Proteomic Profiling of Serum from Patients with Tuberculosis

BACKGROUND: Effective treatment and monitoring of tuberculosis (TB) requires biomarkers that can be easily evaluated in blood samples. The aim of this study was to analyze the serum proteome of patients with TB and to identify protein biomarkers for TB. METHODS: Serum samples from 26 TB patients and 31 controls were analyzed by using nano-flow ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in data-independent mode, and protein and peptide amounts were calculated by using a label-free quantitative approach. The generated data were analyzed by using principal component analysis and partial least squares discriminant analysis, a multivariate statistical method. RESULTS: Of more than 500 proteins identified, alpha-1-antitrypsin was the most discriminative, which was 4.4 times higher in TB patients than in controls. Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis. CONCLUSIONS: Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants. Alpha-1-antitrypsin levels may aid in the diagnosis of TB.

Natural coagulation inhibitors and active protein c resistance in preeclampsia

INTRODUCTION: The etiology of preeclampsia is not fully established. A few studies have shown a relationship between natural coagulation inhibitors and preeclampsia. OBJECTIVES: The purpose of this study was to investigate the status of natural coagulation inhibitors and active protein C resistance (APC-R) in preeclampsia. PATIENTS AND METHODS: We studied 70 women with preeclampsia recruited consecutively and 70 healthy pregnant and 70 nonpregnant women as controls. Plasma protein C (PC), free protein S (fPS), antithrombin III (ATIII) and APC-R were evaluated. RESULTS: ATIII values were found to be significantly lower in preeclamptic patients than in the control groups (p< 0.001). Nevertheless, there was no significant difference between the healthy pregnant and nonpregnant women groups (p=0.141). The fPS values of the preeclamptic and healthy pregnant groups were lower than that of the nonpregnant group (p< 0.001), and the fPS value of the preeclamptic pregnant women was lower than that of healthy pregnant women (p<0.001). The PC value of the preeclamptic pregnant women was lower than that of the control groups (p< 0.001). The PC value of the healthy pregnant women was lower than that of the nonpregnant women (p< 0.001). The mean APC activity values were lower in the preeclamptic patients than that of the control groups (p< 0.001, p< 0.001). The APC-R positivity rates of the preeclamptic groups were higher than that of the control groups (p<0.001). CONCLUSIONS: This study demonstrated that ATIII, fPS, PC values and APC resistance were lower and APC-R positivity was higher in preeclamptic women than in normal pregnant and nonpregnant women.

Placental histomorphology in unexplained foetal loss with thrombophilia.

BACKGROUND & OBJECTIVES: Acquired and genetic thrombotic conditions, both organ and non organ specific, are associated with increased foetal wastage. This study was carried out to examine the placenta from women with abnormal pregnancies and a history of unexplained foetal loss, and to associate with maternal thrombophilia status. METHODS: Placentas from eight women with history of unexplained foetal loss were analyzed for histopathological characteristics. All the women were simultaneously screened for the common acquired and genetic thrombophilia markers i.e., lupus anticoagulants ( LA), IgG / IgM antibodies for anticardiolipin (ACA), beta2 glycoprotein 1 (beta2GPI) and annexin V, protein C (PC), protein S (PS), antithrombin III (AT III), factor V Leiden ( FVL) mutation, prothrombin (PT) gene G20210A, methylene tetrahydrofolate reductase (MTHFR) C 677T, endothelial protein C receptor (EPCR) 23 bp insertion and plasminogen activator inhibitor ( PAI-1 4G/5G) polymorphisms RESULTS: Six of eight women were positive for one or more thrombophilia markers. The placenta in all the cases except one, showed the characteristic features of infarct fibrin deposition and calcification. Among two women who were negative for thrombophilia, one showed clear evidence of thrombus in the placental sections while the other did not show any characteristic infarcts in the placental sections. INTERPRETATION & CONCLUSION: Our findings showed that the histopathological examination of the placentas confirmed thrombophilia as the aetiological cause of thrombosis in 6 of the 8 women. The presence of thrombus in a negative thrombophilia woman suggests yet unidentified thrombophilia markers or probably non-haemostatic factors causing thrombosis.

Etiological profile of stroke and its relation with prothrombotic states.

OBJECTIVE: To study the etiological profile of childhood stroke and its relation with prothrombotic states. METHODS: Children with acute stroke with no evidence of CNS infection or head injury were studied. Stroke was confirmed by CT scan and further evaluated by MRI. Cardiac status was assessed with transthoracic echocardiography. Test for hypercoagulable state (antithrombin III, protein C, protein S, anticardiolipin antibody IgG and IgM and lupus anticoagulant) were done in all patients. RESULTS: A total of 66 children were enrolled--36 cases and 30 controls. Presenting symptoms were motor deficit (72%), seizure (66%), altered sensorium (36%), aphasia (27%). Causes identified were antiphospholipid antibody syndrome (25%), Moya Moya disease (16.6%), cardiac disease (11.1%), vasculitis (5.5%), ATIII deficiency (5.5%), Protein C deficiency (2.7%). Etiology remained unknown in 25% of cases with infarction. Hemorrhage was seen in 8.2% of cases and they had DIC or liver disease as the underlying cause. CONCLUSIONS: Magnetic Resonance Angiography and ELISA for antiphospholipid antibody should be done in all patients with stroke without an obvious cause.

Evaluation of hemostatic factors in children with nephrotic syndrome

Thromboembolism [TE] is one of the serious complications of nephrotic syndrome [NS]. The aim of this study was to evaluate the haemostatic factors in children with nephrotic syndrome. Plasma Level of protein C, Protein S, fibirinogen and antithrombin III [AT III] were evaluated in thirty nephrotic children at relapse and remission period and the results were compared with those of 30 healthy children. The mean age of patients was 5.38 +/- 3.07 years. Plasma Level of protein S and AT III during relapse were significantly lower than their level in remission period and in control group. The mean fibrinogen level during relapse was significantly higher than its level in remission period and in control group. There was no significant difference in protein C levels at relapse with remission period and with control group. Serum albumin levels during relapse were positively correlated with AT III levels. There was no correlation between urinary protein excretion and the haemostatic factors. Despite reduced levels of AT III and protein S and increased levels of fibrinogen, none of our patients revealed thromboembolism. It seems that coexistence of several factors is necessary to induce TE

Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

OBJETIVO: Avaliar os marcadores antitrombina III (AT), fragmento 1 + 2 da trombina (F1+2) e complexo trombina-antitrombina (TAT), bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE) 0,625 mg/dia, isoladamente ou associado ao acetato de medroxiprogesterona (AMP) ou usaram o 17beta-estradiol (50 µg/dia) transdérmico com AMP. Os exames foram realizados antes do tratamento (T0) e após três (T3), seis (T6) e doze (T12) meses após o início do tratamento. AT foi avaliada pelo método amidolítico, enquanto que o F1+2 e o complexo TAT por ELISA. RESULTADOS: Houve redução significante nos níveis de AT em pacientes que receberam ECE associado ao AMP no T3. Não houve redução na AT em mulheres que usaram ECE isoladamente ou aquelas com 17beta-estradiol transdérmico e AMP. O F1+2 aumentou em todos os grupos, mas apenas o grupo com 17beta-estradiol transdérmico e AMP apresentou diferença significante durante o T3. CONCLUSÕES: A associação de ECE e AMP pode reduzir os níveis de AT, enquanto ECE isoladamente ou 17beta-estradiol transdérmico com AMP não modificam-o acentuadamente. Essas alterações poderiam ser mais relevantes clinicamente na análise populacional. Todavia, a terapia de reposição hormonal aumentaria o risco de trombose em mulheres com trombofilia prévia congênita ou adquirida.

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.

Antitrombina III en diabetes mellitus no insulinodependiente de pacientes con infarto del miocardio / Antithrombin III in non insulin dependent diabetes mellitus of patients with myocardial infarction

Objetivo: Determinar si existe alguna relación entre los niveles de antitrombina III y el infarto del miocardio por trombosis coronaria en el paciente diabético no insulinodependiente. Material y métodos: Se realizó un estudio descriptivo en 99 pacientes diabéticos no insulinodependientes. Se midieron niveles plasmáticos de ATIII. En el grupo I se incluyeron 67 de ellos con IM a quienes se les realizó angiografía coronaria. El grupo II se formó con 32 pacientes con DMNID sin infarto del miocardio. Resultados: El grupo I lo integraron 42 pacientes masculinos (63 por ciento) y 25 femeninos (37 por ciento). El intervalo de edades de la población estudiada fue de 42 a 82 años. En la determinación de los niveles de ATIII 50 pacientes (75 por ciento) se encontraron en cifras de referencia (88 a 131 por ciento) y 17 (25 por ciento) con disminución. Los que mostraron nivel de obstrucción coronaria mayor o igual a 85 por ciento fueron 45; de éstos, en 34 (50.7 por ciento) el valor de ATIII se encontró en valores de referencia y en II (16.4 por ciento) con disminución (40 a 83 por ciento). De los 22 con grado de obstrucción menor o igual a 84 por ciento, 16 (24 por ciento) presentaron actividad normal y seis (9 por ciento) mostraron disminución; además, el intervalo de evolución del IM fue de 6 a 60 h, observando que a partir de las 36 h el porcentaje de actividad de la ATIII se encuentra disminuido (40 a 83 por ciento). En el grupo II el porcentaje de actividad de ATIII se encontró dentro de los valores de referencia con un rango de 88 a 115 por ciento. Conclusiones: La actividad de la ATIII no se altera dentro de las primeras 24 h del IM. A pesar de que este estudio no fue diseñado para evaluar la evolución de IM se observó una correlación entre la evolución de éste y la disminución de la actividad de la ATIII

Recherche d'une anomalie constitutionnelle de l'hemostase dans les thromboses

Research of abnormality of heamostasis in thromboembolic disease is very important. In this work, we have studied resistance to activated protein C. Antithrombin III, Protein C, protein S and anticardiolipin antibody in 30 patients who have past history of arterial and venous thrombosis, and in a control population of 25 healthy subjects. We have reported one case [4%] of resistance to activated protein C in healthy subjects and 6 cases [20%] in patients; 4 deficiences of antithrombin III, I deficiency of protein S, and 3 patients with anticardiolipin antibody. The clinical entity of these abnormalities of heamostasis between resistance to activated protein C and deficiencies of coagulation physiologic inhibitors

Antitrombina-III en la preeclampsia-eclampsia: estudio piloto / Antithrombine III in preeclampsia-eclampsia: pilot study

Se estudiaron los niveles funcionales de antitrombina-III en los siguientes grupos: A) mujeres sanas no embarazadas: 11 casos, promedio 107 por ciento; rango 88-120 por ciento; desviación estandar +/- 9.904; pacientes con AT-III menor a 80 por ciento, 0 por ciento B) mujeres sanas embarazadas en el 3er trimeste sin complicaciones: 13 casos, promedio 106 por ciento; rango 89-129 por ciento; desviación estandar +/- 11.647; pacientes con AT-III menor a 80 por ciento, 0 por ciento C) mujeres con preeclampsia leve a severa: 6 casos, promedio 100 por ciento; rango 81-114 por ciento; desviación estandar +/- 10.621; pacientes con AT-III menor a 80 por ciento, 0 por ciento D) mujeres con eclampsia o síndrome de HELLP: 5 casos, promedio 79 por ciento; rango 75-96 por ciento; desviación estandar +/- 10.085; pacientes con AT-III menor a 80 por ciento, 80 por ciento. Prueba estadística F=9.27 valor de p menor a 0.0003. Los niveles plasmáticos de antitrombina-III disminuidos en pacientes con diversos grados de toxemia parecen deberse a coagulación intravascular de bajo grado en preeclampsia y de alto grado de eclampsia y HELLP como principal causa. Debería investigarse su utilidad como prueba de tamizaje para etapas preclínicas y en pruebas de detección temprana y como un indicador de la gravedad de la enfermedad. Estos resultados preliminares justifican la realización de estudios propectivo con mayor número de casos

Hemostatic profile in nephrotic syndrome.

OBJECTIVE: To evaluate the coagulation profile and its relation to steroid therapy, and the frequency of thromboembolic complications and its correlation with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based. SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups, namely, fresh cases, steroid dependent, remission after therapy and steroid resistant. An equal number of age and sex matched children served as controls. In all the study and control subjects, detailed clinical examination, liver function tests, renal function tests and detailed coagulation profile were done. Evaluation of renal veins and inferior vena cava for the presence of thrombosis was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected in 57.5% and the degree of thrombocytosis was directly related to the amount of proteinuria. The mean prothrombin and thrombin times were within normal range in the study children. The activated partial thromboplastine time (APTT) was prolonged in six cases (15%) and three out of these six children had thromboembolic complications. Antithrombin-III level was significantly lower (p < 0.001) whereas protein C and S were significantly elevated (p < 0.001) as compared to controls. The levels became normal with remission of the disease. Steroid therapy significantly increased the levels of proteins C, protein S. AT-III and fibrinogen as compared to controls. Thromboembolic complications were seen in 3 cases (7.6%) and were associated with very low levels of AT-III and protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The importance of coagulation profile in nephrotic syndrome is highlighted and a high index of suspicion for thromboembolic complications is warranted in patients with thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low levels of AT-III, protein C and protein S.

Infartos cerebrais em pacientes jovens relacionados a deficiência de anticoagulantes naturais: proteína C e proteína S / Cerebral infarctions in young patients related to deficiency of natural anticoagulants: protein C and protein S

Infartos cerebrais (IC) em jovens apresentam múltiplas etiologias que diferem do padrao observado nos indivíduos idosos. Deficiências de anticoagulantes naturais têm sido descritas nos últimos anos como causa de IC, principalmente em pacientes com menos de 40 anos. Existe tendência atual de se pesquisar essas deficiências em todos os pacientes jovens com infarto cerebral de causa indeterminada e naqueles com manifestaçoes trombóticas de múltiplos sistemas. Realizamos pesquisa dos níveis de proteína C, proteína S e antitrombina III em pacientes entre 15 e 40 anos com ICs classificados como indeterminados após conclusao protocolo básico de investigaçao. Diagnosticamos dois casos de deficiência de proteína C e um caso de deflciência de proteína S. Concluímos que a investigaçao sistemática de causas hematológicas proporciona decréscimo no número de infartos indeterminados, além de possibilitar a adoçao de condutas específicas que diminuem incidência de novos eventos nos casos diagnosticados.

Dosagem da antitrombina III usando o substrato cromogênico Tos-Gly-Pro-Arg-NAN, em diversas situaçöes patológicas / Antithrombin III dosage using the chromogenic substrate Tos-Gly-Pro-Arg-NAN, in several pathological situations

O uso de método funcional para dosagem de antitrombina III (ATIII) é fundamental para o diagnóstico de deficiência deste inibidor da coagulaçao. OBJETIVO. Padronizar metodologia para dosagem da ATIII no plasma, utilizando-se microplacas, em diferentes situaçoes clínicas. MÉTODOS. A dosagem de ATIII foi feita utilizando-se o substrato cromogênico Tos-Gly-Pro-Arg-NAN, específico para trombina, e sintetizado no Departamento de Biofísica da Escola Paulista de Medicina. RESULTADOS. Dos 21 pacientes com trombose venosa (TV-P), 20 apresentaram valores superiores a 70 por cento (ll3 ñ 22 por cento), dos quais uma paciente de 22 anos apresentava deficiência congênita, com ATIII de 56 por cento e história de TVP recorrente, além de história familiar de TVP. O nível de ATIII em seis pacientes portadores de doença de von Willebrand foi normal (lO9 ñ 28 por cento), como esperado. Em 20 pacientes com insuficiência hepática foi observada reduçao importante do nível de ATIII (42 ñ 19 por cento), pois este inibidor é produzido no hepatócito, sendo bom parâmetro para avaliar a funçao hepática. Os três pacientes portadores de sepse com CIVD apresentaram níveis reduzidos de ATIII (45 + 5 por cento), que é consumida durante processo de ativaçao intravascular da coagulaçao. Os níveis de ATIII mostraram correlaçao significante com o TP e os níveis de fator V, ambos bons parâmetros para avaliaçao da funçao hepática e para monitorizaçao da CIVD. Houve correlaçao significante entre as dosagens realizadas com o substrato Tos-Gly-Pro-Arg-NAN, sintetizado na EPM, e o substrato S-2238 do laboratório Kabi. CONCLUSOES. A medida da ATIII usando substrato cromogênico Gly-Pro-Arg-NAN é de fácil execuçao e é sensível para o diagnóstico da deficiência deste inibidor em pacientes com insuficiência heopática, coagulaçao intravascular disseminada e trombofilia.

Determinación de citidina deaminasa y antitrombina III en hipertensión inducida por el embarazo / Deaminasa cytidine and antithrombin III determination in pregnancy induced hipertension

Se diseña un estudio para evaluar el comportamiento de dos parámetros bioquímicos: Citidina deaminasa (CD) (enzima que participa en el metabolismo de nucleótidos pirimidínicos) y Antitrombina III (AT-III) (principal inhibidor fisiológico de la coagulación), con el objeto de establecer su valor bioquímico en el diagnóstico diferencial y evaluar la severidad del SHIE (Síndrome hipertensivo inducido por el embarazo). Para este propósito se selecciona un grupo de mujeres no gestantes (NG) (n=34), un grupo control de gestantes sanas (GC) (n=30) y uno patológico (n=54) formado por pacientes con diagnóstico de SHIE (moderada, severa y pre-eclampsia). HC (hipertensión crónica) y HC/SHIE (hipertensión preexistente con pre-eclampsia sobreañadida). Se determinan niveles de CD y AT-III en cada uno de estos grupos. Los resultados indican aumento con diferencias significativas (p<0,001) en los niveles de CD, de la HIE (moderada, severa y pre-eclampsia) vs grupo de control, como también entre las pacientes con HC/HIE y gestantes sanas (GC). No se encontraron diferencias significativas entre el grupo control e HC (p>0,01). Se verifican también diferencias significativas (p<0,001) en los niveles de CD entre HIES vs HIE-m; HIE-m vs HC; HIE-s vs HC y HC/HIE vs HC estableciéndose que el valor bioquímico de la determinación de CD, es un método importante en el diagnóstico diferencial de las HIE en relación con la HC, como también entre ésta y HC/HIE. Respecto a los niveles AT-III, se encontró diferencias significativas en no gestantes vs gestantes sanas, siendo menor la actividad en las embarazadas (p<0,001). Los resultados no son concluyentes en grupos patológicos

Diagnostic and prognostic significance of antithrombin III, plasminogen and alpha-2-artiphasmin in jaundiced patients

This study was designed to find out the diagnostic and prognostic usefulness of Antithrombin-III, [AI-III] Plasminogen and Alpha-2 antiplasmin in different types of jaundice. AT-Ill, plasminogen and alpha-2 antiplasmin were studied in 43 jaundiced patients [Hepatic metastasis n = 9 and Hepatocel lular, n = 17, and obstructive, n = 17] and compared to 10 healthy controls. The mean serum levels of alpha-2 antiplasmin, AT-III and plasminogen were significantly decreased in hepatic metastasis and hepatocellular subgroups compared to control and cholestatic subjects. No significant differences were noticed between control subjects and cholestatic patients except for significant elevation in serum level of alpha-2 antiplasmin in the latter. In hepatocelluar jaundiced patients, these parameters were markedly decreased in fulminant hepatitis patients compared to cirrhotics and patients with acute viral hepatitis. Also in Hepatocellular group, a significant negative correlations could be elicited between bilirubin [Total and direct and SGOT on one side and AT-Ill and plasminogen on the other side. Also significant negative correlations were noticed between alpha-2 antiplasmin and each of total bilirubin and SGOT. It can be concluded that alpha-2 antiplasmin, AT-Ill and plasminogen may play a role in etiological diagnosis as well as prognostic follow up of jaundiced patients

Plasma anticoagulant system in patients with pulmonary hypertension

Adults with pulmonary hypertension and polycythemia (N=22) have low levels of plasma antithrombin III (84 ñ 18 vs 98 ñ 13½ for controls, N=35, P<0.005) and protein C (66ñ21 vs 125 ñ 30%, N 8, P<0.0002 but normal levels of total protein S. Data are reported as means ñ SD and percent normal values obtained for pooled plasma from normal healthy adults. Children with the same disorder (N = 6) also had low protein C levels (66 ñ 16 vs 85 ñ 5½, P < 0.025). Total protein S was normal for children, but free protein S was decreased (66 ñ 13 vs 91 ñ 23,, P < 0.02). Since the levels observed in these patients are above those reported for congenital deficiencies, the reduction in plasma levels of anticoagulant proteins may be the result of cronic intravascular coagulation. Furthermore, normal levels of plasminogen and fibrin degradation products suggested a localized disorder or an acquired decrease in fibronolytic activity

Estudio de antitrombina III y tiempo de protombina en diferentes trastornos hepáticos / Study of antithrombin III and Prothombin time in differents hepatic disorders

Se hizo un estudio de los niveles de antitrombina III (AT III) y de tiempo de protombina (T.P), en pacientes que presentaban cinco tipos diferentes de enfermedad hepática (hepatopatía alcohólica crónica, cirrosis no alcohólica, hepatitis viral aguda, hepatitis crónica activa y hepatitis crónica persistente). Se encontró un diferencia significativa p < 0.001 de los valores, al compararlos con 20 controles normales, con excepción de las hepatitis crónicas persistentes y la hepatitis viral aguda p < 0.05. Los valores más alterados se encontraron en las hepatitis crónicas activas y en los cirróticos, lo que coincide con otros autores, en que ambas pruebas y en especial la AT III representan el mejor criterio, para evaluar la severidad del daño hepático, por lo que las recomendamos como pruebas rutinarias en la evaluación de estas patologías.

Antithrombin III estimation immunological versus chromogenic substrate in bilharzial liver fibrosis

Fourty one patients with bilharzial liver fibrosis were investigated for antithrombin III [AT III] by chromogenic substrate method versus radial immuno-diffusion method. A control group of sixteen healthy young adults was also assayed for comparison. There was a significant AT III deficiency in bilharzial liver patients, mainly due to defective synthetic ability of the liver and low grade DIC. A significant positive correlation was found between results of ATIII antigen as measured by chromogenic substrate method. However the antigen values were significantly higher than the activity, possibly due to presence of abnormal nonfunctioning antigen molecules. By comparing the two methods, it was found that the technique of radial immunodiffusion method is much easier with single step, thus it is more precise with less coefficient of variation. However, the chromogenic substrate method offers many advantages. It is more sensitive than the immunodiffusion method and it takes very short time with a relative technical simplicity. Both methods are of equal high specificity and show good correlation between expected and observed results. Cost study showed that both methods were nearly equal. Although the chromogenic substrate method needs a special equipment, however the low reagent consumption reduces much the cost per assay

Antitrombina III y heparinemia en pacientes en hemodialisis / Antithrombin III and heparinemia in patients in hemodialysis

Para disminuir el riesgo de coagulación en el dializador, la heparina ha sido ampliamente usada en pacientes sometidos a hemodiálisis (HD). El efecto anticoagulante de la heparina depende de los niveles de antirombina III (AT III) de la sangre. La heparina acelera la reacción entre la AT III y las enzimas que participan en la coagulación sanguínea formando complejos inactivos equimolares. En trabajos recientes se muestran que los niveles de ATIII son contradictorios en HD. Los objetivos de este trabajo son: 1) evaluar los niveles de AT III en pacientes con insuficiencia renal crónica (IRC) en HD); 2) valorar las variaciones de AT III durante y después de la HD; 3) medir la heparinemia durante y después del tratamiento idalítico; 4) encontrar una prueba de laboratorio simple, pero sensible para medir el nivel de anticoagulación. Se estudian 20 pacientes (7 mujeres y 134 varones) con una edad promedio de 30 años (18 a 55 años) portadores de IRC terminan en plan de HD intermitente, con un filtrado glomerular inferior a 5 ml/min.; 11 pacientes fueron estudiados en 2 oportunidades lo que hace un total de 31 determinaciones. La forma de administración de la heparina fue por vía EV intermitente. La AT III, heparinemia y KPTT, son dosados a partir de muestras sanguíneas antes, durante y luego de cada sesión de HD; además en 12 pacientes se tomaron muestras 24 horas después de la HDEl nivel de AT III en pacientes con IRC se encontró dentro de límites normales. No se encontraron variaciones entre los valores iniciales y durante la HD, lo que podría deberse a que el aumento de la heparinemia es transitorio. El perfil de variación de la heparinemia es similar al observado con el KPTT. En nuestros resultados encontramos que la profilaxis de heparina durante la diálisis en pacientes urémicos pueden ser dadas en una dosis suficiente para prolongar el KPTT a 5 ó 6 veces el valor inicial, sin ningún riesgo de coagulación en el dializador y sin ningún riesgo de inducir una pérdida o consumo de AT III