Trombosis en el recién nacido / Thrombosis in the newborn

La trombosis en recién nacidos (RN) es una patología infrecuente que se asocia principalmente a catéter venoso central. Su presentación clínica puede ser la de un RN asintomático o con sintomatología variable, según la ubicación y tamaño de la trombosis. El diagnóstico generalmente se realiza con ecografía doppler y exámenes específicos según sea la presentación clínica. Con respecto al manejo, actualmente no existe mucha evidencia en RN, pero se suele utilizar trombolíticos/fibrinolíticos extrapolando las investigaciones de adultos. En esta revisión se detalla sobre epidemiología, fisiopatología, factores de riesgo, presentaciones clínicas, diagnóstico y tratamiento. Existe falta de estudios sobre epidemiología nacional y tratamiento en RN, se plantea la necesidad de estos.

Thrombosis in newborns is an infrequent pathology which is mainly associated with a central venous catheter. Its clinical presentation may be that of an asymptomatic newborn or with variable symptoms, depending on the location and size of the thrombosis. The diagnosis is generally made with Doppler ultrasound and specific examinations depending on the clinical presentation. Regarding management, currently there is not much evidence in newborns, but thrombolytics / fibrinolytics are usually used extrapolating from adult investigations. This review details epidemiology, pathophysiology, risk factors, clinical presentations, diagnosis and treatment. There is a lack of studies on national epidemiology and treatment in newborns, the need for these arises.

Incidence of thrombotic events and complications associated to inferior vena cava filters in patients with and without anticoagulation therapy / Incidencia de eventos trombóticos y complicaciones asociadas al uso de filtros de vena cava en pacientes en pacientes con o sin terapia anticoagulante

Abstract Objective: Anticoagulation is the primary management to prevent venous thromboembolism; inferior vena cava filters (IVCFs) provide a mechanical prophylactic alternative when anticoagulation is contraindicated. The aim of this study was to evaluate in IVCF patients, whether the initiation of anticoagulation therapy is associated with decreased rates of recurrent thrombotic events and device-related complications. Methods: This was a retrospective review of patients that underwent insertion of IVCF. Subjects with IVCF were studied in two groups: those initiated on anticoagulation (A) and without anticoagulation (NA). Variables as indications for IVCF, anticoagulation, recurrence of thrombosis, complications, and reinterventions were examined. Results: From April 2007 to March 2014, 54 patients underwent IVCF placement; (61% of females), with mean age of 54 years (standard deviation ± 19). 28 (52%) were initiated on anticoagulation, during a mean follow-up period of 28 months, five experienced recurrent thrombosis and three were on the A group (p=0.5); when comparing patients that developed post-thrombotic syndrome, seven were in the A group and seven in the NA. Two patients with IVC rupture were in the A group (p=0.5), and the only case of IVCF migration occurred in the A group. 11 (20%) patients died from comorbidities nonrelated to the device or procedure (four in the A cohort). Conclusions: Patients with IVCF on anticoagulation have equivalent rates of thrombotic events and device-related complications than those patients NA.

Resumen Objetivo: La anticoagulación es la terapia de elección para la prevención de tromboembolismo venoso; los filtros de vena cava inferior (FVCI) proveen una alternativa mecánica profiláctica cuando la anticoagulación está contraindicada. El objetivo de este estudio fue evaluar si la terapia anticoagulante se asocia con una tasa menor de eventos trombóticos recurrentes y complicaciones relacionadas con el dispositivo. Métodos: Los pacientes fueron categorizados en dos grupos: Aquellos a los que se les inicio anticoagulación (A) y aquellos que no (NA). Variables tales como indicación de la colocación del filtro, anticoagulación, recurrencia de trombosis y complicaciones fueron examinadas. Resultados: De abril de 2007 a marzo 2014, a 54 pacientes se les coloco un filtro (61% fueron mujeres), con una media de edad de 54 años [Desviación estándar (DE) ±19. Veintiocho (52%) fueron iniciados en anticoagulación y durante un seguimiento de 28 meses, 5 pacientes experimentaron recurrencia de trombosis, 3 en el grupo A (p=0.5). Al comparar los pacientes que desarrollaron síndrome posflebítico, 7 pertenecieron al grupo A y 7 al grupo NA. Dos pacientes con ruptura de vena cava pertenecieron al grupo A (p=0.5) y el único caso de migración del dispositivo ocurrió en el grupo A. Once (20%) pacientes fallecieron debido a comorbilidades no relacionadas con el dispositivo o el procedimiento. Conclusión: Pacientes con FVCI en anticoagulación tienen tasas de eventos trombóticos y complicaciones asociadas a los dispositivos equivalentes a aquellos pacientes sin anticoagulación.

Uso de varfarina em pediatria: características clínicas e farmacológicas / Use of warfarin in pediatrics: clinical and pharmacological characteristics

RESUMO Objetivo: Descrever como as crianças respondem à anticoagulação oral com varfarina, verificando a influência da idade, da condição clínica, da via de administração da varfarina e do uso de Nutrição Parenteral Total (NPT), e apresentar a presença de fatores de risco para eventos tromboembólicos (TE). Métodos: Estudo transversal retrospectivo com pacientes ≤18 anos que iniciaram o uso da varfarina em um hospital universitário. Os pacientes foram divididos conforme condição clínica, idade, forma de administração do medicamento e uso de NPT. Foram utilizados os dados dos prontuários dos pacientes, considerando os fatores de risco para TE já descritos na literatura, o tempo e a dose necessária para atingir a primeira Razão Normalizada Internacional (INR) no alvo e eventos adversos nesse período. No período posterior ao alcance de INR, foi verificada a manutenção da anticoagulação, por meio da dose prescrita e dos exames de INR. Resultados: Vinte e nove pacientes foram incluídos no estudo. O principal fator de risco para TE foi o uso de cateter venoso central, em 89,6% dos pacientes. Os pacientes com síndrome do intestino curto e em uso de NPT necessitaram de doses significativamente maiores (p≤0,05) para atingir e manter a INR no alvo. Os pacientes com ≤1 ano levaram mais tempo e necessitaram de uma dose maior para anticoagular e para manter o INR no alvo que os pacientes mais velhos. A mediana de exames de INR abaixo do alvo foi de 48,2% nos grupos estudados. Conclusões: A complexidade da terapia anticoagulante reforça a necessidade da elaboração de protocolos que orientem a prática clínica.

ABSTRACT Objective: To describe how children respond to oral anticoagulation with warfarin, verifying the influence of age, clinical condition, route of administration of warfarin and use of total parenteral nutrition (TPN), as well as to describe risk factors for the occurrence of thrombotic events (TE) in childhood. Methods: A retrospective descriptive study including all patients ≤18 years old for whom warfarin was prescribed in a university hospital. Patients were divided according to clinical condition, age, route of medication administration and use of TPN. Data was collected from the patients' medical records and the analysis considered the risk factors for TE already described in the literature, the time and the dose required in order to reach the first International Normalized Ratio (INR) in the target and the adverse events in this period. After reaching the INR, the maintenance of anticoagulation was verified by the prescribed dose and INR tests. Results: Twenty-nine patients were included in the study. The major risk factor for TE was the use of a central venous catheter in 89.6% of the patients. Patients with short bowel syndrome and total parenteral nutrition required significantly higher doses (p≤0.05) to achieve and maintain the INR in the target. Patients ≤1 year old needed longer periods and required an increased dose of anticoagulation and maintenance than older patients. The mean number of INR examinations below the target was 48.2% in the groups studied. Conclusions: The observed complexity of anticoagulant therapy reinforces the need to develop protocols that guide clinical practice.

Inferior vena cava filters in pulmonary embolism: A historic controversy / Filtros de vena cava inferior en tromboembolia pulmonar: Una controversia histórica

Abstract: Objective: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. Methods: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. Results: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. Conclusion: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.

Resumen: Objetivo: Racionalidad para no utilizar en forma rutinaria filtros de vena cava inferior (FVCI) en pacientes con tromboembolia pulmonar (TEP). Métodos: Analizamos mecanismos de trombosis relacionados con la colocación o retiro de estos dispositivos médicos, incluyendo la importancia del polifosfato inorgánico en la vía de activación de contacto. Analizamos evidencia clínica de estudios aleatorizados controlados en pacientes con y sin cáncer. Mediante tablas de frecuencia estimamos de cada estudio reducción del riesgo absoluto (RRA) y relativo (RRR) y el número necesario a tratar (NNT). Finalmente, examinamos la evolución de nuestros pacientes con TEP llevados a trombolisis con seguimientos a corto y largo plazo. Resultados: FVCI inducen trombosis por diferentes mecanismos: colocación y retiro, adsorción rápida de proteínas y activación de superficie inducida en la vía de activación de contacto. El polifosfato inorgánico es un procoagulante importante para la anticoagulación. Estudios aleatorizados controlados incluyeron 904 pacientes con TEP con y sin cáncer. En términos de RRA, RRR y NNT no existe evidencia para el uso rutinario. En 290 pacientes con TEP probada, importante carga de trombo y disfunción del ventrículo derecho llevados a trombolisis y anticoagulación observamos una evolución favorable en seguimientos a corto y largo plazo. En estos pacientes los FVCI se utilizaron solo en el 5%. Conclusión: Considerando los mecanismos complejos de trombosis relacionados con los FVCI, la evidencia obtenida de los estudios aleatorizados y controlados, así como la RRA, RRR y NNT en pacientes con tromboembolismo venoso con y sin cáncer, no recomendamos el uso rutinario de FVCI.

Trombosis en el recién nacido / Thrombosis in newborn infants

La probabilidad de padecer trombosis es mucho mayor en el período neonatal que en cualquier otra etapa pediátrica. La labilidad del particular sistema hemostático del neonato, sumada a los múltiples factores de riesgo a que está expuesto y la presencia casi constante de catéteres, son responsables de este hecho. Las trombosis venosas son más frecuentes que las arteriales y ocurren principalmente en los miembros, la aurícula derecha y las venas renales. El accidente cerebrovascular puede ser causado por la oclusión del flujo arterial que llega al cerebro o del sistema de drenaje venoso de este. La púrpura fulminans es una patología de altísima gravedad, que debe ser considerada una emergencia médica y se debe a la deficiencia grave de proteína C o, menos frecuentemente, de proteína S o antitrombina. La mayoría de los episodios trombóticos tienen indicación de tratamiento anticoagulante, que se puede realizar con heparina no fraccionada y/o con heparina de bajo peso molecular. La púrpura fulminans requiere terapia de sustitución con proteína C y/o plasma fresco. El tratamiento trombolítico se realiza con activador tisular del plasminógeno y debe quedar reservado solo para aquellas trombosis cuya localización implique compromiso de vida o pérdida de un órgano o de un miembro.

The incidence of thrombosis is higher among newborn infants than in any other stage of pediatric development. This fact is the consequence of labile characteristics of the neonatal hemostatic system, in addition to exposure to multiple risk factors and the wide use of vascular catheters. Venous thromboses, which mainly affect the limbs, the right atrium and renal veins, are more frequently seen than arterial thromboses. A stroke may be caused by the occlusion of the arterial flow entering the brain or by occlusion of its venous drainage system. Purpura fulminans is a very severe condition that should be treated as a medical emergency, and is secondary to severe protein C deficiency or, less frequently, protein S or antithrombin deficiency. Most thrombotic events should be managed with antithrombotic therapy, which is done with unfractionated and/or low molecular weight heparins. Purpura fulminans requires protein C replacement and/or fresh frozen plasma infusion. Thrombolytic therapy is done using tissue plasminogen activator and should only be used for life-, or limb-, or organ-threatening thrombosis.

Atherothrombotic risk factors & premature coronary heart disease in India: A case-control study.

Background & objectives: It was hypothesized that both thrombogenic and atherogenic factors may be responsible for premature coronary heart disease (CHD) in young Indians. A case-control study was performed to determine cardiovascular risk factors in young patients with CHD in India. Methods: Successive consenting patients <55 yr with an acute coronary event or recent diagnosis of CHD were enrolled (cases, n=165). Age- and gender-matched subjects with no clinical evidence of CHD were recruited as controls (n=199). Demographic, anthropometric, clinical, haematological, and biochemical data were obtained in both groups. Univariate and multivariate logistic regression were performed to identify important risk factors. Results: In cases vs. controls mean systolic BP, diastolic BP, platelet counts, LDL cholesterol, non-HDL cholesterol, triglycerides, and fibrinogen were higher and HDL cholesterol lower (P<0.001). The presence of current smoking, low fruit and vegetables intake, high fat intake, hypertension, diabetes, low HDL cholesterol, and high LDL cholesterol, total:HDL ratio, fibrinogen and homocysteine was significantly higher in cases (P<0.05). Multivariate logistic regression analysis (age adjusted odds ratio, 95% confidence intervals) revealed that smoking (19.41, 6.82-55.25), high fat intake (1.66, 1.08-2.56), low fruit and vegetables intake (1.99, 1.11-3.59), hypertension (8.95, 5.42-14.79), high LDL cholesterol [2.49 (1.62-3.84)], low HDL cholesterol (10.32, 6.30-16.91), high triglycerides (3.62, 2.35-5.59) high total:HDL cholesterol (3.87, 2.35-5.59), high fibrinogen (2.87, 1.81-4.55) and high homocysteine (10.54, 3.11-35.78) were significant. Interpretation & conclusions: Our results showed that thrombotic (smoking, low fruit/vegetables intake, fibrinogen, homocysteine) as well as atherosclerotic (hypertension, high fat diet, dyslipidaemia) risk factors were important in premature CHD. Multipronged prevention strategies are needed in young Indian subjects.

Safety and Effectiveness of Central Venous Catheterization in Patients with Cancer: Prospective Observational Study

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catherization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catherization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.

Implante de stents farmacológicos na artéria descendente anterior: indicadores de eventos tardios / Implante de stents farmacológicos en la arteria descendente anterior: indicadores de eventos tardíos / Pharmacological stent deployment in the left anterior descending artery: late event indicators

FUNDAMENTO: A eficácia dos stents farmacológicos em reduzir os índices de eventos cardíacos não é uniforme a todos os subgrupos de lesões ou pacientes. OBJETIVO: Avaliar a evolução clínica tardia dos pacientes submetidos a implante de stents farmacológicos nas lesões ateroscleróticas da artéria descendente anterior e identificar, entre as características clínicas, angiográficas e do ultra-som intravascular, quais as que permitem predizer risco de eventos cardíacos. MÉTODOS: De maio de 2002 a agosto de 2005, foram tratados 205 pacientes com implante de 236 stents farmacológicos guiados pelo ultra-som intravascular. RESULTADOS: Com um acompanhamento médio de 711 dias, a taxa de trombose do stent foi de 0,48 por cento, a mesma observada para infarto agudo do miocárdio ou cirurgia de revascularização. A taxa de revascularização da lesão tratada foi de 7,31 por cento e a taxa global de eventos de 10,24 por cento. Os indicadores de eventos, conforme análise multivariada, foram o implante de mais de um stent na mesma artéria, lesões concêntricas e área mínima intra-stent medida pelo ultra-som intravascular menor que 3,88 mm². CONCLUSÃO: Baseados nos dados obtidos, concluímos que a revascularização da artéria descendente anterior com implante de stents farmacológicos escolhidos e otimizados pelo ultra-som intravascular apresenta baixo índice de eventos tardios. O implante de dois stents farmacológicos para o tratamento das lesões longas foi o principal fator independente para a ocorrência de eventos tardios. A área luminal final maior que 3,88 mm² obtidos nos segmentos de pequenos diâmetros de referência é um indicador independente de evolução livre de eventos.

BACKGROUND: The efficacy of pharmacological stents in decreasing the incidence of cardiac events is not homogeneous for all lesions or patient subgroups. OBJECTIVE: 1) To evaluate the late clinical evolution of patients submitted to pharmacological stent implantation in atherosclerotic lesions of the left anterior descending artery; 2) to identify, among the clinical, angiographic and intravascular ultrasonographic characteristics, the ones predictive of cardiac event risk. METHODS: From May 2002 to August 2005, 205 patients were treated with 236 pharmacological stent implants, guided by the intravascular US (IVUS). RESULTS: After a mean follow-up period of 711 days, the rate of stent thrombosis was 0.48 percent, the same observed for acute myocardial infarction or revascularization surgery. The revascularization rate of the treated lesion was 7.31 percent and the general event rate was 10.24 percent. The event indicators, according to the multivariate analysis were the implant of more than one stent in the same artery, concentric lesions and the minimal intra-stent area measured by IVUS < 3.88 mm². CONCLUSION: Based on the data obtained, we conclude that the revascularization of the left anterior descending artery with pharmacological stent implant, chosen and optimized by IVUS, presents a low incidence of late events. The implant of two pharmacological stents for the treatment of long lesions was the main independent factor for the occurrence of late events. The final luminal area > 3.88 mm² obtained in the small reference-diameter segments is an independent indicator of event-free evolution.

FUNDAMENTO: La eficacia de los stents farmacológicos para reducir los índices de eventos cardiacos no es la misma para todos los subgrupos de lesiones o pacientes. OBJETIVO: Evaluar la evolución clínica tardía de los pacientes sometidos a implante de stents farmacológicos en las lesiones ateroscleróticas de la arteria descendente anterior e identificar, entre las características clínicas, angiográficas y de ultrasonido intravascular, cuales son las que permiten predecir riesgos de eventos cardiacos MÉTODOS: De mayo de 2002 a agosto de 2005, se trataron a 205 pacientes con implante de 236 stents farmacológicos guiados por ultrasonido intravascular. RESULTADOS: Con un seguimiento promedio de 711 días, la tasa de trombosis del stent fue del 0,48 por ciento, la misma que se observó para infarto agudo de miocardio o cirugía de revascularización. La tasa de revascularización de la lesión tratada fue del 7,31 por ciento y la tasa global de eventos fue del 10,24 por ciento. Los indicadores de eventos, conforme análisis multivariada, fueron el implante de más de un stent en la misma arteria, lesiones concéntricas y área mínima intrastent medida por el ultrasonido intravascular menor que 3,88 mm². CONCLUSIÓN: Tomando como base los datos obtenidos con esta investigación, concluimos que la revascularización de la arteria descendente anterior con implante de stents farmacológicos, elegidos y optimizados por el ultrasonido intravascular, presenta un bajo índice de eventos tardíos. El implante de dos stents farmacológicos para el tratamiento de las lesiones largas fue el principal factor independiente para la ocurrencia de eventos tardíos. El área luminal final mayor que 3,88 mm², obtenida en los segmentos de pequeños diámetros de referencia es un indicador independiente de evolución libre de eventos.

Prevalence of Antiphospholipid antibodies in Syrian patients with thrombosis

Antiphospholipid antibodies [aPL] are a heterogeneous family of antibodies associated with thrombosis and other complications. To study the prevalence of aPL in patients with thrombosis at Aleppo University Hospitals, Syria. One hundred and fifty-seven patients with venous and arterial thrombosis and 63 healthy controls were studied. Anticardiolipin antibodies [aCL] and Lupus anticoagulant [LA] were determined. Thirty-four out of 157 [21.7%] patients with thrombosis had some type of aPL. aPL was also found in four healthy subjects [4/63=6.3%]. Eighteen patients [11.5%] were positive for LA, 20 [12.7%] for aCL antibodies and 4 [2.6%] were positive for more than one aPL. Patients without risk factors for thrombosis and having positive aPL were 23/34 [67.7%]. Fourteen out of 78 [17.9%] patients with arterial thrombosis, and 20/79 [25.3%] with venous thrombosis were positive for at least one aPL. Our study showed a significant prevalence of aPL in patients with thrombosis. It seems that aPL is a risk factor for venous and arterial thrombosis, especially in patients with no conventional risk factors

Stent thrombosis.

Technology of drug-eluting stent (DES) implantation is relatively young. DES have remarkably reduced the incidence of stent-restenosis (SRS) and the need for target vessel revascularization (TVR). Yet it has added a small but significant risk of late and very late stent thrombosis (ST). The incidence of ST varies between 0.3-2.8% with a mean of 1.3%. ST occurs both with bare-metal stents (BMS) and drug-eluting stents (DES) but the time course differs with an excess of ST in the first six months of implantation with BMS while the number of ST is more with DES after 6 months of implantation. Despite this difference, there are no overall differences between BMS and DES regarding the end points of death or myocardial infarction (MI) on long term (3-5 years) follow-up. Endothelial dysfunction and incomplete neointimal coverage of stent strut remain the basic underlying mechanisms responsible for ST in DES. Stent thrombosis, though infrequent, is a dreadful condition. Over 30% may die suddenly. 60% develop massive MI with cardiogenic shock, poor LVEF and serious arrhythmias. The beneficial effects of primary percutaneous intervention (PCI) for ST are not spectacular, and TIMI flow grade III, is achieved in less than 80% cases, while distal embolization and residual dissection of coronary artery are frequently encountered. Proper selection and optimization of stent with prolonged dual antiplatelet therapy may prevent the undesirable stent thrombosis after DES implantation.

Trombofilia primaria en México: parte VI: falta de asociación estadística entre las condiciones trombofílicas heredadas / Primary thrombophilia in México: VI: lack of statistical association among the inherited thrombophilic conditions

Objetivo: En un periodo de 70 meses estudiamos de manera prospectiva a 100 pacientes mestizos mexicanos con algún marcador clínico de trombofilia: a) Trombosis antes de los 40 años, b) Historia familiar de trombosis, c) Trombosis recurrente sin la presencia de un factor precipitante aparente, d) Trombosis en sitios anatómicos inusuales, o e) Resistencia a la terapia antitrombótica convencional. Métodos: En estos pacientes, investigamos el síndrome de las plaquetas pegajosas, la mutación 677 C —>T del gen de la 5,10-metilentetrahidrofolato reductasa (MTHFR), el fenotipo de resistencia a la proteína C activada (RPCa), la presencia de anticuerpos antifosfolípidos, las mutaciones Leiden, Cambridge, Liverpool y Hong Kong del gen del factor V, el haplotipo HR2 del mismo gen del factor V, el polimorfismo G20210A de la región 3´-no traducida del gen de la protrombina y las deficiencias de proteínas C y S y de antitrombina III. Resultados: En el 94 % de los casos encontramos por lo menos alguna alteración; de estos casos con alteración, la mayoría (81 %) tuvo dos o más condiciones trombofílicas asociadas. El análisis multivariado de todas estas variables sólo mostró asociación estadística entre la mutación tipo Leiden del gen del factor V y el fenotipo de RPCa (r = .495; p < 0.001). Conclusiones: Se concluye que, realizando este grupo de estudios, es posible identificar alguna alteración trombofílica en la mayoría de los pacientes mestizos mexicanos con algún marcador clínico de trombofilia y que las alteraciones no se asocian entre sí.

OBJECTIVE: Over a 70-month period, 100 consecutive Mexican mestizo individuals with a clinical marker associated with a primary hypercoagulable state were studied. METHODS: We prospectively assessed: the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C-->T mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene. RESULTS: Of the 100 consecutive patients prospectively accrued in the study, only 29% were males. In only 6 individuals could we not record any abnormality, whereas in most individuals (81%), two to five co-existing abnormalities were identified. In a multivariate analysis of the association of all these assesments, the only significant association was found between the factor V Leiden mutation and the aPCR phenotype (r = .495; p < 0.001). CONCLUSIONS: These results confirm previous observations on thrombophilia in Mexico underlining that it is a multifactorial disease. They also suggest that the abnormalities detected are not associated to each other.

Factor V Leiden y mutación de la protrombina G20210A en pacientes con trombosis venosa y arterial / Factor V Leiden and prothrombin G20210A among Chilean patients with venous and arterial thrombosis

Background: Factor V Leiden and G20210A mutation of prothrombin gene are two important genetic polymorphisms associated with an increased risk for thrombosis. Aim: To establish the prevalence of factor V Leiden and prothrombin G20210A mutation in the Chilean population and their association to venous and arterial thromboembolism. Material and methods: A case-control study was conducted where 149 patients with thrombosis (87 with arterial and 62 with venous thrombosis) confirmed by CAT-scan, electrocardiogram and cardiac enzymes or Doppler depending on the case, and 160 healthy blood donors were genetically analyzed for the presence of both polymorphisms. Results: Factor V Leiden mutation was found in 5.4% of patients and in 1.3% of healthy controls (p=0.04). Heterozygosity for G20210A prothrombin mutation was found in 5.4% of patients and in 2.5% of the control group (p=NS). When arterial and venous thrombosis were considered as separate entities, 4.6% of patients with arterial thrombosis and 6.5% with venous thrombosis presented factor V Leiden (p=NS). Likewise, 8.1% of patients with venous thrombosis and 3.5% of patients with arterial thrombosis had G20210A prothrombin mutation (p=NS). Conclusions: In non selected consecutive Chilean patients with arterial and venous thrombosis the frequency of factor V Leiden and prothrombin G20210A is less than we could expect from their prevalence in the general population.

Perioperative Anticoagulation in Patients with Mechanical Heart Valves Undergoing Elective Surgery: Results of a Survey Conducted among Korean Physicians

The optimal perioperative anticoagulation management in patients on warfarin therapy is poorly defined due to the lack of randomized trials. Because guidelines are heterogeneous, it was hypothesized that "treatment strategies are not uniform in clinical practice". Between February 2003 and May 2003, a questionnaire with 4 different clinical scenarios was distributed to physicians by e-mail, or direct contact was made by a survey monitor. Two scenarios described the cases of patients with a mechanical heart valve (MHV) in the mitral position, with additional risk factors for a systemic embolism; one undergoing major (scenario 1) and the other minor surgery (scenario 3). Two scenarios described patients with an aortic MHV; one undergoing major (scenario 2) and the other minor (scenario 4) surgery. Different preoperative and postoperative management options were offered. The treatment options for all scenarios were the same. Of the 90 questionnaires distributed, 52 (57.8%) were returned. Hospitalization for full-dose intravenous unfractionated heparin (IV UH) was the most commonly selected strategy in the preoperative phase for scenarios 1 (59%), 2 (42%) and 3 (44%). In scenario 4, 34% chose IV UH. Outpatient, full- dose, subcutaneous UH or low-molecular-weight heparin (LMWH) was the most selected option in the postoperative phase for all scenarios, with the exception of number 4 (52.9% in scenario 1, 34% in scenario 2, 32%, in scenario 3 and 28% in scenario 4). Even among expert clinicians, the management of perioperative anticoagulation is heterogeneous. In particular, the definition of risk categories and the optimal intensity of antithrombotic drugs need to be defined by well-designed prospective studies.

Incidência de trombo intracardíaco e de tromboembolismo nos três primeiros meses após o implante de bioprótese valvar / Incidence of intracardiac thrombus and thromboembolism in the first three months after bioprosthetic valve implantation

OBJETIVO: Avaliar a incidência de trombo intracardíaco e de tromboembolismo nos três primeiros meses após a troca valvar por bioprótese e identificar fatores de risco para a formação de trombo. MÉTODO:Incluídos 184 pacientes, entre 15 e 75 anos de idade, submetidos a implante de bioprótese e realizados ecocardiogramas transtorácico e transesofágico (ETE) na fase hospitalar, média 8,4±3 dias, e três meses após, média 97,4±21,7 dias. RESULTADOS: Incidência de trombo foi significativamente mais elevada nos pacientes com prótese em posição mitral ou mitroaórtica (21,0 por cento) do que em posição aórtica (2,8 por cento), p<0,001. A análise de regressão logística multivariada identificou a prótese em posição mitral ou mitroaórtica como a única variável independente para a formação de trombo. No seguimento de três meses o ETE evidenciou trombo em 35 (20,7 por cento) dos 169 pacientes com evolução ecocardiográfica, 31,7 por cento nos mitrais e 3,1 por cento nos aórticos, p<0,001. No 3º mês a análise de regressão logística multivariada também identificou a prótese em posição mitral ou mitroaórtica como a única variável independente para a formação de trombo. Durante os três meses de seguimento, três (1,6 por cento) pacientes faleceram e oito (4,3 por cento) apresentaram fenômeno embólico, todos para território cerebral. CONCLUSÃO: A incidência de trombo nos três primeiros meses, após o implante da bioprótese foi 14,1 por cento nos 10 primeiros dias e 20,7 por cento em três meses; a prótese em posição mitral ou mitroaórtica foi identificada como fator de risco para a formação de trombo; a incidência de fenômenos embólicos diagnosticados clinicamente foi inferior à proporção de trombo atrial documentado pelo ecocardiograma.

Anti-Heparin-Platelet Factor 4 Antibody is a Risk Factor for Vascular Access Obstruction in Patients Undergoing Hemodialysis

Since heparin is an anticoagulant commonly used in hemodialysis and the patients on hemodialysis are repeatedly exposed to heparin, heparin may be the cause of the development of heparin-dependent antibodies and thrombotic complications in patients on hemodialysis. The purpose of this study was to determine the prevalence and the clinical significance of the antibodies against heparin-platelet factor 4 complexes as determined by enzyme immunoassay in patients on maintenance hemodialysis. The prevalence of anti-heparin-platelet factor 4 antibodies was higher in hemodialysis patients than in normal subjects (8.8 vs 0.0%, p<0.05). The number of past episodes of vascular access obstruction per year was significantly higher in the anti-heparin-platelet factor 4 antibody positive group than antibody negative group. Anti-heparin-platelet factor 4 antibody positive patients experienced more frequent vascular access obstructions than control subjects. In conclusion, anti-heparin-platelet factor 4 antibody might be a risk factor for vascular access obstructions in patients with end-stage renal disease on maintenance hemodialysis.

Coronary stent thrombosis: time course and clinical outcome.

The current clinical practice of stent implantation has changed over the last few years. We analysed the incidence and time course of stent thrombosis in patients undergoing successful coronary angioplasty and stenting over the last three years. All the patients were treated with aspirin and ticlopidine. A total of 13 patients experienced stent thrombosis. The mean age was 52+/-12 years; 12 were smokers and 10 had a recent history of myocardial infarction. None of these patients had received abciximab. The median time from stent implantation to stent thrombosis was 10 hours, with all the stent occlusions occurring within 18 hours of stent implantation procedure. All the patients underwent a repeat intervention at a median time of 30 minutes after the clinical suspicion of stent occlusion. On follow-up of 1 to 24 months, three patients developed reocclusion. In the present era of coronary angioplasty and stenting, when interventional procedures are not pre-planned and patients are treated with aspirin and ticlopidine or clopidogrel at the time of stent implantation, the incidence of stent thrombosis is low; it is seen mainly in patients with recent myocardial infarction, majority of them being smokers, and occurs within 18 hours in all the patients.

Prothrombotic factors in nephrotic syndrome.

Nephrotic syndrome is a hypercoagulable state with variable prevalence of clinical thrombosis. The role of platelet aggregation, fibrinogen and antithrombin III and protein S levels in the pathogenesis of hypercoagulable state in these patients is controversial. Since no study on Indians is available, the clinical and laboratory profile of 22 patients of nephrotic syndrome (age 18-35 years with an MF ratio of 4:3), have been studied. The coagulation profile revealed a prolonged APTT in 12 patients (54.5%), and a prolonged TT in four (18.1%). In the rest APTT and TT were normal. PT was raised in two patients. Fibrinogen, an acute phase reactant was raised in five patients (22.7%). Antithrombin III levels were reduced in 19 patients (86.4%), normal in one and raised in two patients. Free Protein S levels were high in 12(54.5%), normal in seven and decreased in three patients. Platelet aggregation with adrenaline and adenosine diphosphate was raised in 6 patients. Ultrasonographically detected deep vein thrombosis was seen in one patient only (4.5%) who had ATIII levels of 48%. This low incidence can be explained by elevated protein S levels which was found to be raised in 12(54.5%) cases, protein S being an anticoagulant factor. This low level of clinical thrombosis in Indian patients of nephrotic syndrome may be an ethnic variable factor. It is thus concluded that although patients with nephrotic syndrome have a hypercoagulable state, clinical thrombosis is rarely seen in Indian patients with nephrotic syndrome.