise ou imediatamente encaminhados à terapia de resgate. O ECG foi realizado pré-TNK e 60 min-pós. Os pacientes foram categorizados em dois grupos: aqueles com reperfusão ideal (TIMI-3 e MBG-3) e aqueles com reperfusão inadequada (fluxo TIMI <3). Foi definido o critério de reperfusão do ECG pela redução do segmento ST >50%. Consideramos p-valor <0,05 para as análises, com testes bicaudais. Resultados O critério de reperfusão pelo ECG apresentou valor preditivo positivo de 56%; valor preditivo negativo de 66%; sensibilidade de 79%; e especificidade de 40%. Houve fraca correlação positiva entre a redução do segmento-ST e os dados angiográficos de reperfusão ideal (r = 0,21; p <0,001) e baixa precisão diagnóstica, com AUC de 0,60 (IC-95%; 0,57-0,62). Conclusão Em nossos resultados, a redução do segmento-ST não conseguiu identificar com precisão os pacientes com reperfusão angiográfica apropriada. Portanto, mesmo pacientes com reperfusão aparentemente bem-sucedida devem ser encaminhados à angiografia brevemente, a fim de garantir fluxo coronário macro e microvascular adequados.

Abstract Background Primary percutaneous coronary intervention is considered the "gold standard" for coronary reperfusion. However, when not available, the drug-invasive strategy is an alternative method and the electrocardiogram (ECG) has been used to identify reperfusion success. Objectives Our study aimed to assess ST-Segment changes in post-thrombolysis and their power to predict recanalization and using the angiographic scores TIMI-flow and Myocardial Blush Grade (MBG) as an ideal reperfusion criterion. Methods 2,215 patients with ST-Segment Elevation Myocardial Infarction (STEMI) undergoing fibrinolysis [(Tenecteplase)-TNK] and referred to coronary angiography within 24 h post-fibrinolysis or immediately referred to rescue therapy were studied. The ECG was performed pre- and 60 min-post-TNK. The patients were categorized into 2 groups: those with ideal reperfusion (TIMI-3 and MBG-3) and those with inadequate reperfusion (TIMI and MBG <3). The ECG reperfusion criterion was defined by the reduction of the ST-Segment >50%. A p-value <0.05 was considered for the analyses, with bicaudal tests. Results The ECG reperfusion criterion showed a positive predictive value of 56%; negative predictive value of 66%; sensitivity of 79%; and specificity of 40%. There was a weak positive correlation between ST-Segment reduction and ideal reperfusion angiographic data (r = 0.21; p <0.001) and low diagnostic accuracy, with an AUC of 0.60 (95%CI: 0.57-0.62). Conclusion The ST-Segment reduction was not able to accurately identify patients with adequate angiographic reperfusion. Therefore, even patients with apparently successful reperfusion should be referred to angiography soon, to ensure adequate macro and microvascular coronary flow.

Flegmasía cerulea dolens. tratamiento con fibrinolisis sistémica / Phlegmasia cerulea dolens. Treatment with systemic fibrinolysis

Resumen La flegmasia cerulea dolens es una complicación rara y poco frecuente de la trombosis venos a profunda. Los principales factores predisponentes son los procesos neoformativos, estados de hiper coagulabilidad, insuficiencia cardíaca congestiva, embarazo, inmovilización prolongada y cirugías. Se caracteriza por edema masivo, dolor intenso y cianosis. Sin tratamiento evoluciona con isquemia, necrosis y amputación del miembro comprometido. No existe consenso en su tratamiento, pero éste debe ser rápido, multidisciplinario y agresivo. La anticoagulación con heparina, la fibrinólisis sistémica, la trombectomía percutánea con fibrinólisis local, la trombectomía quirúrgica, la fasciotomía, la colocación de filtro de vena cava inferior y la amputación son algunos de los tratamientos propuestos.

Abstract Phlegmasia cerulea dolens (FCD) is a rare complication of deep vein thrombosis. Its cause is unknown. The main predisposing factors for the disease are neoformative processes, hypercoagulable states, congestive heart failure, pregnancy, prolonged immobilization, and surgeries on the affected limb. FCD is characterized by massive edema, severe pain, and cyanosis. The diagnosis is clinical. It is associated in most cases with pulmonary embolism and can lead to loss of the compromised limb if not treated in time. So far there is no consensus on its treatment. In clinical practice the use of anticoagulation with heparin, local thrombolysis, systemic fibrinolysis, surgical thrombectomy, fasciotomy, and inferior vena cava filter are described. In irreversible cases amputation is required. We present the case of a patient with FCD, the treatment performed and the evolution.

Uso y resultados de la fibrinolisis intravenosa en una unidad cerebrovascular / Use and results of intravenous fibrinolysis in a stroke unit

Resumen La fibrinólisis intravenosa con activador del plasminógeno tisular recombinante (rTPA) y la utilización de unidades cerradas, demostraron disminuir sustancialmente la morbimortalidad en pacientes con accidente cerebrovascular isquémico (ACVi). Sin embargo, los datos publicados en Argentina son escasos. Describimos la experiencia en la utilización de fibrinólisis en pacientes con ACVi agudo antes y después de la implementación de una unidad cerebrovascular (UCV) en un Centro Integral de Neurología Vascular de la Ciudad de Buenos Aires durante 17 años. Se realizó un análisis retrospectivo de pacientes consecutivos tratados con rTPA entre enero 2003 y diciembre 2019. Se evaluaron tiempos de tratamiento, de internación, complicaciones post tratamiento y discapacidad a 3 meses. Para su análisis se evaluaron los períodos pre y post apertura de la UCV, período 1 (P1 de 2003-2011) y P2 (2012 -2019). Se realizó fibrinolisis intravenosa en 182 pacientes. La apertura de UCV resultó en aumento del porcentaje de fibrinólisis sobre el total de los ACVi ingresados (4% en P1 vs. 10% en P2, p < 0.001), acortamiento del tiempo puerta-aguja (75 minutos en P1 vs. 53 minutos en P2, p < 0.00001) y mayor proporción de pacientes tratados dentro de los 60 minutos del ingreso hospitalario (36% en P1 vs. 76% en P2, p < 0.00001). Además, hubo reducción de la mediana de internación de 9 días en P1 a 5 días en P2 (p < 0.00001). En conclusión, la UCV parece optimizar la utilización de fibrinólisis en el ACVi agudo, aumentando el porcentaje de pacientes tratados, reduciendo el tiempo puerta-aguja y disminuyendo el de internación.

Abstract Intravenous fibrinolysis with recombinant tissue plasminogen activator (rTPA) and use of stroke units improve morbidity and mortality in patients with acute ischemic stroke (AIS). However, data published in Argentina are scarce. We describe the experience in the use of fibrinolysis in patients with acute ischemic stroke (AIS) before and after the implementation of a stroke unit in a Comprehensive Stroke Center in Buenos Aires during the last 17 years. Retrospective analysis of consecutive patients treated with rTPA between January 2003 and December 2019. Treatment times, hospitalization time, post-treatment complications and disability at 3 months were evaluated. For the analysis, the pre and post opening periods of the stroke unit were evaluated, Period 1 (P1, from 2003 to 2011) and Period 2 (P2, from 2012 to 2019). Intravenous fibrinolysis was performed in 182 patients. Opening of the stroke unit resulted in an increase in the percentage of fibrinolysis over the total number of admitted strokes (4% in P1 vs. 10% in P2, p < 0.001), shortening of the door-to-needle time (75 minutes in P1 vs. 53 minutes in P2, p < 0.00001) and higher proportion of patients treated within 60 minutes of hospital admission (36% in P1 vs. 76% in P2, p < 0.00001). In addition, there was a reduction in the median hospital stay from 9 days in P1 to 5 days in P2 (p < 0.00001). In conclusion, stroke units seem to optimize the use of fibrinolysis in acute stroke, increasing the percentage of patients treated, reducing door-to-needle time, and reducing hospitalization time.

Coagulación intravascular diseminada / Disseminated intravascular coagulation

Resumen La coagulación intravascular diseminada es un estado alterado de la coagulación secundario a cuadros inflamatorios locales o sistémicos. Se caracteriza por un aumento de la coagulación y una inadecuada fibrinólisis endógena que da como resultado la formación de fibrina intravascular, trombosis microvascular multiorgánica y un excesivo consumo de los factores de coagulación sanguínea, esto desencadena sangrados severos y trombosis, los cuales conducen a falla orgánica y circulatoria como principal manifestación clínica. Este artículo tiene como objetivo realizar una revisión del estado del arte describiendo su definición, etiología, fisiopatología, manifestaciones clínicas y actualidades en su diagnóstico y tratamiento. Para esto, se realizó una búsqueda bibliográfica en PubMed utilizando el término MeSH "Disseminated Intravascular Coagulation", seleccionándose 63 artículos por la relevancia y pertinencia de su información al objetivo de la investigación. De esta manera, se espera brindar al clínico las herramientas necesarias para responder adecuadamente frente a esta patología. MÉD.UIS.2020;33(2):75-84.

Abstract Disseminated Intravascular Coagulation is an altered state of coagulation secondary to local or systemic inflammatory symptoms. It is characterized by increased coagulation and inadequate endogenous fibrinolysis resulting in intravascular fibrin formation, multi-organ microvascular thrombosis, and excessive consumption of blood coagulation factors, this triggers severe bleeding and thrombosis, which lead to organic and circulatory failure as the main clinical manifestation.This article aims to review the state of the art describing its definition, etiology, pathophysiology, clinical manifestations and news in its diagnosis and treatment. Accordingly, a bibliographic search was carried out in PubMed using the MeSH term "Disseminated Intravascular Coagulation", selecting 63 articles for the relevance and pertinence of their information to the objective of the investigation. Therefore, it is expected to provide the clinician with the necessary tools to adequately respond to this pathology. MÉD.UIS.2020;33(2):75-84.

Trastornos hereditarios de la coagulación en adolescentes con sangrado menstrual excesivo, ¿debemos evaluar la vía fibrinolítica? / Inherited bleeding disorders in adolescents with excessive menstrual bleeding: should we evaluate the fibrinolytic pathway?

Resumen: Introducción: El Sangrado Menstrual Excesivo (SME) es un problema frecuente en la adolescencia. La prevalencia de trastornos hereditarios de la coagulación (THC) como causa del SME no está bien establecida y la participación de defectos de la vía fibrinolítica ha sido poco explorada. Objetivo: Determinar la prevalencia de THC y defectos de la fibrinólisis en adolescentes con SME. Pacientes y Método: Se incluyeron 93 adolescentes, edad 11 a 18 años. Los antecedentes personales y familiares de sangra do se obtuvieron con un cuestionario estandarizado. Se controló exámenes: tiempo de protrom- bina (TP), tiempo de tromboplastina parcial activada (TTPa), estudio del factor Von Willebrand, recuento y función plaquetaria. Los pacientes que no fueron diagnosticados como THC, se evaluaron adicionalmente con el tiempo de lisis del coágulo. Resultados: 41 pacientes (44%) fueron diagnos ticados como THC: Enfermedad de Von Willebrand n = 28, defectos de la función plaquetaria n = 8, hemofilia leve n = 5. Se confirmó disminución del tiempo de lisis del coágulo en 31 pacientes. El 54% de pacientes diagnosticado como THC, tuvo SME como la primera manifestación hemorrágica. Conclusión: Estos resultados apoyan la necesidad de evaluación de la coagulación, incluyendo la vía fibrinolítica, en el estudio de adolescentes con SME.

Abstract: Introduction: Heavy Menstrual Bleeding (EMB) is a frequent problem in adolescence. The prevalence of inherited bleeding disorders (IBD) as a cause of EMB is not well established and the involvement of fibri nolytic pathway defects has been poorly explored. Objective: To determine the prevalence of IBD and fibrinolysis defects in adolescents with EMBs. Patients and Method: 93 adolescents (11 to 18 years old) were included. Personal and family history of bleeding were obtained through a standard ized questionnaire. The following lab tests were performed: prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor quantification, and platelet count and function. Those patients who were not diagnosed with IBD were further evaluated with clot lysis time assay. Results: 41 patients (44%) were diagnosed as IBD (Von Willebrand disease n = 28, platelet func tion defects n=8, mild hemophilia n = 5. Decreased clot lysis time was found in 31 patients. 54% of patients diagnosed with IBD had EMB as the first hemorrhagic manifestation. Conclusion: These results support the need to evaluate the coagulation process, including the fibrinolytic pathway in the study of adolescents with EMB.

Consenso colombiano de fibrinólisis selectiva con catéter en enfermedad vascular tromboembólica / Colombian consensus on selective thrombolysis with catheter in thromboembolic vascular disease

Resumen En los pacientes con trombosis arterial o venosa, in situ o por embolia, el uso de fibrinolíticos (como el rtPA) administrados directamente en el trombo a través de un catéter selectivo en el sitio de la oclusión, permite una resolución más rápida de la oclusión trombótica o embólica con menos dosis total del agente fibrinolítico y por ende con menos complicaciones hemorrágicas que con el uso sistémico. Las indicaciones en las cuales se puede considerar la fibrinólisis selectiva con catéter son básicamente la isquemia aguda de una extremidad por oclusión arterial, la tromboembolia pulmonar, la trombosis venosa profunda iliofemoral (proximal), la trombosis venosa profunda proximal axilo-subclavia, la trombosis de los accesos venosos para diálisis y en los pacientes pediátricos en los casos de trombosis o embolia arterial con extremidad isquémica y en casos seleccionados de trombosis venosa profunda proximal de extremidades. En este consenso describirá cada una de las indicaciones a través de un protocolo para el manejo con rtPA en cada situación, cómo monitorizar su uso y cómo tartar las complicaciones hemorrágicas.

Abstract In patients with arterial or venous thrombosis, in situ or due to an embolism, the use of fibrinolytics (such as recombinant tissue-type plasminogen activator, rtPA) administered directly into the clot through a selective catheter into the occlusion site. This can lead to a more rapid resolution of the thrombotic or embolic occlusion with a lower dose of the fibrinolytic agent, and therefore with less problems with haemorrhages than with systemic use. The situations in which selective fibrinolysis with a catheter can be considered are mainly, acute ischaemia of a limb due to a blocked artery, pulmonary thromboembolism, proximal ileo-femoral deep venous thrombosis, proximal axillo-subclavian deep venous thrombosis, and in the thrombosis of the venous access for dialysis It is also indicated in paediatric patients in cases of arterial thrombosis or embolisms with an ischaemic limb, and in selective cases of proximal deep venous thrombosis of the limbs. In this consensus, a description will be given of each one of the indications, with a protocol for the management with rtPA in each one of them, as well as monitoring its use and the management of haemorrhage complications.

Infarto Agudo del Miocardio: conducta en el período prehospitalario / AMI: Management in the pre-hospitalization period

RESUMEN: El tratamiento del Infarto Agudo del Miocardio con supradesnivel del segmento ST debe iniciarse en el escenario prehospitalario, en el sitio del primer contacto médico. El diagnóstico electrocardiográfico precoz debe ser realizado, idealmente, dentro de los primeros 10 min después de la consulta y confirmado por un especialista. A este respecto, la teletransmisión del electrocardiograma a un centro de llamados atendido por especialistas en horario 24/7 es un modelo muy eficiente, idealmente como parte de una red de tratamiento. El control del dolor y la administración de agentes antiplaquetarios son imperativos y si la intervención coronaria percutánea (angioplastia primaria) no es factible dentro de las ventanas de tiempo universalmente recomendadas, se debiera realizar un tratamiento fibrinolítico, seguido por angioplastia diferida.

ABSTRACT: Treatment of acute myocardial infarction should be initiated in the prehospital scenario at the site of first medical contact. Prompt electrocardiographic diagnosis should be performed ideally within 10min after consultation and diagnosis confirmed by a specialist. Teletransmission of the electrocardiogram to a call center staffed with specialists on a 24/7 basis is a very efficient model, ideally as part of a network of treatment. Pain control and administration of antiplatelets agents are mandatory and if primary percutaneous intervention is not feasible within time limits universally recommended, prehospital fibrinolyisis should be performed followed by deferred angioplasty.

Impact of arterial procedures on coagulation and fibrinolysis - a pilot study

Abstract Objective: The main goal of our study was to assess the impact of vascular procedures on the activity of hemostatic and fibrinolytic pathways. Methods: We enrolled 38 patients with ≥ 45 years old undergoing surgery for abdominal aortic aneurysm or peripheral artery disease under general or regional anesthesia and who were hospitalized at least one night after the procedure. Patients undergoing carotid artery surgery and those who had acute bypass graft thrombosis, cancer, renal failure defined as estimated glomerular filtration rate < 30 ml/min/1.73m2, venous thromboembolism three months prior to surgery, or acute infection were excluded from the study. We measured levels of markers of hemostasis (factor VIII, von Willebrand factor:ristocetin cofactor [vWF:CoR], antithrombin), fibrinolysis (D-dimer, tissue plasminogen activator [tPA], plasmin-antiplasmin complexes), and soluble cluster of differentiation 40 ligand (sCD40L) before and 6-12h after vascular procedure. Results: Significant differences between preoperative and postoperative levels of factor VIII (158.0 vs. 103.3, P<0.001), antithrombin (92.1 vs. 74.8, P<0.001), D-dimer (938.0 vs. 2406.0, P=0.005), tPA (10.1 vs. 12.8, P=0.002), and sCD40L (9092.9 vs. 1249.6, P<0.001) were observed. There were no significant differences between pre- and postoperative levels of vWF:CoR (140.6 vs. 162.8, P=0.17) and plasmin-antiplasmin complexes (749.6 vs. 863.7, P=0.21). Conclusion: Vascular surgery leads to significant alterations in hemostatic and fibrinolytic systems. However, the direction of these changes in both pathways remains unclear and seems to be different depending on the type of surgery. A study utilizing dynamic methods of coagulation and fibrinolysis assessment performed on a larger population is warranted.

Terapia con fibrinólisis local dirigida por catéter en tromboembolismo pulmonar de riesgo intermedio / Therapy with local fibrinolysis directed by catheter in intermediate risk pulmonary thromboembolism

Resumen Introducción: en pacientes con tromboembolia pulmonar (TEP) aguda, la fibrinólisis arterial local puede tener una relación muy favorable entre beneficios y riesgos. Objetivo: caracterizar las condiciones epidemiológicas y clínicas de los pacientes con TEP agudo de riesgo intermedio que han recibido terapia fibrinolítica urgente dirigida por catéter. Métodos: estudio descriptivo de una serie de casos de pacientes atendidos en la Fundación Cardiovascular de Colombia (período 2012-2016) con diagnóstico de TEP de riesgo intermedio llevados a terapia fibrinolítica mediante catéter pulmonar. Resultados: se incluyeron 27 casos (26 pacientes, 57±20 años, 52% mujeres). La confirmación de embolia pulmonar aguda se realizó mediante angiotomografía. El 85% de los casos mostró signos ecocardiográficos de disfunción ventricular derecha, 74% elevación de troponinas, y 82% elevación de BNP o pro-BNP. El tiempo puerta-aguja desde el diagnóstico hasta la fibrinólisis fue de 29±31 horas (máx-min, 2-120). El tratamiento endovascular incluyó alteplasa (dosis total, 47±18 mg) y fragmentación-aspiración mecánica mediante catéter pulmonar. El 78% de los pacientes mostró disminuciones en la PAPm >10% del valor inicial [i.e., pacientes respondedores, ΔPAPm=-27±11% (-9±5 mmHg)]. Cinco pacientes fueron clasificados como no-respondedores (ΔPAPm=-2±7%, -1±4 mmHg). La estancia en UCI fue de 7±5 días (1-19), y la hospitalaria 13 días (1-36). No se presentaron complicaciones de sangrado mayor ni de otra índole. La supervivencia a 90 días fue de 100%. Conclusiones: esta serie observa que la fibrinólisis arterial pulmonar induce una mejoría hemodinámica inmediata en una alta proporción de pacientes con TEPa, con un balance beneficio-riesgo favorable en ausencia de complicaciones atribuibles inmediatas o tardías. (Acta Med Colomb 2019; 44: 17-24).

Abstract Introduction: in patients with acute pulmonary embolism (PE), local arterial fibrinolysis can have a very favorable relationship between benefits and risks. Objective: to characterize the epidemiological and clinical conditions of patients with intermediate-risk of acute PE who have received urgent fibrinolytic therapy directed by catheter. Methods: a descriptive study of a series of cases of patients treated at the Cardiovascular Foundation of Colombia (2012-2016 period) with a diagnosis of intermediate-risk PE who received fibrinolytic therapy using a pulmonary catheter. Results: 27 cases were included (26 patients, 57 ± 20 years, 52% women). Confirmation of acute pulmonary embolism was performed by angiotomography. 85% of the cases showed echocardiographic signs of right ventricular dysfunction, 74% elevation of troponins, and 82% elevation of BNP or pro-BNP. The door-needle time from diagnosis to fibrinolysis was 29 ± 31 hours (max-min, 2-120). The endovascular treatment included alteplase (total dose, 47 ± 18 mg) and mechanical fragmentation-aspiration by pulmonary catheter. 78% of the patients showed decreases in PAPm> 10% of the initial value [i.e., responding patients, ΔPAPm = -27 ± 11% (-9 ± 5 mmHg)]. Five patients were classified as non-responders (ΔPAPm = -2 ± 7%, -1 ± 4 mmHg). The stay in the ICU was 7 ± 5 days (1-19), and the hospital stay was 13 days (1-36). There were no complications of major or other bleeding. The 90-day survival was 100%. Conclusions: this series shows that pulmonary arterial fibrinolysis induces an immediate hemodynamic improvement in a high proportion of patients with intermediate-risk PE with a favorable benefit-risk balance in the absence of immediate or delayed attributable complications. (Acta Med Colomb 2019; 44: 17-24).

Coagulation abnormalities and bleeding in pregnancy: an anesthesiologist's perspective

During pregnancy, the procoagulant activity increases (manifested by elevation in factor VII, factor VIII, factor X, and fibrinogen levels), while the anticoagulant activity decreases (characterized by reduction in fibrinolysis and protein S activity), resulting in hypercoagulation. Standard coagulation tests, such as prothrombin time or activated partial thromboplastin time, are still used despite the lack of evidence supporting its accuracy in evaluating the coagulation status of pregnant women. Thromboelastography and rotational thromboelastometry, which are used to assess the function of platelets, soluble coagulation factors, fibrinogen, and fibrinolysis, can replace standard coagulation tests. Platelet count and function and the effect of anticoagulant treatment should be assessed to determine the risk of hematoma associated with regional anesthesia. Moreover, anesthesiologists should monitor patients for postpartum hemorrhage (PPH), and attention should be paid when performing rapid coagulation tests, transfusions, and prohemostatic pharmacotherapy. Transfusion of a high ratio of plasma and platelets to red blood cells (RBCs) showed high hemostasis success and low bleeding-related mortality rates in patients with severe trauma. However, the effects of high ratios of plasma and platelets and the ratio of plasma to RBCs and platelets to RBCs in the treatment of massive PPH were not established. Intravenous tranexamic acid should be administered immediately after the onset of postpartum bleeding. Pre-emptive treatment with fibrinogen for PPH is not effective in reducing bleeding. If fibrinogen levels of less than 2 g/L are identified, 2–4 g of fibrinogen or 5–10 ml/kg cryoprecipitate should be administered.

Platelet function, coagulation and fibrinolysis in patients with previous coronary and cerebrovascular ischemic events

OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.

Technique of external ventricular drainage with intraventricular administration of recombinant tissue plasminogen activator for patients with secondary intraventricular hemorrhage - Case series in a single institution

INTRODUCTION@#Intraventricular hemorrhage (IVH) as an extension of spontaneous intracerebral hemorrhage is an independent predictor of mortality. The Clot Lysis: Evaluating Accelerated Resolution of IVH phase 3 (CLEAR III) trial is a randomized, double-blinded, placebocontrolled, multiregional trial recently conducted to determine whether external ventricular drainage (EVD) plus intraventricular recombinant tissue plasminogen activator (rtPA, alteplase) improved outcome, in comparison to EVD plus saline. This study is an application of the rationale and principles of management in CLEAR III trial and related literature.@*METHODS@#There are five patients described in this case series. Report followed the PROCESS guidelines.@*RESULTS@#30-day mortality in this series is 2 out of 5 while actual allcause mortality is 4 out of 5. Modified Graeb scores and IVH scores of all subjects have decreased after the intervention. However, good functional status defined as modified Rankin scale (mRS) score of 0-3 has not been achieved with the intervention. Efficacy of completely resolving IVH and hydrocephalus has been achieved in 2 out of 5 which translated to a benefit of survival to one of the two. Shunt dependence has been avoided by the subjects except for the one with the caudate intracerebral hemorrhage. Complications related to the intervention have been noted and discussed@*CONCLUSION@#In this single-institution study, patients for which rtPA was used for intraventricular fibrinolysis of IVH clot in addition to EVD as surgical treatment for hydrocephalus resulted to a 30-day survival of 3 out of 5 in this series, while actual survival is 1 out of 5. The intervention was efficacious in decreasing the Modified Graeb scores and IVH scores of all study subjects at end of treatment. Functional status of mRS 5 is the highest score achieved among survivors.

¿Trombolisis o trombólisis? / Thrombolysis?

En medicina se emplean términos compuestos para describir fenómenos o accio-nes específicas, como "hemolisis", "trombolisis" y "fibrinolisis", en ocasiones de forma inadecuada y sin respetar su origen lingüístico. Aunque al usarlos en la práctica muchas veces se usa la acentuación llana antietimológica (probablemente por influencia del francés), el sufijo 'lisis' tiene una connotación particular.