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    Cristina Duboscq

    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... more
    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.
    The bleeding disorder in patients with factor XI deficiency has presented practical and conceptual challenges for clinicians and basic scientists.In FXI deficient patients, the most frequent symptoms are menorrhagia and epistaxis, while... more
    The bleeding disorder in patients with factor XI deficiency has presented practical and conceptual challenges for clinicians and basic scientists.In FXI deficient patients, the most frequent symptoms are menorrhagia and epistaxis, while severespontaneous hemorrhage is rare. However, current diagnostic tests can not accurately predict bleeding trends in patients with FXI deficiency, since the symptoms are highly variable among patients and are poorly correlated with plasma FXI levels.The objective of this study was to perform a retrospective study of 14 patients with FXI deficiencywho attended the Hematology Service of the British Hospital of Buenos Aires between 2007 and 2019.Fourteen patients who attended the Hematology Service with prolonged APTT or bleeding were studiedThe mean age was 52 years. The average of FXI levels in the patients was 31%. Five patients were studied for their personal bleeding history (FXI level between 0.1% and 48%) and nine patients were diagnosed during the pre-surgical examination. The main reason for medical consultation was for scheduled surgery.The mean of the APTT was 54 seconds (range: 40-90). All presented correction with normal pool. Five patients with severe FXI deficiency (<15%) showed an APTT between 54 and 90 seconds (mean 70.8).In this group of patients, we found patients with severe FXI deficiency who did not bled (FXI level <15%) and patients with mild deficiencies who bled. This discrepancy observed between the level of FXI and the clinical manifestations agrees with that reported in the literature.Due to the lack of an easily accessible test, which discriminates against patients at risk of bleeding from those who do not, all patients with FXI levels of less than 40% received treatment before any surgical procedure.
    Complejo Protrombinico UNC (CP-UNC) is a plasma derived concentrate containing coagulation factors II, IX and X. It is prepared in Argentina and has the approval of the National Administration of Drugs, Foods and Medical Devices (ANMAT).... more
    Complejo Protrombinico UNC (CP-UNC) is a plasma derived concentrate containing coagulation factors II, IX and X. It is prepared in Argentina and has the approval of the National Administration of Drugs, Foods and Medical Devices (ANMAT). In the present case report we described the use of CPUNC for reversal of hypoprothrombinemia prior to liver transplantation (two patients) and vitamin K antagonists (two patients). CP-UNC was used in different doses according weight, patient's clinical situation and laboratory data. The parameters of effectiveness, adverse drug reactions (ADR) and viral markers (MV) were evaluated in each case. The results showed that the CP-UNC improved the laboratory parameters within the expected values. An acute coronary syndrome was reported in one patient. It was categorized as possible using the Naranjo algorithm. There were no hemorrhagic complications in the other patients. Until now, no RAM reports have been received under the Pharmacovigilance Program...
    Base de dados : LILACS. Pesquisa : 177479 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos... more
    Base de dados : LILACS. Pesquisa : 177479 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 177479. ...
    Se detallan todos los pasos a llevar a cabo para realizar isoelectroenfoque en geles de poliacrilamida de 1 mm de espesor adheridos a un celofan como soporte. El gel se adhiere firmemente al celofan durante todos las operaciones (corrida,... more
    Se detallan todos los pasos a llevar a cabo para realizar isoelectroenfoque en geles de poliacrilamida de 1 mm de espesor adheridos a un celofan como soporte. El gel se adhiere firmemente al celofan durante todos las operaciones (corrida, tincion y destenido) y el soporte lo protege de las roturas, razon por la cual es facilmente manejable. Se discute la optimizacion de las condiciones de trabajo para anfolito no comercial. Se muestra la buena resolucion obtenida con dicho anfolito de sueros humanos normales y patologicos
    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... more
    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.
    Proteinuria is the hallmark of nephrotic syndrome and a surrogate of progression of renal disease and a risk factor of cardiovascular morbidity. Once proteinuria occurs secondary to glomerular damage, its reabsorption at the proximal... more
    Proteinuria is the hallmark of nephrotic syndrome and a surrogate of progression of renal disease and a risk factor of cardiovascular morbidity. Once proteinuria occurs secondary to glomerular damage, its reabsorption at the proximal tubule causes a constant interstitial inflammation that will eventually lead to a graduate loss of kidney function due to fibrosis, ischemia and tubular atrophy. The plasminogen-plasmin system plays a local critical role in amplifying podocyte damage, deepening the generation of edema, cross-linking inflammatory components at the interstitium and determining the terminal fibrotic processes. Plasmin activity also causes inflammation through the complement system. The interaction between the complement and the plasminogen-plasmin systems is critical in the progression of interstitial inflammation. Plasmin is capable of cleaving C3 and C5 components of the complement system. Moreover, C3a and C5a fractions are chemoattractants of neutrophils and monocytes. The complement system is also involved in microvascular thrombosis contributing to glomerular sclerosis and interstitial fibrosis through ischemic processes. A regulator of plasmin activity is plasminogen activator inhibitor-1, a leading molecule involved in fibrosis and sclerosis, particularly augmented in glomerulopathies. Unraveling the interactions between the plasminogen-plasmin and complement systems will undoubtedly lead to more specific therapies for glomerular diseases.
    Base de dados : LILACS. Pesquisa : 177479 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos... more
    Base de dados : LILACS. Pesquisa : 177479 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 177479. ...
    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... more
    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 r...
    Base de dados : LILACS. Pesquisa : 177479 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos... more
    Base de dados : LILACS. Pesquisa : 177479 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 177479. ...
    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,... more
    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.
    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... more
    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.
    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... more
    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 gastrointestin...
    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... more
    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 co...
    Resumen es: El endotelio es un organo que esta involucrado en numerosos procesos fisiologicos, principalmente el de mantener la fluidez de la sangre. Las celulas e...
    Se detallan todos los pasos a llevar a cabo para realizar isoelectroenfoque en geles de poliacrilamida de 1 mm de espesor adheridos a un celofan como soporte. El gel se adhiere firmemente al celofan durante todos las operaciones (corrida,... more
    Se detallan todos los pasos a llevar a cabo para realizar isoelectroenfoque en geles de poliacrilamida de 1 mm de espesor adheridos a un celofan como soporte. El gel se adhiere firmemente al celofan durante todos las operaciones (corrida, tincion y destenido) y el soporte lo protege de las roturas, razon por la cual es facilmente manejable. Se discute la optimizacion de las condiciones de trabajo para anfolito no comercial. Se muestra la buena resolucion obtenida con dicho anfolito de sueros humanos normales y patologicos
    The aim of this study was to assess the extent of influence of citrate concentration on the results of routine coagulation assays (prothrombin time (PT) and ...
    D-dimer is a marker of thrombin and plasmin generation. The usefulness of D-dimer measurement as a negative predictive value in the exclusion of thromboembolic disease in patients with low or moderate clinical pretest has been... more
    D-dimer is a marker of thrombin and plasmin generation. The usefulness of D-dimer measurement as a negative predictive value in the exclusion of thromboembolic disease in patients with low or moderate clinical pretest has been demonstrated for some time. However, the appearance of new methodologies, which express the results in different units and have a different degree of approval for use in thromboembolic disease, exclusion algorithm has generated a degree of confusion. The objective of this review is to compile and disseminate the recommendations of the different international guidelines on the use of D-dimer in the diagnosis of thromboembolic disease. The different degrees of approval of the Food and Drug Administration are discussed for the laboratory methods (help in the diagnosis vs. exclusion), the units in which the results should be expressed, what information should be included when a D-dimer result is reported, how to establish the cut-off points of the different method...
    Platelets are one of the most widely used blood components in transfusion medicine, given their importance in the prevention of bleeding disorders in patients with multifactorial thrombocytopenia and Asian non-immunological etiology, as... more
    Platelets are one of the most widely used blood components in transfusion medicine, given their importance in the prevention of bleeding disorders in patients with multifactorial thrombocytopenia and Asian non-immunological etiology, as well as in the management of traumatic or blood-related surgical treatments. Given its extensive use and the constant demand for it to be used within the different procedures associated with medicine, it is the objective of both hemotherapy services and blood banks to ensure that blood product components are constantly available to meet such requirements. The main challenge with this resource is its short useful life (5–7 days) which limits its availability, especially in the Latin American context where the production of blood components as well as the resources allocated for this purpose by state entities to blood banks, are generally limited. Cryopreservation at –80°C using dimethylsulfoxide as a preservative solution is a technique used since the...
    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... more
    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 r...
    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... more
    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.
    The diagnosis of lupus anticoagulant (IL) according to the classical algorithm (ISTH) is prolongation of some of the screening tests (Russel or APTT sensitive), the non-correction of the mixing test and the shortening of the elongated... more
    The diagnosis of lupus anticoagulant (IL) according to the classical algorithm (ISTH) is prolongation of some of the screening tests (Russel or APTT sensitive), the non-correction of the mixing test and the shortening of the elongated test times in presence of high concentration of phospholipids. The guide of the British Hematology Society (BSH) suggests that, in the absence of other coagulation abnormalities, if a sample is positive screen and confirmatory test although the tests of mixtures are negative, should be considered positive for IL. The CLSI guide suggests performing the tests in the following order screenconfirm- mix; recommends that the mixing test be carried out only when the first two do not have a clear result and if other abnormalities are suspected. The objective is to compare the final diagnosis for lupus anticoagulant (IL) applying the BSH/CLSI guidelines vs the classical algorithm (ISTH). Population: 196 samples of positive lupus inhibitor by BSH and CLSI referr...
    Resumen es: La proteina S (PS) regula el sistema de coagulacion mostrando actividad de cofactor de la Proteina C activada (PCa) con la cual forma un complejo equimo...
    Purpura fulminans is a hematological emergency characterized by cutaneous necrosis and laboratory disseminated intravascular coagulation (DIC) parameters. It can appear associated with severe infections, as an autoimmune process after... more
    Purpura fulminans is a hematological emergency characterized by cutaneous necrosis and laboratory disseminated intravascular coagulation (DIC) parameters. It can appear associated with severe infections, as an autoimmune process after benign infections in childhood or be the presenting symptom of a congenital protein C or S deficiency. A clinical case of purpura fulminans associated with acquired protein S deficiency is described in a 6-year-old patient with severe Streptococcus Pneumoniae pneumonia.
    El inhibidor adquirido contra el factor VIII o “hemofilia adquirida” (HA) es una patología autoinmune que suele presentarse como un sangrado súbito en pacientes sin coagulopatía previa. El diagnóstico de esta patología debe ser rápido,... more
    El inhibidor adquirido contra el factor VIII o “hemofilia adquirida” (HA) es una patología autoinmune que suele presentarse como un sangrado súbito en pacientes sin coagulopatía previa. El diagnóstico de esta patología debe ser rápido, sobre todo en aquellos casos en que la presentación es una hemorragia que puede comprometer la vida del paciente. En esta actualización se analizan las pruebas globales y específicas utilizadas en su detección y los ensayos Bethesda y Nijmejen que permiten la cuantificación del inhibidor para monitorear el tratamiento. Es importante la función del laboratorio en el diagnóstico precoz de esta patología y para eso se debe conocer y pensar en su existencia cuando se presenta un paciente con sangrado, un aPTT prolongado que no corrige con plasma normal, un FVIII disminuido y pruebas de inhibidor lúpico negativo.

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