Hemostatic disorders induced by skin contact with Lonomia obliqua (Lepidoptera, Saturniidae) caterpillars.

Patients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital São Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

Hemostatic disorders induced by skin contact with Lonomia obliqua (Lepidoptera, Saturniidae) caterpillars

Patients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital Sao Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

Hemostatic disorders induced by skin contact with Lonomia obliqua (Lepidoptera, Saturniidae) caterpillars

ABSTRACT Patients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital São Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

Role of the inflammatory response in the hemorrhagic syndrome induced by the hemolymph of the caterpillar Lonomia achelous.

INTRODUCTION: Contact with the caterpillar of Lonomia achelous causes a hemorrhagic syndrome in humans prompted by two processes, an initial mild DIC that is later masked by overwhelming fibrinolytic activity. Although the venom affects both the hemostatic and inflammatory systems separately, it is not clear whether the hematological and hemostatic disturbances may in part be due to an indirect effect via inflammatory mediators. Here we report results on the crosstalk between these systems, particularly the effect of the pro-inflammatory cytokine TNF-α on hemostatic parameters. MATERIALS AND METHODS: the nitric oxide and TNF-α responses, as well as activation of the coagulation and fibrinolytic systems, were measured in macrophages and endothelial cells treated with Lonomia achelous hemolymph (LAH). The same responses were then determined, in a mouse model of LAH envenomation, after treatment with an anti-TNF-α antibody. RESULTS: Both macrophages and endothelial cells responded strongly to LAH in terms of pro-inflammatory mediator release and fibrinolytic activities as well as pro-coagulant activity (TF activity) in endothelial cells. Treatment with antibody against TNF-α decreased both TNF-α and NO3-/NO2- serum levels in the mice, after LAH injection. Blocking TNF-α also modified significantly the serum levels of plasminogen, fibrinogen and FXIII in mice, as well as decreased TF activity in endothelial cells. CONCLUSIONS: LAH may induce a hemostatic effect through endothelial and macrophage activation. These activated cell release hemostatic enzymes as well as pro-inflammatory mediators, principally TNF-α, that potentiate this release in an autocrine fashion, amplifying the fibrinolytic effect, which may in turn exacerbate the hemorrhagic manifestations. As far as we are aware, this is the first report of the relationship between the hemostatic system and the inflammatory responses in a hemorrhagic syndrome induce by animal secretions.

Activity and levels of factor XIII in a Venezuelan admixed population: association with rs5985 (Val35Leu) and STR F13A01 polymorphisms.

INTRODUCTION: The single nucleotide polymorphism Val35Leu has been described within the A subunit of gene Factor XIII (FXIII-A) in association with an increase of FXIII activity. In the gene's promoter region STR F13A01 is present, however there is no available data related about its influence on the expression of FXIII. MATERIALS AND METHODS: Blood samples were obtained from apparently healthy and unrelated biologically individuals from northeastern area of Venezuela. The system Val35Leu was amplified by PCR-RFLP using MseI as restriction enzyme. FXIIIA and FXIIIB levels were measured by rocket- immunoelectrophoresis. FXIII activity was measured with a Berichrom kit and fibrinogen by clot weigh method. RESULTS: FXIII-A had an activity range between 50-184% and FXIII-B between 50-155%. FXIII activity had a range of 59-147%. Fibrinogen was found between 122-502 mg/dL. None of these values showed association with Val35Leu genotypes. In the third fibrinogen tertile a higher FXIII activity was found (96 ± 24%) and a higher frequency of Leu/Leu genotype (7.02%). A significant correlation between fibrinogen and FXIII activity (r = 0.2706, p > 0.01) was observed. Nine different alleles were detected in the STR polymorphism, with the most frequent alleles being 7 (24.70%), 6 (15.06%), 5 (22.29%), 4 (18.07%), and 3.2 (13.25). The results suggest an increase in FXIII activity as the number of repetitions in F13A01 increased up to allele 5. CONCLUSIONS: This study offers new genetic information of FXIII activity and levels reference values from Venezuelan human population.

[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.

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

El objetivo del presente trabajo fue determinar la relación de las concentraciones de fibrinógeno con factores de riesgo cardiovascular isquémicos en hombres aparentemente sanos de Maracaibo,Venezuela. Se estudiaron 246 hombres aparentemente sanos, con edades entre 31 a 65 años, mediante evaluación médica y de laboratorio. Se determinaron las concentraciones de fibrinógeno por coagulometría, lípidos y glicemia por métodos enzimáticos e insulina por radioinmunoanálisis. El 31,7% se ubicó en el tercil más alto de fibrinógeno (>311 mg/dL) y a su vez presentó valores significativamente superiores de colesterol total (p < 0,03) y de LDL-C (p < 0,01). Además, los individuos ubicados en este tercil mostraron una correlación significativa y positiva entre las concentraciones de triglicéridos y los niveles de insulina (p < 0,02) y HOMA-IR (p < 0,01). Por otra parte, el análisis de correlación demostró también una asociación positiva y significativa entre las concentraciones de fibrinógeno y los niveles de colesterol total (p < 0,02) en el grupo total, a expensas de los sujetos con antecedentes familiares de enfermedad cardiovascular isquémica (colesterol total: p < 0,02 y LDL-C: p < 0,003). En conclusión, las altas concentraciones de fibrinógeno encontradas en el 31,7% de los hombres aparentemente sanos y la positiva y significativa asociación de esta variable con el colesterol total y las lipoproteínas de baja densidad, en los sujetos con antecedentes familiares de enfermedad cardiovascular isquémica, hacen aconsejable incluir el estudio del fibrinógeno en la evaluación cardiovascular de estos últimos individuos en particular.

[Effect of Tityus discrepans scorpion venom on global coagulation test. Preliminary studies]. / Efecto del veneno del escorpión Tityus discrepans sobre las pruebas globales de la coagulación. Estudios preliminares.

Tityus discrepans (Td) scorpion venom modifies clotting times in humans. We studied the in vitro venom effect on partial thromboplastin time (PTT), prothrombin time (PT) and its direct clotting activity, using fresh human plasma and purified fibrinogen as substrates. Whole venom (WV) was fractioned with a Protein Pak 125 molecular exclusion column (0.5 mL/min, CH3COONH4 20 mM, pH 4.7). Six fractions (F1 through F6) with retention times ranging from 12.8 to 31 min were obtained. WV (78 to 625 microg/mL) and fraction F1 (10 to 42.5 microg/mL), shortened PTT; WV (700 to 1000 microg/mL) and fraction F6 (16.5 to 700 microg/mL), prolonged PTT. WV (40 to 240 microg/mL) and fraction F2 (5 to 40 microg/mL), prolonged PT. No thrombin-like activity was found with this venom on human plasma or purified fibrinogen. Td venom contains procoagulant components, able to shorten PTT. In addition, the venom contains anticoagulant components which prolong PT and PTT.

Efecto del veneno del escorpión Tityus discrepans sobre las pruebas globales de la coagulación: estudios preliminares / Effect of Tityus discrepans scorpion venom on global coagulation test: preliminary studies

El veneno del escorpión Tityus discrepans (Td) altera los tiempos de coagulación en humanos. En este trabajo se estudió el efecto in vitro de este veneno sobre el tiempo de tromboplastina parcial (TTP), el tiempo de protrombina (TP) y su actividad coagulante directa, utilizando como substrato plasma humano fresco y/o fibrinógeno purificado. El veneno completo (VC) fue fraccionado con una columna de exclusión molecular Protein Pak 125™ (0,5 mL/min, CH3COONH4 20 mM, pH 4,7). Seis fracciones (F1 a F6) eluyeron con tiempos de retención entre 12,8 y 31 minutos. El VC (78-625 µg/mL) y la fracción F1 (10-42,5 µg/mL), acortaron el TTP; el VC (700-1000 µg/mL) y la fracción F6 (16,5-700 µg/mL), alargaron esta prueba. El VC (40-240 µg/mL) y la fracción F2 (5-40 µg/mL), prolongaron el TP. No se detectó actividad coagulante parecida a trombina sobre plasma humano o fibrinógeno purificado. Estos resultados evidencian que en el veneno de Td existen componentes con acción procoagulante, que acortan el TTP. Además, presenta componentes anticoagulantes que inducen un alargamiento del TP y TTP.

[Fibronectin. Structure and functions associated to hemostasis. Review]. / Fibronectina. Estructura y funciones asociadas a la hemostasia. Revisión.

Fibronectin is an adhesive glycoprotein present in a soluble form in plasma and in an insoluble form in the extracellular matrix of many tissues. The human plasma level of this protein is about 300 +/- 100 microg/mL. It is synthesized and secreted by a wide variety of cells, consequently is one of the components of greater distribution in the body that participates in the biochemical reactions of diverse physiological and pathological processes. Due to the presence of multifunctional domains in its structure, fibronectin interacts with diverse components of the coagulation and fibrinolysis. It may bind to collagen, fibrinogen, fibrin, heparin, factor XIII and platelets, among others, regulating processes of importance in hemostasis such as: platelet adhesion and aggregation, tissue remodelling during wound healing, and activation of fibrinolysis by the plasminogen activators.

Fibronectina: estructural y funciones asociadas a la hemostasia: revisión / Fibronectin: structure and functions associated to hemostasis: review

La fibronectina es una glicoproteína adhesiva presente en forma soluble en plasma e insoluble en la matriz extracelular de la mayoría de los tejidos. La concentración de esta proteína en plasma es de proximadamente 300 ± 100 µg/mL. Es sintetizada y secretada por una veriedad de células, por lo tanto es uno de los componentes de mayor distribución en el cuerpo, que participa en las reacciones bioquímicas de diversos procesos fisiológicos y patológicos. Debido a la presencia de dominios multifuncionales en su estructura, la fibronectina interacciona con diversos componentes de la coagulación y fibrinólisis. Es capaz de unirse a colágeno, fibrinógeno, fibrina, heparina, factor XIII y plaquetas, entre otros, regulando procesos de importancia en la hemostasia como: adhesión y agregación plaquetaria, remodelación de tejidos durante la cicatrización de la lesión, y activación de la fibrinólisis mediada por los activadores del plasminógeno.

Haemostatic changes related to fibrin formation and fibrinolysis during the first trimester in normal pregnancy and in recurrent miscarriage.

We have studied some biophysical properties of the fibrin network during the normal state of pregnancy and in patients with recurrent miscarriage (RM), in the first trimester of pregnancy. The fibrin polymerization process, followed by turbidity, showed that the rate of fibrin monomer assembly and the final turbidity was increased in the pregnant group (normal and with history of RM) compared to non-pregnant women (normal and RM), which is consistent with the increased fibrinogen concentration during pregnancy. No changes were observed in the Darcy constant (Ks) of RM clots, pregnant or not; however, in pregnant control subjects the Ks increased (p = 0.03). The fibrin lysis rate was increased in pregnant women compared to non-pregnant, being faster in women with RM. The rheological properties of the fibrin network in the non-pregnant group (control and RM patients) were similar; in the pregnant state, the fibrin network of the control group was 1.3 times stiffer compared to the control non-pregnant women, and almost unchanged in RM patients. In this study we have found changes in the clot structure that seem to be related to normal pregnancy and an increased rate of the fibrin lysis process in the RM patients, which may have clinical relevance.

Parámetros hemostáticos en placenta de pacientes con embarazo normal y con preeclampsia severa / Hemostatic system parameters of placental extracts in normal pregnancy and severe preeclampsia

Con el objeto de buscar el mejor entendimiento del mecanismo hemostático en la preeclampsia, se estudiaron extractos de placentas obtenidos de 26 mujeres embarazadas normales (EN) y 12 pacientes con preeclampsia severa (PES), en los cuales se determinaron trombomodulina (TM), factor tisular (FT), activador tisular del plasminógeno (t-PA), inhibidores del activador del plasminógeno 1 y 2 (PAI-1 y PAI-2) y el inhibidor del factor tisular (TFPI). Los resultados mostraron concentraciones similares de FT, TM y PAI-2 en ambos grupos, t-PA incrementado no significativamente y el TFPI y el PAI-1 presentaron un incremento significativo en las placentas de PES

Prevalence of the coagulation factor XIII polymorphism Val34Leu in women with recurrent miscarriage.

BACKGROUND: Recurrent miscarriage (RM) syndrome is not an uncommon obstetrical problem of multifactorial etiology. We investigated the role of the coagulation factor XIII (FXIII) Val34Leu polymorphism in RM. METHODS: We recruited 80 subjects (40 normal and 40 with history of RM; of each group 20 pregnant and 20 non-pregnant) and analyzed the prevalence of this polymorphism. The women recruited for the present study had similar age and did not have history of any hemostatic disorders. FXIII levels and activity and the rate of fibrin cross-linking by FXIII genotype Val34Val and Val34Leu were studied. RESULTS: Genotype analyses of patients and normal revealed that the frequencies distribution of Val/Val and Val/leu were statistically similar (P<0.05): 62.5% and 60%, and 37.5% and 40%, respectively; no Leu/leu genotype was found. The FXIII-A subunit levels and activity were also found similar between Val/Val and Val/leu genotypes in the different groups, pregnant and non-pregnant, normal or with RM. The rate of FXIII alpha and gamma-chains fibrin cross-linking was not different between the 2 genotypes. CONCLUSION: From our results we conclude that FXIII Val34Leu polymorphism does not appear to be associated to RM.

Fibrinogen Guarenas, an abnormal fibrinogen with an Aalpha-chain truncation due to a nonsense mutation at Aalpha 467 Glu (GAA)-->stop (TAA).

Fibrinogen Guarenas is a dysfibrinogenemia with a nonsense mutation at G4731T that causes an Aalpha-chain truncation at Ser 466. This abnormal fibrinogen is associated with a bleeding diathesis, severe in the proposita and mild in one brother, even though the fibrinogen levels in plasma are normal. All other family members are asymptomatic. Fibrinogens from the proposita and one family member, the mother of the proposita, both heterozygous for the mutation, were studied. Turbidity curves of fibrin polymerization showed that the lateral association of protofibrils was impaired and the maximum rate of polymerization was slightly diminished. The binding of albumin to fibrinogen was increased compared to control due to the presence of a free sulfhydryl group because of the missing disulphide bridge between Aalpha-Cys 442-472 in the mutated molecules. The abnormal fibrinogen formed much less alpha-polymer, and gamma-dimer formation was delayed compared to the control. Plasminogen activation by t-PA in the presence of fibrin was decreased. When Guarenas clots were perfused with fibrinolytic enzymes, clot degradation was retarded. Clot structure studied by confocal 3D microscopy showed that the fibrin network was dense, made up of thin and highly branched fibers, which accounted for the decreased flow rates by buffer permeation and increased rigidity of the fibrin clots, measured using a torsion pendulum. It seems that the increased clot rigidity, decreased porosity, hypofibrinolysis and t-PA induced fibrinolysis, by itself are not necessarily associated with thrombotic disorders in dysfibrinogenemia.

[Hemostatic system parameters of placental extracts in normal pregnancy and severe preeclampsia]. / Parámetros hemostáticos en placenta de pacientes con embarazo normal y con preeclampsia severa.

To better understand the role of the hemostatic mechanism in preeclampsia, placental extracts obtained from 26 normal pregnant women (NP) and 12 patients with severe pre-eclampsia (SPE) were analyzed to determine thrombomodulin (TM), tissue factor (TF), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) 1 and 2, and TF pathway inhibitor (TFPI). The results showed similar concentrations of TF, TM and PAI-2 in both groups, while tPA increased no significantly and TFPI and PAI-1 increased significantly in SPE placentas.

Biophysical characterization of fibrinogen Caracas I with an Aalpha-chain truncation at Aalpha-466 Ser: identification of the mutation and biophysical characterization of properties of clots from plasma and purified fibrinogen.

Fibrinogen Caracas I is a dysfibrinogenemia with a mild bleeding tendency; a novel nonsense mutation, in the gene coding the Aalpha-chain, identified in this study as G4731T, giving rise to a new stop codon at Aalpha-Glu 467. Fibrinogen from two family members, the mother and sister of the propositus, both heterozygous for the mutation were studied, analyzing clots made from both plasma and purified fibrinogen. Clot structure and properties were characterized by turbidity, permeation, scanning electron microscopy and rheological studies. Permeation through Caracas I plasma clots was decreased, consistent with the decreased final turbidity. As shown by scanning electron microscopy, plasma clots from the patients were composed of very thin fibers, with increased fibrin density and reduced pore size. Viscoelastic measurements revealed that fibrinogen Caracas I plasma clots were much stiffer and less subject to compaction. These results demonstrate a key role of the carboxyl-terminal alpha chains of fibrin in lateral aggregation during polymerization and reinforce the utility of studying plasma clots. It is important to point out that the biophysical studies with fibrinogen purified by two different methods yielded contradictory results, which can be accounted for by selective purification of certain molecular species as seen by two-dimensional electrophoresis.

[Hemorrhagic syndrome induced by caterpillars. Clinical and experimental studies. Review]. / Síndrome hemorrágico producido por contacto con orugas. Estudios clínicos y experimentales. Revisión.

Patients affected with the hemorrhagic syndrome caused by contact with caterpillars of the Lonomia genus show digestive, pulmonary and intraperitoneal bleeding in combination with hematomas and echymosis. Hematuria is also frequently seen. Blood coagulation tests show prolongation of PT, aPTT and ThT. There is a decrease of Fg, FV, FXIII, Pg and alpha 2AP. Factor VIII and FvW are increased while the platelet count is unaffected. FDP's are increased and D-dimers are present in most cases. Treatment with whole blood or fresh frozen plasma worsens the clinical picture causing a severe drop in the platelet count often leading to renal failure and death. However, if antifibrinolytics, either alone or in combination with cryoprecipitate or purified fibrinogen, are administered, no change in the platelet count can be detected and the patients recover rapidly. It is concluded that this syndrome is caused by a mild disseminated intravascular coagulation (DIC) in combination with a hyperfibrinolytic state; the former being partially obscured by the latter, that manifests on administration of whole blood or fresh frozen plasma. Activators of FII, FV and Pg, and compounds showing FXa, plasmin and kallikrein-like activities have been identified in the Lonomia achelous venom. Proteases capable of degrading FXIII and extracellular matrix protein and an inhibitor of FV have also been isolated from these species. In Lonomia oblique, activators of FII and FX and an enzyme with phospholipase-like activity have been identified. In rabbits, subcutaneous injection of crude extract and one of the chromatographically purified fractions of Lonomia achelous venom causes a decrease of Fg, Pg and FXIII. Intravenous administration of the same fraction causes lysis of preformed thrombus with decrease of Fg, Pg and FXIII in combination with inhibition of thrombus growth. It should be noted that, under the same conditions, injection of Lonomia obliqua prothrombin activator causes a DIC.

Síndrome hemorrágico producido por contacto con orugas: estudios clínicos y experimentales: revisión / Hemorrahagic syndrome induced by caterpillars: clinical and experimental studies: review

Pacientes afectados con síndrome hemorrágico inducido por contacto con orugas del género lanomia presentan desde el punto de vista clínico: hematomas, equimosis, hematuria, hemoragias digestivas, pulmonares y peritoneales que pueden conducir a la muerte. Los estudios de la hemostasia han demostrado: recuento de plaquetas normal, con alargamiento de las pruebas globales de coagulación (TP. aTPT y TT), disminuyendo del Fg, FV, FXIII, Pg y &2AP, elevación del factor VIII:c, FvW, PDF y diemeros D con un recuento plaquetario normal. La administración de sangre total o plasma fresco congelado induce una disminución severa del número de plaquetas con agravamiento del cuadro clínico. La administración de fibrinógeno humano purificado (grado terapéutico) ó crioprecipitado y antifibrinolíticos producen una recuperación clínica rápida sin modificación del número de plaquetas. Se concluye que en estos pacientes existe una hiperfibrinolisis con una coagulación intravascular diseminada (CID) leve que se manifiesta al administrar sangre total o plasma fresco congelado. Actualmente se recomienda para la terapia el fibrinógeno humano purificado (grado terapéutico) o crioprecipitado, de acuerdo a los valores del fibrinógeno. Se debe administrar también antifibrinolíticos como aprotinina, y en caso de no disponer de este inhibidor, usar EACA o ácido tranexámico, vigilando la evolución de las plaquetas. No debe administrarse sangre total ni plasma fresco congelado. En Brasil se esta usando un suero anti-lonomia obliqua producido en caballos. En Lanomia achelous se han identificado activadores del FII, FV y del Pg; compuestos parecidos a la plasmina, al FXa y a la calicreína, además de una proteasa que degrada al FXIII y un inhibidor del FV. En la lonomia obliqua se han identificado activadores del FII y del FX y un compuesto parecido a la fosfolipasa A2. El extracto crudo de la lonomia achelous y una de las fracciones cromatográficas, al ser administrados subcutáneamente a conejos producen descenso del Fg, Pg y FXIII. La inyección endovenosa de la proteasa que degrada al FXIII induce lisis de trombos preformados en la vena yugular de conejos, e inhibición del crecimiento posterior del trombo remanente, con descenso del Fg, Pg y FXIII. En la lonomia oblicua, el activador de la protrombina administrado por vía endovenosa induce una CID

[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.