Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

BACKGROUND: Dysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population. METHODS: Part 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome. RESULTS: Antithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high. CONCLUSIONS: Decreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.

Distúrbios de coagulação em pacientes com osteonecrose da cabeça femoral / Coagulation disorders in patients with femoral head osteonecrosis

Objetivo: Comparar a ocorrência de trombofilias em pacientes com osteonecrose idiopática da cabeça femoral em relação aos pacientes com osteonecrose secundária da cabeça femoral. Métodos: Um total de 24 pacientes consecutivos foram avaliados, sendo oito portadores de osteonecrose idiopática e 16 de osteonecrose secundária. Os exames realizados na detecção de trombofilias foram as dosagens de proteína C, proteína S e antitrombina e as pesquisas de mutações nos genes da protrombina e do fator V. Comparamos estatisticamente os resultados através do cálculo da razão de chances ou odds ratio das diferentes trombofilias entre os dois grupos. Resultados: O odds ratio para a deficiência da proteína S e deficiência da proteína C entre os grupos idiopático e secundário foram respectivamente 5 e 2,14. Desta maneira, um indivíduo com osteonecrose idiopática possui uma chance 5 vezes maior de apresentar deficiência da proteína S e 2,14 vezes maior de apresentar deficiência da proteína C do que um indivíduo com osteonecrose secundária. Conclusão: Pacientes com osteonecrose idiopática têm maiores chances de apresentar trombofilias do que aqueles com osteonecrose secundária, sugerindo que estes distúrbios de coagulação podem desempenhar um papel importante na patogênese dos casos de osteonecrose onde não há inicialmente nenhum fator de risco identificável. Nível de Evidência III, Estudo de Caso-Controle.

Objective: To compare the occurrence of thrombophilic disorders in patients with idiopathic osteonecrosis of the femoral head and patients with secondary osteonecrosis of the femoral head. Methods: Twenty-four consecutive patients were enrolled, with eight of them presenting idiopathic osteonecrosis and 16 presenting secondary osteonecrosis. The tests for detection of thrombophilic disorders were measurements of protein C, protein S and antithrombin levels and detection of prothrombin and factor V gene mutations. We compared the results using the odds ratio statistics for the thrombophilic disorders between the two groups. Results: The odds ratio for the protein S deficiency and protein C deficiency between the idiopathic and secondary groups were 5 and 2.14, respectively. Thus, an individual with idiopathic os teonecrosis has 5 times more chance of presenting protein S deficiency and 2.14 times more chance of presenting protein C deficiency than an individual with secondary osteonecrosis. Conclusion: Patients with idiopathic osteonecrosis have more chances of presenting thrombophilias than those with secondary osteonecrosis, suggesting these coagulation disorders can play an important role in the pathogenesis of the osteonecrosis in cases where there was no initial risk factor recognized. Level of Evidence III, Case-Control Study.

Determination of serum C and S protein and factor V leiden in sickle cell disorder in Khozestan province

Sickle cell disease [SCO] is due to beta chain mutation and substitution of valine for glutamic acid in sixth position,that is cause increasing polymerization and vaso-occlusion. Decrease of protein C, protein S and increase in factor V leiden activity contribute to hypercoagulation state in SCO, recently.The aim of this study was to determinate the differences of serum C and S protein and factor V leiden between sickle cell patients and control subjects. In this randomized case-control study, protein C, protein S and factor V leiden activity were measured in 100 SCO patients in crisis phase. And were compared between 50 age- gender -race- matched controls and SCD patients in, hydroxyurea intake, blood transfusion, levels of HbF, age and gender by Chi-Square and Anova statistical tests in SPSS software. In 100 patients 47 were males and 53 females, mean age was20.2 [range 3-58, 1SD +/- 1.03]. Protein C and protein S levels were significantly low [both P<0.0001] in 35% and 24% patient; respectively. But in controls it was not like this. Factor V leiden was increased significantly [P<0.00l] in 27% of patient and 4% of controls. A significant [P=0.02] correlation was detected between protein S levels and age groups. Protein C and protein S levels reduced and factor V leiden activity increased in SCD patients and cause hypercoagulable state in these patients

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.

Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis / Prevalência de marcadores comuns de trombofilia e fatores de risco em pacientes indianos com trombose venosa primária

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56 percent) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9 percent each), followed by low protein S (16.6 percent). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

CONTEXTO E OBJETIVO: A trombose venosa ocorre como resultado da interação de fatores genéticos e adquiridos, incluindo resistência à proteína C ativada (APC-R), os níveis de fibrinogênio, antitrombina, proteína C, proteína S, anticoagulante lúpico e anticorpos anticardiolipina. Este estudo teve como objetivo verificar a prevalência de fatores trombofílicos frequentes em indianos com trombose venosa primária. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado em Mumbai. MÉTODOS: Foram testadas amostras de 78 pacientes com diagnóstico confirmado de trombose venosa e 50 controles. Foi realizada a dosagem sérica semiquantitativa (funcional) de proteína C, proteína S e antitrombina e a dosagem quantitativa de fibrinogênio (método de Clauss). Anticoagulantes lúpicos foram identificados por meio do tempo de tromboplastina parcial ativada sensível ao lúpus, e anticorpos anticardiolipina dependentes de β2-glycoproteína-I por ELISA. APC-R foi medida por método baseado em coagulação com plasma deficiente em fator V e veneno de Crotalus viridis. A análise estatística utilizou Epi-info (versão 6). RESULTADOS: A veia poplítea foi o local mais frequentemente afetado; 44 amostras (56 por cento) tiveram resultados anormais. Os achados mais frequentes foram elevação do fibrinogênio e APC-R (17,9 por cento cada), e baixa proteína S (16,6 por cento). CONCLUSÕES: Corroborando com a literatura, este estudo mostrou que a elevação do nível de fibrinogênio e a triagem para APC-R são importantes na avaliação de pacientes com trombose venosa, pois, individualmente ou em combinação, podem ter levado ao episódio trombótico primário. A frequência dos outros marcadores de trombofilia foi mais alta entre os doentes quando comparados aos controles, porém sem diferença estatisticamente significante.

Warfarin-Induced Penile Necrosis in a Patient with Heparin-Induced Thrombocytopenia

A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531x10(9)/L. The patient was anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day, oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and LMWH was discontinued at third hospital day. On the third day of oral anticoagulation therapy, he complained of left leg swelling and prolonged painful penile erection of 24 hr-duration. His platelet count reached a nadir 164x10(9)/L at that time, and the patient had a deficiency of protein C and S, with an activity level of 16% and 20% of normal value. Warfarin was stopped and he underwent penile aspiration. The next day, left leg edema and penile erection was disappeared, but penile and glans penis necrosis was started. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis.

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.

Influencia de las variables preanalíticas en la determinación de proteína S / Influence of preanalytical variables in S protein determination

La proteína S (PS) regula el sistema de coagulación mostrando actividad de cofactor de la Proteína C activada (PCa) con la cual forma un complejo equimolecular. En presencia de iones calcio este complejo inactiva por proteólisis los factores V y VIII activados por trombina. La proteína S plasmática circula 40% libre (fracción que presenta actividad de cofactor de la PCa) y 60% unida al C4-BP (proteína ligante de la fracción C4 del complemento). El objetivo fue comparar el dosaje de PS realizado por método coagulable e inmunoturbidimétrico e investigar cómo las variables preanalíticas afectan los niveles de PS determinados. Se obtuvieron los siguientes resultados: método coagulable: CV intra ensayo: (n=20): 4%, CV interensayo (n=20, 3 días): 3,4%. Método inmunoturbidimétrico: CV intraensayo (n=20): 3,7%.CV Inter. ensayo (n=20,3 días): 4,5%. Existe buena correlación (R2=0,94) entre ambos métodos, cuando la calibración por el método coagulable se realiza en la misma corrida analítica que las muestras. Cuando se realizó el estudio de Bland y Altman los dos métodos mostraron ser comparables en todos los niveles de PS estudiados. No se observaron diferencias significativas entre las muestras determinadas frescas y conservadas a -20 y -80 °C descongeladas solo una vez.

Protein S has an essential anticoagulant function acting as activated Protein C cofactor and forming an equimolecular complex with it. In the presence of calcium this complex regulates the coagulation process inactivating thrombin activated factors V and VIII by proteolysis. In plasma there are two different forms: a) free Protein S which acts as the cofactor of activated protein C (representing about 40% of total Protein S) and b) C4-BP(C4 binding protein) bound protein S which exhibits no activity as cofactor of activated Protein C (representing about 60% of total PS). The objetive was to compare the PS dosage determination by two methods: immunoturbidimetric and clotting, and to investigate how pre-analytical variables affect the results. The following results were obtained: Clotting method: CV intra assay: (n=20): 4%, CV interassay (n=20, 3 days): 3.4%; immunoturbidimetric method CV intra assay (n=20): 3.7%: CV inter assay (n=20.3 days): 4.5%. There is a good correlation (R2 = 0.94) between both methods; when the clotting method is calibrated in batch with the samples. There is significant difference between fresh and frozen ( -20 °C and -80 °C) samples when the latter have been desfrozen only once.

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

Trombofilia primaria: 41 nuevos casos / Primary thrombophilias: 41 new cases

Se presentan 37 casos de trombosis, en su mayoría jóvenes, con antecedentes trombóticos familiares y con diagnóstico de trombofilia primaria o hereditaria además de cuatro familiares de primer grado de estos pacientes en los cuales se confirmó la portación familiar de trombofilia. La anamnesis reveló que el 82 por ciento presentó la primera trombosis antes de los 45 años; tuvo más de una trombosis en un 59 por ciento y tenía antecedentes familiares en 49 por ciento. Los defectos trombofílicos determinantes encontrados fueron: deficiencia de proteína S (27 por ciento); resistencia a proteína C activada por factor V Leiden (24,3 por ciento); deficiencia proteína C (21,6 por ciento) y antotrombina III (16,2 por ciento); mutación G20210 A del gen protrombina (8,1 por ciento). Entre los defectos adquiridos estudiados simultáneamente, un 27,2 por ciento de los casos presentaron anticoagulante lupico y ninguno hiperhomocisteína. La existencia de mas de un factor de riesgo trombofílico se observó en el 24.3 por ciento de los pacientes. En el estudio de los 4 parientes de primer grado se encontró factor V Leiden en uno; factor V Leiden mas anticoagulante lupico en uno y deficiencia proteína S en dos. El trabajo anterior publicado en 2004 motivó a los pacientes que no se hicieron el estudio a tomar conciencia de su situación y de la necesidad de controlarse, lo que demuestra la importancia de difundir esta patología aún poco conocida.

Assessment of anticardiolipin antibodies, circulating lupus anticoagulant, protein C, protein S, antithrombin III and activated protein C resistance and their relation to thomboembolic and other clinical manifestations in Behcet's disease

Venous and arterial thrombosis occurs in patients with Behcet's disease and is associated with significant morbidity and mortality. Studies on a possible association between the occurrence of thrombosis and thrombophilia in patients with this disease have been controversial. The objective of this study was to assess the frequency and clinical relevance of anticardiolipin antibodies [aCL] and other thrombophilic factors and their relationship to thromboembolic and clinical manifestations in Behcet's disease [BD]. IgG, IgM and IgA anticardiolipin antibodies [aCL] isotypes, presence of circulating lupus anticoagulant [LAC], protein C, protein S, antithrombin III and activated protein C resistance were investigated in 25 patients with BD and 25 patients with various rheumatic diseases not known to be associated with venous or arterial thromboembolic phenomena served as controls. Twelve of the patients with BD [48%] had either deep vein thrombosis [8 patients], arterial thromboembolic phenomena [4 patients], or both [2 patients]. The IgA aCL elevated in14 [56%] patients with BD compared with one [4%] patient in the control group [P<0.01]. IgG aCL levels were elevated in 13 [52%] patients with Behcet's disease [BD] compared with one [4%] patient in the control group [P<0.01].Also patients with BD do not have decreased protein S, or antithrombin III activity, activated protein C resistance, circulating lupus anticoagulant [LAC], or elevated LgM aCL. No significant differences were found between any variable in both groups. No association between elevated IgMaCL levels and venous or arterial thrombosis and no statistical correlation was found between any factor and clinical manifestations of the disease. A significant number of patients have elevated levels of IgA and IgG aCL but they are not associated with venous or arterial thrombosis. These results do not suggest a primary role for aCL in BD and do not support the role of coagulation abnormalities in the pathogenesis of thromboembolic complications of Behcet's disease but suggest vascular inflammation as the main pathogenetic event in the vascular lesions in Behcet's disease

Protein S deficiency is common in a healthy Thai population.

Currently, venous thromboembolism is a growing menace in Asians, approaching to that of Western countries. The most common genetic mutations causing thrombosis in Caucasians are factor V Leiden and prothrombin mutation. However both are very rare in Asians. On the other hand, natural anticoagulant protein (protein S, protein C and antithrombin) deficiencies are more common in Asian than in Western thrombotic patients. The prevalence of these deficiencies is very low in healthy Caucasians (0.02-0.3%). It is possible that the prevalence is higher in an Asian general population. However there have been very few prevalence studies to prove this hypothesis. Protein S deficiency was found in 3.7% (13/352, 95% confident interval 1.72-5.66) healthy Thais. Seven of them were type III deficiency. Similar to previous studies, total and free protein S levels were lower in females, but positively and negatively correlated with age, respectively. In contrast, one protein C deficiency (0.27%, 1/370) and no antithrombin deficiency (0/206) were detectable in our population. Furthermore, the authors found that antithrombin was significantly lower in women and there was a positive correlation between protein C activity and age. In conclusion, protein S deficiency is more common in Thais than in Caucasians. This result remains to be confirmed by a large population-based study.

Proteína S libre en embarazadas normales: comparación entre dos métodos / Free protein S (PS) in normal pregnancy: A comparison between two analytical methods

Background: Pregnancy is a physiological hypercoagulable state with an increased incidence of thromboembolic phenomena. There is an increase in the concentrations of most clotting factors, a decrease in concentration of some of the natural anticoagulants and reduced fibrinolytic activity. Changes in PS levels have also been reported. Aim: To establish referral range values of functional PS and free PS antigen, during the second (2nd T) and third trimester (3rd T) of normal gestation. Patients and methods: Forty one normal pregnant women were included in our study, 20 during the 2nd T (22-24 weeks) and 21 during the 3rd T (29-38 weeks). Functional PS was measured by a clot based test and free PS antigen by ELISA. Results: Free PS Antigen was 65.8±18.3% during the 2nd T and 62.3±16.5% during the 3rd T. The figures for normal controls were 106±6.5%. Functional PS was 43.8±13.3 and 25.9±14.6% during the 2nd T and 3rd T, respectively. The figures for normal controls were 97±24% (p <0.001 compared with pregnant women). Free PS antigen did not change from the 2nd to the 3rd T (p=NS), however functional PS fell significantly from the 2nd to the 3rd T (p <0.001) and was significantly lower than free PS antigen in both trimesters (p <0.001). Conclusions: Pregnancy is associated to a decrease in PS. This abnormality is more pronounced for functional PS than free PS antigen and functional PS falls progressively during pregnancy. These assays should not be used to screen for PS deficiency during pregnancy because they could lead to a misdiagnosis.

Associação da proteína S100P e do receptor de estrogênio com o potencial evolutivo de lesões proliferativas epiteliais mamárias em pacientes com calcifiçações radiológicas / S100P and estrogen receptor associated with evolutive potential of epithelial proliferative breast lesions in patients with radiologic calcifications

Os estudos das lesões proliferativas pré-malígnas com marcadores de diferenciação celular e de atividade proliferativa têm sugerido que o estrogênio exerce papel importante na transformação dessas lesões, atuando através do seu receptor e agindo no núcleo das células alvo estimulando a proliferação celular. Trabalhos com culturas de células de diferentes linhagens identificaram a proteína S100P como participante no processo de transformação neoplásica maligna celular. No presente trabalho, estudamos a expressão imuno-histoquímica da S100P, do receptor de estrogênio e MIB-1 em pacientes submetidas à biópsia por agulha na rotina diagnóstica em patologia mamária e comprovamos a associação do receptor de estrogênio e da S100P. /The use of cell differentiation and proliferation markers in pre-malignant lesions has brought up the important hole of oestrogen in the malignancy transforming process. Others works based on cells culture from different lines have identified S100P, a binding-calcium protein, as participating of immortalization and cell differentiation. In the present work, we have studied the immunohistochemical expression of oestrogen receptor, S100P and MIB-1, among patients submitted to vacuum assisted breast biopsy in a routine process...

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

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.

Técnicas diagnósticas de laboratorio en trombofilias congénitas / Diagnostic laboratory techniques for hereditary trombophillias

Las alteraciones hereditarias de los inhibidores naturales de la coagulación y de los componentes del sistema fibrinolítico, están asociadas con enfermedad tromboembólica. Como no siempre es posible determinar la causa de la trombofilia, se analizan aquí distintas metodologías que pueden ser de utilidad para arrojar más luz sobre este problema; y que están disponibles en la bibliografía, para medir la actividad funcional y la concentración de antitrombina III, proteína C, proteína S, cofactor II de la heparina, glicoproteína rica en histidina, lipoproteína A, fibrinógeno, plasminógeno y homocisteína. En todos los casos es conveniente comenzar primero con la determinación de la actividad funcional de la proteína en estudio y, en caso de encontrar una alteración, se completará el estudio con una cuantificación inmunológica u otra metodología que permita obtener mayor información sobre la alteración