Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

[Effect of oral and intramuscular vitamin K on the factors II, VII, IX, X, and PIVKA II in the infant newborn under 60 days of age]. / Efecto de la vitamina K oral e intramuscular sobre los factores II, VII, IX, X y PIVKA II en el recién nacido hasta los 60 días de edad. Relación con la alimentación.

BACKGROUND: Neonates on exclusive breast feeding that do not receive vitamin K at birth are at higher risk hemorrhagic disease of the newborn. AIM: To compare the effect of oral or intramuscular administration of vitamin K1 (VK1), on clotting factors II, VII, IX, X and PIVKA II, in children until the 60 days of age with exclusive breast feeding or mixed feeding. PATIENTS AND METHODS: Forty healthy full term infants, distributed in two groups, A: 20 with mixed feeding (formula-feeding and breast-feeding) and B: 20 with exclusive breast feeding, were studied. Nine infants of each group received 1 mg of VK1 intramuscularly and eleven 2 mg VK orally 5 ml of cord blood was collected initially from each infant. Venous blood samples were taken on 15, 30 and 60 days of age. RESULTS: All factors increased in a progressive form reaching levels over 50% at 60 days of age, in both groups. PIVKA II decreased significantly during the study period (p < 0.01). Factor II increased more in children with mixed feeding that received intramuscular vitamin K, than in the rest of study groups. No other differences between groups were observed. No infant had an abnormal bleeding during the study period. CONCLUSIONS: Oral administration of vitamin K is as effective as the intramuscular route in the prevention of the hemorrhagic disease of the newborn.

[Lupus anticoagulant in preeclampsia and non-proteinuria gestational hypertension in primiparous women]. / Anticoagulante lúpico en preeclampsia e hipertensión gestacional no proteinúrica en primigestas.

The purpose of this study was to determine the relationship between the lupus anticoagulant and the proteinuric and non-proteinuric Gestational Hypertension in primigravids without subjacent pathology. Sixty- five patients with a single gestation of twenty or more weeks long were studied. Thirty four patients (Group A) were pregnant women with a normal blood pressure. Hypertensive disease developed during pregnancy (according to Davey and MacGillivray, classification) affected 31 patients (Group B). A test to determine the presence of the lupus anticoagulant was performed on all of them, according to the method of the diluted Russel viper venom. None of the patients developed any other symptomatic subjacent pathology. Fifty-five percent of the Group B patients developed proteinuric gestational hypertension (preeclampsia) and forty-five percent of them non-proteinuric gestational hypertension. The test to determine the lupus anticoagulant was negative in all the patients from both groups. The results suggest that the presence of a lupus anticoagulant is unlikely in the proteinuric and non-proteinuric gestational hypertension in primigravidas without subjacent pathology, therefore it remains as a controversial study issue.

[Effect of stress electrocardiogram on platelet function, concentration of von Willebrand factor and fibrinogen in hypertensive patients and healthy subjects]. / Efecto del electrocardiograma de esfuerzo sobre la función plaquetaria, concentración del factor von Willebrand y del fibrinógeno en pacientes hipertensos e individuos sanos.

The aim of the present study was to investigate the effect of the treadmill electrocardiogram (TMECG) on thrombotic risk factors in hypertensive patients and normal individuals. Twenty patients, 10 males and 10 females between 40 and 55 years of age, were studied and twenty normal persons of matching sex and age were chosen as controls. Blood samples were obtained before and immediately after the TMECG. Platelet counts and function as well as fibrinogen and von Willebrand factor (vWF) levels were determined in each sample. A significant increase in platelet number and aggregation with collagen and ristocetin was observed in all groups after the TMECG. Fibrinogen and von Willebrand factor levels were also significantly increased in all individuals. It is known that platelets play an important role in the formation of thrombi and the enhancement in their number and activity, in certain circumstances, might favor the development of a thrombotic episode. Elevated fibrinogen concentrations are considered an independent cardiovascular risk factor. The above changes in patients with other predisponent factors for cardiovascular events, such as arterial hypertension, enhances the possibility of a vasooclusive episode. It is recommended therefore, that before suggesting a physical activity to a hypertensive patient, other parameters, such as age, previous training and the existence of other cardiovascular risk factors should be considered.

[Prevalence of the activated protein C resistance in indigenous and Black populations of the western Venezuela]. / Prevalencia de la resistencia a la proteína C activada en poblaciones indígena y negra del occidente de Venezuela.

The Activated Protein C Resistance (APCR) is the common phenotype of Factor V Leiden (arg506gln), which is considered as a thrombotic risk factor. The aim of this study was to determine the prevalence of APCR and its association with Factor V Leiden in indian and black populations from Zulia State in western Venezuela. Blood samples were taken from 80 Yukpa indians from Sierra de Perijá and 91 black individuals from the southeast of Lago de Maracaibo. APCR was determined by the Dahlback's method with the modifications of Jorquera et al. and Trossaert et al. The results were expressed as n-APC-SR (positive value < or = 0.75). Factor V Leiden genotype was identified by PCR and restriction analysis standard methods at the Institute of Human Genetics (Greifswald, Germany). No significative difference was found between n-APC-SR from indians (mean +/- SEM 1.13 +/- 0.02, CI 95% = 1.07-1.19) and black people (1.07 +/- 0.02, CI 95% = 1.03-1.12). APCR prevalence from indians was 1.25% (1 out of 80) who was heterozygote case for F V Leiden and 4.4% (4 out of 91) from blacks (one case was heterozygous for F V Leiden). No thrombotic event personal or familial was demonstrate. Our data represent the first report related to the association between APCR and F V Leiden in venezuelan indian and black individuals. APCR without the Factor V Leiden expression suggest a different type of mutation in the Factor V molecule. In spite of high endogamy in the indian group, we can not discard the role of foreign genes in both populations. The determination of the prevalence of this phenotype and its molecular marker in various ethnic groups is important for the interpretation of their role as risk factors for thrombotic disease.

[Anemia in indigenous population of the West of Venezuela]. / Anemia en poblaciones indígenas del occidente de Venezuela.

The purpose of the study was to investigate the frequency of nutritional anemia among western venezuelan indians. Three hundred and ninety nine Yucpa indians from the communities of Aroy, Marewa and Peraya were studied. The concentrations of hemoglobin, serum iron, total iron binding capacity, serum ferritin, serum folate and serum vitamin B12 and the frequency of anemia and nutrient deficiency were determined. Anemia was found in 71.7% of people from Aroy, 52.25 from Marewa and in 74.4% from Peraya. No nutrient deficiencies were found in 48.1% of cases with anemia, while iron deficiency anemia was present in 39% of the population studied, and folate and or vitamin B12 deficiency were associated with anemia in only 12.9% of cases. The high frequency of anemia, unrelated to nutrient deficiency, among the Yucpa indians, is attributed to the prevalence of chronic infectious diseases such as hepatitis and parasitic infections, as well as skin and respiratory infectious processes.

[Mouth-washing with tranexamic acid in patients treated with oral anticoagulants subjected to oral surgery procedures]. / Enjuague bucal con ácido tranexámico en pacientes tratados con anticoagulantes orales, sometidos a procedimientos quirúrgicos odontológicos.

The purpose of the present work was to observe local hemostatic function during dental surgery in patients under oral anticoagulant therapy with an INR between 1.7 and 2.5. Thirty seven dental treatments were performed in 15 patients. Group A: nineteen dental treatments (13 scalings, 1 root canal therapy and 5 dental extractions), treated with oral rinse with tranexamic acid (250 mg dissolved in 10 ml of water). Group B: eighteen dental procedures (13 scaling, 1 root canal therapy and 14 dental extractions), in which oral rinse was utilized. Antibiotics were indicated for those patients with root canal therapy or with signs of infection. A cool soft diet was recommended to all patients during the three days following the surgical procedure. Only in five (13.5%) dental extractions (1 from group A and 4 from B) bleeding prolonged was observed, however periodontal disease was also present in those patients hone of them required blood products or withdrawal of the anticoagulant. The results suggest that mouth washing with tranexamic acid prevents excessive oral bleeding in patients treated with oral anticoagulants with an INR between 1.7 and 2.5.

Prevalence of anemia, iron, folic acid and vitamin B12 deficiency in two Bari Indian communities from western Venezuela.

The hematological status of 406 Bari indians from two communities was studied. One hundred and seventy nine individuals were from Campo Rosario a village located in a low arid plain south to the Perijá mountain range and 287 were from Saimadoyi, a fertile valley in the heart of the mountain. Anemia was found in 54% and 31% of the people from Campo Rosario and Saimadoyi respectively. Low serum iron was present in 28% of the population in both communities while low serum ferritin levels were encountered in 20% of the population from Campo Rosario and 5% of the people from Saimadoyi. A high prevalence of serum folate and vitamin B12 deficiency (91% and 64% respectively) was found in Campo Rosario, in contrast only 5% of the population from Saimadoyi had low folate and none were vitamin B12 deficient. While there was a positive significant correlation between hemoglobin and serum iron concentrations (r = 0.517, p < 0.001), no significative correlation was found between the other parameters studied. The high prevalence of anemia and nutrient deficiency among the Bari indians, can be attributed to inadequate diets and the varied diseases encountered in the population.

[Immunologic characteristics of undernutrition. I. The undernourished patient in nutritional recovery]. / Aspectos inmunológicos del desnutrido. I. El desnutrido en recuperación nutricional.

Malnutrition in children is a well known critical factor that determines immunocompetence changes with altered immune response and higher risk to many diseases, especially in developing countries. Moreover, it is related to increased morbi-mortality rates mainly due to infections. For those reasons, 12 undernourished children, age 5 to 24 months were studied along 8 weeks at the Nutritional Recovery Center of Chiquinquira Hospital in Maracaibo, Venezuela. There were 5 cases of kwashiorkor, 5 marasmatics, 1 mixed marasmus/kwashiorkor and 1 case with moderate malnutrition. After a control blood sample was taken and cutaneous tests were done, a nutritional recovery program was began. At regular time intervals and at the end of the study, tests were done again by measuring seric immunoglobulins (IgG, IgA, IgM), secretory IgA (IgAs), C3 and C4 complement, lymphocytic sub-populations, and auto antibodies; cutaneous hipersensitivity tests were also done. As a control group, 10 apparently healthy children of matching age and sex were also studied with the same parameters. Results show that basal seric Igs did not differ significantly from the control group and did not change along the recovery program period, but there was a significant decrease in IgAs at all times of the study. C4 did not change and C3 was lower than control (p < 0.05) but returned to normal value at the end of the recovery period. CD3 and CD4 lymphocytes showed the same pattern. Only two patients showed positive skin tests and auto antibodies were not detected. It is concluded that there is indeed an altered immune competence with low levels of C3, IgAs, and CD3-CD4 lymphocytes that is reversible after nutritional recovery.

[Hemoglobin and nutrient concentration in middle-class adolescents. Relationship with school performance]. / Concentración de hemoglobina y nutrientes en adolescentes de clase social media. Relación con el rendimiento académico.

Concentrations of hemoglobin and serum nutrients that participate in the erythropoiesis (iron, folic acid and vitamin B12) were studied in 213 adolescents (112 male, 101 female) belonging to a medium income group that assisted at a private secondary educational institution. The purpose of the present work was to observe the hematologic and nutrient status in this group and its relationship with the academic achievement. The level of academic performance was determined using the Final mean grades (0 to 20 points scale) and the Academic Achievement index (A.A.I.) calculated as the ratio of approved courses over the total. A high prevalence of iron (16.6%) and folate (14.2%) deficiency was found in the total group with predominance in the female adolescents. It was noted a relationship between anemic men and A.A.I. (p < 0.05) and no other difference was observed between individuals with nutritional deficiency and their academic achievement. Therefore, when it was established as cut-off point 20 micrograms/L for ferritin, a good correlation was found between iron status and academic achievement index (r = 0.411, p < 0.01). The hematologic and biochemical data were correlated with academic parameters. A positive correlation was obtained between A.A.I. and hemoglobin, total iron binding capacity (TIBC) in males. When using Final mean grades, a positive correlation was shown with folic acid (males) and vitamin B12 (females). This work reveals a high incidence of iron and folate deficiency, specially in the female adolescent group. These findings may be due to a inadequate dietary intake combined with an increase of nutritional requirements and probably parasitic infestation. These factors may contribute to an impairement of the academic achievement. It will be important the assessment of iron and folate status of the adolescent for the normal and integral development of his cognitive and psychomotor functions.

[Effects of the administration of vitamin K on the activity of Factor II, VII and X in healthy newborns]. / Efecto de la administración de la vitamin K sobre la actividad de los factores II, VII y X en neonatos sanos.

The study was designed to know the effect of oral vitamin K (VK) treatment, on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II (PIVCA II) on full term infants. Seventy healthy newborns were studied and each was randomly placed in one of two groups: Group A, newborns that received human milk and milk formula (mixed feeding)and group B, newborns that were exclusively breast fed. These groups were also divided in two subgroups: I received 2mg of VK1 orally and II (control) did not receive VK. Clotting activity of the coagulation factors and PIVCA II was determined from blood plasma obtained immediately after birth and 48 hours after VK administration. Basal activity of the factors analyzed was similar in all groups with values ranging from 25% to 40%. After 48 hours a significant increase in all factors studied and a decrease of PIVKA II was observed in those children who received oral VK. The results suggest that oral VK effectively increases VK dependent factors and prevents the risk of hemorrhagic disease in the newborn, with the advantage of being less traumatic and less risky to the infant than intramuscular VK.

Platelet function in patients with lupus anticoagulant and thrombosis.

In a group of 337 patients with a history of thrombotic episodes, pregnancy losses and/or thrombocytopenia, 66 cases of lupus anticoagulant (LA) were found. Spontaneous platelet aggregation and the aggregatory responses of platelet rich plasmas (PRP) from 14 patients, with a history of thrombotic episodes, with anticardiolipin (ACA) levels above 21 IgG antiphospholipid antibodies units and normal platelet counts were studied and compared with those of 8 patients with history of thrombosis and negative LA and ACA (controls). Epinephrine, adenosine diphosphate, collagen and ristocetin were used as platelet aggregation inducers. Early collagen-whole blood interaction (BASIC WAVE), as a measure of platelet recruitment, and the levels of von Willebrand factor were also determined. The results of each test were compared with those of nine patients, used as controls, with thrombotic antecedents but negative LA and ACA. None of the patients with LA, or the control group, showed spontaneous platelet aggregation. The aggregatory responses, when epinephrine, ADP or collagen were added to the patient's PRP, were within normal range in most cases (64.2%, 52% and 72% respectively). The highest rate of hyperaggregation after the above mentioned inducers, was 12% and corresponded to the response to collagen. On the contrary, platelet aggregation rate with ristocetin was higher than 100% in 61.0% of the problem group, with no significative difference from the controls. The BASIC WAVE was of low rate and similar in the two groups studied. The von Willebrand factor was significantly higher (150 +/- 55%) in the problem group than in the controls (98 +/- 25.6%) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Antiphospholipid antibodies. Review]. / Anticuerpos antifosfolípidos. Revisión.

The antiphospholipid antibodies (APA), are immunoglobulins directed against anionic phospholipids that adopt a hexagonal configuration after incubation at 37 degrees C. They are usually IgG, IgM, IgA or a combination of them. Initially these antibodies were designated as "lupus anticoagulant", because they were found in patients with systemic lupus erythematosus, and because they prolong coagulation tests that need phospholipids in the system. The APA antibodies can be found associated with a variety of diseases, immunological, infectious, malignant disorders etc. They can also be drug related, can be found during pregnancy and even in non pregnant normal persons. The main clinical manifestations are thrombosis, thrombocytopenia and recurrent fetal losses. The diagnosis of APA is usually made, in the absence of antibodies against clotting factors, when a prolonged partial thromboplastin time can not be corrected with normal plasma. Prothrombin time, plasma recalcification time or the diluted Russell viper venom clotting time, are also used for the diagnosis. The antibodies and the specific phospholipid or phospholipids involved are usually demonstrated by enzymatic methods (ELISA). Depending on the clinical symptoms, the presence of APA can go without treatment or need anticoagulant or immunosuppressive therapy. Human endovenous immunoglobulin and plasmapheresis have also been used, especially during pregnancy.

[Effect of low doses of estrogens in menopausal women]. / Efecto de bajas dosis de estrógenos en mujeres menopáusicas.

The effect of hormonal therapy in serum glucose, lipoproteins and the hemostatic system was studied in menopausal women, who were distributed in three groups: Group I (15 patients) received placebo in cycles of 21 days, followed by 7 days of rest; Group II (16 patients), received natural estrogens conjugated with progesterone in a sequential way, also in cycles of 21 days: Group III (16 patients), was treated with triphasic oral contraceptives in the same cyclical fashion. The patients completed 6, 12 or 18 cycles of the treatment. The results were as follows: The glucose levels were decreased by the 18th cycle in group II (P < 0.01). The HDL-cholesterol levels and the cholesterol/HDL cholesterol index were unchanged, however the basal levels of LDL-cholesterol in group III were high, but normal after 12 cycles of treatment. The coagulation factors did not changed significantly with the hormonal treatment, however fibrinogen was increased after 18 cycles under placebo. The von Willebrand factor and antithrombin III remained stable. Platelet aggregation with ADP increased after 12 cycles in group III (p < 0.05), and no changes were found with collagen. The above results suggest that the hormonal treatment in menopausal women, either with natural estrogens and progesterone or with triphasic oral contraceptives, has little effect in the lipidic concentrations of sera in these patients, however it can increase platelet activity, specially with prolonged treatment with semisynthetic estrogens.

[Hepatitis C in hemophiliac patients in Maracaibo, Venezuela]. / Hepatitis C en pacientes hemofílicos en Maracaibo, Venezuela.

Infection with the hepatitis C virus is one of the risks of transfusion therapy. Considering that in Venezuela, there are not enough data that permit one to establish the frequency of hepatitis C in transfused patients, the purpose of this work was to investigate the presence of anti hepatitis C virus (HCV) antibodies in 56 hemophilic patients from Zulia State, Venezuela. Thirty six (64%) had received fresh frozen plasma and/or cryoprecipitate. Another fourteen (25%) also received lyophilized F VIII or prothrombin complex; six patients (10%) were never transfused. The positive samples (EIA 2nd. generation) were reconfirmed by RIBA-2. Twenty two of the patients were positive for HCV. The presence of anti-HCV antibodies was mainly detected in patients that received more than 10.000 U of the deficient factor. Four of the patients with HCV were also positive for the Human Immunodeficiency Virus (HIV). The results suggest that although the transfusion of blood derivatives carries the risk of HCV transmission, our patients show a low prevalence of this disease, probably due to the infrequent use of clotting factors lyophilizates.