Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.

Lack of association between the prothrombin rs1799963 polymorphism and juvenile myoclonic epilepsy / Ausência de associação entre o polimorfismo G20210A (rs1799963) da protrombina e epilepsia mioclônica juvenil

Juvenile myoclonic epilepsy (JME) accounts for 26% of generalized idiopathic epileptic syndromes. The highest levels of thrombin activity are closely involved in the development of neurological diseases, including epilepsy. The prothrombin c.20210G>A (rs1799963) variation, which alters prothrombin mRNA stability, is associated with high plasma prothrombin levels. Objective : The present study was designed to investigate whether the SNP rs1799963 is a risk factor for JME in the northeastern Brazilian population. Results : The polymorphism was genotyped in 207 controls and 123 patients using polymerase chain reaction-restriction fragment length polymorphism method. No significant differences were observed in the genotype and allele frequencies of this polymorphism between cases and controls. Conclusion : These results present no evidence for an association of rs1799963 with JME. Further studies including other types of epilepsy are required to investigate the involvement of prothrombin gene in the genetic susceptibility to chronic seizure. .

Epilepsia mioclônica juvenil (EMJ) representa 26% das síndromes epilépticas idiopáticas generalizadas. Níveis elevados de atividade da trombina estão intimamente envolvidos no desenvolvimento de distúrbios neurológicos, incluindo epilepsia. A variante c.20210G>A (rs1799963) do gene de protrombina, que altera a estabilidade do RNAm, está associada com altos níveis de protrombina no plasma. Objetivo: Investigar se o SNP rs1799963 é um fator de risco para EMJ em uma amostra da população do nordeste brasileiro. Resultados : O polimorfismo foi genotipado em 123 pacientes e 207 controles usando a reação de polimerase em cadeia com restrição de polimorfismo. Não observamos diferença significativa nas frequências alélicas e genotípicas deste polimorfismo, entre as populações de pacientes e controle. Conclusão : Estes resultados não demonstram evidências para uma associação do polimorfismo rs1799963 com EMJ. Estudos posteriores, incluindo outros tipos de epilepsia, são necessários para investigar o envolvimento do gene protrombina na susceptibilidade genética a crises crônicas. .

The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma

BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.

The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma

BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.

Development and Application of a Self-management Program based on Prothrombin INR Monitoring for Patients with Cardiac Valve Replacement

PURPOSE: The purpose of this study was to develop and evaluate a self-management program based on INR monitoring for patients with cardiac valve replacement. METHODS: This program was comprised of five weekly sessions based on Sousa's Enhance-Behavior Performance Model. The first session included individual teaching, and the other four sessions included Prothrombin Time International Normalized Ratios (PT INR) self-monitoring, telephone counseling and self-management checklist recording. Participants were patients who had cardiac valve replacement. They were randomly assigned to the experimental or control group. Sixteen in the experimental group participated in the self-management program and seventeen in the control group participated in general care. Self-management knowledge, self-efficacy, self-management behavior and PT INR were measured as dependent variables. Data were analyzed using Mann Whitney U-test, t-test and ANCOVA. RESULTS: The experimental group showed significantly higher post-test scores in self-management knowledge (t=5.86, p <.001), self-efficacy (F=18.32, p <.001), and self-management behavior (t=3.44, p =.002) compared to the control group. Also, the experimental group showed significantly higher frequency in maintaining the treatment range of PT INR compared to the control group (chi2=4.80, p =.028). CONCLUSION: The results of the research on the self-management program based on PT INR monitoring showed that it is effective in improving self-management knowledge, self-efficacy, and self-management behavior as well as maintaining treatment range of PT INR of patients with cardiac valve replacement.

Alteraciones de la hemostasia en el síndrome drepanocítico / Hemostasis alterations in sickle cell syndrome

El síndrome drepanocítico (SD) comprende un grupo de anemias hemolíticas hereditarias de tipo multisistémico asociadas a la hemoglobina S. Los pacientes que padecen este síndrome tienen un mayor riesgo, en comparación con individuos sanos, de presentar accidentes cerebrovasculares, hipertensión pulmonar, necrosis avascular de articulaciones, síndrome torácico agudo y complicaciones durante el embarazo, asociados a un estado de hipercoagulabilidad inducido por alteraciones en los diferentes componentes de la hemostasia, que incluyen la activación del endotelio y de los sistemas plaquetario, de la coagulación y de la fibrinólisis. Esta revisión resume las alteraciones en la hemostasia reportadas en los pacientes con SD, en los cuales se ha demostrado: mayor interacción de células endoteliales con leucocitos, hematíes y plaquetas; aumento de la expresión de proteínas de adhesión, como el factor von Willebrand y sus multímeros de alto peso molecular; aumento de la adhesión y la agregación plaquetaria y de la expresión de proteínas en sus membranas. En el sistema de coagulación se ha detectado aumento en la expresión del factor tisular (FT) en micropartículas derivadas de diferentes células, aumento de marcadores de activación de este sistema, entre estos los fragmentos 1.2 de la protrombina y los complejos trombina-antitrombina y una disminución de las proteínas C y S que actúan como anti-coagulantes. Adicionalmente, se han encontrado aumentados los marcadores de activación del sistema fibrinolítico como los dímeros D y los complejos plasmina/antiplasmina. Todas estas manifestaciones favorecen la aparición de complicaciones trombóticas, implicadas en el deterioro de la calidad de vida de los pacientes. Se recomienda implementar en el diagnóstico y seguimiento de esta enfermedad, la determinación de variables del sistema hemostático, con el fin de identificar alteraciones en etapas tempranas y aplicar terapias que puedan prevenir complicaciones trombóticas.

Sickle cell syndrome (SCS) includes a group of congenital hemolytic anemias associated to the presence of hemoglobin S, which is characterized by acute pain episodes and progressive damage of different organs. Some patients with sickle cell syndrome have shown, when compared with healthy individuals, an increased risk of presenting stroke, pulmonary hypertension, avascular necrosis of joints, acute chest syndrome and pregnancy complications, associated to a hypercoagulable state induced by alterations in different components of hemostasis, such as changes that include activation of the endothelium, platelet activity, coagulation and fibrinolytic systems. This paper compiles hemostasis disorders, associated with thrombotic manifestations, reported until now in sickle cell syndrom. These patients have an increase in activation markers of the coagulation system, such as prothrombin fragment 1.2, thrombin-antithrombin complex, etc., depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system and increased tissue factor expression. Similarly, abnormal expression of glycoproteins and increased adhesion and platelet aggregation have been reported. All these alterations produce a hypercoagulable state, which induces, among other things, the appearance of thrombotic complications. In view of the importance of controlling the different complications that can occur in patients with sickle cell syndrome, we recommend the implementation, in diagnosis and monitoring studies, of the evaluation of the different components of the hemostatic system, identifying alterations at an early stage and applying effective treatments to prevent thrombotic complications.

Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

BACKGROUND/AIMS: The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS: Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 +/- 1.3 ng/mL (mean +/- SD). RESULTS: The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS: Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.

Thrombophilic mutations in blood donors in Duhok-Iraq

Thrombophilia is a mulitfactorial disease due to the interplay between acquired and inherited factors. Factor V Leiden [G1691A], Prothrombin [G20210A] and MTHFR [C677T] are among the important inherited causes. The prevalence of these three thrombophilic mutations has not been addressed collectively in Iraqis, including the population of Duhok. Determine the prevalence of thrombophilic mutations among healthy blood donors form Duhok. One hundred and fifty random healthy blood donors from the regional blood bank in Duhok-Iraq were investigated using multiplex PCR and reverse hybridization to oligonucleotide specific probes to detect Factor V leiden and MTHFR C677T mutations. While the first hundred donors were also screened using the same technology for Prothrombin G20210A mutation. Factor V Leiden and Prothrombin G20210A carrier states were found in 1.25% and 3% of the individuals screened for them, respectively. The MTHFR C677T homozygous and heterozygous states were confirmed in 8 and 44% respectively. This study demonstrated that while the prevalence of Prothrombin and MTHFR mutations were rather consistent with pattern seen in surrounding countries in the Mediterranean region, Factor V Leiden prevalence was the least ever reported from any other population in the region. The latter finding suggests that the contribution of Factor V leiden to thrombotic states in Northern Iraq may not be as significant as it is in other countries in the region

Alteraciones hepáticas en la Leishmaniasis Visceral (Kalazar) en niños: revisión sistemática de la literatura / Liver injury in visceral Leishmaniasis in Children: systematic review

La Leishmaniasis Visceral o Kalazar es una infección parasitaria causada por subespecies del género Leishmania donovani y transmitida por insectos flebotomíneos. Puede evolucionar con compromiso hepático caracterizado por citólisis severa, colestasis, hipertensión portal, hepatomegalia persistente y fibrosis hepática. Estos tipos de presentaciones dificultan el diagnóstico y agravan el pronostico. Se admite que la extensión y frecuencia de este compromiso hepático han sido poco evaluados. Objetivo: Sistematizar las alteraciones hepáticas de Kalazar en la infancia descritas en relatos de casos publicados. Metodología: revisión sistemática de la literatura utilizando las bases de datos LILACS, MEDLINE y EMBASE. Se incluyeron artículos en portugués, español, inglés y francés. Se siguieron los procedimientos de revisión sistemática recomendados por el NHS Centre for Reviews and Dissemination, University of Cork. La clasificación de los artículos (relatos de casos) se basó en la cantidad de información de cada relato de caso en relación a las variables previamente sistematizadas en este estudio. Resultados: 11 (un 55%) artículos fueron incluidos abarcando 28 relatos de casos. La albúmina sérica y el tiempo de protrombina mostraron una asociación con la evolución de la enfermedad: (p = 0,05). Conclusiones: el compromiso epático, incluso grave, puede ocurrir al inicio de la enfermedad. El Kalazar debe ser considerado en el diagnóstico diferencial de hepatitis asociadas a fiebre prolongada, así como en síndromes colestásicos en la infancia en áreas endémicas para la enfermedad.

Visceral Leisshimaniosis or Kalazar is a parasitic infection caused by Leishimania Donovani subspecies. It is transmitted by phlebotomineos and may lead to liver and spleen enlargements as well as immunological impairment. Sometimes it is described liver injury simulating acute or chronic viral hepatitis and even portal hypertension. The liver injury makes difficult the diffencial diagnosis of Kalazar and other liver diseases in endemic regions. Objective: To define and clarify the liver injury spectrum described in published cases reports. Methods: Systematic revision of published data on Kalazar and liver injury, using the following databank: LILACS, MEDLINE and EMBASE. Only paper published in French, English, Portuguese and Spanish were taken into consideration. The procedures for systematic review recommended by the NHS Centre for Reviews and Dissemination, University of Cork, were adopted. The paper quality classification was based on the number of reported variables previously defined in our study. Results: Only 11/ 28 (55%) publications were includedin our analysis because they filled the minimal required data. Acute and chronic liver disease were well documented in these articles. Serum albumin and prothombine time were associated with severity of liver disease (P< .05). Conclusion: “Liver involvement, even when it is severe, may occur at tha begining of the disease. Kalazar should be considered as a differential diagnosis of cholestasis, acute and chronic liver injury, as well as portal hypertension in children.

[Evaluation of coagulation factors II,VII and XIII in patients with atherosclerosis]

Atherosclerosis is a common cardiovasclur disease and particularly in industrial societies, is the first cause of mortality. Since many factors and some molecular changes [like enzymes, lipids, lipoproteins, free radicals, peroxidation, of lipids and coagulation factors] have have a great influence on development of atherosclerosis, considering these factors is important in management of the mentioned disease. Since changes in coagulation factors are effective as well, this investigation was done to obtain more information about this concept, which may help us in identification, treatment and prevention. This investigation was carreid out in cardiovascular ward of Taleghani hospital on 200 cases [94 males and 106 females] age between 35 and 70 years old, without the history of tromboembolic disease, OCP consumption, cancer and diabetus mellitus. We obtained 6cc of venous blood from each participant and in heparinized it in a test tube. After serum removal, the value of coagulation factors [II, VII and XIII] was measured by radioimmunoassay method. According to our results, among females with mean age of 56.76 years old and mean weight of 68.91 Kg, the mean values of plasma coagulation factors [II, VII and XII] were 99.2, 136.9 and 109.7 Iu/dl, respectively. In male group who had the mean age of 55.2 years old and mean weight of 72.9 Kg, the mentioned values were as 101.8, 1040.3 and 110.6 Iu/dl, respectively. Based on above results, we may say that coagulation factors II, VII and XII, have no specific relationship with atherosclerosis and the levels of these factors do not change in atherosclerotic patients. In several previous reports, there have been a debateful controversy about the increase or decrease of the levels of these factore. However, some have reported no considerable changes. Nevertheless, in some cases, variation in the levels of these factors has been related to the polymorphism, the phenomenon which may affect irranian people, as well

Trombose venosa profunda e câncer: análise das mutações em fatores trombofílicos hereditários / Prevalence of factor V Leiden, FII G2002100 A, FXIII Val34Leu and MTHFR C6777T polymorfisms in cancer patients with or without venous trombosis

Trombose venosa é uma complicação comum em pacientes com neoplasias. Estudou-se a prevalência das mutações do FV, FII, FXIII e MTHFr em 211 pacientes oncológicos, 64 com tromboembolismo venoso. Detectou-se a prevalência do fator V Leiden em 1.5 por cento no grupo com trombose e 2.7 por cento no grupo sem trombose (O.R.= 0.586, I.C.= 0.064-5.352); mutação da protrombina em 1.5 por cento versus 1.3 por cento (O. R.= 1.169, I. C. = 0.104-13.135); mutação do fator XIII em 29.6 por cento versus 28.5 por cento (O. R. =1.056, I. C. =0.554-2.011) e mutação na MTHFr em 53.1 por cento versus 60.5 por cento (O. R. = 0.764, I. C. = / Thrombosis is a common complication in patients with cancer. We prospectivelly investigated the prevalence of FVL, FII, FXIII and MTHFr mutations in 211 cancer patients, 64 presenting VTE. We detected a prevalence of FVL in 1.5 per cent (1 of 64) in the thrombosis group and 2.7 per cent (4 of 147) in non DVT group(O.R.= 0.586, C.I.= 0.064-5.352); prothrombin mutation in 1.5 per cent versus 1.3per cent(O.R.=1.169, C.I.= 0.104-13.135); FXIII mutations in 29.6 per cent versus 28.5 per cent (O.R.=1.056, C.I.=0.554-2.011) and MTHF mutations in 53.1 per cent versus 60.5 per cent (O.R.=0.764, C.I.=0.421-1.386)...

Utilidad del fragmento 1 + 2 de protrombina y del dímero de fibrina en la detección de hipercoagulabilidad en pacientes obstétricos con factores de riesgo de trombosis / Usefulness of 1 + 2 prothrombin fragment and of dimer of fibrin in detecting hyporcoagulability in obstetricial patients with thrombosis risk

La cuantificación del fragmento 1+2 de protrombina se hizo por método inmunoenzimático en 75 mujeres (55 embarazas y 20 post-cesárea) y el dímero D por determinación semicuantitativa mediante aglutinación en placa en 97 casos (77 embarazadas y 20 post-cesárea). El fragmento 1+2 se encontró significativamente elevado en el 85 por ciento de los casos, sin embargo no mostró tener utilidad predictiva de enfermedad tromboembólica. La cuantificación del dímero D no fue detectada en 40 casos, en 33 fluctuó entre 500 y 1000 ng/ml y en los 24 restantes fue superior a los 2000 ng/ml. Valores mayores a 1000 ng/ml fueron observados en el 78 por ciento de las que tenían antecedentes de enfermedad tromboembólica, en las de cesárea 60 por ciento, en el 37 por ciento de las hipertensas y en 23 por ciento de las diabéticas. El dímero D que en el 59 por ciento de las embarazadas y puérperas registró valores superiores a 500 ng/ml tiene valor predictivo, ya que en 24 casos que cursaban con más de 2000 ng/ml, el 25 por ciento presentaron ETE y/o anormalidades de la coagulación sugestivos de actividad trombótica. Estos hallazgos no fueron observados en la 73 mujeres evaluadas que tuvieron dD negativo o < de 1000 ng/ml

Marcadores de generacion de trombina en insuficiencia renal de niños con sindrome uremico hemolitico epidemico / Markers of thrombin generation in kidney failure of children with epidemic hemolytic uremic syndrome

Se presentan aquí los niveles de los marcadores tempranos de activación de la coagulación y del TNF-alpha en 12 niños con la forma epidémica del síndrome urémico hemolítico, de 16 meses de edad, (12-18) (mediana y rango) Todos los pacientes se recuperaron de las enfermedad dentro de las 2 a 4 semanas de evolución. Se tomaron cuatro muestras de sangre: al ingreso al hospital, luego en la primera y segunda semana y en la remisión. Las determinaciones del F1+2 TAT y TNF-alpha se realizaron por técnicas de ELISA comerciales, mientras que el factor von Willebrand se determinó por el método de Laurell. Los valores de F1+2 y del TAT al ingreso fueron 7.8 nM (3.7-12.3) y 22.7 ng/ml (8-76) respectivamente. Además, se encontró correlación significativa entre los niveles de F1+2 vs creatinina sérica, r:0.47 p < 0.001; F1+2 vs úrea sérica, r:0.66 p < 0.001; TAT vs creatinina sérica, r:0.77 p < 0.001; TAT vs urea , r:0.59 p <0.001. La mediana del FvW al ingreso en 11/12 niños fue de 260 por ciento (170-420). Los niveles del FvW se correlacionaron con los del F1+2; r:0.77 p < 0.001 y con los del TAT, r:0.41 p < 0.01. Los valores de estos marcadores séricos tendieron a normalizarse con la mejoría de la enfermedad. Se encontró una correlación negativa entre el recuento plaquetario y los niveles del F1+2, r:-0.64 p<0.001. Los niveles de TNF-alpha estuvieron aumentados en 5 niños, 22.2 pg/ml (17.2-53.7). Los resultados sugieren que estas anormalidades pueden ser atribuidas a un estímulo común sobre células endoteliales.

Splenectomy associated with ligature of the left gastric vein in children with surgical schistosomiasis: analysis of the hepatic functional reserve

Foram submetidas 40 crianças, portadoras de esquistosomíase mansônica hepatoesplenica e sangramento de varizes esofágicas, à esplenectomia e ligadura da veia gástrica esquerda. Foram acompanhadas durante 48 meses de pós-operatório, determinando-se a reserva funcional hepática durane esse período. Antes do tratamento cirúrgico, 13 crianças foram classificadas como grau A de Child's e 27 como grau B. A concentraçäo média da albumina sérica era 3.16g/dl mais ou menos 0.62g/dl. Apenas em 1 paciente a concentraçäo de bilirubina sérica era pouco maior do que 2 mg/dl. Após a intervençäo operatória, 15 pacientes foram diagnosticados como grau A de Child's e 25 como grau B. A concentraçäo média de bilirrubina sérica foi de 3.25g/dl mais ou menos 0.50g/dl. Um paciente apresentava ainda na evoluçäo pós-operatória concentraçäo de bilirrubina sérica maior que 2mg/dl mais ou menos 0.050g/dl. Um paciente apresentava ainda na evoluçäo pós-operatória concentraçäo de bilirrubina sérica maior que 2mb/dl. Houve melhora significante após operaçäo dos níveis de protrombina plasmática. Conclui-se que näo houve deterioraçäo da reserva funcional hepática nos pacientes operados

Effect of different oral anticoagulant intensities on prothrombin fragment 1 + 2 in Thai patients with mechanical heart valve prostheses.

The minimal intensity of oral anticoagulant required for antithrombotic protection in patients with a mechanical heart valve is still debatable, and that of the Westerner may not be directly applied to Thai patients. Our preliminary clinical review suggested that International Normalized Ratio (INR) 2-3 might be enough but it needs further supporting evidence. Therefore, we studied the effect of different anticoagulant intensities, expressed as INR, on the in vivo coagulation activation by measuring prothrombin fragment 1 + 2 (F1 + 2) in 116 patients with mechanical heart valve replacements. The patients had received warfarin for not less than one month with different intensities. The mean +/- S.D. of F1 + 2 level in 30 normal controls was 0.7 +/- 0.17 nmol/L. After excluding two outliers, the maximum linear correlation between INR and F1 + 2 was -0.658 (p < 0.001) when only patients whose intensities were lower than INR3 were taken into account. Adding more data from the patients having higher intensities decreased the correlation coefficient. The patients were subsequently classified by INR values in the range INR 1.1-1.9, 2-3 and 3.1-4.2. The F1 + 2 in each group was 0.6 +/- 0.30, 0.28 +/- 0.13 and 0.24 +/- 0.13 nmol/L respectively. The F1 + 2 in the first group did not differ from normal (p = 0.119) but was higher than the others (p = 0.000). The latter two groups had no difference between them (p = 0.112). Hence, from the laboratory point of view, we did not see additional benefit in the reduction of thrombin activation by the anticoagulant intensities higher than the range INR 2-3. The evidence supported that this therapeutic range might be enough for Thai patients with mechanical heart valves.

Effect of oral water soluble vitamin K on PIVKA-II levels in newborns.

Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost, pain, anxiety to parents and risk of transmission of infection. Oral route is a better alternative. Oral absorption of vitamin K has been shown to be equally good using special oral preparations. However, this preparation is not available in India. A prospective study was carried out on 51 full term, healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K (menadione sodium bisulphite) could be as effective. Fourteen babies received 1 mg vitamin K intramuscularly, 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth. PIVKA-II levels were measured in cord blood and at 72-78 hours of age in all babies as a marker of vitamin K deficiency. The overall PIVKA-II prevalence in cord blood was 64.7%. At 72-78 hours, PIVKA-II was present in 50% of babies in IM group, 58.3% of babies in oral group and in 76.9% of babies in 'no vitamin K' group (p > 0.05). The PIVKA-II levels decreased or did not change at 72-78 hours in 91.6% of babies in oral group versus 92.8% of babies in IM group (p > 0.05). On the other hand, PIVKA-II levels increased in 30.7% of babies who did not receive vitamin K as against in 7.8% of babies receiving vitamin K in either form (p < 0.05). Hence, vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K (menadione sodium bisulphite) given orally to term healthy babies is effective in preventing vitamin K deficiency state.

Colchicina na doença hepática crônica de etiologia alcoólica. Estudo duplo-cego, randomizado, de seus efeitos sobre os níveis séricos das proteínas plasmáticas e evoluçäo clínica dos pacientes / Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on the serum levels of plasma proteins and clinical evolution of the patients

Pacientes portadores de hepatopatia crônica de etiologia alcoólica, quando tratados com colchicina durante período de 12 meses, apresentaram índices de recuperaçäo dos níveis plasmáticos de albumina e protrombina significantemente superiores aos de pacientes fazendo uso de placebo. Entretanto, nenhuma diferença estatística pôde ser observada entre os dois grupos quanto à taxa de mortalidade e de admissäo hospitalar dos pacientes, no período estudado. OBJETIVO. Analisar a evoluçäo clínica e os níveis plasmáticos de albumina, pré-albumina, transferrina e protrombina em portadores de hepatopatia crônica alcoólicaem uso de colchicina ou placebo, durante período de 12 meses. MÉTODOS. em um estudo duplo-cego, 41 pacientes portadores de hepatopatia crônica de etiologia alcoólica foram randomizados para receber placebo (20 pacientes) ou colchicina (21 pacientes), avaliando sua evoluçäo clínica e dos níveis das proteínas plasmáticasalbumina, pré-albumina e transferrina por imunodifusäo radial e do tempo e atividade de protrombina pelo método de Quick modificado. RESULTADOS. Apenas 7,3 por cento dos pacientes näo completaram os 12 meses de seguimento do estudo. Näo se observaram diferenças significantes entre os grupos, no que se refere à taxa de mortalidade ou ao número de internaçöes hospitalares. Quanto aos níveis séricos protéicos, observaram-se valores significantemente superiores no grupo da colchicina do que no grupo placebo, para as médias das variaçöes percentuais dos níveis de albumina (17,9 por cento colchicina x 3,6 por cento placebo, p<0,05) e da atividade de protrombina (19,2 por cento colchicina x 2,1 por cento placebo, p<0,05). As variaçöes dos valores da pré-albumina, apesar de apresentarem o mesmo comportamento observado para os níveis de albumina e protrombina, näo atingiram significância estatística. Já os níveis de transferrina sérica näo diferiram entreos dois grupos. CONCLUSÄO. Estes resultados sugerem que a administraçäo de colchicina tenha um efeito benéfico sobre os níveis de proteínas plasmáticas nos pacientes com hepatopatia crônica de etiologia alcoólica.