[From apixaban to aspirin in the prevention of recurrent venous thromboembolism]. / Desde el apixaban hasta la aspirina, en la prevencíon del tromboembolismo venoso recurrente.

For more than a decade, the only treatments available for the prevention of recurrent venous thromboembolism, were vitamin K inhibitors, or low molecular weight heparins (LMWH). Both have been very useful for this purpose; however, with the inconvenience of required frequent laboratory tests and the risk of provoking major hemorrhages. LMWH also carry the risk for immune reactions and the high cost of using it for an extended period of time. With the advent of the new anticoagulants, there is no need for laboratory tests, but there is no way to individualize the dose, or to neutralize their effect. They are also very expensive. Several recent articles have shown that aspirin, as the only treatment for the prevention of recurrent venous thromboembolism, gave good results in comparison to placebo. It has also been found that, after hip replacement surgery, the frequency of thromboembolism was similar in those patients treated with aspirin and those treated with LMWH. These results could open a new path in the search for the ideal treatment for the prevention of recurrent venous thromboembolism.

[Use of warfarin and low range INR in the prevention of recurrent venous thrombosis]. / Uso de warfarina y bajo rango de INR en la prevención de trombosis venosa recurrente.

The object of this work was to determine the efficacy of a low range International Normalized Ratio (INR) between 1.5 and 1.9, in preventing recurrent venous thrombosis and the hemorrhagic manifestations that can complicate anticoagulation with warfarin. Thirty nine patients, 10 to 78 years of age were studied between January 2006 and November 2009. All of them had been treated with warfarin, for at least 6 months, due to deep venous thrombosis or pulmonary embolism. The subjects were separated, at random, into two groups. In group A (20 patients), the doses of warfarin were adjusted until the INR was stabilized between 1.5 and 1.9; in group B, the INR was maintained between 2 and 3. The coagulant activities of plasma factors II, VII, IX and X were determined in a week and between the fourth and fifth weeks, after stabilization of the INR. Plasma activities of the coagulation factors assayed were abnormally low in both groups, in the two opportunities they were determined, although significantly lower in group B (p<0.05). No thromboembolic episodes occurred during the study, in any of the patients. One of the patients from group A and four from group B, presented minor hemorrhagic manifestations (p N.S.) The above results suggest that a range on INR lower that 2, could be sufficient to prevent recurrent thrombotic episodes while diminishing the frequency of hemorrhagic complications associated with the use of warfarin. However, it is necessary to continue incorporating more individuals in the study to obtain greater certainty in the analysis of these results.

[Treatment of chronic immune thrombocytopenic purpura. Looking for something better. Review]. / Tratamiento de la púrpura trombocitopénica inmune crónica. Buscando algo mejor. Revisión.

Chronic Immune Thrombocytopenic Purpura (cITP) has become a field of multiple therapeutic assays. More than 20 types of treatment have been developed to obtain a favorable and prolonged platelet response. The treatment of cITP is oriented to inhibit the antiplatelet antibodies production by interference with the macrophage of the reticulum endothelial system and a blockade of the antigenic response with a decrease in the amplification of the immunological response. Steroids of the glucocorticoids type and splenectomy constitute the first line of treatment. Failure of these treatments leads to the use of second line drugs such as non steroid immuno-supressors and the immunoglobulins type IgG and anti-D. Therapeutic assays with others immunomodulators have been reported. The introduction of new drugs destined to increase the megakaryocytic bone marrow platelet production, has opened a new way to treat the cITP. However, the splenectomy remains as the simplest, safest and most effective treatment in cITP. The principal criteria does not have to be focused on obtaining a normal platelet count, but to reach safe hemostatic levels in absence of hemorrhage, for a prolonged time. On the other hand, despite the persistence of thrombocytopenia, the hematologist can choose to maintain the patient with no treatment and with only a strict clinical observation. It is obvious that the cost-benefit from the different treatments is inclined towards those of lower cost and minimal secondary effects.

[Relationship of fibrinogen with cardiovascular risk factors in healthy men from Maracaibo, Venezuela]. / Relación del fibrinógeno con factores de riesgo cardiovascular en hombres aparentemente sanos de Maracaibo, Venezuela.

The purpose of this paper was to determine the relationship between fibrinogen concentration and cardiovascular ischaemic risk factors in a group of apparently healthy men from Maracaibo, Venezuela. Two hundred and forty six individuals, ages 31 to 65 years were evaluated by means of clinical and laboratory examination. In each person plasma fibrinogen concentration was measured by coagulometry, serum glucose and lipids by enzymatic methods and insulin by radioimmunoanalysis. 31.7% of subjects had fibrinogen values in the highest tertil of the whole group (> or = 311 mg/dL), they also showed significantly higher values of total cholesterol (p < 0.03) and LDL-C (p < 0.01). In addition, the individuals in this tertil showed a significant and positive correlation between the values of triglycerides with insulin (p < 0.02) and with HOMA-IR (p < 0.01). On the other hand, correlation analysis also showed a positive significant association between the fibrinogen levels and total cholesterol (p < 0.02), dependent of individuals with family history of ischaemic cardiovascular disease (total cholesterol: p < 0.02 and LDL-C: p < 0.003). In consideration of the high concentrations of fibrinogen found in 31.7% of apparently healthy men and their significant positive correlation with total cholesterol and LDL-C, on the group of men with a family history of ischaemic cardiovascular disease, it would be advisable to include the determination of fibrinogen in the cardiovascular evaluation of these particular subjects.

[Frequency and clinical implications of lupus anticoagulant in patients with terminal chronic renal failure in hemodialysis]. / Frecuencia e implicaciones clínicas del Anticoagulante Lúpico en pacientes con Insuficiencia Renal Crónica Estadio V en Programa de Hemodiálisis en Maracaibo, Venezuela.

The objective of the present study was to determine the frequency of lupus anticoagulant (LA), in patients with terminal chronic renal failure (TCRF), and its association with thrombotic events. Sixty three patients were separated into two groups: Group A, consisted of 32 patients under treatment with hemodialysis, and Group B was formed of 31 patients who were treated in a conservative manner. Presence of LA was found in 4 patients from Group A and none from Group B. Seven thrombotic events were registered, all in patients from Group A, and three of the episodes happened in 2 patients with LA, showing a statistically significant difference with LA negative patients from the same Group A (p < 0.001). Three of the LA positive patients suffered from type 2 diabetes and all of them had been under dialysis for less obtained by than 6 months. Vascular access was catheterization which means that 57.1% of patients with this type of procedure were positive for LA. The present results show a strong relationship between the presence of LA and thrombotic episodes in patients with TCRF, under hemodialysis with the use of catheter, instead of a permanent vascular access. Due to the fact that prolonged use of catheters for hemodialysis has been related to positive LA, it is advisable to screen patients under dialysis for the presence of this antibody, and to promote the prompt availability of a permanent vascular access, in order to prevent complications, such as thrombosis.

Increased C-reactive protein and decreased Interleukin-2 content in serum from obese individuals with or without insulin resistance: Associations with leukocyte count and insulin and adiponectin content.

AIMS: Chronic inflammation in obesity is associated with co-morbidities such as, hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in this inflammation and C-reactive protein (CRP) and Interleukin-2 (IL-2) can be important effectors during the immune response in obesity; however, the initial inflammatory events in obesity remain unclear. The aim of this study was to determine the circulating levels of CRP, IL-2, insulin and adiponectin, their association and the association with leukocyte count in obese individuals without co-morbidities and with or without insulin resistance (IR). MATERIALS AND METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of CRP, IL-2, insulin, adiponectin, lipids, glycated hemoglobin, glycemia, for homeostasis model assessment of insulin resistance (HOMA-IR), arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Associations were determined by Pearson's correlation. RESULTS: None of the studied groups presented co-morbidities and two groups of obese individuals with normal or high levels of insulin (IR) were found. Increased CRP concentration and decreased IL-2 and adiponectin concentrations in obese were observed. Positive correlation between leukocyte type counts with CRP in obese with IR was found; however, no correlations with IL-2 in obese were observed. Insulin in obese were positively correlated with CRP and negatively correlated with IL-2 in IR obese individuals. Adiponectin in obese was negatively correlated with CRP. CONCLUSION: CRP and IL-2 may represent two important effectors in the early inflammatory events in obese individuals without co-morbidities. Adiponectin and insulin may be involved in anti-inflammatory events.

[Homocysteinemia and its relationship with the methylentetrahydrofolate reductase polymorphism in various ethnic groups from western Venezuela]. / La homocisteinemia y su relación con el polimorfismo de la metilentetrahidrofolato reductasa en varios grupos etnicos del occidente de Venezuela.

The prevalence of hyperhomocysteinemia and C677T MTHFR polymorphism was studied in various ethnic groups from Western Venezuela (60 Wayuu Indians, 42 italian immigrants and 77 Venezuelan mestizos) in relation with the prevalence of hyperhomocysteinemia and the C677T MTHFR polymorphism. Homocysteinemia was determined by polarized fluorescence immunoassay in an IMX system, serum folate was measured by radioimmunoanalysis and the MTHFR genotype was determined by PCR and restriction analysis. Hyperhomocysteinemia was defined as a value over 2 SD above the mean value for normal MTHFR (CC677) in each group. The prevalence of MTHFR variants (C677T and 677TT) was elevated in all ethnic groups (78% among the wayuu, 76% among Italians and 63% among mestizos) with a significant association between the concentrations of homocysteine and the levels of serum folate among the wayuu (p < 0.0001) and the mestizos (p < 0.001) only. Hyperhomocysteinemia was associated with MTHFR variants in 23% of the wayuu (OR: 6.17, CI 95: 0.74-51.36), 9.5% of the Italians (OR: 0.93, CI 95: 0.085-10.10) and 20.7 of the Venezuelans mestizos (OR: 5.2, CI 95: 1.08-24.90, p > 0.03). There was no relationship between hyperhomocysteinemia and folate deficiency in any of the groups studied. In conclusion, despite a high prevalence of C677T MTHFR variants in these ethnic groups of western Venezuela, the lack of no evidence of hyperhomocysteinemia combined with folate deficiency may imply that the nutritional status of these groups plays an important role in the control of hyperhomocysteinemia as a risk factor for cardiovascular disease.

[Plasma homocysteine concentration and its relationship with the development of preeclampsia. Effect of prenatal administration of folic acid]. / Concentraciones de homocisteína plasmática en embarazadas y su relación con el desarrollo de preeclampsia. Efecto de la administración prenatal de ácido fólico.

The increase of plasmatic homocysteine (Hc) in pregnant women, who later develop preeclampsia/eclampsia, the cause of this increment and its pathogenic role in toxemia of pregnancy, are still controversial. The objectives of the present research were to determine the plasmatic He concentrations during the first and second trimesters of pregnancy and the effect of folic acid administration on these values, and in the prevention of preeclampsia. Ninety six pregnant women of low economic background were studied on the first prenatal consultation: 27 women in the first trimester of pregnancy and 59 in the second. After 8 hours of fasting, venous blood was extracted and each patient was provided with 1 mg folic acid tablets and instructed to ingest one tablet daily, and to come back to the laboratory after three months. Plasma homocysteine and serum folic acid were determined for each patient before and after the folic acid treatment, by using the IMX system (Abbott Lab) and radioimmunoassay, respectively. Basal homocysteine concentrations were 4.0 +/- 2.1 micromol/L and 4.8 +/- 2.1 micromol/L in the first and second trimesters respectively, with no significant modifications after three months of folic acid. Although the degree of desertion from the study was high, it was possible to determine the evolution of 65 pregnancies. Ten of them developed preeclampsia (15.4%). No significant differences were found in Hc concentrations, or the frequency of hyperhomocysteinemia in the different stages of pregnancy, between women with normal gestation and those who developed preeclampsia. The small sample size of these groups, preclude any valid conclusion, however the results do not suggest that Hc concentration or folic acid administration influence the development of toxemia of pregnancy.

[Relation of socioeconomic levels and life style to fibrinogen and von Willebrand factor in healthy Venezuelans and those with ischemic cardiopathy]. / Relación entre el nivel socioeconómico y hábitos de vida, con el fibrinógeno y el factor von Willebrand en venezolanos sanos y con cardiopatía isquémica.

Previous studies in Europe, U.S.A and Japan have revealed an inverse relationship between socioeconomic levels and fibrinogen concentration. Similar results have been reported in a smaller number of studies for concentrations of von Willebrand factor. In this opportunity we present results on the relationship between smoking, drinking, physical activity, age and socioeconomic level on fibrinogen and von Willebrand factor concentrations in a Venezuelan sample. The control population consisted of 978 men and 968 women. Patients with coronary heart disease were 172 males and 78 females. The presence of one or more of the following conditions: smoking or less than 5 years of having quit, non drinkers or drinking in excess, and a reduced physical activity, was considered a health related risk factor for high levels of these two haemostatic variables. Our results indicate that in Controls, the socioeconomic level had a significant effect on fibrinogen and von Willebrand factor levels, only in women: those of lower socioeconomic levels had the highest concentrations. This difference was maintained when age was taken into account. Health related behaviors had no significant effect on either variable. In patients, age had no effect on either variable. The health behavior risk factor had a significant effect only on fibrinogen of male patients, and socioeconomic level had a significant effect only on the fibrinogen of female patients. More studies in Venezuela are recommended, in order to increase our knowledge on the relationship between socioeconomic levels, haemostatic markers and the occurrence of coronary heart disease.

Increased proinflammatory markers and lipoperoxidation in obese individuals: Inicial inflammatory events?

BACKGROUND: Chronic inflammation associated to obesity increases the risk for developing insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. The initial factors involved in generating the inflammatory events in the obesity remain unclear. Therefore, this study was aimed to determine inflammatory and oxidative markers in the blood of obese individuals with normal clinical and biochemical parameters and with or without IR. METHODS: Nineteen obese non-diabetic and nine lean subjects were studied for serum levels of TNF-α, IL-1ß, adiponectin, angiotensin II, insulin, malondialdehyde (MDA) and the expressions of RAGE (advanced glycation end product receptor), AT1 (Ang II receptor), s100A12 protein (RAGE ligand) and nuclear factor-κB (NF-κB) in circulating mononuclear cells (CMC) by available antibodies and commercial kits. CMC were also cultured to determine pro-inflammatory mediators. RESULTS: Insulin was increased in obese subjects with IR. Decreased serum adiponectin in obese individuals and increased TNF-α, IL-1ß and CMC bearing RAGE, AT1 and s100A12 in obese individuals without IR were found. High values of serum MDA in obese subjects were observed. Similar TNF-content in cultures from obese and controls, increased cellular IL-1ß content in cultures from obese individuals without IR and high content of MDA in supernatants from obese individual cultures were observed. CONCLUSIONS: The inflammatory events were mainly observed in obese individuals without IR. The absent of inflammatory events and high levels of insulin in obese subjects with IR, suggest a protector role of insulin for developing inflammatory events. These data can represent initial aspects of the chronic inflammation observed in the obesity.

[Nutritional anemia of pregnancy in the Zulia state. 30 years later]. / Anemia nutricional del embarazo en el estado Zulia. Treinta años después.

Thirty years ago, we reported a high frequency of nutritional anemia among pregnant women of low socioeconomic class, from Zulia State, Venezuela. Today, preliminary results, show an increase of anemia from 20% in the year of 1972 to 44% at the end of the first trimester of gestation, and from 53% to 63% at the end of the third trimester. These results could be the reflection of the impairment of the economic conditions in the country and the failure of the prenatal care services in preventing or treating anemia in pregnancy.

[Prevalence of obesity and hyperinsulinemia: its association with serum lipid and lipoprotein concentrations in healthy individuals from Maracaibo, Venezuela]. / Prevalencia de obesidad e hiperinsulinemia en una poblacion aparentemente sana de Maracaibo, Venezuela y su relación con las concentraciones de lípidos y lipoproteínas del suero.

The aim of this study was to analyse the prevalence of obesity and hyperinsulinemia and their association with lipid profile alterations on apparently healthy individuals from Maracaibo, Venezuela. We evaluated 306 men and 41 women, ages ranging from 33 to 65 years. All subjects underwent cardiovascular evaluation and laboratory examination after 10-12 h fasting, for glycaemia, total cholesterol, TG, VLDL-C, LDL-C and HDL-C as well as insulin. Seventy-four percent of men and 56.1% of women showed obesity (BMI > 25 Kg/m2). Men showed high concentrations of TG (48.3%), total cholesterol (40.2%), VLDL-C (48.3%) and LDL-C (33.9%) and low HDL-C levels (48%). The most frequent alteration on the lipid profile in women was high total cholesterol (46%) and LDL-C (51.2%). Men had significantly higher insulin concentrations than women (p < 0.005). After they were classified as obese or non obese, the obese subjects (men and women) showed higher prevalence of lipid profile alterations and insulin concentrations than non obese. The insulin concentration in obese men correlated with BMI, TG, VLDL-C and HDL and, in women with BMI, TG and VLDL-C. In conclusion, a high percentage of men and women in this study showed obesity and this obesity, specially in men, was strongly associated with lipid profile alterations and high insulin concentrations both well known cardiovascular risk factors.

[Hemostatic coronary risk factors in a healthy population of Maracaibo, Venezuela]. / Factores hemostáticos de riesgo coronario en una población sana de la ciudad de Maracaibo, Venezuela.

The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study.

Association of obesity with leukocyte count in obese individuals without metabolic syndrome.

AIMS: Inflammation in obesity is associated to insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in obesity associated inflammation. The initial factors that generate the inflammatory events in the obesity remain unclear. Therefore, the aim of this study was to determine the association of circulating leukocytes with clinical and biochemical parameters in obese individuals with clinical and biochemical parameters in normal range and with or without IR. METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of insulin, lipids, glycated hemoglobin, glycemia, for clinical parameters as HOMA-IR, arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Association between leukocytes and studied parameters was determined by Pearson's correlation. RESULTS: Two groups of obese individuals were observed: with high levels of insulin (with IR) and with normal levels (without IR). Positive correlations were observed between leukocyte and lymphocyte counts with body mass index and HOMA-IR and negative correlation with decreased HDL levels. Lymphocytes correlated with increased levels of insulin. Leukocytes and neutrophils correlated positively with increased visceral fat and liver steatosis. These associations were absent in the obese group without IR. N/L ratio did not show correlations with studied parameters. The leukocyte associations were mainly observed in obese individuals with IR. CONCLUSIONS: These data may represent initial leukocyte associations with morbidity features and define two different obese individuals that may evolve to the chronic inflammation observed in the obesity.

Uso de warfarina y bajo rango de INR en la prevención de trombosis venosa recurrente / Use of warfarin and low range INR in the prevention of recurrent venous thrombosis

El objetivo de este trabajo fue determinar la efectividad de un rango de la Razón Normalizada Internacional (INR) entre 1,5 y 1,9 en la prevención de la recurrencia de trombosis venosa y de las complicaciones hemorrágicas asociadas al uso de warfarina. Entre enero del 2006 y noviembre del 2009, se estudiaron 39 pacientes, con edades entre 10 y 78 años y diagnóstico de trombosis venosa profunda y/o embolismo pulmonar que recibieron warfarina al menos durante 6 meses. Los sujetos fueron separados aleatoriamente en dos grupos: a 20 pacientes se le ajustó la dosis para mantener el INR entre 1,5 y 1,9 y a 19 pacientes se les mantuvo el INR entre 2 y 3. A cada individuo se le cuantificó la actividad plasmática de los factores II, VII, IX y X a la primera y entre la cuarta y quinta semanas, luego de estabilizado el INR. En ambos grupos, la actividad de los factores se encontró por debajo del valor normal con diferencia significativa entre los grupos (p<0,05). No se detectó recurrencia de trombosis durante el seguimiento. Solo se presentaron manifestaciones hemorrágicas menores en un sujeto con INR entre 1,5 y 1,9 y en cuatro del otro grupo (p = NS). Los resultados del presente trabajo sugieren que un rango de INR entre 1,5 y 1,9, provee un esquema de anticoagulación eficaz para la prevención de recurrencia de trombosis venosa con menor frecuencia de hemorragias. Sin embargo, es necesario seguir incorporando más individuos en el estudio para obtener mayor certeza en el análisis de estos resultados.

The object of this work was to determine the efficacy of a low range International Normalized Ratio (INR) between 1.5 and 1.9, in preventing recurrent venous thrombosis and the hemorrhagic manifestations that can complicate anticoagulation with warfarin. Thirty nine patients, 10 to 78 years of age were studied between January 2006 and November 2009. All of them had been treated with warfarin, for at least 6 months, due to deep venous thrombosis or pulmonary embolism. The subjects were separated, at random, into two groups. In group A (20 patients), the doses of warfarin were adjusted until the INR was stabilized between 1.5 and 1.9; in group B, the INR was maintained between 2 and 3. The coagulant activities of plasma factors II, VII, IX and X were determined in a week and between the fourth and fifth weeks, after stabilization of the INR. Plasma activities of the coagulation factors assayed were abnormally low in both groups, in the two opportunities they were determined, although significantly lower in group B (p<0.05). No thromboembolic episodes occurred during the study, in any of the patients. One of the patients from group A and four from group B, presented minor hemorrhagic manifestations (p N.S.) The above results suggest that a range on INR lower that 2, could be sufficient to prevent recurrent thrombotic episodes while diminishing the frequency of hemorrhagic complications associated with the use of warfarin. However, it is necessary to continue incorporating more individuals in the study to obtain greater certainty in the analysis of these results.