Serum markers thrombophilia in pregnant women with Systemic Lupus Erythematosus / Marcadores Séricos para Trombofilia em Gestantes com Lúpus Eritematoso Sistêmico

Abstract Objectives: to determine the frequency of serum markers for hereditary and acquired thrombophilia and their association with pregnancy in women with Systemic Lupus Erythematosus (SLE). Methods: a case-control study was conducted among 25 pregnant women with SLE (study group) and 32 pregnant women without known disease and with at least one previous pregnancy (control group). The presence of antiphospholipid antibodies and hereditary thrombophilia were examined in both groups. We used the y2 Test with Yates correction or Fisher's Exact Test to verify the associations and calculate the relative risk. Results: thrombophilia was present in 72.0% of pregnant women with SLE and in 6.0% of patients in the control group. A significant association was found between the presence of SLE and serum markers for hereditary thrombophilia / antiphospholipid antibodies (p<0.05). The relative risks for antiphospholipid antibodies were 13.20 (ICR95%= 1.81 - 96.46) in pregnant women with SLE, 7.26 (CI95%= 1.77 - 29.86) for the presence of serum markers of hereditary thrombophilia and 7.92 (CI95%= 2.62 - 3.94) for the presence of hereditary thrombophilia and/or antiphospholipid antibodies. Conclusions: the identification of markers for hereditary and/or acquired thrombophilia in pregnant women with lupus may be clinically useful to determine which patients have a higher risk of obstetric complications.

Resumo Objetivos: determinar a frequência e a associação ente LES em gestantes e a ocorrência de marcadores séricos para trombofilias hereditárias e adquiridas no grupo de gestantes estudadas. Métodos: foi realizado estudo caso-controle com 25 gestantes portadoras de Lúpus Eritematoso Sistêmico (grupo estudo) e 32 gestantes sem doença conhecida, com pelo menos uma gestação anterior (grupo controle). A presença de anticorpos antifosfolípides e trombofilia hereditária foi examinada em ambos os grupos. Utilizamos o Teste y2 com correção de Yates ou Teste Exato de Fisher para verificar as associações e calcular o risco relativo. Resultados: verificou-se a presença de trombofilias em 72,0% das gestantes portadoras de LES e em 6,0% das pacientes do grupo controle. Encontrou-se significante associação entre a presença de LES em gestantes e marcadores séricos para trombofilias hereditárias/anticorpos antifosfolípides (p<0,05). Identificou-se risco relativo para presença de anticorpos antifosfolípides de 13,20 (1,81<RR<96,46) em gestantes portadoras de LES, 7.26 (IC95%=1.77-29.86) para presença de marcadores séricos de trombofilias hereditárias e de 7.92 (IC95%= 2.62 - 23.94) considerando a presença de trombofilias hereditárias e/ou presença de anticorpos antifosfolípides. Conclusões: a identificação de marcadores para trombofilia hereditária e/ou adquirida em gestantes com lúpus pode ser clinicamente útil para determinar quais pacientes apresentam maior risco de complicações obstétricas.

Prevalence of thrombophilic gene polymorphisms [FVL G1691A and MTHFR C677T] in patients with myocardial infarction

Inherited thrombophilia may be caused by mutations, polymorphisms in a variety of genes mainly involved in haemostatic pathways was to find the prevalence of thrombophilic gene factor V Leiden [FVL] and methylene tetrahydrofolate reductase [MTHFR] gene polymorphism in patients with myocardial infarction [MI], aiming at early diagnostic methods and guiding preventive procedures. This study was carried on 30 patients who survived their first MI as compared to 15 healthy volunteers. Patients and controls were subjected to history, physical examination. Factor VL G1691A and MTHFR C677T genotypes were determined by RT PCR. The prevalence of heterozygous FVL GA genotype was significantly higher among MI patients as compared to the control group. The prevalence of mutant homozygous AA was significantly higher in MI patients as compared to control. The low risk cases had a higher frequency of GA genotype as compared to high risk cases. As regards MTHFR C677T gene polymorphism, the prevalence of heterozygous MTHFR C677T CT genotype showed significant increase in MI patients compared with the control group. The prevalence of mutant homozygous TT genotype was significantly higher in MI patients as compared to the control group. The low risk cases had a higher frequency of heterozygous MTHFR C677T CT genotype than high risk cases The prevalence of heterozygous [FVL G1691 A] and MTHFR C677T gene polymorphisms was significantly increased in MI patients compared with the control group and these gene polymorphisms are probably risk factors for myocardial infarction among Egyptian cases especially if integrated with other environmental and genetic risk factors. We recommended screening high risk patients for this polymorphism and the use of specific thromboprophylaxis to prevent recurrent thrombotic disease

Clinical profile, common thrombophilia markers and risk factors in 85 young Indian patients with arterial thrombosis / Perfil clinico, marcadores comuns de trombofilia e fatores de risco em 85 pacientes indianos jovens com trombose arterial

CONTEXT AND OBJECTIVE: Arterial thrombosis may occur consequent to hereditary thrombophilia and increased lipoprotein(a) [Lp(a)] and fibrinogen. Our aim was to study the prevalence of common thrombophilia markers in 85 consecutive cases of arterial thrombosis. DESIGN AND SETTING: A retrospective study was conducted from 85 consecutive young patients treated as outpatients or admitted due to stroke or myocardial infarction at a tertiary care hospital. METHODS: Eighty-five Indian patients (age < 45 years) presenting ischemic stroke (n = 48) or myocardial infarction (n = 37) and 50 controls were studied for seven thrombophilia markers including antithrombin (AT), factor V, protein C, protein S, activated protein C resistance (APC-R), fibrinogen and Lp(a). Functional assays for protein C, protein S, factor V and APC-R were performed using clotting-based methods. Semi-quantitative estimation of fibrinogen was done using Clauss's method and Lp(a) using immunoturbidimetry. Statistical analysis was done using the Epi Info 6 software. RESULTS: Thirty-three samples (38.8%) tested positive for one or more thrombophilia markers. The three commonest abnormalities were elevated Lp(a) (20%), fibrinogen (17.6%) and low APC-R (14.2%). Low levels of protein C, protein S and AT were present in 4.7, 9.4 and 7% of the patients, respectively. Overall, the risk factor profile was: smoking (33%), positive family history (15.3%), hyperlipidemia (7%), hypertension, diabetes mellitus and obesity (2.3% each). CONCLUSIONS: An association was found between low levels of protein C, protein S and AT and arterial thrombosis, but only elevated fibrinogen levels, smoking, positive family history and hyperlipidemia showed statistical significance. .

CONTEXTO E OBJETIVO: Trombose arterial pode ocorrer em consequência de trombofilias hereditárias e de lipoproteína (a) [Lp (a)] e fibrinogênio aumentados. Nosso objetivo foi estudar a predominância de marcadores comuns da trombofilia em 85 casos consecutivos de trombose arterial. TIPO DE ESTUDO E LOCAL: Um estudo retrospectivo foi realizado sobre 85 pacientes jovens tratados consecutivamente no ambulatório ou admitidos por infarto do miocárdio ou acidente vascular cerebral (AVC) num hospital de cuidado terciário. MÉTODOS: Oitenta e cinco pacientes indianos (idade < 45 anos) que se apresentaram com AVC isquêmico (n = 48) ou infarto do miocárdio (n = 37) e 50 controles foram estudados para sete marcadores de trombofilia que incluíram antitrombina (AT), fator V, proteína C, proteína S, resistência ativada da proteína C (APC-R), fibrinogênio e Lp (a). Os ensaios funcionais da proteína C, proteína S, fator V e APC-R foram executados por métodos baseados em coagulação. A avaliação semiquantitativa do fibrinogênio foi feita pelo método de Clauss e a Lp(a) por imunoturbimetria. A análise estatística foi feita pelo software Epi Info 6. RESULTADOS: Trinta e três amostras (38.8%) foram positivas para um ou vários marcadores do trombofilia. As anomalias mais comuns foram Lp (a) (20%), fibrinogênio (17.6%) e APC-R (14.2%) elevados. Baixos níveis da proteína C, proteína S e AT foram detectados em 4.7%, 9.4% e 7% dos pacientes, respectivamente. Globalmente, os perfis dos fatores de risco foram: fumo (33%), antecedentes familiares positivos (15.3%), hiperlipidemia (7%), hipertensão, diabetes mellitus e obesidade (2.3% cada). CONCLUSÕES: Uma associação foi encontrada entre baixos níveis de proteína C, proteína S, AT e trombose arterial, ...

Marcadores séricos de trombofilias hereditárias e anticorpos antifosfolípides em gestantes com antecedentes de pré-eclâmpsia grave / Serum markers of inherited thrombophilia and antiphospholipid antibodies in pregnant women with previous history of severe pre-eclampsia

OBJETIVO: Verificar a frequência e a associação de marcadores séricos para trombofilias hereditárias e adquiridas em gestantes com histórico de pré-eclâmpsia grave em gestação anterior. MÉTODOS: Estudo tipo caso-controle composto por 81 gestantes com histórico de pré-eclâmpsia grave em gestação anterior (grupo de estudo) e 32 gestantes sem antecedente de pré-eclâmpsia grave em gestação anterior (grupo controle). Foi rastreada a presença de anticorpos antifosfolípides e trombofilias hereditárias em ambos os grupos. Foi utilizado o teste χ² com correção de Yates para verificar as associações e calcular os riscos relativos. RESULTADOS: Verificou-se a presença de trombofilias em 60,0 por cento das pacientes com histórico de pré-eclâmpsia e em 6,0 por cento das pacientes do grupo controle. Encontrou-se significante associação entre pré-eclâmpsia grave em gestação anterior e presença de marcadores para trombofilias hereditárias/anticorpos antifosfolípides (p<0,05). Identificou-se risco relativo para desenvolvimento de pré-eclâmpsia grave de 1,57 (1,34

PURPOSE: To determine the frequency and the association of serum markers for inherited and acquired thrombophilias in pregnant women with a history of severe pre-eclampsia in previous pregnancies. METHODS: Case-control study consisting of 81 pregnant women with a history of severe pre-eclampsia in previous pregnancies (study group) and 32 women with no history of severe pre-eclampsia in previous pregnancies (control group). The presence of inherited thrombophilia and antiphospholipid antibodies was screened in both groups. We used the chi-square test with Yates correction to assess associations and calculate the relative risks. RESULTS: The presence of thrombophilia was detected in 60.0 percent of patients with a previous history of pre-eclampsia and in 6.0 percent of the control patients. A significant association was found between pre-eclampsia in a previous pregnancy and the presence of markers for hereditary thrombophilia/antiphospholipid antibodies (p<0.05). The relative risk to develop pre-eclampsia was found to be 1.57 (1.34

Valor pronóstico de los niveles de interleucina-6 en pacientes con infarto agudo del miocardio con elevación del segmento ST / Prognostic value of serum levels of interleukin-6 in patients with ST-segment elevation acute myocardial infarction

Introducción: La interlucina-6 (IL6) participa en la aterogénesis y en el fenómeno aterotrombótico más catastrófico: el infarto agudo del miocardio con elevación del ST (IAM CEST). El objetivo de esta investigación fue evaluar el pronóstico de los niveles elevados de IL6 para eventos cardiovasculares mayores en pacientes con IAM CEST. Material y métodos: Estudiamos pacientes consecutivos con diagnóstico de IAM CEST de acuerdo con los criterios convencionales establecidos por la ACC/AHA/ESC. Se determinó IL6 sérica a las 24 horas de iniciado el evento, mediante quimioluminiscencia. Las variables de desenlace fueron arritmias, angina, falla cardiaca, reinfarto no fatal y muerte, o la combinación de ellas durante la hospitalización. Resultados: Incluimos 97 pacientes; el punto de corte de IL6 para identificar a los pacientes con alto riesgo fue de 20 pg/ml. En el grupo I (< 20 pg/ml) fueron 46 pacientes y en el grupo II (> 20 pg/ml), 51 (IL6 11.52 + 4.83 pg/ml versus 63.19 + 44.4 pg/ml, p < 0.0001). Fue más frecuente la muerte (2.2 versus 15.7 %, p = 0.023, RR 1.16 IC 95 % = 1.02-1.31) y el punto final combinado durante la hospitalización en el grupo II (21.7 versus 51 %, p = 0.003, RR = 1.59, IC 95 % = 1.16-2.19). La clase de Killip > 2 y los niveles de IL6 > 20 pg/ml fueron factores independientes para el punto final combinado. Conclusiones: Los niveles de IL6 > 20 pg/ml en IAM CEST se asociaron significativamente a más eventos cardiovasculares durante la hospitalización.

BACKGROUND: Interleukin-6 (IL6) plays a role in atherogenesis as well as in most atherothrombotic phenomenon such as ST-segment elevation acute myocardial infarction (STEAMI). Our objective was to evaluate serum levels of IL6 as prognostic value for major clinical in-hospital events in patients with STEAMI. METHODS: We studied consecutive patients with diagnosis of STEAMI according to ACC/AHA/ESC criteria. Twenty four hours after the acute event, IL6 was determined by chemiluminescence method. The major cardiovascular end points were arrhythmias, angina, heart failure, reinfarction and death. RESULTS: Included were 97 patients. The level of IL6 to identify high-risk patients was 20 pg/ml. Forty six patients had <20 pg/ml (group I), and 51 patients had >20 pg/ml (group II). Mean value of IL6 was 11.52 +/- 4.83 pg/ml vs. 63.19 +/- 44.4 pg/ml (p <0.0001). Death was more frequent (2.2 vs. 15.7%, p = 0.023, RR 1.16 95% CI 1.02-1.31) and the end point combined during hospitalization in group II was 21.7 vs. 51% (p = 0.003 RR 1.59 95% CI 1.16-2.19). Multivariate logistic regression analysis identified Killip class > or = 2 and IL6 levels > or = 20 pg/ml as predictors for in-hospital end point. CONCLUSIONS: Serum levels of IL6 >20 pg/ml in the first 24 h after STEAMI were significantly associated with higher frequency of in-hospital outcomes such as arrhythmias and death.

Evaluation of the role of thrombophilia associated factors in pre-eclampsia

To evaluate the role of thrombophilia associated factors in pre-eclamptic pregnant women. A case control study was conducted on 30 severe pre-eclamptic pregnant women [group A], and 30 normotensive pregnant women [group B] from Shatby University Maternity Hospital. Routine laboratory tests, protein C, protein S, antithrombin III, factor V Leiden and anticardiolipin antibodies [IgM, IgG] were measured for both groups. Informed consent of the patients was taken. There was not any significant difference in the values of factor V Leiden, protein C, protein S, antithrombin III, and anticardiolipin IgG between pre-eclamptic and normotensive pregnant women. However, anticardiolipin IgM was shown to be significantly higher in the pre-eclamptic patients. Severe pre-eclamptic patients were 3.5 times more likely to develop elevated levels of anticardiolipin IgM. Routine screening for inherited thrombophilia disorders is not recommended in pre-eclamptic females

Assessment of the role of some haemostatic parameters in patients with cryptogenic stroke

Cryptogenic stroke [CS] is a stroke of unexplained aetiology, in 1/3 the of cases, the cause of stroke remains undetermined inspite of full investigations. Patient with CS are thought to have a state of hypercoagulablity. To unmask some of the pathogenic mechanisms underlying cryptogenic stroke through assessment of some genetic disorders including C6[77]T mutation methyl-enetetrahydrofolate reductase gene, activated protein C [APC] resistance and role of thrombin anti-thrombin complex concentration [TAT] in plasma as indicators of hypecoagulable state. The study was conducted on 20 Egyptian patients divided into 2 groups, group I included 10 patients [6 males and 4 females] with cryptogenic stroke aged less than 50 years and group II included 10 age and sex matched patients with non-cryptogenic stroke. All of the 20 cases studied were subjected to panel of investigations including routine laboratory tests and imaging studies in orders to exclude any risk factors for stroke in group I patients and to determine risk factor of stroke in group II. Both groups were investigated for C6[77]T mutation in methylenetetrahydrofolate reductase gene, activated protein C [APC] resistance and thrombin anti-thrombin complex concentration [TAT] in plasma. No statistical significant difference was found between the two groups as regard C6[77]T mutation in methylenetetrahydrofolate reductase gene, [APC] resistance and TAT concentration in plasma [p value >0.05]. However, TAT level was found to be positively correlated with the clinical severity in non-cryptogenic stroke [p value <0.05]. C6[77]T mutation in methylenetetrahydrofolate gene, [APC] resistance and TAT concentration in plasma are not independent risk factors for cryptogenic stroke. TAT could be used as indicator of clinical severity and prognosis in patient with non-cryptogenic stroke

Relationship between polymorphisms in thrombophilic genes and preeclampsia In Egyptian population

Hypertensive disorders are a major cause of maternal and fetal death especially in developing nations. Preeclampsia has a familial component suggesting that one or more common alleles may act as susceptibility genes. Some families may have [private] predisposing mutations. Preeclampsia and its association with thrombophilia remain controversial, due to inconsistent results in different studies. The aim of this study was to evaluate the relationship between thrombophilic genes mutations and preeclampsia in pregnant women in our region. We compared 15 consecutive women with preeclampsia with 10 normal pregnant women. All women were tested for mutations of factor V lieden, Factor II [prothrombin gene], Factor XIII, B fibrinogen, plasminogen activator inhibitor -1 4G/5G [PAI-1 4G/5G], methylenetetrahydrofolate reductase [M.THR], angiotensin -converting enzyme [ACE] I/D, apolipoproteins [APO E and APO B] genes. This study was based on reverse - hybridization technique using cardiovascular disease strip [CVD] assay. PAI-1 4G/5G polymorphism was highly significantly increased in patient group as compared to control group [60% versus 0%, p= 0.000]. No significant differences were noticed as regards other thrombophilic genes in control and patient groups. We suggest that the pattern of PAI 4G/5G polymorphism might represent a useful marker of increased risk of preeclampsia in our region. Also our findings suggest that women with severe complications of pregnancy should be tested for markers of thrombophilia

Evaluación de inhibidores fisiológicos de la coagulación en pacientes diabéticos tipo 2 / Evaluation about coagulation physiological inhibitors in type 2 diabetic patients

La diabetes mellitus está asociada a disturbios en la hemostasis que pueden contribuir al desarrollo de enfermedad vascular diabética. El objetivo de este trabajo fue estudiar la coagulación en una población diabética de Uruguay y compararla con una población de referencia normal. Se trabajó con 100 pacientes diabéticos tipo 2, de ambos sexos (49 mujeres y 51 hombres), con edades comprendidas entre 42 y 79 años, y una población control representada por 130 individuos aparentemente sanos (73 mujeres y 57 hombres) cuyas edades oscilaron entre 37 y 78 años, los que fueron tomados como referencia. Se realizaron las determinaciones de tiempo de protrombina (TP), fibrinógeno (Fib), proteína C (PC), proteína S (PS), antitrombina III (ATIII) e inhibidor del activador de plasminógeno (PAI) en plasma citratado. El TP y el Fib se realizaron por nefelometría, la PC, ATIII y PAI se midieron cromogénicamente y la PS se determinó por coagulometría. Se encontró que los inhibidores fisiológicos de la coagulación PS y ATIII son significativamente menores en la población diabética, en tanto que los factores procoagulantes Fib y PAI son significativamente mayores, comparados con la población de referencia. De los hallazgos precedentes se confirma una tendencia a un disbalance hemostático que contribuiría al estado protrombótico que acompaña a un alto porcentaje de la población diabética.

Diabetes mellitus is associated with disturbances in hemostasis, which may contribute to the development of diabetic vascular disease. Coagulation tests were performed both in diabetic patients and healthy individuals in Uruguay. The results obtained were compared. Diabetic patients were 100, with ages between 42 and 79 years, 49 females and 51 males. Reference population were 130 healthy individuals between 37 and 78 years, 73 females and 57 males. Prothrombin time (PT), fibrinogen( Fib), protein C (PC), protein S (PS), antithrombin III (ATIII) and plasminogen activator inhibitor (PAI) were measured on citrated plasma. PT and Fib were determined nephelometrically, PC, ATIII y PAI were measured cromogenically and PS was determined by coagulometry. Coagulation physiological inhibitors outcomes such as PS and ATIII showed significantly lower levels in the diabetic patient than in the healthy person, and at the same time, Fib and PAI, which are procoagulant factors, have significantly higher concentrations in the diabetic patient than in the healthy person. These findings permit to assess that an impaired haemostatic balance is present in the diabetic population, which may contribute to the hypercoagulability that accompanies a high percentage of these patients.

Thrombophilia profile in Thai patients with arterial thrombotic disorders.

BACKGROUND: Arterial thrombosis is attributed mainly to atherosclerosis and the roles of hypercoagulability remain unclear In addition, there are ethnic variations in thrombophilia profiles. OBJECTIVE: The authors performed a survey of the thrombophilia profile in Thai patients with arterial thrombosis MATERIAL AND METHOD: The authors analyzed 103 consecutive cases of proven arterial thrombosis and requested thrombophilia profile in Chulalongkorn Hospital during 2003-2004. The mean age was 42.5 years. The proportions of stroke, peripheral arteries, and other sites were 70.9%, 22.3% and 6.8%, respectively. RESULTS: Abnormal profile was found in 35.0% with the prevalence of hyperhomocysteinemia, low protein S, antiphospholipid antibody and low protein C was 15.5%, 12.6%, 9.7%, and 5.8%, respectively. There was no difference in clinical characteristics between cases with or without detectable abnormalities. However, the authors found significant associations of low protein S with poor outcome and HIV seropositivity with antiphospholipid. CONCLUSION: The present study found that the defective protein C pathway may be the most common thrombophilia found in Thais with arterial thrombosis. Future study is required to prove the cause-effect relationship and its clinical significance.

Disturbance of some coagulation and fibrinolytic factors in essential hypertension

Hypertension is an established risk factor for acute coronary events. Growing evidence is now apparent that hypertension is accompanied by hypercoagulable and/or hypofibrinoltic state, both of which can be the cause of several cardiovascular risk factors noticed with hypertension. To show the relationship between hypertension and some components of fibrinolytic and coaguIation systems . In this study, the plasma levels of fibrinogen, FVII, D-dimer, t-PA and PAI-I were studied in three groups of male persons. A hypertensive group of patients [16], complicated hypertensive group [16] and a group of normotensive persons [16] were included in this work Patients were selected from outpatient clinic of Cardiology Department, Assiut University Hospital, during the period from December 2001 until December 2002. The mean plasma levels of fibrinogen, FFVII, t-PA, PAZ-I and D dimer before treatment of the hypertensive and complicated hypertensive groups were significantly higher than that of the normotensive group .The mean plasma levels of these factors [except FVII] in the complicated hypertensive group were significantly higher than that of the hypertensive group. After treatment of these groups, the mean plasma levels of all factors decreased significant and there was no significant difference between the two groups. It is clear from this study that there are disturbances in the levels of coagulation and fibrinolytic factors in hypertensive patients particularly in the complicated hypertensive patients. This indicates severity of disturbance of these factors in hypertensive patients making them risk factors for the development of coronary heart disease, myocardial infarction, unstable angina, etc

Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-β2-glycoprotein-I antibodies / Resistencia a la proteína C activada y actividad de anticoagulante lúpico inducidas por plasma y por anticuerpos purificados humanos del IgG anti β2-glicoproteína I

ABSTRACT Introduction. We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-β2-glycoprotein-I (anti-β2GP-I) antibodies. Patients and methods. We studied plasma and sera samples from 29 patients with persistently positive anti-β2GP-I: 22 with thrombosis (12 with primary APS, 10 with APS secondary to SLE) and seven without thrombosis (all with SLE); 25 healthy subjects were studied as controls. We detected anticardiolipin antibodies (ACA); IgG (and its subclasses) and IgM anti-β2GP-I, on irradiated and non-irradiated plates by ELISA. APCR was assessed by the activated partial thromboplastin time (APTT)-based assay and by the modified test. The FV Leiden mutation was studied by PCR. LA determination included screening and confirmatory dRVVT. Serum anti-β2GP-I were affinity purified on sepharose columns and their isotype, subclass, and reactivity against various antigens were studied by ELISA. Results. We found that titers of IgG anti-β2GP-I on irradiated plates were higher than on non-irradiated plates (p = 0.002), IgG2 was the predominant subclass. Fifteen patients (13 with thrombosis) had LA and 15 (also 13 with thrombosis) induced the APCR phenotype. Eleven (all with thrombosis) had both. Two patients were heterozygous for the Leiden mutation. Two purified antibodies, monospecific for β2GP-I, induced an in vitro APCR phenotype and LA activity. Conclusions. Our results seem to indicate that the inhibition of the APC anticoagulant function by IgG2 anti-β2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS.

Introducción. Investigamos la resistencia a la proteína C activada (RPCA) y la actividad de anticoagulante lápico (AL), inducidas por anticuerpos anti-β2-glicoproteína-I (anti-β2GP-I). Pacientes y métodos. Estudiamos los plasmas y sueros persistentemente positivos para anti-β2GP-I de 29 pacientes: 22 tuvieron trombosis (12 con síndrome de antifosfolípidos (SAF) primario y 10 con SAF secundario a lupus erítematoso generalizado (LEG)) y siete sin trombosis (todos con LEG). Como controles estudiamos 25 sueros de personas clínicamente sanas. Detectamos anticuerpos anticardiolipina, anti-β2GP-I IgG (y sus subclases) e IgM por ELISA en placas irradiadas y no irradiadas. Evaluamos la RPCA por medio del tiempo parcial de tromboplastina activada y por la prueba modificada. Estudiamos la mutación FV de Leiden por PCR y el anticoagulante lápico con el método de dRVVT screening y confirmatorio. Después de purificar los anti-β2GP-I séricos con una columna de antígeno unido a sefarosa, analizamos por ELISA sus isotipos, subclases y reactividad contra β2GP-I y algunos fosfolípidos. Resultados. Los títulos de anti-β2GP-I IgG fueron más altos en placas irradiadas que en no irradiadas (p = 0.002), predominó la subclase IgG2. Quince plasmas (13 de pacientes con trombosis) tuvieron AL y 15 (13 también de pacientes con trombosis) indujeron el fenotipo de RPCA. Once plasmas (todos de pacientes con trombosis) indujeron ambas actividades. Dos pacientes fueron heterocigotos para la mutación de Leiden. Dos anticuerpos purificados monoespecíficos para β2GP-I indujeron el fenotipo de la RPCA y la actividad de AL in vitro. Conclusiones. Nuestros resultados sugieren que la RPCA, inducida por los anti-β2GP-I que concomitantemente tienen actividad de AL, puede tener implicaciones patogénicas en la trombofílía del SAF.

Determinación de factores trombofílicos en pacientes con trombosis venosas retinianas / Markers of thrombophilia in patients with retinal vein thrombosis

Background: Thrombophilia is an alteration of hemostasis that increases the risk to venous or arterial thrombosis. This condition may be the underlying cause of retinal vein thrombosis. Aim: To study the presence of thrombophilia in patients with retinal vein thrombosis. Patients and methods: Prospective study of 55 patients aged 22 to 86 years, with retinal vein thrombosis (central or branch). Antithrombin III, coagulant protein C, functional protein S, resistance to activated C protein, homocysteine, prothrombin G20210A gene, lupus anticoagulant and anticardiolipin antibodies were measured in all. Results: Seventeen patients had thrombophilic markers (antiphospholipid syndrome in seven, hyperhomocysteinemia in six and resistance to protein C in three). Of these 17 patients, 53percent had high blood pressure, 35percent an abnormal serum lipid profile and 23percent a personal history of thrombosis. The thrombosis was central in 12 (ischemic in four) and of a branch in five (ischemic in two). Conclusions: Thrombophilic markers must be assessed in patients with retinal vein thrombosis.

Combination of thrombophilia markers in acute myocardial infarction of the young.

BACKGROUND: The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. But, there have been very few studies in India which have investigated some of the thrombophilia markers. AIM: To look for combined thrombophilia in MI patients. SETTINGS AND DESIGN: One hundred twenty patients of myocardial infarction (age below 40 yrs.) were recruited 8-10 weeks after stabilization. Hundred age and sex-matched healthy controls were also recruited in the present study. METHODS AND MATERIAL: Following thrombophilia markers were screened in these patients--plasma fibrinogen, protein C, protein S, antithrombin III, factor V Leiden, PT G20210A polymorphism, MTHFR C677T, homocysteine, fibrinogen b448 Arg/Lys polymorphism and CBS T833C mutation. STATISTICAL ANALYSIS: Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 10.0, SPSS Inc., Chicago, USA. RESULTS AND CONCLUSION: Elevated fibrinogen levels, homocysteine (p< 0.001 and homocysteine with odds ratio 6.26) and factor V Leiden (p=0.038) were independently associated with MI in our patients. A total of 37 patients (42.5%) had the presence of more than one thrombophilia markers in combination. Out of these, 10 had the presence of three markers in combination and 1 had five thrombophilia markers in combination. Only 2 controls had prothrombotic markers in combination. Combined prothrombotic risk factors were significant in cases in comparison to controls (p< 0.001). Further larger studies on a nationwide basis recruiting a large number of young MI patients should be done to substantiate these findings.

Resistência à proteína C ativada / Resistance to activeted protein C

O fator V da coagulaçäo, quando ativado, participa como um co-fator essencial na ativaçäo da pró-trombina pelo fator X ativado. O fator V ativado é inativado pela proteína C ativada, numa reaçäo potencializada pela proteína S. Uma mutaçäo no éxon 10 (Arg 506 Gln) do gene do fator V dß origem a uma molécula do fator V que näo é adequadamente inativada pela proteína C ativada, o que causa a chamada resistência à proteína C ativada.