Mean platelet volume as a prognostic factor for venous thromboembolic disease / Volumen plaquetario medio como factor pronóstico de la enfermedad tromboembólica venosa

ABSTRACT Background: Mean platelet volume (MPV) is a risk factor for cardiovascular and inflammatory diseases. Aim: To evaluate the association between high MPV and 90-day mortality after an episode of venous thromboembolism (VTE). Material and Methods: Retrospective cohort of 594 patients with a median age of 73 years (58% women) with a first episode VTE, included in an institutional Thromboembolic Disease registry between 2014 and 2015. MPV values were obtained from the automated blood cell count measured at the moment of VTE diagnosis. Volumes ≥ 11 fL were classified as high. All patients were followed for 90 days to assess survival. Results: The main comorbidities were cancer in 221 patients (37%), sepsis in 172 (29%) and coronary artery disease in 107 (18%). Median MPV was 8 fl (8-9), brain natriuretic peptide 2,000 pg/ml (1,025-3,900) and troponin 40 pg/ml (19.5-75). Overall mortality was 20% (121/594) during the 90 days of follow-up. Thirty three deaths occurred within 7 days and 43 within the first month. The loss of patients from follow-up was 5% (28/594) at 90 days. Mortality among patients with high MP was 36% (23/63). The crude mortality hazard ratio (HR) for high MPV was 2.2 (95% confidence intervals (CI) 1.4-3.5). When adjusted for sepsis, oncological disease, heart disease, kidney failure and surgery, the mortality HR of high MPV was 2.4 (CI95% 1.5-3.9) in the VTE group, 2.3 (CI95% 1.5-4.4) in the deep venous thrombosis group, and 2.9 (CI95% 1.6 −5.6) in the pulmonary embolism group. Conclusions: High MPV is an independent risk factor for mortality following an episode of VTE.

Antecedentes: El volumen plaquetario medio (VPM) es un factor de riesgo de complicaciones cardiovasculares y enfermedades inflamatorias. Objetivo: Evaluar la asociación entre VPM alto y la mortalidad a los 90 días después de un episodio de tromboembolismo venoso (ETV). Material y Métodos: Cohorte retrospectiva de 594 pacientes adultos con una edad media de 73 años (58% mujeres) con un primer episodio de ETV incluidos en un registro de enfermedad tromboembólica institucional entre 2014 y 2015. Se obtuvieron valores de VPM desde el hemograma tomado en el momento del diagnóstico de ETV y un volumen ≥ 11 fL fue clasificado como alto. Todos los pacientes fueron seguidos durante 90 días para determinar sobrevida. Resultados: Las comorbilidades fueron cáncer en 221 pacientes (37%), sepsis en 172 (29%) y enfermedad coronaria en 107 (18%). La mediana de VPM fue 8 fl (89), el péptido natriurético cerebral fue de 2.000 pg/ml (1.025-3.900) y la troponina fue de 40 pg/ml (19,5-75). La mortalidad global a 90 días fue 20% (121/594). Treinta y tres muertes ocurrieron dentro de los 7 días y 43 en el primer mes. La pérdida de seguimiento de pacientes fue de 5% (28/594) a los 90 días. La mortalidad en el grupo con VPM alto fue 36% (23/63). La razón de riesgo (HR) cruda de la mortalidad para un VPM alto fue de 2,2 (intervalos de confianza (IC) de 95% 1,4-3,5). Cuando se ajustó por sepsis, enfermedad oncológica, enfermedad cardíaca, insuficiencia renal y cirugía, la HR de muerte para un VPM alto fue de 2,4 (IC95% 1,5-3,9) en el grupo de ETV; 2,3 (IC95% 1,5-4,4) en el grupo de trombosis venosa profunda; y 2,9 (CI95% 1,6 −5,6) en el grupo de embolia pulmonar. Conclusiones: Un VPM alto es un factor de riesgo independiente de mortalidad después de un episodio de ETV.

Inflammatory markers are beneficial in the early stages of cerebral venous thrombosis / Los marcadores inflamatorios son beneficiosos en las primeras etapas de la trombosis venosa cerebral

ABSTRACT Cerebral vein thrombosis (CVT) is a rare but serious cause of acute stroke. Inflammation is a hypothetical etiological factor in CVT. Objective: The aim of this study was to evaluate inflammatory marker levels in CVT patients and compare these with healthy individuals. Methods: This prospective case-control study was conducted with 36 newly-diagnosed CVT patients age- and sex-matched with 40 healthy individuals. The laboratory investigations included a serum hemogram, full biochemistry profiles, high sensitivity C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-HDL cholesterol ratio (MHR) values were calculated and compared between the patients and healthy participants. Results: The mean age was 41.4 ± 11.8 years for patients, and 39.3 ± 12.5 for controls. Lymphocyte, total bilirubin, indirect bilirubin, and HDL levels were significantly lower in CVT patients (p < 0.05), while CRP, and ESR values were significantly higher. In the CVT patients the mean NLR and PLR values were significantly higher than in the control individuals. Smoking rates, alcohol consumption, white blood cell, neutrophil, platelet, and MHR values were similar in both groups (p > 0.05). Conclusions: We suggest that NLR, PLR, CRP, ESR, and bilirubin can be used in clinical practice for prediction of CVT in suspected patients as they are inexpensive parameters and widely available. However, further large-scale studies are required to confirm this relationship.

RESUMEN la trombosis de la vena cerebral (CVT) es una causa rara pero grave de accidente cerebrovascular agudo. La inflamación es un factor etiológico hipotético en CVT. Objetivo: El objetivo de este estudio fue evaluar los niveles de marcadores inflamatorios en pacientes con CVT y compararlos con los sujetos sanos. Métodos: Este estudio prospectivo de casos y controles se realizó con 36 pacientes con TVC recién diagnosticados y 40 sujetos sanos con edad y sexo similares. Las investigaciones de laboratorio incluyeron hemograma sérico, perfiles bioquímicos completos, proteína C-reactiva (CRP) de alta sensibilidad y velocidad de sedimentación eritrocitaria (ESR). Se calculó la relación de neutrófilos a linfocitos (NLR), relación de plaquetas a linfocitos (PLR) y monocitos a HDL-colesterol (MHR) y se compararon entre pacientes y sujetos sanos. Resultados: La edad media fue de 41,4 ± 11,8 años para los pacientes y de 39,3 ± 12,5 para los controles. Los niveles de linfocitos, bilirrubina total, bilirrubina indirecta y HDL fueron significativamente más bajos en pacientes con CVT (p ≤ 0.05), mientras que los valores de CRP y ESR fueron significativamente más altos. En los pacientes con CVT, los valores medios de NLR y PLR fueron significativamente más altos que en los sujetos control. Las tasas de tabaquismo, consumo de alcohol, glóbulos blancos, neutrófilos, plaquetas y MHR fueron similares en ambos grupos (p > 0.05). Conclusiones: Sugerimos que la NLR, la PLR, la CRP, la ESR y la bilirrubina se pueden usar en la práctica clínica para la predicción de la CVT en pacientes sospechosos, ya que son parámetros económicos y están ampliamente disponibles. Sin embargo, se requieren más estudios a gran escala para confirmar esta relación.

Monitoring of coagulation by intraoperative thromboelastometry of liver transplantation in a patient using warfarin - case report / Monitoração da coagulação pela tromboelastometria no intraoperatório de transplante hepático em um paciente usando varfarina - relato de caso

Abstract Introduction: Advanced hepatic disease may - in addition to the widely recognized hemorrhagic complications - occur with thrombotic events. We describe the case of a cirrhotic patient taking warfarin and whose coagulation management during liver transplantation was guided by thromboelastometry (ROTEM®). Case report: A 56 year-old male patient diagnosed with alcohol cirrhosis using warfarin (2.5 mg.day−1) for partial portal vein thrombosis with the International Normalized Ratio (INR) of 2.14. At the beginning of surgery, the ROTEM® parameters were all normal. In the anhepatic phase, EXTEM and INTEM remained normal, but FIBTEM showed reduction of amplitude after 10 min and maximum clot firmness. Finally, in the neohepatic phase, there was a slight alteration in the hypocoagulability of most of the parameters of the EXTEM, INTEM and FIBTEM, besides a notable correction of the Coagulation Time (CT) in HEPTEM compared to the CT of the INTEM. Therefore, the patient did not receive any transfusion of blood products during surgery and in the postoperative period, being discharged on the 8th postoperative day. Discussion: Coagulation deficit resulting from cirrhosis distorts INR as a parameter of anticoagulation adequacy and as a determinant of the need for blood transfusion. Thus, thromboelastometry can provide important information for patient management.

Resumo Introdução: A doença hepática avançada pode, além das complicações hemorrágicas amplamente reconhecidas, ocorrer com eventos trombóticos. Descrevemos o caso de um paciente cirrótico em uso de varfarina, cujo manejo da coagulação durante o transplante de fígado foi guiado por tromboelastometria (ROTEM®). Relato de caso: Paciente do sexo masculino, 56 anos, diagnosticado com cirrose alcoólica, recebendo varfarina (2,5 mg.dia−1) para trombose parcial da veia porta, com razão normalizada internacional (INR) de 2,14. No início da cirurgia, os parâmetros ROTEM® estavam todos normais. Na fase não hepática, EXTEM e INTEM permaneceram normais, mas FIBTEM mostrou redução da amplitude após 10 min e firmeza máxima do coágulo. Por fim, na fase neo-hepática houve uma ligeira alteração da hipocoagulabilidade na maioria dos parâmetros de EXTEM, INTEM e FIBTEM, além de uma correção notável do tempo de coagulação (CT) de HEPTEM em comparação com o CT de INTEM. Portanto, o paciente não recebeu transfusão de hemoderivados durante a cirurgia e no período pós-operatório, obteve alta no oitavo dia de pós-operatório. Discussão: O déficit de coagulação resultante da cirrose distorce o INR como um parâmetro da adequação da anticoagulação e como um determinante da necessidade de transfusão de sangue. Portanto, a tromboelastometria pode fornecer informações importantes para o manejo do paciente.

BISAP-O y APACHE-O: utilidad en la predicción de severidad en la pancreatitis aguda según la clasificación modificada de Atlanta / BISAP-O y APACHE-O: utility in predicting severity in acute pancreatitis in modified Atlanta classification

Objetivo: Valorar los puntajes BISAP y APACHE II en predecir severidad según la clasificación Atlanta 2012 y determinar si el factor obesidad añadido a dichos puntajes mejora su predicción. Material y métodos: Se realizó un estudio prospectivo entre enero de 2013 y abril de 2014 de todos los pacientes con pancreatitis aguda según la nueva clasificación Atlanta 2012. Se confeccionó curvas ROC para los puntajes BISAP, BISAP-O, APACHE-II y APACHE-O y se seleccionó puntos de corte apropiados con los que se calculó la sensibilidad, especificidad, VPP, VPN, RPP y la RPN. Resultados: Se estudió a 334 pacientes. El 65,27% presentó sobrepeso u obesidad. La etiología fue biliar en el 86,53%. Sólo 8,38% presentó pancreatitis severa y 1,5% falleció. Las áreas bajo la curva ROC y puntos de corte seleccionados fueron: BISAP: 0,8725, 2; BISAP-O: 0,8246, 3; APACHE-II: 0,8547, 5; APACHE-O: 0,8531, 6. Con dichos puntos de corte la sensibilidad, especificidad, VPP, VPN, RPP y la RPN fueron: BISAP: 60,71%, 91,83%, 40,48%, 96,23%, 7,43, 0,43; BISAP-O: 60,71%, 86,93%, 29,82%, 96,03%, 4,76, 0,45; APACHE-II: 85,71%, 76,14%, 24,74%, 98,31%, 3,6, 0,19; APACHE-O: 82,14%, 79,41%, 26,74%, 97,98%, 4, 0,22. Conclusiones: Los sistemas BISAP, BISAP-O, APACHE-II, y APACHE-O pueden usarse para identificar a los pacientes con bajo riesgo de severidad en razón de su alto VPN, sin embargo su uso debe ser prudente considerando que la RPP y RPN no alcanza niveles óptimos, indicando que su valor en la predicción de severidad es limitado. Por otro lado el añadir el factor obesidad no mejoró su capacidad predictiva.

Objective: To assess the BISAP and APACHE II scores in predicting severity according to the 2012 Atlanta classification and whether the obesity factor added to these scores improves prediction. Material and methods: A prospective study between January 2013 and April 2014 including all patients with acute pancreatitis was performed according to the new Atlanta 2012 classification. ROC curves were fabricated for BISAP, BISAP-O, APACHE-II scores and Apache O and appropriate cutoffs were selected to the sensitivity, specificity, PPV, NPV, RPP and RPN. Results: We studied 334 patients. 65.27% were overweighted or obese. The biliar etiology was 86.53%. Only 8.38% had severe pancreatitis and 1.5% died. Areas under the ROC curve and cut points selected were: BISAP: 0.8725, 2; BISAP-O: 0.8246, 3; APACHE-II: 0.8547, 5; APACHE-O: 0.8531, 6. Using these cutoffs the sensitivity, specificity, PPV, NPV, RPP and RPN were BISAP: 60.71%, 91.83%, 40.48%, 96.23 %, 7.43, 0.43; BISAP-O: 60.71%, 86.93%, 29.82%, 96.03%, 4.76, 0.45; APACHE-II: 85.71%, 76.14%, 24.74%, 98.31%, 3.6, 0.19; APACHE-O: 82.14%, 79.41%, 26.74%, 97.98%, 4, 0.22. Conclusions: BISAP, BISAP-O, APACHE-II and APACHE-O systems can be used to identify patients at low risk of severity because of its high NPV, however their use should be cautious considering that the RPP and RPN do not reach optimal levels indicating that their value in predicting severity is limited. On the other hand adding the obesity factor did not improve their predictive ability.

Uso de warfarina y bajo rango de INR en la prevención de trombosis venosa recurrente / Use of warfarin and low range INR in the prevention of recurrent venous thrombosis

El objetivo de este trabajo fue determinar la efectividad de un rango de la Razón Normalizada Internacional (INR) entre 1,5 y 1,9 en la prevención de la recurrencia de trombosis venosa y de las complicaciones hemorrágicas asociadas al uso de warfarina. Entre enero del 2006 y noviembre del 2009, se estudiaron 39 pacientes, con edades entre 10 y 78 años y diagnóstico de trombosis venosa profunda y/o embolismo pulmonar que recibieron warfarina al menos durante 6 meses. Los sujetos fueron separados aleatoriamente en dos grupos: a 20 pacientes se le ajustó la dosis para mantener el INR entre 1,5 y 1,9 y a 19 pacientes se les mantuvo el INR entre 2 y 3. A cada individuo se le cuantificó la actividad plasmática de los factores II, VII, IX y X a la primera y entre la cuarta y quinta semanas, luego de estabilizado el INR. En ambos grupos, la actividad de los factores se encontró por debajo del valor normal con diferencia significativa entre los grupos (p<0,05). No se detectó recurrencia de trombosis durante el seguimiento. Solo se presentaron manifestaciones hemorrágicas menores en un sujeto con INR entre 1,5 y 1,9 y en cuatro del otro grupo (p = NS). Los resultados del presente trabajo sugieren que un rango de INR entre 1,5 y 1,9, provee un esquema de anticoagulación eficaz para la prevención de recurrencia de trombosis venosa con menor frecuencia de hemorragias. Sin embargo, es necesario seguir incorporando más individuos en el estudio para obtener mayor certeza en el análisis de estos resultados.

The object of this work was to determine the efficacy of a low range International Normalized Ratio (INR) between 1.5 and 1.9, in preventing recurrent venous thrombosis and the hemorrhagic manifestations that can complicate anticoagulation with warfarin. Thirty nine patients, 10 to 78 years of age were studied between January 2006 and November 2009. All of them had been treated with warfarin, for at least 6 months, due to deep venous thrombosis or pulmonary embolism. The subjects were separated, at random, into two groups. In group A (20 patients), the doses of warfarin were adjusted until the INR was stabilized between 1.5 and 1.9; in group B, the INR was maintained between 2 and 3. The coagulant activities of plasma factors II, VII, IX and X were determined in a week and between the fourth and fifth weeks, after stabilization of the INR. Plasma activities of the coagulation factors assayed were abnormally low in both groups, in the two opportunities they were determined, although significantly lower in group B (p<0.05). No thromboembolic episodes occurred during the study, in any of the patients. One of the patients from group A and four from group B, presented minor hemorrhagic manifestations (p N.S.) The above results suggest that a range on INR lower that 2, could be sufficient to prevent recurrent thrombotic episodes while diminishing the frequency of hemorrhagic complications associated with the use of warfarin. However, it is necessary to continue incorporating more individuals in the study to obtain greater certainty in the analysis of these results.

Asociación de variantes funcionales en genes del metabolismo de la homocisteína con riesgo de trombosis venosa profunda e hiperhomocisteinemia en individuos del Sur de Chile / Association of functional variants in homocysteine metabolism genes, deep venous thrombosis risk and hyperhomocysteinemia in Southern Chilean subjects

Introducción: La Trombosis Venosa Profunda (TVP) es un importante problema de salud en la sociedad moderna. Evidencia reciente sugiere una asociación entre variantes funcionales en genes del metabolismo de la homocisteína con TVP. Sin embargo, los resultados entre poblaciones son contradictorios. En este trabajo, evaluamos la potencial asociación entre la presencia de polimorfismos en genes del metabolismo de la homocis-teína y susceptibilidad a TVP e hiperhomocisteinemia en sujetos chilenos. Métodos: Un total de 231 individuos, 77 pacientes con diagnóstico de TVP y 154 controles fueron incluidos en el estudio. Polimorfismos en los genes Metilenotetrahi-drofolato reductasa (MTHFR) y Cistationina p-sintetasa fueron genotipificados por PCR-RFLP Las concentraciones de homocisteína basal fueron cuantificadas mediante Inmunoensayo de Fluorescencia Polarizada. Resultados: La distribución genotípica y frecuencias alélicas del polimorfismo MTHFR C677T fue significativamente diferente entre pacientes y controles (p<0.01). Odds Ratio para TVP asociada al genotipo homocigoto fue 3.68 (I.C. 95 por ciento: 1.628-8.337, p<0.01). Por el contrario, la distribución genotípica de la variante CBS 844ins68 fue similar en ambos grupos (OR=1.82, I.C. 95 por ciento: 0.636-5.234, p=0.257). Además, los portadores del genotipo homocigoto MTHFR 677TT presentaron niveles más elevados de homocisteína plasmática. Conclusiones: El polimorfismo MTHFR C677T constituye un biomarcador de riesgo de TVP en población chilena, y se relaciona a mayores niveles de homo-cisteína en sujetos homocigotos. Los resultados sugieren que la detección molecular de esta variante debería ser incluida en el estudio básico de Trombofilia en nuestra población.

Background: Deep Venous Thrombosis (DVT) is an important health problem in modern society. Recent evidence suggests an association between functional variants in homocysteine metabolism genes and DVT. However, findings in different populations have been contradictory. In this work, we evaluated the potential association between the presence of polymorphisms in homocysteine metabolism genes, DVT susceptibility and hyperhomocysteinemia in Chilean subjects. Methods: A total of 231 individuals, 77 patients with diagnosis of DVT and 154 controls were included in this study. Common variants in Metylenete-trahydrofolate reductase (MTHFR) and Cistationine p-synthetase (CBS) genes were genotyped by PCR-RFLP. Basal homocysteine was quantified by Fluorescence Polarization Immunoassay. Results: Genotype distribution and allelic frequencies of MTHFR C677T polymorphism were significantly different between patients and controls. Odds Ratio for DVT associated to homozygous status was 3.68 (95 percent C.I., 1.628-8.337, p<0.01). On the other hand, the genotype distribution of the CBS 844ins68 variant was similar in both groups (OR 1.82, 95 percent C.I.: 0.636-5.234, p=0.257). In addition, the individuals carrying the MTHFR 677TT homozygous genotype exhibited higher levels of homocysteine. Conclusion: The MTHFR C677T polymorphism constituted a molecular biomarker of DVT in Chilean population, and related to higher levels of homocysteine in homozygote subjects. The results suggest that the molecular detection of this polymorphism should be included in the basic screening for thrombophilia in our population.

Síndrome de Lemierre: relato de caso / Lemierre syndrome: case report

A síndrome de Lemierre é uma doença rara, mais comum em jovens, causada frequentemente pelo Fusobacterium necrophorum. Inicia-se com faringite e propaga-se até a veia jugular interna, promovendo uma fonte de bacteremia contínua e êmbolos sépticos pulmonares. Manifestações clínicas incluem febre, alterações respiratórias e massa cervical. O diagnóstico é realizado por tomografia computadorizada e duplex scan, além de hemocultura ou cultura direta. O tratamento é realizado com antibióticos beta-lactâmicos resistentes a beta-lactamases, sendo a cirurgia raramente necessária. Paciente do sexo feminino, 34 anos, com quadro de orofaringite, evoluiu em 48 horas com queda do estado geral, febre, aumento de volume e dor em região cervical esquerda...

Lemierre syndrome is a rare disease. It often affects young adults and is most frequently caused by Fusobacterium necrophorum. The initial event is pharyngitis, which extends to the internal jugular vein, serving as source of continuous bacteremia and septic pulmonary emboli. Clinical manifestations include fever, respiratory distress, and swollen cervical lymph nodes. Diagnosis is established based on blood culture or direct blood culture and confirmed by computed tomography and/or duplex scan. Treatment consists of administration of beta-lactamase resistant beta-lactam antibiotics...

Varfarina previne obstruções venosas pós-implante de dispositivos cardíacos em pacientes de alto risco: análise parcial / Warfarin prevents venous obstruction after cardiac devices implantation in high-risk patients: partial analysis

OBJETIVOS: Avaliar a utilidade da varfarina na prevenção dessas complicações nos pacientes de alto risco. MÉTODOS: Estudo clínico prospectivo, randomizado, cego, em pacientes submetidos ao primeiro implante transvenoso de DCEI, com FEVE<0,40 e/ou MPT ipsilateral ao implante definitivo. Após o procedimento, os pacientes foram randomizados para o uso diário de placebo ou varfarina. Avaliações clínicas e laboratoriais foram realizadas periodicamente. A pesquisa de obstruções venosas foi feita pela venografia por subtração digital, seis meses após o implante. De fevereiro de 2004 a novembro de 2006, foram selecionados 101 pacientes, havendo homogeneidade das características clínicas e operatórias de ambos os grupos (P=NS). RESULTADOS: No grupo Varfarina, 31,4 por cento dos pacientes apresentaram obstruções venosas em comparação a 57,1 por cento do grupo Placebo (RR= 0,57; IC 95 por cento= 0,33 a 0,98; P= 0,015). No grupo Varfarina, 72 por cento dos exames de INR realizados encontraram-se em nível terapêutico. Houve um caso de sangramento gastrintestinal, que justificou a interrupção do uso da varfarina e mudança para o grupo Placebo. CONCLUSÃO: Os resultados preliminares mostraram que o uso profilático da anticoagulação mostrou-se seguro e reduziu significativamente a incidência de obstruções venosas pós-implante de DCEI nos pacientes de alto risco.

OBJECTIVES: To evaluate the efficacy of prophylactic use of warfarin in patients with high risk of lead-associated thrombosis. METHODS: Clinical, prospective, randomized and blinded study, in patients submitted to first transvenous leads implantation with LVEF <0.40 and/or previous ipsilateral temporary pacing. After device implantation, patients were randomly assigned to placebo or warfarin. Periodical clinical and laboratorial evaluations were performed to anticoagulant management. After a six-month period, every patient was submitted to a digital subtraction venography. From February 2004 to November 2006, 101 patients underwent randomization. Baseline characteristics were similar in both groups (P=NS). RESULTS: Venographic analysis showed 31.4 percent of venous obstructions in patients assigned to warfarin as compared with 57.1 percent in patients assigned to placebo (RR= 0.57 [95 percent CI, 0.33 to 0.98]; P=0.015). In the warfarin group, 72 percent of the PT/INR tests were in therapeutic INR range. Only one patient required warfarin discontinuation and cross-over to placebo group due to gastrointestinal bleeding. CONCLUSIONS: These preliminary results showed that the anticoagulation therapy has been safe and reduced the frequency of venous thrombosis after transvenous cardiac devices implantation in high risk patients.

Evaluación del impacto de la variante genética C677T de la enzima metilentetrahidrofolato reductasa en el pronóstico de trombosis venosa profunda / Impact of the C677T genetic variant of metilentetrahydrofolate reductase on the prognosis of deep venous thrombosis

Introducción: Diversos estudios han relacionado diferentes factores trombofílicos al desarrollo de trombosis venosa profunda (TVP). Entre las alteraciones adquiridas y hereditarias asociadas a trombofilias destacan las relacionadas al metabolismo de la homocisteína. Sin embargo, los resultados observados son contradictorios e influenciados por diversos factores, entre ellos la etnia. Objetivo: Considerando la escasa información sobre las bases genéticas de la TVP en Chile, el objetivo del presente estudio fue investigar la posible asociación entre la mutación C677T del gen de la metilentetrahidrofolato reductasa (MTHFR) y TVP en individuos de nuestra región. Métodos: Fueron evaluados 60 pacientes con TVP (17 a 87 años) y 120 controles (21 a 81 años), de ambos sexos, todos provenientes a la IX Región de La Araucanía. La presencia de TVP fue confirmada mediante ecografía Doppler. La genotipificación de la mutación C677T fue realizada mediante la técnica de PCR-RFLP. Resultados: El genotipo homocigoto TT para la mutación C677T del gen MTHFR fue más frecuente en los individuos con TVP (28 por ciento vs. 15 por ciento, p=0.047). Similarmente, el alelo mutado 677T fue también más frecuente en los pacientes con TVP (0.53 vs. 0.39, p=0.018). La Odss ratio (OR) asociada a la variante 677T confirma la interacción encontrada(OR= 2.0, IC 95 por ciento 1.06 – 3.79, p<0.05). Conclusión: Los datos sugieren que la mutación C677T del gen MTHFR contribuye para el desarrollo de TVP en la población analizada. Sin embargo, hasta que más antecedentes sean reunidos, nosotros no recomendamos incluir la genotipificación de esta mutación en el screening de rutina de trombofilias.

Background: Several studies relate the presence of diverse thrombophilic factors to the development of deep venous thrombosis (DVT). Alteration of homocisteine metabolism has been associated to hereditary and acquired forms of thrombophilia. However, several factors may modify this relationship, among them the subject’s ethnic origin. Aim: To investigate a possible association of the C677T mutation of metilentetrahydrofolate reductase (MTHFR) to DVT. Methods: Sixty patients with DVT, aged 17 to 87 years, and 120 control subjects (21 to 81 years old), males and females, all residents of the Araucania region were evaluated. DVT was confirmed by duplex ultrasonography. PCR-RFLP was used to determine de presence of the C677T mutation Results: The homozygous TT genotype for C677T was more frequent in DVT subjects (28 percent) as compared to controls (15 percent, p=0.047). The mutated alelle of C677T was also more frequent in the DVT group (53 percent vs 39 percent, p=0.018). The OR for DVT associated to C677T was 2.0 (95 percent CI 1.06 – 3.79, p<0.05) Conclusion: The data suggest that the C677T mutation of MTHFR is associated to DVT. However, more information is needed before making a recommendation for use of gene characterization of this mutation in screening for thrombophilia.

Splenic and portal vein thrombosis following laparoscopic splenectomy in a pediatric patient with chronic myeloid leukemia

CONTEXT: Splenic or portal vein thrombosis is a rare complication following splenectomy. CASE REPORT: We report a case of splenic and portal venous thrombosis in a 10-year-old girl with chronic myeloid leukemia who underwent laparoscopic splenectomy prior to bone marrow transplant. Clinical suspicion of such thrombosis should be high for patients who have had splenectomy. The diagnosis is confirmed by Doppler ultrasound or contrast-enhanced computed tomography; magnetic resonance imaging magnetic resonance angiography or arteriography can also be used. Proposals for postoperative screening protocols are discussed. Patients with primary myeloproliferative disorders are at increased risk of portal vein thrombosis, independent of surgical intervention, perhaps due to platelet dysfunction resulting from abnormalities of pluripotent stem cells. Marked splenomegaly (with larger draining veins) is thought to increase the risk of thrombosis.

CONTEXTO: Trombose em veia portal ou esplênica é uma complicação rara pós-esplenectomia. RELATO DE CASO: Descrevemos um caso de trombose venosa portal e esplênica em uma menina de 10 anos de idade com leucemia mielóide crônica, a qual foi submetida a uma esplenectomia laparoscópica antes de um transplante de medula óssea. A suspeita clínica de tal trombose deve ser alta em pacientes que sofreram esplenectomia, e o diagnóstico é confirmado pelo ultra-som Doppler. Tomografia com contraste, ressonância magnética, angioressonância ou arteriografia podem também ser utilizados. Proposta de protocolo pós-operatório para avaliação de trombose é discutida.

Efeitos da terapia estrogênica transdérmica isolada ou associada à progesterona micronizada nos fatores de coagulação em mulheres menopausadas com e sem sobrepeso / Effects of transdermic estrogen therapy, isolated or in association with micronized progesterone, on clotting factors in overweight or normal postmenopausal women

Analisamos efeitos da reposição hormonal sobre coagulação em 45 mulheres menopausadas, divididas em Grupo 1 (N= 22, histerectomizadas) e Grupo 2 (N= 23, menopausa espontânea), com idade média de 51,6 anos e IMC médio de 27,1 kg/m², sem diferenças significativas no basal. No grupo 1 usamos 17-beta estradiol, 50 mcg/dia, transdérmico contínuo. No grupo 2 foi associada progesterona micronizada 200 mg/dia cíclica por 12 dias. Avaliou-se mensalmente por 3 meses a média de 2 amostras de TAP, PTT, fibrinogênio e plaquetas. No grupo total houve encurtamento do PTT a partir da 2ª avaliação (p= 0,006). Fibrinogênio no grupo 2 sofreu menor queda no grupo 1 a partir da 2ª avaliação (p= 0,0005). As pacientes com IMC > 25 apresentaram maior encurtamento do TAP (p= 0,040) e menor queda do fibrinogênio (p= 0,033) do que as de IMC < 25. Efeitos pró-trombóticos predominaram, especialmente nas mulheres com sobrepeso e que usaram progesterona.

Laboratory approach in Thai patients with venous thrombosis.

This retrospective study aimed to analyze laboratory findings in Thai patients with venous thrombosis in Phramongkutklao Hospital from August 1997 to October 2004. Blood samples obtained from 166 patients with ages ranging from 10 months to 87 years were tested for protein S (PS), protein C (PC), antithrombin (AT), factor V Leiden (FVL) and prothrombin G20210A. It was found that low levels of PS, PC, and AT were observed in 23 patients (13.9%), 21 patients (12.7%) and 11 patients (6.6%), respectively. The incidence of combined low levels of anticoagulant factors occurred in 23 patients (13.9%). Three patients (1.8%) were positive for FVL. All patients were negative for prothrombin G20210A. Additionally, 85 patients (51.2%) were negative for all tests. In conclusion, it is recommended that the screening tests for anticoagulant factors PS, PC and AT be used to investigate the causes of thrombosis in Asian populations due to their cost-effectiveness. However, the detection of gene mutations inducing thrombosis should be considered.

Hiperhomocisteinemia como factor de riesgo trombótico en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido / Hyperhomocysteine like thrombocytic risk factor in patient with systemic lupus erythematous with antiphospholipid syndrome

Objetivos: Determinar la prevalencia de hiperhomocisteinemia (hiperhcy) en pacientes con lupus eritematoso sistémico (LES) con y sin síndrome antifosfolípido (SAF); comparar los niveles de homocisteína (Hcy) entre pacientes con LES (con y sin SAF asociado) y un grupo de controles sanos y determinar la correlación entre hiperhcy y la presencia de anticuerpos antifosfolípidos. Pacientes y métodos: Se estudiaron 44 ptes con LES, portadores o no de SAF. Se los dividió en 2 grupos: 17 con LES y SAF y 27 con LES sin SAF y se compararon con 24 controles sanos. A todos se les realizó interrogatorio, examen físico y pruebas de laboratorio: anticuerpo s anticardiolipinas (aCL), anticoagulante lúpico y Hcy. Se consideró hiperhcy a valores superiores a 9. A los ptes con hiperhcy se los trató con ácido fólico + B6 + B 12 durante un mes. Análisis estadístico: variables cualitativas: Chi cuadrado o Exacta de Fischer y cuantitativas: test T de Student o MannWhitney test. Resultados y conclusiones: Hubo 35 manifestaciones trombóticas en los 44 pacientes. Se encontró Hiperhcy en 27 ptes con LES (61.4%), de los cuales 12 tenían SAF. La diferencia entre los valores de Hcy de los pacientes con o sin SAF no fue significativa (p=0,42). Comparando las concentraciones de Hcy entre pacientes y controles, la diferencia fue muy significativa (p=O,002).También tuvo significación estadística la diferencia entre las concentraciones de Hcy de los pacientes con LES sin SAF vs. controles (p=0,015) y LES con SAF vs. controles (p=0,003). A 33 ptes se les dosó aCL: 20 (60,6%) fueron (+). De estos, 15 (75%) tenían hiperhcy. De los 27 pacientes con LES que tenían hiperhcy, sólo 18 cumplieron con el mes de tratamiento con a.fólico+ B6+ B 12. 16 de 18 (88,8%) normalizaron o disminuyeron la Hcy.

Objectives: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrome; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. Patients and methods: we studied 44 SLE patients: 17 had antiphospholipid syndrome and 27 didn't have it, and we compared them to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitBI2 a month along. Statistical analysis: qualitative variables: chi square or Fischer's; quantitative variables: Student's T test or Mann Whitney’s test. Results and conc1utions: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrome. Hcy concentrations patients vs. controls was statistically different (p=0,002). There was also statistically different the hcy concentration from SLE patients with SAF vs controls (p=O,003) and without SAF vs. controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL( +). 15(75%) of them had hiperhcy.

Antithrombin III assay using thrombin in disseminated intravascular coagulation (DIC), other thromboembolic disorders and hepatic diseases.

Fifty cases comprising 11 cases of disseminated intravascular coagulation (DIC), 16 cases of venous thromboses and 23 cases of hepatic diseases were studied for AT III levels using clotting assay. Twelve samples were subjected to ATIII estimation by the commercially available synthetic chromogenic assay. Twenty age and sex matched controls were also analysed to find out the reference value for the techniques. Low AT III levels, if present, were correlated with other markers of DIC, viz FDP and D-dimer assays. There was a decrease in the AT III levels in all the three disease categories with a significant difference between the AT III levels of the three disease categories. In DIC, lowest levels were observed which correlated well with FDP and D-dimer levels. There was no significant difference between the average AT III levels measured by both the clotting and synthetic chromogenic assay with the former procedure being relatively inexpensive.

Anticardiolipin antibodies in young Iraqi adults with deep venous thrombosis

To determine the prevalence and clinical significance of anticardiolipin antibodies [ACA] in young Iraqis with Deep venous thrombosis [DVT]. A total of 50 unselected young Iraqi adults [<45 years] with Doppler confirmed DVT were evaluated. The evaluation included full relevant history, Prothrombin Time, Partial Thromboplastin Time, Kaolin Clotting time [KCT], KCT index [to screen for Lupus Anticoagulant [LA] in patients not on oral anticoagulants], and lgG and IgM ACA titres [by ELISA]. The median age of the DVT patients was 32.5 years with a M:F ratio of 1:2.6. The overall prevalence of Antiphopholipid Antibodies [APA] [those with elevated ACA and/or LA] was 16%, while it was 9.5% in the subcategory with single DVT attack. The subcategory of patients with recurrent DVT [8 patients] had significantly higher frequency of APA [OR 9.5] and lgG ACA titres compared to those with a single episode [p=0.01583 and 0.01 respectively]. Higher frequencies of APA were also encountered in the subcategories with history of Pulmonary embolism, Stroke and recurrent fetal loss, compared to those without such histories [OR of 3.2, 6.7 and 7.7 respectively]. The findings of this study are consistent with worldwide reports on prevalence and significance of APA. The high frequency of these antibodies in young Iraqi patients and their association with recurrent thrombotic events, in addition to the bulk of the literature suggesting higher recurrence rates and mortality in those with the antibodies on cessations of therapy, warrants pursuing the policy of evaluating all Iraqi young adults at diagnosis or just prior stopping therapy for APA, and considering long term appropriate anticoagulation in those with the antibodies, to reduce recurrence and mortality

Venous thrombosis: prevalence of prothrombotic defects in north Indian population.

431 patients with thrombosis of different venous system were evaluated for underlying acquired and inherited prothrombotic states. Associated acquired risk factors were observed to be present in 28.7% patients and possible inherited in 32.3%, in the rest, no cause could be identified. Major acquired risk factors included coexistence of liver disease (12.2%), oral contraceptives (4.1%), puerperium (2.5%), malignancy (2.3%) and lupus anticoagulant (2%). Low levels of protein C were detected in 21.1% and of which 11.3% were attributed to acquired factors. Protein S deficiency was found in 19.0% and of these 10.4% cases were associated with acquired risk factors. Antithrombin III (AT III) deficiency was detected in 6.4% of patients, of which 4.8% were secondary to acquired factors. In the rest, deficiency of protein C, protein S and AT III were attributed to inherited factors as no associated acquired risk factor was present. Activated protein C resistance (APC-R) was present in 12.5% cases.

Prevalence of anticardiolipin antibodies in various thrombotic conditions: a hospital-based study.

Thrombosis is one of the leading cause of death, globally, anticardiolipin antibodies (aCL) has been implicated as one of the most common acquired protein defect causing thrombosis. This study was undertaken to evince the incidence of aCL in various thrombotic settings. MATERIAL AND METHODS: Three hundred and two patients were retrospectively screened for the incidence of aCL The sera were screened for aCL IgG using enzyme linked immunosorbent assay. Detail clinical and epidemiological data were obtained from hospital records and clinical examination. RESULTS: Among the 302 patients, 134 (44.37%) were below the age of 40 years (juvenile-onset thrombosis), mean age being 35.3 years. High titres of aCL IgG was seen in 65 (20.77%) patients. Deep vein thrombosis (DVT), seen in 90 (29.8%) was the most common thrombotic condition. Other sites of thrombosis were coronary artery (19.2%), central nervous system territory arteries (17.21%) and peripheral arteries (5.29%); the incidence of aCL IgG in these sites were 13.79%, 25.0% and 18.75% respectively. CONCLUSION: aCL is the most common acquired thrombophilic defect. Epidemiological data of our population is required for evaluating the strategy for further research of thrombosis in this condition.