Rivaroxaban Levels in Patients' Plasmas are Comparable by Using Two Different Anti Xa Assay/Coagulometer Systems Calibrated with Two Different Calibrators.

BACKGROUND: Rivaroxaban oral anticoagulant does not need laboratory monitoring, but in some situations plasma level measurement is useful. The objective of this paper was to verify analytical performance and compare two rivaroxaban calibrated anti Xa assays/coagulometer systems with specific or other branch calibrators. METHODS: In 59 samples drawn at trough or peak from patients taking rivaroxaban, plasma levels were measured by HemosIL Liquid anti Xa in ACLTOP 300/500, and STA liquid Anti Xa in TCoag Destiny Plus. HemosIL and STA rivaroxaban calibrators and controls were used. CLSI guideline procedures EP15A3 for precision and trueness, EP6 for linearity, and EP9 for methods comparison were used. RESULTS: Coefficient of variation within run and total precision (CVR and CVWL respectively) of plasmatic rivaroxaban were < 4.2 and < 4.85% and BIAS < 7.4 and < 6.5%, for HemosIL-ACL TOP and STA-Destiny systems, respectively. Linearity verification 8 - 525 ng/mL a Deming regression for methods comparison presented R 0.963, 0.968 and 0.982, with a mean CV 13.3% when using different systems and calibrations. CONCLUSIONS: The analytical performance of plasma rivaroxaban was acceptable in both systems, and results from reagent/coagulometer systems are comparable even when calibrating with different branch material.

[Fibrinolytics in lung thromboembolism. New alternatives for a controversial prescription]. / Fibrinolíticos en tromboembolismo de pulmón. Nuevas alternativas para una indicación controvertida.

The use of fibrinolytics in lung thromboembolism (PTE) is a subject under debate since its first description in the 1960s. This therapy, which can rapidly resolve the mechanical obstruction in the pulmonary artery, has the limiting of a high hemorrhagic risk. Precisely because of the prohibitive incidence of major and cerebral bleeding and the lack of benefit in survival, the use of systemic thrombolytics is only indicated in the small number of patients with severe PE and hemodynamic instability. In moderate-risk PE, even with right ventricular (RV) dysfunction, they are not indicated. In recent years, an alternative has arisen, by combining low doses of fibrinolytics released locally into the pulmonary artery through a catheter that may, or may not, be attached to ultrasound at the site of thrombosis. This way of administering thrombolytics can correct acute pulmonary hypertension and eliminate the thrombus without major or CNS bleeds. Although the published studies are very encouraging, the evidence is still poor, a laboratory of hemodynamics is required at all times and this procedure is not free of risks, with a considerable cost. At the moment, only a small number of patients with moderate PE and poor prognosis seem to have an indication for this new alternative.

[Síndrome de Paget-Schrötter: presentación de cuatro casos]. / Paget-Schrötter syndrome: description of four cases.

Deep vein thrombosis (DVT) of the upper limb is a rare entity, estimated to account for 10% of all cases of DVT. Classically, they are classified into primary (idiopathic, due to subclavian vein compression or exercise related) and secondary (cancer, thrombophilia, trauma, shoulder surgery, associated to venous catheters or due to hormonal causes). The Paget- Schrötter syndrome is a primary thrombosis of the subclavian vein in the subclavian-axillary junction, related either to repetitive movements or to exercise; leading to microtrauma in the endothelium with consequent activation of the coagulation cascade. Clinically, it presents abruptly with pain, edema and feeling of heaviness in the affected limb. The treatment varies from thrombolytics and anticoagulation to surgical intervention, depending on the time of evolution. We present four cases of exercise-related subclavian vein thrombosis.

[Renal function and plasma dabigatran level measured at trough by diluted thrombin time assay]. / Función renal y nivel plasmático de dabigatrán en el valle, medido por un ensayo de trombina diluida.

Dabigatran etexilate (direct thrombin inhibitor) is effective in preventing embolic stroke in patients with atrial fibrillation. It does not require laboratory control, but given the high renal elimination, its measurement in plasma is important in renal failure. The objectives of the study were to verify the analytical quality of the diluted thrombin time assay for measurement of dabigatran plasma concentration (cc), correlate cc with classic coagulation assays, prothrombin time (PT) and activated partial thromboplastin time (APTT), and evaluate them according to the creatinine clearance (CLCr). Forty plasma samples of patients (34 consecutive and 6 suspected of drug accumulation) receiving dabigatran at 150 (n = 19) or 110 (n = 21) mg/12 hours were collected. Blood samples were drawn at 10-14 hours of the last intake. Dabigatran concentration was determined by diluted thrombin time (HemosIl DTI, Instrumentation Laboratory (IL). PT and APTT (IL) were performed on two fotooptical coagulometers, ACL TOP 300 and 500 (IL). DTI presented intra-assay coefficient of variation < 5.4% and inter-assay < 6%, linearity range 0-493 ng/ml. Patients' cc: median 83 (4-945) ng/ml. Individuals with CLCr in the lowest tertile (22.6-46.1 ml/min) showed significantly higher median cc: 308 (49-945), compared to the average 72 (12-190) and highest tertile, 60 (4-118) ng/ml. Correlation between cc and APTT or PT were moderate, r2 = 0.59 and -0.66, p < 0.0001, respectively. DTI test allowed us to quantify plasma dabigatran levels, both in patients with normal or altered renal function, representing a useful tool in clinical situations such as renal failure, pre surgery or emergencies.

[Acquired haemophilia (acquired factor VIII inhibitor)]. / Hemofilia adquirida (inhibidor adquirido del factor VIII).

Acquired haemophilia is a rare disorder. The clinical picture ranges from mild ecchymosis and anaemia to life threatening bleeding in up to 20% of patients. The disease is produced by an antibody against Factor VIII and it usually occurs in the elderly, with no previous history of a bleeding disorder. It can be associated to an underlying condition such as cancer, autoimmune disorders, drugs or pregnancy. It has a typical laboratory pattern with isolated prolonged activated partial thromboplastin time (aPTT) that fails to correct upon mixing tests with normal plasma and low levels of factor VIII. Treatment recommendations are based on controlling the acute bleeding episodes with either bypassing agent, recombinant activated factor VII or activated prothrombin complex concentrate, and eradication of the antibody with immunosuppressive therapy.

[Hughes-Stovin Syndrome, a case report]. / Síndrome de Hughes-Stovin.

The Hughes-Stovin syndrome is a rare entity characterized by deep vein thrombosis and pulmonary artery aneurysms of unknown etiology and pathogenesis. Some authors considered a variant of Behcet's disease. Its natural course is usually fatal. The symptoms are cough, dyspnea, hemoptysis, chest pain and fever. The treatment goes from steroids and cytotoxic agents to surgery. We present the case of a 41 year old man who shows dyspnea, hemoptysis, and chest pain leading to the diagnosis of deep venous thrombosis of the right leg, lung thromboembolism and pulmonary artery aneurysms. He was treated with high-dose corticosteroids and 6 cyclophosphamide pulses of 1 gram each per 6 months with complete regression of aneurysms and symptomatology.

[How to generate recommendations for venous thromboprophylaxis in health institutions?] / Cómo generar recomendaciones de tromboprofilaxis venosa en instituciones de salud.

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

[Venous thromboembolic prophylaxis. Guidelines for adults in Argentina]. / Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina.

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Evaluation of survival and functionality in frozen platelets.

OBJECTIVE: Prolong platelet survival and functionality up to 28 days. METHODS: A sample of apheresis platelets was evaluated, distributed in 3 groups according to the cryopreservative solution used: DMSO5%+2%albumin; DMSO5%+NaCl0,9% and DMSO5%+Dextrose2%. They were then frozen at -80 °C and thawed at 7, 14 and 28 days. The in vitro survival and viability were assessed by the post-thaw platelet count and the CD41, CD61 and CD42a staining percentages by flow cytometry. The functionality was determined with the percentage of post-stimulation aggregation with 1Nm-thrombin using the Chromo-Log490 aggregometer. The control group (CG) consisted of fresh platelets under constant agitation at 22 °C. RESULTS: A total of 72 platelet aliquots was analyzed. The CG presented a platelet-count of 1934 ± 0.5 × 109/L and a 100% viability. The percentages of CD41, CD61 and CD42a labeling were 99, 98.5 and 96.5%, respectively. The percentage of aggregation was 99%. On day 7 of the post-freezing, the platelet count for groups 1, 2 and 3 was 1,844 ± 102, 1,856 ± 76 and 1,752 ± 226, with the viability of 98, 96 and 95%, respectively. On day 14, the counts were 1,722 ± 238, 1,649 ± 215 and 1,578 ± 223 with the viability of 96, 95 and 94% and, on day 28, they were 1,602 ± 374, 1,438.6 ± 429 and 1,406.6 ± 436, with the viability of 96, 94 and 93%, respectively. Group1 presented a higher expression of membrane antigens. Aggregation percentages were 90, 98 and 89% at day 7, 88%, 98 and 87% at day 14 and 84%, 95 and 82% at day of the 28 post-freezing, respectively, with group2 presenting the best results. CONCLUSION: The results support cryopreservation as a reasonable method to prolong platelet survival up to 28 days, maintaining its functionality and viability greater than 50%.

[Colonic pseudotumoral involvement as an expression of severe plasminogen deficiency]. / Compromiso pseudotumoral colónico como expresión de déficit grave de plasminogéno.

Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.

La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.

[Use of parenteral anticoagulants in patients with coronary syndrome]. / Uso de anticoagulantes parenterales en pacientes con síndromes coronarios.

Anticoagulant treatment, together with antiplatelet therapy, plays an important role in the treatment of acute coronary syndromes. Its use is associated with a reduction in new ischemic events, stent thrombosis, and lower mortality. However, in clinical practice there is great heterogeneity in its use, leading to suboptimal results in treatment. This paper conducts a narrative review on the use of parenteral anticoagulants in patients with acute coronary syndromes, depending on the clinical scenario, as well as the revascularization strategy used and the bleeding risk. The different anticoagulant schemes available in acute coronary syndromes with and without segment ST elevation are addressed, based on the updated evidence. Finally, evidence-based strategies for risk stratification for bleeding and therapeutic management are developed.

El tratamiento anticoagulante, en conjunto con la anti agregación, cumple un rol de suma importancia en el tratamiento de los síndromes coronarios agudos. Su uso está asociado a reducción de nuevos eventos isquémicos, trombosis del stent e incluso menor mortalidad. No obstante, en la práctica clínica existe una gran heterogeneidad en su utilización, llevando a resultados subóptimos en el tratamiento. Este trabajo ofrece una revisión narrativa sobre el uso de anticoagulantes parenterales en pacientes con síndromes coronarios agudos, dependiendo del escenario clínico, así como también de la estrategia de revascularización implementada y el riesgo hemorrágico. Se abordan los diferentes esquemas anticoagulantes disponibles en síndromes coronarios agudos con y sin elevación del segmento ST, basados en la evidencia actualizada hasta la fecha. Finalmente, se desarrollan herramientas para la estratificación del riesgo de sangrado y su manejo terapéutico.

Cross-sectional study of adherence to venous thromboembolism prophylaxis guidelines in hospitalized patients. The Trombo-Brit study.

BACKGROUND: DVT is the main cause of death in hospitalized patients and thromboprophylaxis is the only way to prevent these deaths. International recommendations suggested that active monitoring of DVT/PE prophylaxis can improve the efficacy in Hospitals. METHODS: We performed a cohort study in three consecutives periods to evaluate DVT prophylaxis in 388 adults hospitalized in a General Hospital. RESULTS: 85% of the population had high risk factors for DVT. Thromboprophylaxis was in accordance with local and International guidelines (ACCP 2008) in 72.7% and 86% of the patients respectively. No significant difference could be founded between clinical and surgical patients. One every 10 patients received higher prophylaxis than suggested by guidelines and two out of ten received deficient or no prophylaxis. The worst 2 groups of patients were those with moderate/low risk of DVT and the group with a contraindication to pharmacologic prophylaxis. We observed a progressive improvement of the DVT prophylaxis in the 3 periods of evaluation. CONCLUSIONS: Although the rate of recommended thromboprophylaxis is higher than many other reports in the region we still have some areas where we need to improve. Regular audits like these are very helpful to find out what specific areas of the hospital needs some careful attention in order to have a better quality of assistance.

Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.

[MANAGEMENT RECOMMENDATIONS FOR DIRECT ORAL ANTICOAGULANTS (DOACs) ANTI Xa AND ANTI IIa]. / RECOMENDACIONES DE MANEJO DE LOS ANTICOAGULANTES ORALES DIRECTOS (DOACS) ANTI Xa Y ANTI IIa.

Direct oral anticoagulants have emerged as the drugs that have changed the management of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagulants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas propiedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

[Anticoagulation and atrial fibrillation]. / Terapia anticoagulante en fibrilación auricular.

Atrial fibrillation is the most frequent cardiac arrhythmia in adults. Its frequency increases with age, being its incidence 1.5% in individuals 50 to 59 years old and 8-10% from 80 to 89 years. Atrial fibrillation increases 5 fold the risk of suffering stroke and actually causes 15% of all strokes. Its management focuses primary in the prevention of thromboembolic phenomena, heart rate and rhythm control. Anticoagulation, when indicated, has demonstrated to be the main tool in the prevention of these thromboembolic events. Although the bleeding complication is frequent in this population and increases with age, anticoagulation benefits are greater than the risks of bleeding. Due to the clinically heterogeneous nature of this arrythmia and the difficulty of establishing appropriate treatment for each particular case, the American College of Cardiology, the American Heart Association, European Society of Cardiology and American College of Chest Physicians have established guidelines to improve the management of these patients. The review of this condition and the proposed directives can notably facilitate and improve the management of the patients with atrial fibrillation.

Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

[Experience with idarucizumab as a reverse agent of dabigatran]. / Experiencia con idarucizumab como agente reversor de dabigatrán.

Direct oral anticoagulants (DOACs), among them dabigatran, have a favorable benefit-risk profile compared with warfarin, and no monitoring of the anticoagulant effect is required. However, reversing the anticoagulant effect immediately is very useful in cases of life-threatening bleeding and emergency surgical procedure requirement. Idarucizumab, a humanized monoclonal antibody fragment, is currently the only reversal agent of a DOAC available in Argentina. Idarucizumab immediately reverse the effect of dabigatran. We present a series of 8 real-life clinical cases who received idarucizumab to reverse the effect of dabigatran. All of the patients were older than 65 years, were receiving 110 or 150 mg every 12 hours of dabigatran and 7/8 were anticoagulated because of atrial fibrillation. Three had a debatable indication for DOACs and another, a higher dose than recommended. Two required reversal due to emergency surgery, and 6 cases had life-threatening bleeding: three gastrointestinal hemorrhages and three intracranial bleeding (Two had a head trauma). In all cases normalization of surgical hemostasis or control of critical bleeding was observed. No hemorrhagic or thrombotic complications were observed after antidote administration. Two died within 30 days of administration of idarucizumab, due to causes unrelated to the reversal. None of our patients required administration of a second dose of idarucizumab. Our result is similar to that reported in international literature.

Los anticoagulantes orales directos (AOD), entre ellos dabigatrán, poseen un perfil riesgo-beneficio favorable comparados con warfarina y además no requieren monitoreo del efecto anticoagulante. Sin embargo, en ocasiones de sangrado con amenaza de vida o requerimiento de procedimiento quirúrgico de emergencia, es de gran utilidad revertir inmediatamente el efecto anticoagulante. Idarucizumab, fragmento de un anticuerpo monoclonal humanizado, revierte inmediatamente el efecto de dabigatrán y es actualmente el único agente reversor de un AOD disponible en Argentina. Presentamos una serie de 8 pacientes a los que se les administró idarucizumab para revertir el efecto de dabigatrán. Todos eran mayores de 65 años, recibían 110 o 150 mg cada 12 horas de dabigatrán y 7/8 estaban anticoagulados por fibrilación auricular; tres tenían indicación discutida para AOD y otro, una dosis mayor a la recomendada. Dos requirieron reversión debido a una cirugía de urgencia, y 6 tuvieron sangrado con amenaza de vida: tres hemorragias digestivas y tres sangrados intra-craneanos (en dos ocasiones traumático). En todos los casos se observó normalización de la hemostasia quirúrgica o control de sangrado crítico. No se observaron complicaciones trombóticas posteriores a la administración del antídoto. Dos fallecieron dentro de los 30 días de la administración por causas no relacionadas con la reversión. Ninguno de nuestros pacientes requirió administración de una segunda dosis de idarucizumab. Nuestro resultado es similar a lo informado en la literatura internacional.

[Argentine Consensus in effective management of anticoagulation clinics for the use of vitamin k antagonists]. / Consenso Argentino en gestión efectiva de clínicas de anticoagulación para el uso de antagonistas de la vitamina k.

Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.

El tratamiento de un paciente anticoagulado con antagonistas de la vitamina K (AVK) sigue siendo un desafío, especialmente en regiones donde, por el costo, los dicumarínicos son todavía la alternativa más buscada a la hora de elegir un anticoagulante oral. Las clínicas de anticoagulación han demostrado ser la forma más eficiente y segura de evitar complicaciones trombóticas y hemorrágicas y de mantener al paciente en rango óptimo de tratamiento. Sin embargo, requieren de una adecuada infraestructura y personal capacitado para que funcionen eficientemente. En este consenso argentino se propone una serie de parámetros para la gestión efectiva de una clínica de anticoagulación. El objetivo es lograr una elevada calidad desde el punto de vista clínico-asistencial a través de un laboratorio de hemostasia de excelencia. Los criterios desarrollados en el documento fueron consensuados por un amplio grupo de expertos especialistas en hematología y en bioquímica de todo el país. Estos criterios deben adaptarse a la irregular disponibilidad de recursos de cada centro, pero siempre se los debe tener en cuenta a la hora de indicar el tratamiento anticoagulante con estas drogas. Tener en consideración estas premisas nos permitirá optimizar la atención del enfermo anticoagulado con AVK y de esta forma minimizar las intercurrencias trombóticas y hemorrágicas a las que está expuesto, para así honrar nuestra promesa de no dañar al paciente.

Efficacy of extended thrombo-prophylaxis in major abdominal surgery: what does the evidence show? A meta-analysis.

Venous thromboembolism (VTE) is a frequent complication following major abdominal surgery. The use of low-molecular-weight heparins (LMWH) to prevent thrombotic events in these patients is a common and well documented practice. However, there is some controversy surrounding the duration of the prophylaxis, as it has been suggested that the risk persists for several weeks after surgery. The objective of this meta-analysis is to systematically review the clinical studies that compared safety and efficacy of extended use of LMWH (for three to four weeks after surgery) versus conventional in-hospital prophylaxis. An electronic data base search was performed. Only randomized, controlled studies were eligible. Data on the incidence of deep vein thrombosis (DVT), VTE and bleeding were extracted. Only three studies fulfilled the inclusion criteria. The indication for surgery was neoplastic disease in 70.6% (780/1104) of patients. The administration of extended LMWH prophylaxis significantly reduced the incidence of VTE, 5.93% (23/388) versus 13.6% (55/405), RR 0.44 (CI 95% 0.28 - 0.7); DVT 5.93% (23/388) versus 12.9% (52/402), RR 0.46 (CI 95% 0.29 - 0.74); proximal DVT 1% (4/388) versus 4.72% (19/402), RR 0.24 (CI 95% 0.09 - 0.67). We found no significant difference in major or minor bleeding between the two groups: 3.85% (21/545) in the extended thrombo-prophylaxis (ETP) group versus 3.48% (19/559) in the conventional prophylaxis group; RR 1.12 (CI 95% 0.61 - 2.06). There was no heterogeneity between the studies. We conclude that ETP with LMWH should be considered as a safe and useful strategy to prevent VTE in high-risk major abdominal surgery.

Alta variabilidad en la determinación del Factor IX en muestras de plasma adicionadas con nonacog beta pegol entre distintos pares de reactivos/sistemas de detección / High variability in the determination of Factor IX in plasma samples spiked with nonacog beta pegol between different reagents/detection system pairs / Alta variabilidade na determinação do Fator IX em amostras de plasma enriquecidas com nonacog beta pegol entre diferentes pares de reagentes/ sistema de detecção

Resumen La hemofilia B es un trastorno hemorrágico hereditario, ligado al cromosoma X, que se caracteriza por el déficit del factor IX (FIX) de la coagulación. Para mejorar la calidad de vida de los pacientes y la adherencia al tratamiento se han desarrollado concentrados de factores recombinantes modificados para extender su vida media, denominados factores de vida media extendida (EHL: extended half life concentrates). El nonacog beta pegol (N9-GP) es una molécula de FIX humano recombinante glicopegilada que tiene una vida media de 93 h con una sola dosis y ha mostrado un porcentaje de recuperación mayor que otras moléculas. Para diagnosticar y monitorear el tratamiento del paciente hemofílico se determina la actividad del FIX con el ensayo coagulable en una etapa (OSA: one stage assay) y/o en el ensayo cromogénico. El objetivo de este trabajo, realizado en tres centros, fue medir la recuperación de N9-GP con 10 reactivos de APTT diferentes en tres plataformas, en muestras deficientes en FIX adicionadas in vitro con N9-GP, en cuatro niveles de concentración diferentes. Los resultados muestran una heterogeneidad en la actividad de N9-GP medidos por OSA con los diferentes reactivos de APTT cuando se realizaron las calibraciones con el estándar específico de cada coagulómetro. Se obtuvo un porcentaje de recuperación mayor de 92% con Cephascreen, Actin FSL y APTTest elágico en las tres plataformas evaluadas. Estos reactivos serían los únicos apropiados cuando se usa el OSA calibrado con plasma comercial para monitorear el tratamiento de los pacientes que reciben N9-GP.

Abstract Hemophilia B (HB) is an X-linked hereditary bleeding disorder characterised by coagulation factor IX (FIX) deficiency. To improve the quality of life of patients and adherence to treatment, recombinant factor concentrates glicomodified to extend their half-life have been developed. These are called extended half-life factors (EHL: extended half-life concentrates). Nonacog beta pegol (N9-GP) is a glycopegylated recombinant human FIX molecule that has a half-life of 93 h with a single dose and has shown a higher recovery percentage than other molecules. For diagnosis and monitoring the treatment of hemophiliac patients, FIX activity is determined with the One Stage Clotting Assay (OSA) and/or the chromogenic assay. The objective of this work, carried out in three centres, was to measure the recovery of N9-GP with 10 different APTT reagents on three platforms, in FIX deficient samples spiked in vitro with N9-GP, at four different concentration levels. The results show a heterogeneity in the activity of N9-GP measured by OSA with the different APTT reagents when the calibrations were performed with the specific standard of each coagulometer. A recovery percentage greater than 92% was obtained with Cephascreen, Actin FSL and APTTest ellagic in the three platforms evaluated. These reagents would be the only ones appropriate when using the commercial plasma-calibrated OSA to monitor the treatment of patients treated with N9-GP.

Resumo A hemofilia B é uma doença hemorrágica hereditária ligada ao cromossomo X caracterizada pela deficiência do fator de coagulação IX (FIX). Para melhorar a qualidade de vida dos pacientes e a adesão ao tratamento, foram desenvolvidos concentrados de fatores recombinantes modificados para prolongar sua meia-vida, chamados de fatores de meia-vida estendida (EHL: extended half life concentrates). Nonacog beta pegol (N9-GP) é uma molécula de FIX humano recombinante glicopeguilada que tem meia-vida de 93 h com uma dose única e mostrou uma porcentagem de recuperação maior do que outras moléculas. Para diagnosticar e monitorar o tratamento de pacientes hemofílicos, a atividade do FIX é determinada com o ensaio coagulável em um estágio (OSA: One Stage Assay) e/ou o ensaio cromogênico. O objetivo deste trabalho, realizado em três centros, foi medir a recuperação de N9-GP com 10 reagentes de APTT diferentes em três plataformas, em amostras deficiente de fator IX adicionadas in vitro com N9-GP, em quatro níveis de concentração diferentes. Os resultados mostram uma heterogeneidade na atividade de N9-GP medidos por OSA com os diferentes reagentes de APTT quando as calibragens foram realizadas com o padrão específico de cada coagulômetro. Uma porcentagem de recuperação superior a 92% foi obtida com Cephascreen, Actin FSL e APTTest elágico nas três plataformas avaliadas. Esses reagentes seriam os únicos apropriados ao usar o OSA calibrado com plasma comercial para monitorar o tratamento de pacientes tratados com N9-GP.