RESUMO
Thromboembolic diseases are a major cause of mortality in human and the currently available anticoagulants are associated with various drawbacks, therefore the search for anticoagulants that have better safety profile is highly desirable. Compounds that are part of the dietary routine can be modified to possibly increase their anticoagulant potential. We show mannose 2,3,4,5,6-O-pentasulfate (MPS) as a synthetically modified form of mannose that has appreciable anticoagulation properties. An in silico study identified that mannose in sulfated form can bind effectively to the heparin-binding site of antithrombin (ATIII) and heparin cofactor II (HCII). Mannose was sulfated using a simple sulfation strategy-involving triethylamine-sulfur trioxide adduct. HCII and ATIII were purified from human plasma and the binding analysis using fluorometer and isothermal calorimetry showed that MPS binds at a unique site. A thrombin inhibition analysis using the chromogenic substrate showed that MPS partially enhances the activity of HCII. Further an assessment of in vitro blood coagulation assays using human plasma showed that the activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged in the presence of MPS. A molecular dynamics simulation analysis of the HCII-MPS complex showed fluctuations in a N-terminal loop and the cofactor binding site of HCII. The results indicate that MPS is a promising lead due to its effect on the in vitro coagulation rate.Communicated by Ramaswamy H. Sarma.
Assuntos
Cofator II da Heparina , Manose , Humanos , Cofator II da Heparina/química , Cofator II da Heparina/metabolismo , Manose/farmacologia , Coagulação Sanguínea , Anticoagulantes/farmacologia , Anticoagulantes/química , Heparina/farmacologia , Antitrombina III/farmacologia , Antitrombina III/fisiologia , Antitrombinas/farmacologia , Trombina/químicaRESUMO
Mice deficient in the anticoagulants antithrombin (Serpinc1) or protein C (Proc) display premature death due to thrombosis-related coagulopathy, thereby precluding their use in gene function studies and thrombosis models. We used RNA interference to silence Serpinc1 and/or Proc in normal adult mice. The severe coagulopathy that followed combined "knockdown" of these genes is reported. Two days after siRNA injection, thrombi (occlusive) were observed in vessels (large and medium-sized) in multiple tissues, and hemorrhages were prominent in the ocular, mandibular, and maxillary areas. Tissue fibrin deposition and reduction of plasma fibrinogen accompanied this phenotype. The coagulopathy was prevented by dabigatran etexilate treatment. Silencing of Serpinc1 alone yielded a comparable but milder phenotype with later onset. The phenotype was absent when Proc was targeted alone. We conclude that RNA interference of Serpinc1 and/or Proc allows for evaluation of the function of these genes in vivo and provides a novel, controlled mouse model for spontaneous venous thrombosis.
Assuntos
Antitrombina III/genética , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Proteína C/genética , Trombose Venosa/genética , Trombose Venosa/fisiopatologia , Doença Aguda , Animais , Antitrombina III/fisiologia , Transtornos da Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/fisiopatologia , Feminino , Inativação Gênica , Fígado/fisiologia , Camundongos , Fenótipo , Proteína C/fisiologia , RNA Interferente Pequeno/genética , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Hyperglycemia and endotoxemia have been associated with coagulation abnormalities in horses. Studies in humans suggest greater disturbances in coagulation with hyperglycemia and concurrent endotoxemia. OBJECTIVES: To compare coagulation parameters in horses administered with lipopolysaccharide (LPS) with and without concurrent hyperglycemia. ANIMALS: Twelve healthy adult horses. METHODS: Hyperglycemia (180-240 mg/dL) was maintained for 6 hours in 6 horses (GLU-LPS) using 140 mg/kg IV bolus of dextrose followed by a 20% dextrose constant rate infusion. A similar volume of saline was administered to an additional 6 horses (SAL-LPS). LPS (20 ng/kg) was administered to each horse. Fibrogen concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin antithrombin concentration (TAT), and thromboelastometry were measured at baseline and after 1, 1.5, 2, 2.5, 3, 4, 6, and 22 hours. Repeated measures analysis of variance was used to examine temporal changes. RESULTS: Increases in PT (P = .001) and TAT (P = .027) were observed in the GLU-LPS group. Changes in thromboelastometry parameters including increased clot formation time (In-TEM, P = .006; Ex-TEM, P = .002) and decreased alpha angle (Ex-TEM, P = .04) and maximal clot firmness (Ex-TEM, P = .014) were observed in the SAL-LPS group. Differences between SAL-LPS and GLU-LPS groups were limited to increased maximal clot firmness (Ex-TEM) at 3, 6, and 22 hours (P < .001) in the SAL-LPS group. CONCLUSIONS AND CLINICAL IMPORTANCE: Minor alterations in coagulation parameters identified for each group are most likely not clinically relevant. Observed differences between groups do not suggest that concurrent hyperglycemia and endotoxemia are associated with greater coagulation abnormalities in horses.
Assuntos
Coagulação Sanguínea/fisiologia , Endotoxemia/veterinária , Cavalos/sangue , Hiperglicemia/veterinária , Animais , Antitrombina III/fisiologia , Endotoxemia/sangue , Feminino , Fibrinogênio/análise , Hiperglicemia/sangue , Masculino , Tempo de Tromboplastina Parcial/veterinária , Peptídeo Hidrolases/fisiologia , Tempo de Protrombina/veterinária , Distribuição Aleatória , Tromboelastografia/veterináriaRESUMO
Coagulation of blood is of multidisciplinary interest. Cardiac surgery produces major changes in the delicate balance between pro-and anti-coagulant serum factors. The role of antithrombin iii has been analysed after finding evidence that associated decreased levels of protein activity to postoperative morbidity and mortality. Supplementing exogenous antithrombin is considered with the aim of optimising outcomes. Its intrinsic anticoagulant and anti-inflammatory properties have stimulated a growing interest, and suggests new lines of research.
Assuntos
Antitrombina III/fisiologia , Procedimentos Cirúrgicos Cardíacos , Antitrombina III/análise , Antitrombina III/uso terapêutico , Deficiência de Antitrombina III/tratamento farmacológico , Deficiência de Antitrombina III/etiologia , Deficiência de Antitrombina III/mortalidade , Circulação Extracorpórea/efeitos adversos , Humanos , Síndrome de Resposta Inflamatória Sistêmica/etiologiaRESUMO
We have previously shown that ristocetin, an activator of glycoprotein Ib/IX/V, induces release of soluble CD40 (sCD40) ligand via thromboxane (TX) A(2) production from human platelets. In the present study, we investigated the effect of antithrombin-III (AT-III), an anticoagulant, on the ristocetin-induced glycoprotein Ib/IX/V activation in human platelets. AT-III inhibited ristocetin-stimulated platelet aggregation. The ristocetin-induced production of 11-dehydro-TXB(2), a stable metabolite of TXA(2), and the release of sCD40 ligand were suppressed by AT-III. AT-III also reduced the ristocetin-stimulated secretion of platelet-derived growth factor (PDGF)-AB. AT-III failed to affect U46619-, a TXA(2) receptor agonist, induced levels of p38 mitogen-activated protein kinase phosphorylation or sCD40 ligand release. AT-III reduced the binding of SZ2, a monoclonal antibody to the sulfated sequence in the α-chain of glycoprotein Ib, to the ristocetin-stimulated platelets. These results strongly suggest that AT-III reduced ristocetin-stimulated release of sCD40 ligand due to inhibiting TXA(2) production in human platelets.
Assuntos
Anticoagulantes/fisiologia , Antitrombina III/fisiologia , Plaquetas/fisiologia , Agregação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Tromboxano A2/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Anticorpos Monoclonais/química , Anticoagulantes/farmacologia , Antitrombina III/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Antígenos CD40/metabolismo , Humanos , Fosforilação , Ativação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Plasma Rico em Plaquetas/citologia , Ligação Proteica , Processamento de Proteína Pós-Traducional , Ristocetina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The coagulation system in children is complex and ever changing, a fact encapsulated in the term developmental hemostasis. Studies confirm that there are quantitative and almost certainly qualitative differences in the coagulation system with age, and the control of these changes comes from something external to the liver. What remains uncertain is the magnitude of the qualitative changes and the implications of the changes for the growing child. At the very least, developmental hemostasis probably provides a protective mechanism for neonates and children and hence contributes to the decreased risk of thromboembolic and/or hemorrhagic events in these age groups. In addition, developmental hemostasis could also reflect the role that hemostatic proteins play in physiological development and hence the demand of other processes, such as angiogenesis. Finally, without doubt, developmental hemostasis affects the interactions of anticoagulant drugs with the coagulation system. This article will initially discuss the most recent evidence with respect to qualitative age-related changes in the coagulation system. Subsequently the article will discuss the coagulation system during childhood in light of the three aforementioned areas of clinical impact and suggest possible strategies to further understand this complex and exciting field of study.
Assuntos
Coagulação Sanguínea/fisiologia , Desenvolvimento Infantil/fisiologia , Adulto , Envelhecimento/fisiologia , Anticoagulantes/farmacologia , Antitrombina III/fisiologia , Criança , Enoxaparina/farmacologia , Fibrinogênio/química , Hemostasia/fisiologia , Humanos , Recém-Nascido , Transplante de Fígado , Peso Molecular , Neovascularização Fisiológica/efeitos dos fármacos , Tromboembolia/etiologiaAssuntos
Deficiência de Antitrombina III , Deficiência de Proteína C , Deficiência de Proteína S , Trombofilia/genética , Anticoagulantes/uso terapêutico , Antitrombina III/fisiologia , Deficiência de Antitrombina III/complicações , Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/genética , Coagulação Sanguínea/fisiologia , Feminino , Humanos , Masculino , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Proteína C/fisiologia , Deficiência de Proteína C/complicações , Deficiência de Proteína C/diagnóstico , Deficiência de Proteína C/genética , Proteína S/fisiologia , Deficiência de Proteína S/complicações , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/genética , Trombofilia/tratamento farmacológico , Trombose/etiologiaRESUMO
CONTEXT: Uterine leiomyomas occur in 30-70% of reproductive-age women. Leiomyoma reduce implantation, increase miscarriage risk, and increase menstrual bleeding. We hypothesized that endometrial defects induced by leiomyoma result in menorrhagia and reproductive dysfunction. OBJECTIVES: We evaluated the effect of leiomyoma on endometrial gene expression essential for implantation and hemostasis both in vivo and in primary endometrial stromal cells (ESC). DESIGN AND SETTING: We conducted a case control and in vitro study at a university medical center. PATIENTS: The study included 24 subjects with or without leiomyoma. INTERVENTION/MAIN OUTCOME MEASURED: Endometrium, myometrium, leiomyoma, and ESC were obtained. Immunohistochemistry was used to evaluate TGF-ß3, bone morphogenetic protein (BMP) receptors (BMPRs), plasminogen activator inhibitor 1 (PAI-1), and thrombomodulin in vivo. BMP-2 secretion was assessed by ELISA. ESC were treated with recombinant human (rh) BMP-2 or rhTGF-ß3. Expression of HOXA10, LIF, BMPRs, antithrombin III (ATIII), thrombomodulin, and PAI-1 was assessed by quantitative RT-PCR. RESULTS: ESC from controls secreted more BMP-2 than those from women with leiomyoma. HOXA10 and LIF expression increased after rhBMP-2 treatment of normal but not leiomyoma-associated ESC. In vivo leiomyoma-associated endometrium expressed lower levels of BMPR 1A, 1B, and 2 than controls. Leiomyoma expressed high levels of TGF-ß3; TGF-ß3 treatment of ESC reduced expression of BMPRs. Similarly, leiomyoma-associated endometrium expressed less PAI-1 and thrombomodulin in vivo. In ESC, TGF-ß3 reduced expression of PAI-1, ATIII, and thrombomodulin. CONCLUSIONS: Leiomyoma-secreted TGF-ß3 induces BMP-2 resistance in endometrium by down-regulation of BMPR-2, likely causing defective endometrial decidualization. TGF-ß3 also reduces expression of PAI-1, ATIII, and thrombomodulin in endometrium, likely contributing to menorrhagia. A single molecular signal targeting endometrium may mediate both leiomyoma-induced infertility and bleeding.
Assuntos
Coagulação Sanguínea/genética , Proteína Morfogenética Óssea 2/biossíntese , Proteína Morfogenética Óssea 2/fisiologia , Decídua/fisiologia , Leiomioma/patologia , Fator de Crescimento Transformador beta3/fisiologia , Neoplasias Uterinas/patologia , Adulto , Antitrombina III/fisiologia , Células Cultivadas , DNA Complementar/biossíntese , DNA Complementar/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Infertilidade Feminina/etiologia , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , Leiomioma/complicações , Leiomioma/genética , Menorragia/etiologia , Menorragia/patologia , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/fisiologia , RNA/biossíntese , RNA/genética , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/fisiologia , Trombomodulina/fisiologia , Fator de Crescimento Transformador beta3/genética , Neoplasias Uterinas/complicações , Neoplasias Uterinas/genéticaRESUMO
This review is focused on the role of heparin in the maintenance of hematological homeostasis. Description of the main components of the hemostatic system is presented. The mechanism of heparin action as an anticoagulating and fibrinolytic agent are analyzed. A hypothesis is forwarded to explain the role of heparin in animals and humans as a key substance promoting stabilization, regulation and distribution of different active blood components bound into complexes with heparin.
Assuntos
Hemostasia , Heparina/fisiologia , Animais , Antitrombina III/fisiologia , Coagulação Sanguínea/fisiologia , Fatores de Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Endotélio Vascular/fisiologia , Fibrinólise/fisiologia , Humanos , Músculo Liso Vascular/fisiologia , Serina Proteases/fisiologia , Trombose/sangue , Vasoconstrição/fisiologiaRESUMO
Although antithrombin-III (AT-III), an anti-coagulant, has been shown to affect human platelet functions, the direct effect of AT-III on platelets is still unknown. We recently reported that the collagen-induced phosphorylation of the heat shock protein 27 (HSP27) via the p44/p42 mitogen-activated protein (MAP) kinase is sufficient for granule secretion and the release of soluble CD40 ligand (sCD40L) from platelets but not platelet aggregation. In the present study, we investigated whether AT-III affects the collagen-induced secretion of the platelet-derived growth factor (PDGF)-AB and sCD40L release. AT-III inhibited collagen-stimulated platelet aggregation. The collagen-induced secretion of PDGF-AB was significantly suppressed by AT-III. AT-III also reduced sCD40L release. AT-III markedly attenuated the collagen-induced phosphorylated levels of p44/p42 MAP kinase. In addition, AT-III suppressed collagen-induced HSP27 phosphorylation. These results strongly suggest that AT-III reduced collagen-stimulated platelet granule secretion due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.
Assuntos
Anticoagulantes/farmacologia , Antitrombina III/farmacologia , Plaquetas/metabolismo , Ligante de CD40/metabolismo , Colágeno/farmacologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Vesículas Secretórias/metabolismo , Antitrombina III/fisiologia , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Humanos , Agregação Plaquetária/efeitos dos fármacos , Vesículas Secretórias/efeitos dos fármacosRESUMO
Thrombogenesis depends on biochemical reactions affected by blood flow dynamics. While mathematical models of mural thrombogenesis provide a means of understanding how blood flow affects thrombus growth, comparisons to experimental data are needed to validate the models and enable prediction of thrombus growth under diverse conditions. In this paper, we present mathematical models of mural thrombogenesis under flow and validation of the models with experimental data collected from a thrombogenic vascular graft segment. The grafts were placed in exteriorized high-flow arteriovenous (AV) shunts in baboons. Radiolabeled platelet deposition onto the thrombogenic segment, a marker of thrombus size, and plasma thrombin-antithrombin (TAT) concentration downstream of the graft, a marker of local thrombin generation, were monitored over time. The mathematical model of mural thrombogenesis consisted of transport-reaction equations in which platelets and thrombin were explicitly considered. We found that the transport-reaction model captured the order of magnitude of TAT sampled levels, while calculated rates of platelet deposition agreed well with radioimaging results. Analysis of experimental and modeling data indicates that, at least during part of thrombus growth progression, thrombin generation is in excess and platelet adhesion rates would be sustained even at lower local thrombin concentrations.
Assuntos
Plaquetas/fisiologia , Modelos Teóricos , Trombose/fisiopatologia , Animais , Antitrombina III/fisiologia , Masculino , Papio , Papio hamadryas , Contagem de Plaquetas , Reprodutibilidade dos Testes , Trombina/fisiologia , Fatores de TempoRESUMO
Sepsis is often associated with systemic intravascular activation of coagulation, potentially leading to widespread microvascular deposits of fibrin, and thereby contributing to multiple organ dysfunction. A complex interaction exists between activation of inflammatory systems and the initiating and regulating pathways of coagulation. A diagnosis of sepsis-associated disseminated intravascular coagulation can be made by a combination of routinely available laboratory tests, for which simple diagnostic algorithms have become available. Strategies to inhibit coagulation activation may theoretically be justified and are being evaluated in clinical studies.
Assuntos
Coagulação Intravascular Disseminada/sangue , Sepse/sangue , Anticoagulantes/uso terapêutico , Antitrombina III/fisiologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/terapia , Glicocálix/fisiologia , Humanos , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/terapia , Plasma , Transfusão de Plaquetas , Proteína C/fisiologia , Sepse/diagnóstico , Sepse/terapia , Tromboplastina/fisiologiaRESUMO
Effects of dose and duration of phenobarbital (PB) administration and those of co-administration of PB and vitamin K on blood coagulation-related parameters were examined in specific pathogen-free (SPF) rats of Sprague-Dawley strain kept on an ordinary diet. In Experiment 1, oral administration of PB (0, 25, 50, 100 or 150 mg/kg/day) for 2 weeks induced increases in hepatic cytochrome P450 content and CYP2B expression, prolongation of coagulation time (activated partial thromboplastin time (APTT) and Thrombotest (TBT)) and an increase in anti-thrombin III (AT III) concentration in a dose-dependent manner. In Experiment 2, PB administration (100 mg/kg/day) for up to 14 days produced time-dependent increases in hepatic cytochrome P450 content and CYP2B (CYP2B1 and CYP2B2) expression. APTT was prolonged from day 1 and AT III concentration was increased from day 2, whereas the coagulation time (TBT) was prolonged from day 7. In Experiment 3, APTT prolonged by PB (100 mg/kg/day) was shortened after vitamin K(2) (30 mg/kg/day) co-administration, although AT III concentration was still increased. This suggests that not AT III but PB-induced vitamin K deficiency may play an important role in PB-induced prolongation of coagulation time in SPF rats kept on an ordinary diet.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fenobarbital/toxicidade , Vitamina K/farmacologia , Animais , Antitrombina III/análise , Antitrombina III/fisiologia , Relação Dose-Resposta a Droga , Masculino , Tempo de Tromboplastina Parcial , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Vitamina K/metabolismoRESUMO
The cell-extracellular matrix interface is a crowded space whose structure is dependent on macromolecular assemblies that are dynamic in time, molecular composition and location. Signals travel from one cell to another (or to the same cell) by the regulated assembly/disassembly of molecular complexes. These signals can evoke relatively simple biological responses such cell proliferation and migration, but once integrated, they guide cell fate in complex biological phenomena such as embryonic development and organism homeostasis. Heparan sulfate proteoglycans are ubiquitous components of this space and important actors of these processes in all tissue-organized life forms. A key feature of heparan sulfate is its size, 40 nm to 160 nm, which enables it to integrate self-assembling macromolecular structures over substantial length scales. What is the structure of heparan sulfate? Why do we think heparan sulfate is so important? How do we try to explain its activity? What do we know about its interactions? These questions together with a final look to the future are the "menu" of this review.
Assuntos
Proteoglicanas de Heparan Sulfato/fisiologia , Heparitina Sulfato/fisiologia , Animais , Anticoagulantes/farmacologia , Antitrombina III/química , Antitrombina III/fisiologia , Cães , Genes Supressores de Tumor , Heparina/farmacologia , Heparina/fisiologia , Humanos , N-Acetilglucosaminiltransferases/genéticaRESUMO
In this review, we discuss the anesthetic implications of the new anticoagulant and antiplatelet drugs, focusing our discussion mainly on neuroaxial/regional anesthesia and central catheter placement issues. We offer practical recommendations for their use.
Assuntos
Anestesia , Anticoagulantes/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Animais , Anticoagulantes/efeitos adversos , Antitrombina III/fisiologia , Inibidores do Fator Xa , Fibrinogênio/antagonistas & inibidores , Heparina/efeitos adversos , Heparina/uso terapêutico , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Trombina/antagonistas & inibidoresRESUMO
INTRODUCTION: Patients with chronic kidney disease exhibit features of a hypercoagulable state and have endothelial dysfunction, which may contribute to their increased cardiovascular risk. We examined the relationship between coagulation activation and vascular function in patients with chronic kidney disease. MATERIALS AND METHODS: We measured parameters of the tissue factor pathway of blood coagulation (tissue factor, factor VIIc and factor X); natural inhibitors (tissue factor pathway inhibitor, protein C, free and total protein S, antithrombin III) and markers of coagulation activation (thrombin-antithrombin complexes, prothrombin fragment 1+2) in 66 stage 4&5 chronic kidney disease patients and 36 healthy controls. Their relationship with markers of vascular function (flow mediated dilatation, soluble E-selectin and thrombomodulin) and a mediator of inflammation (interleukin-6) was determined. RESULTS: Up-regulation of the tissue factor pathway (increased tissue factor and factor VIIc), increased prothrombin fragment 1+2 and significant reductions in antithrombin III and the ratio of free protein S: total protein S were found in patients compared to healthy controls. Increased tissue factor antigen was significantly and independently correlated with creatinine and interleukin-6 (P<0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r=0.58; P<0.001). Changes in coagulation and anti-coagulation were independent of all measures of endothelial function. CONCLUSIONS: Significant activation of the TF pathway of coagulation and depletion or reduction of some natural anticoagulants in chronic kidney disease was correlated with the degree of renal dysfunction, but not correlated with the abnormalities of vascular function. These data are consistent with a hypercoagulable state in chronic kidney disease that may be independent of endothelial based regulation but associated with an inflammatory state.
Assuntos
Coagulação Sanguínea/fisiologia , Endotélio Vascular/fisiologia , Falência Renal Crônica/fisiopatologia , Trombofilia/fisiopatologia , Idoso , Antígenos/fisiologia , Antitrombina III/fisiologia , Fenômenos Biológicos , Biomarcadores/sangue , Creatinina/sangue , Selectina E/sangue , Fator VII/fisiologia , Fator X/fisiologia , Feminino , Humanos , Interleucina-6/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/fisiologia , Proteína S/metabolismo , Protrombina/fisiologia , Diálise Renal/efeitos adversos , Solubilidade , Trombomodulina/sangue , Trombofilia/complicações , Tromboplastina/fisiologiaRESUMO
For the first time, positive influence was shown of a complex blood heparin-antitrombin III on the state of the coagulant and fibrinolytic system of blood in patients with acute virus myocarditis that favours the normalization of clinical and laboratory indicators, improvement of the state of patients and reduction of average bed-day indicator (hospital stay) till 25 and 35 days in accordance with severity of clinical course of the disease and can be recommended as a choice of medicine.
Assuntos
Antitrombina III/análise , Coagulação Sanguínea/fisiologia , Heparina/sangue , Miocardite/sangue , Índice de Gravidade de Doença , Viroses/sangue , Doença Aguda , Adolescente , Adulto , Antitrombina III/fisiologia , Terapia Combinada , Quimioterapia Combinada , Heparina/fisiologia , Humanos , Pessoa de Meia-Idade , Miocardite/terapia , Miocardite/virologia , Troca Plasmática , Viroses/terapia , Adulto JovemRESUMO
Antithrombin (AT) is a potent inactivator of thrombin and factor Xa and the major inhibitor of blood coagulation. Inherited AT deficiencies are uncommon, with prevalences in the general population between 1 in 500 and 1 in 5000. They are either quantitative (type I) or qualitative (type II). Type II is subdivided into the more common, but less thrombogenic, type IIb deficiency caused by a defect in the heparin-binding region of AT and the less common, but more thrombophilic, type IIa variant caused by mutations in the thrombin-binding site. A pleiotropic type IIc deficiency also exists. In the evaluation of a thrombophilic individual, a functional AT assay (AT activity) should be used and the diagnosis of AT deficiency only established after acquired causes have been ruled out and repeat AT testing on an additional sample has been performed. A subsequent antigenic AT assay result leads to differentiation between type I and type II deficiency. Further specialized tests help subclassify the type II deficiencies, but this is typically not carried out for clinical purposes, even though it might be helpful to assess thrombosis risk. AT deficiency is associated with an increased risk for venous thromboembolism (VTE) and pregnancy loss. The association with arterial thrombosis is only weak. VTE prophylaxis and treatment management will be discussed in this article and existing treatment guidelines presented. The lack of data surrounding the use of AT concentrates and the resulting ambiguity as to when to use such concentrates will be discussed.
Assuntos
Anticoagulantes/uso terapêutico , Deficiência de Antitrombina III/genética , Antitrombina III/fisiologia , Coagulação Sanguínea/fisiologia , Tromboembolia Venosa/tratamento farmacológico , Idoso , Antitrombina III/farmacologia , Antitrombina III/uso terapêutico , Deficiência de Antitrombina III/classificação , Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/fisiopatologia , Resultado da Gravidez , Recidiva , Fatores de Risco , Trombofilia/genética , Trombofilia/fisiopatologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/genéticaRESUMO
Microparticles (MPs), shed during the storage of platelets, support blood coagulation and could be helpful in restoring the haemostatic system in thrombocytopenic patients. The mechanisms by which MPs support haemostasis under flow conditions were investigated. Fluorescent-labelled MPs were perfused at shear rates of 100 and 1000/s over surfaces coated with collagen, fibrinogen, von Willebrand factor (VWF) or surface-adherent platelets. Adhesion was monitored in real-time by fluorescence microscopy. In addition, thrombin-antithrombin (TAT) complex formation was measured in flowing thrombocytopenic blood. MPs attained the capacity to firmly adhere to collagen, VWF, fibrinogen and surface-adherent platelets at high and low shear rate. Antibodies against glycoprotein Ibalpha and alpha(IIb)beta(3) were used to demonstrate the specificities of these interactions. The addition of MPs to thrombocytopenic blood did not affect platelet adhesion. TAT complex formation was increased in the presence of MPs in capillaries coated with fibrinogen, but not on collagen fibres. We confirmed that MPs adhere to a damaged vascular bed in vivo after infusion in denuded arteries in a mouse model. MPs have platelet-like adhering properties and accelerate thrombin generation. These properties strongly support the notion that MPs can be beneficial in maintaining normal haemostasis when platelet function is impaired or reduced, as in thrombocytopenic patients.