RESUMO
BACKGROUND: Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin binding with plasminogen, inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a) have been reported in several populations. AIM: The study examined the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. METHODS: We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin binding by immuno-enzymatic assay and short tandem repeat (STR) polymorphic marker genetic analysis by capillary electrophoresis. RESULTS: Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg dL(-1)) relative to Mazahuas (8.2 mg dL(-1)), Mayas (8.25 mg dL(-1)) and Mayos (6.5 mg dL(-1)). Phenotype distribution was different in Mayas and Mazahuas as compared with the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. CONCLUSION: There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in the Native Mexican and the Mestizo group.
Assuntos
Etnicidade/genética , Indígenas Norte-Americanos/genética , Lipoproteína(a)/genética , Polimorfismo Genético , Feminino , Fibrina/metabolismo , Marcadores Genéticos , Genética Populacional , Humanos , Indígenas Norte-Americanos/etnologia , Lipoproteína(a)/sangue , Masculino , México/etnologia , Fenótipo , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genéticaRESUMO
High plasma concentrations of lipoprotein (a) [Lp(a)] are now considered a major risk factor for atherosclerosis and cardiovascular disease. This effect of Lp(a) may be related to its composite structure, a plasminogen-like inactive serine-proteinase, apoprotein (a) [apo(a)], which is disulfide-linked to the apoprotein B100 of an atherogenic low-density lipoprotein (LDL) particle. Apo(a) contains, in addition to the protease region and a copy of kringle 5 of plasminogen, a variable number of copies of plasminogen-like kringle 4, giving rise to a series of isoforms. This structural homology endows Lp(a) with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby inhibits binding of plasminogen and plasmin formation. This mechanism favors fibrin and cholesterol deposition at sites of vascular injury and impairs activation of transforming growth factor-beta (TGF-beta) that may result in migration and proliferation of smooth muscle cells into the vascular intima. It is currently accepted that this effect of Lp(a) is linked to its concentration in plasma, and an inverse relationship between apo(a) isoform size and Lp(a) concentrations that is under genetic control has been documented. Recently, it has been shown that inhibition of plasminogen binding to fibrin by apo(a) from homozygous subjects is also inversely associated with isoform size. These findings suggest that the structural polymorphism of apo(a) is not only inversely related to the plasma concentration of Lp(a), but also to a functional heterogeneity of apo(a) isoforms. Based on these pathophysiological findings, it can be proposed that the predictive value of Lp(a) as a risk factor for vascular occlusive disease in heterozygous subjects would depend on the relative concentration of the isoform with the highest affinity for fibrin.
Assuntos
Arteriosclerose/fisiopatologia , Lipoproteína(a)/fisiologia , Apolipoproteínas A/genética , Arteriosclerose/metabolismo , Homocisteína/sangue , Humanos , Lipoproteína(a)/sangue , Lipoproteína(a)/química , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Polimorfismo Genético , Ativador de Plasminogênio Tecidual/metabolismoRESUMO
Acetyl-salicylic acid inhibits thromboxane A2 production and reduces the risk of vascular occlusive events by 20 to 25%. Ticlopidine inhibits ADP-dependent platelet aggregation and reduces the same risk by 30 to 35%, but produces some adverse effects. Clopidogrel is a ticlopidin-derived antiplatelet-drug, with the same mechanism of action; reduces the expression of the glycoprotein IIb/IIIa, the fibrinogen receptor on the platelet surface. Clopidogrel has the same clinical efficacy of ticlopidin and lowers the incidence of adverse effects. In this study, we evaluated the effects of one daily dosis of 75 mg of clopidogrel on platelet function in 33 subjects with coronary artery disease. Before treatment and after the 6th and 12th week, the following parameters were evaluated: 5 microM-ADP and 20 micrograms/mL collagen-induced platelet aggregation, bleeding time and fibrinogen concentration. In basal and in the 6th and 12th week samples, ADP-induced platelet aggregation was 90.7% +/- 13.2, 54.6% +/- 23.2 and 49.2% +/- 23.7 respectively, that represents a significant reduction of 38.6% and 44.4%. Reduction of collagen-induced platelet aggregation was not significative. Plasmatic fibrinogen did not suffer variation during treatment. Bleeding time was significant prolonged from 4.1 minutes to 15.4 and 14.6 minutes (3.7-3.5 times compared with the test before treatment). There were no haemorrhagic complications, only digestive discomfort in fewer than 3% of patients. We concluded that clopidogrel is a safe and efficacious drug for patients, it efficiently reduces ADP-induced platelet aggregation and prolongs bleeding time.
Assuntos
Doença das Coronárias/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Difosfato de Adenosina , Adulto , Idoso , Clopidogrel , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Trombofilia , Animais , Animais Geneticamente Modificados , Fatores de Coagulação Sanguínea/genética , Fatores de Coagulação Sanguínea/fisiologia , Suscetibilidade a Doenças , Fibrinólise/fisiologia , Humanos , Lipoproteína(a)/genética , Lipoproteína(a)/fisiologia , Isquemia Miocárdica/genética , Deficiência de Proteína S/complicações , Fatores de Risco , Trombofilia/sangue , Trombofilia/congênito , Trombofilia/etiologia , Trombofilia/genética , Trombose/epidemiologia , Trombose/etiologiaRESUMO
The aim of this trial was to estimate changes in the coagulation and fibrinolysis systems during the thrombolytic treatment with recombinant human tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction and correlate with hemorrhagic complications. We studied 17 patients with a 3 hours-continuous systemic infusion of 100 mg of rt-PA. Prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen splits products, plasminogen, alfa-2-antiplasmin (a-2AP) and antithrombin III (AT-III) were performed before, during and after infusion. Most patients showed lengthening coagulation times. Fibrinogen and plasminogen were decreased and PDF was increased. No variations in alpha-2AP or AT-III were observed. The recuperation of fibrinogen levels occurred in 3 hours and there was hyperfibrinogenemia after day 3. No hemorrhagic complication was observed in patients with abnormalities in these coagulation or fibrinolytic tests.
Assuntos
Fibrinólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Adulto , Idoso , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Proteínas Recombinantes/uso terapêutico , Fatores de TempoRESUMO
The recently described antiphospholipid antibodies syndrome (APA) is recognized because recurrent abortion, thrombocytopenia and repeated arterial and/or, venous thrombosis plus the demonstration of serum antibodies reactive with anionic phospholipids. We studied 51 patients who attend the anticoagulation clinic at our Institute. In a representative sample, we search for serum IgG specific for cardiolipin using an standard assay. We did not pick up unrecognized APA cases. The low frequency of this condition could be an explanation for our negative results in non-selected cases. Besides, this study denies a relationship between the chronic use of coumarin anticoagulants and development of peculiar antibodies.
Assuntos
Cardiolipinas/imunologia , Doenças Cardiovasculares/imunologia , Imunoglobulina G/análise , Adulto , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Feminino , Hospitais Especializados , Humanos , Masculino , México , Pessoa de Meia-Idade , Fosfolipídeos/imunologia , Gravidez , Prevalência , SíndromeRESUMO
This article analyzes the historic evolution of the Starr-Edwards prosthesis manufacture and its association to hemolysis. It describes also the information related to bioprosthesis and hemolysis. The mechanisms involved in mechanical hemolysis are discussed (turbulent flux, red cells trapping, construction material and autoimmunity). Reviews the pathophysiology and criteria for clinical and laboratory diagnosis of hemolysis. We describe the value of the quantitation of unconjugated bilirubin, free plasmatic hemoglobin, DHL and it's DHL1 iso enzyme, methemalbumin and urinary hemosiderin for the specific diagnosis of this entity. Finally we comment on the utility of bed rest, cellular maturity inductors, propranolol and sulfinpyrazone therapy for the control of the hemolytic process.