RESUMEN
COVID-19's long-lasting and complex impacts have become a global concern, with diverse clinical outcomes. This study evaluated 226 participants to understand the clinical spectrum of COVID-19/Long COVID (LC), exploring how disease severity correlates with sociodemographic factors and biomarkers. Determinants related to COVID-19 severity included age (P < 0.001), lower education (P < 0.001), ethnicity (P = 0.003), overweight (P < 0.001), MTHFR gene rs1801133 (P = 0.035), cardiovascular diseases (P = 0.002), diabetes mellitus (DM) (P = 0.006), Factor VIII (FVIII) (P = 0.046), von Willebrand factor (VWF) (P = 0.002), and dimer D (DD) (P < 0.001). Six months later, in a portion of the monitored participants, a significant reduction in FVIII (P < 0.001), VWF (P = 0.002), and DD (P < 0.001) levels was observed, with only DD returning to normal values. Different systemic sequelae were identified, with higher incidences of joint pain and myalgia in participants with a clinical history of DM, chronic lung disease (CLD) and sustained high interleukin 6 values in the convalescent phase. CLD, COVID-19 severity and high DD levels increased the risk of developing dyspnea and palpitations. Women were more likely to develop lower limb phlebitis long-term, while sustained elevated FVIII in the convalescent phase was associated with an increased risk of swelling. Regular physical activity had a protective effect against swelling. This study highlights factors contributing to COVID-19 severity/LC, emphasizing endothelial cell activation as a potential mechanism.
Asunto(s)
Biomarcadores , COVID-19 , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factor de von Willebrand , Humanos , COVID-19/sangre , Femenino , Masculino , Biomarcadores/sangre , Persona de Mediana Edad , Pronóstico , Factor de von Willebrand/metabolismo , Factor de von Willebrand/análisis , Adulto , Anciano , SARS-CoV-2/aislamiento & purificación , Factor VIII/metabolismo , Factor VIII/análisis , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismoAsunto(s)
Consenso , Hemofilia A , Hemofilia B , Factores de Coagulación Sanguínea/efectos adversos , Factores de Coagulación Sanguínea/uso terapéutico , Diagnóstico Diferencial , Factor IX/análisis , Factor IX/inmunología , Factor VIII/análisis , Factor VIII/inmunología , Femenino , Pruebas Genéticas , Hemartrosis/diagnóstico , Hemartrosis/etiología , Hemartrosis/terapia , Hemofilia A/complicaciones , Hemofilia A/diagnóstico , Hemofilia A/genética , Hemofilia A/terapia , Hemofilia B/complicaciones , Hemofilia B/diagnóstico , Hemofilia B/genética , Hemofilia B/terapia , Hemostasis/genética , Humanos , Isoanticuerpos/análisis , Estilo de Vida , Masculino , México , Cuidados Preoperatorios/métodosRESUMEN
The role of inflammation in thrombotic complications of primary antiphospholipid syndrome (PAPS) is controversial. The aim of this study was to evaluate levels of inflammation and coagulation markers in patients with thrombotic PAPS (t-PAPS). Patients with t-PAPS and individuals with no history of thrombosis were enrolled. The association of t-PAPS with levels of tumor necrosis factor (TNF)-α, C-reactive protein (hs-CRP), interferon (IFN)-α, interleukins (IL)-6, -8, factor VIII (FVIII), von Willebrand factor (VWF) and tissue factor (TF) was evaluated by regression models. The levels of these markers were also compared between controls and subgroups of t-PAPS patients with triple positivity, recently diagnosed thrombosis, recurrent thrombosis and venous thrombosis. Patients with t-PAPS (n = 101) had a 8.6-fold increased levels of TNF-α, 90% increased levels of hs-CRP, 80% increased levels of IL-6, 30% increased levels of FVIIIAg, 50% increased levels of VWF and 66% increased levels of TF as compared to controls (n = 131), and the differences did not change after adjustments for sex, age and cardiovascular risk factors. Inflammatory markers were elevated in t-PAPS regardless of the aPL profile, number of previous thrombosis or time elapsed since diagnosis. TNF-α and IL-8 levels were higher in t-PAPS patients with venous thrombosis, in comparison with those with arterial thrombosis and controls. Patients with t-PAPS presented with increased levels of inflammatory and coagulation markers, which suggests that t-PAPS is associated not only with hypercoagulability but also with a persistent inflammatory state.
Asunto(s)
Síndrome Antifosfolípido/sangre , Inflamación/sangre , Trombosis/sangre , Adulto , Síndrome Antifosfolípido/complicaciones , Biomarcadores/sangre , Coagulación Sanguínea , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Factor VIII/análisis , Femenino , Humanos , Inflamación/complicaciones , Interferón-alfa/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Trombosis/etiología , Factor de von Willebrand/análisisRESUMEN
B-domainless factor VIII (FVIII) ectopically expressed in megakaryocytes (MKs) is stored in α granules of platelets (pFVIII) and is capable of restoring hemostasis in FVIIInull mice, even in the presence of circulating inhibitors. However, our prior studies have shown that this ectopically expressed pFVIII can injure developing MKs. Moreover, the known risks of prolonged thrombocytopenia after bone marrow transplantation are significant challenges to the use of this strategy to treat individuals with severe hemophilia A and particularly those with intractable clinically relevant inhibitors. Because of these limitations, we now propose the alternative therapeutic pFVIII strategy of infusing pFVIII-expressing MKs or platelets derived from induced pluripotent stem cells (iPSCs). pFVIII-expressing iPSC-derived MKs, termed iMKs, release platelets that can contribute to improved hemostasis in problematic inhibitor patients with hemophilia A. As proof of principle, we demonstrate that hemostasis can be achieved in vitro and in vivo with pFVIII-expressing platelets and show prolonged efficacy. Notably, pFVIII-expressing platelets are also effective in the presence of inhibitors, and their effect was enhanced with recombinant FVIIa. Human pFVIII-expressing iMKs improved hemostasis in vitro, and derived platelets from infused human pFVIII-expressing iMKs improved hemostasis in FVIIInull mice. These studies indicate the potential therapeutic use of recurrent pFVIII-expressing MK or platelet infusions with prolonged hemostatic coverage that may be additive with bypassing agents in hemophilia A patients with neutralizing inhibitors.
Asunto(s)
Factor VIII/genética , Hemofilia A/terapia , Megacariocitos/trasplante , Transfusión de Plaquetas , Animales , Área Bajo la Curva , Plaquetas/citología , Plaquetas/metabolismo , Factor VIII/análisis , Factor VIII/metabolismo , Factor VIIa/uso terapéutico , Hemofilia A/mortalidad , Humanos , Masculino , Megacariocitos/citología , Megacariocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Curva ROC , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Previous cross-sectional studies showed that some patients with haemophilia A (HA) without inhibitor presented a pro-inflammatory profile during factor VIII (FVIII) replacement therapy. Furthermore, an anti-inflammatory/regulatory state was described in HA patients after inhibitor development. However, no study investigated the levels of these biomarkers before exposure to exogenous FVIII. This study investigated the immunological profile of previously untreated patients (PUPs) with HA in comparison with non-haemophiliac boys. A panel of chemokines and cytokines was evaluated in the plasma of 40 PUPs with HA and 47 healthy controls. The presence of microparticles was assessed in the plasma of 32 PUPs with HA and 47 healthy controls. PUPs with HA presented higher levels of CXCL8 (IL8), IL6, IL4, IL10, IL2, IL17A (IL17), and lower levels of CXCL10 (IP-10) and CCL2 (MCP-1) than the age-matched healthy controls (P < 0·05). We also observed higher levels of microparticles derived from endothelium, erythrocytes, platelets, leucocytes, neutrophils, and T lymphocytes in patients in comparison with controls (P < 0·05). Compared with controls, PUPs with HA presented a distinct immunological profile, characterized by a prominent pro-inflammatory status that appears to be regulated by IL4 and IL10.
Asunto(s)
Citocinas/sangre , Factor VIII/análisis , Hemofilia A/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Micropartículas Derivadas de Células , Quimiocinas/sangre , Hemofilia A/sangre , Humanos , Lactante , Mediadores de Inflamación/sangre , MasculinoRESUMEN
La enfermedad de von Willebrand (EvW) es el resultado de una deficiencia cuantitativa y/o cualitativa del factor de von Willebrand (FvW). Esta clasificado como un defecto extrínseco de las plaquetas, donde el fallo de respuesta hemostática se atribuye a la deficiencia de un factor del plasma necesario para la función normal de las plaquetas. Este estudio tiene como objetivo describir sistemáticamente el diagnóstico de la EvW tipo 1, tomando como ejemplo el reporte de un caso de un perro que presenta intensa epistaxis bilateral tratado en el hospital veterinario.
The von Willebrand disease (vWD) results from a quantitative and / or qualitative deficiency of von Willebrand factor (vWF). It is classified as a platelet- extrinsic defect, wherein the hemostatic response failure is attributed to deficiency of a plasma factor required for normal platelet function. This study aims to describe systematically the diagnosis of vWD type 1 exemplified in a case report of a dog treated at a veterinary teaching hospital due to intense bilateral epistaxis.
A doença de von Willebrand (DvW) resulta de uma deficiência quantitativa e/ou qualitativa do fator de von Willebrand (FvW). É classificada como um defeito extrínseco à plaqueta, em que a falha da resposta hemostática é atribuída à deficiência de um fator plasmático necessário para a função plaquetária normal. Este estudo visa descrever de maneira sistemática o diagnóstico da doença de (DvW) tipo 1 exemplificada em um relato de caso de um cão atendido em hospital veterinário de ensino devido a uma intensa epistaxe bilateral.
Asunto(s)
Animales , Perros , Enfermedad de von Willebrand Tipo 1/diagnóstico , Enfermedad de von Willebrand Tipo 1/veterinaria , Epistaxis/veterinaria , Factor VIII/análisis , Hemostasis , Anomalías Congénitas/veterinaria , HemorragiaRESUMEN
La enfermedad de von Willebrand (EvW) es el resultado de una deficiencia cuantitativa y/o cualitativa del factor de von Willebrand (FvW). Esta clasificado como un defecto extrínseco de las plaquetas, donde el fallo de respuesta hemostática se atribuye a la deficiencia de un factor del plasma necesario para la función normal de las plaquetas. Este estudio tiene como objetivo describir sistemáticamente el diagnóstico de la EvW tipo 1, tomando como ejemplo el reporte de un caso de un perro que presenta intensa epistaxis bilateral tratado en el hospital veterinario.(AU)
The von Willebrand disease (vWD) results from a quantitative and / or qualitative deficiency of von Willebrand factor (vWF). It is classified as a platelet- extrinsic defect, wherein the hemostatic response failure is attributed to deficiency of a plasma factor required for normal platelet function. This study aims to describe systematically the diagnosis of vWD type 1 exemplified in a case report of a dog treated at a veterinary teaching hospital due to intense bilateral epistaxis.(AU)
A doença de von Willebrand (DvW) resulta de uma deficiência quantitativa e/ou qualitativa do fator de von Willebrand (FvW). É classificada como um defeito extrínseco à plaqueta, em que a falha da resposta hemostática é atribuída à deficiência de um fator plasmático necessário para a função plaquetária normal. Este estudo visa descrever de maneira sistemática o diagnóstico da doença de (DvW) tipo 1 exemplificada em um relato de caso de um cão atendido em hospital veterinário de ensino devido a uma intensa epistaxe bilateral.(AU)
Asunto(s)
Animales , Perros , Enfermedad de von Willebrand Tipo 1/diagnóstico , Enfermedad de von Willebrand Tipo 1/veterinaria , Hemostasis , Factor VIII/análisis , Epistaxis/veterinaria , Anomalías Congénitas/veterinaria , HemorragiaRESUMEN
Acquired haemophilia is a rare disorder. The clinical picture ranges from mild ecchymosis and anaemia to life threatening bleeding in up to 20% of patients. The disease is produced by an antibody against Factor VIII and it usually occurs in the elderly, with no previous history of a bleeding disorder. It can be associated to an underlying condition such as cancer, autoimmune disorders, drugs or pregnancy. It has a typical laboratory pattern with isolated prolonged activated partial thromboplastin time (aPTT) that fails to correct upon mixing tests with normal plasma and low levels of factor VIII. Treatment recommendations are based on controlling the acute bleeding episodes with either bypassing agent, recombinant activated factor VII or activated prothrombin complex concentrate, and eradication of the antibody with immunosuppressive therapy.
Asunto(s)
Hemofilia A , Autoanticuerpos/sangre , Factor VIII/análisis , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Hemorragia/terapia , HumanosRESUMEN
La hemofilia adquirida es una enfermedad de muy poco frecuente presentación. El paciente habitualmente consulta con equimosis y hematomas extensos en la piel y tejido celular subcutáneo, anemia y en algunas oportunidades un sangrado grave, que si no se controla puede ser fatal hasta en el 20% de los casos. Se produce por un autoanticuerpo dirigido contra el factor VIII de la coagulación y suele ocurrir en pacientes añosos sin historia de sangrados, pero también puede presentarse asociado a neoplasias, enfermedades autoinmunes, medicamentos y en mujeres jóvenes asociado al embarazo. Tiene un perfil de laboratorio característico con un tiempo de tromboplastina parcial activada (aPTT) prolongado, que no corrige con plasma normal, y niveles de factor VIII disminuidos. El tratamiento recomendado es muy específico, ya que para controlar el sangrado se utilizan agentes de puenteo (productos que sortean el efecto del inhibidor), factor VII recombinante activado o concentrado de complejo de protrombina activada, y medicación inmunosupresora para erradicar el autoanticuerpo.
Acquired haemophilia is a rare disorder. The clinical picture ranges from mild ecchymosis and anaemia to life threatening bleeding in up to 20% of patients. The disease is produced by an antibody against Factor VIII and it usually occurs in the elderly, with no previous history of a bleeding disorder. It can be associated to an underlying condition such as cancer, autoimmune disorders, drugs or pregnancy. It has a typical laboratory pattern with isolated prolonged activated partial thromboplastin time (aPTT) that fails to correct upon mixing tests with normal plasma and low levels of factor VIII. Treatment recommendations are based on controlling the acute bleeding episodes with either bypassing agent, recombinant activated factor VII or activated prothrombin complex concentrate, and eradication of the antibody with immunosuppressive therapy.
Asunto(s)
Humanos , Hemofilia A/diagnóstico , Hemofilia A/inmunología , Hemofilia A/tratamiento farmacológico , Autoanticuerpos/sangre , Factor VIII/análisis , Hemorragia/terapiaRESUMEN
Increased factor VIII (FVIII) levels are a prevalent and independent risk factor for venous thromboembolism (VTE). The low density lipoprotein receptor-related protein 1 (LRP1) has been associated with FVIII catabolism. After a median of 10 years of the first thrombotic episode, we evaluated FVIII activity levels in 75 patients with VTE and high FVIII levels and in 74 healthy controls. Subsequently, we evaluated the regions of F8 and LRP1 genes coding sites of affinity between these proteins, with the objective of determining genetic alterations associated with plasma FVIII levels. After a median time of 10 years after the VTE episode, FVIII levels were significantly higher in patients when compared to controls (158.6â IU/dL vs. 125.8â IU/dL; P ≤ 0.001]. Despite the fact that we found 14 genetic variations in F8 and LRP1 genes, no relationship was found between FVIII levels with these variations. We demonstrated a persistent increase of FVIII levels in patients with VTE, but in a much lower magnitude after 10 years when compared to 3-years after the episode. Moreover, we observed no relationship of genetic variations in the gene regions coding affinity sites between LRP1 and FVIII with FVIII levels.
Asunto(s)
Factor VIII/análisis , Variación Genética , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Tromboembolia Venosa/sangre , Adulto , Estudios de Casos y Controles , Exones , Factor VIII/genética , Factor VIII/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Intrones , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/química , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético , Unión Proteica , Tromboembolia Venosa/patologíaRESUMEN
BACKGROUND: The recessive X-linked disorder hemophilia A (HA) is rarely expressed in female carriers, most of whom express about half of normal factor VIII activity ( FVIII: C). OBJECTIVE: To propose an integrative assessment model for the binary role of the phase between the mutated F8 and the active X-chromosome (Xa) in FVIII: C in HA carriers. METHODS: We studied 67 females at risk of severe HA, comprising five symptomatic females ( FVIII: C < 1.5 IU dL(-1) ) and 14 controls. A correlation study between FVIII: C (observed vs. expected) and X-chromosome inactivation (XCI) patterns (XIPs; androgen receptor gene [AR] system) in blood leukocyte DNA was performed in carriers, by comparison of a model correlating FVIII: C and XIP with arbitrary models devoid of biological significance, and with FVIII: C levels in non-carriers (mean model) as a proxy from background data dispersion not influenced by XIP. RESULTS: We provide proof-of-concept example from a family presenting with extremely skewed XIPs in which the severe HA phenotype appeared in a heterozygous carrier of a crossover between AR and F8 loci that phased the mutated F8 with the maternally inherited Xa. Furthermore, four cases of severe HA affected women who had a combination of a heterozygous F8 mutation and extremely skewed XIPs in leukocytes or oral mucosa are presented. Correlation analyses between FVIII: C levels and XIPs in carriers (n = 38) but not in non-carriers (n = 20) showed highly significant differences between the proposed correlation model and models without biological significance. The data support a binary influence of XCI, either increasing or decreasing the FVIII: C, subject to the underlying phase set between the F8 mutation and XCI. CONCLUSIONS: Our evidence suggests that the phase between XCI and mutated F8 acts as a molecular switch conditioning FVIII: C levels and HA expression in carriers.
Asunto(s)
Cromosomas Humanos X , Factor VIII/genética , Hemofilia A/genética , Mutación , Inactivación del Cromosoma X , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Factor VIII/análisis , Femenino , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Hemofilia A/sangre , Hemofilia A/diagnóstico , Herencia , Heterocigoto , Humanos , Lactante , Persona de Mediana Edad , Linaje , Fenotipo , Receptores Androgénicos/genética , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Identifying coagulation abnormalities in patients with combined bleeding and thrombosis history is clinically challenging. Our goal was to probe the complexity of dysregulated coagulation in humans by characterizing pathophysiologic mechanisms in a patient with both bleeding and thrombosis. The patient is a 56-year-old female with a history of haematomas, poor wound healing, and thrombosis (retinal artery occlusion and transient cerebral ischaemia). She had a normal activated partial thromboplastin time, prolonged thrombin and reptilase times, and decreased functional and antigenic fibrinogen levels, and was initially diagnosed with hypodysfibrinogenaemia. This diagnosis was supported by DNA analysis revealing a novel FGB mutation (c.656A>G) predicting a Q189R mutation in the mature chain that was present in the heterozygote state. However, turbidity analysis showed that purified fibrinogen polymerisation and degradation were indistinguishable from normal, and Bß chain subpopulations appeared normal by two-dimensional difference in-gel electrophoresis, indicating the mutated chain was not secreted. Interestingly, plasma thrombin generation testing revealed the patient's thrombin generation was higher than normal and could be attributed to elevated levels of factor VIII (FVIII, 163-225%). Accordingly, in an arterial injury model, hypofibrinogenaemic mice (Fgn(+/-)) infused with factor VIII demonstrated significantly shorter vessel occlusion times than saline-infused Fgn(+/-) mice. Together, these data associate the complex bleeding and thrombotic presentation with combined hypofibrinogenaemia plus plasma hypercoagulability. These findings suggest previous cases in which fibrinogen abnormalities have been associated with thrombosis may also be complicated by co-existing plasma hypercoagulability and illustrate the importance of "global" coagulation testing in patients with compound presentations.
Asunto(s)
Afibrinogenemia/genética , Factor VIII/análisis , Fibrinógeno/genética , Trastornos Hemorrágicos/genética , Mutación Missense , Mutación Puntual , Trombina/biosíntesis , Trombofilia/genética , Afibrinogenemia/sangre , Afibrinogenemia/complicaciones , Sustitución de Aminoácidos , Animales , Biopolímeros , Pruebas de Coagulación Sanguínea , Trombosis de las Arterias Carótidas/sangre , Trombosis de las Arterias Carótidas/genética , Modelos Animales de Enfermedad , Electroforesis en Gel Bidimensional , Factor VIII/toxicidad , Femenino , Fibrinógeno/química , Fibrinólisis , Eliminación de Gen , Trastornos Hemorrágicos/sangre , Trastornos Hemorrágicos/etiología , Heterocigoto , Humanos , Ataque Isquémico Transitorio/etiología , Ratones , Ratones Mutantes , Persona de Mediana Edad , Oclusión de la Arteria Retiniana/etiología , Trombofilia/sangre , Trombofilia/etiologíaRESUMEN
OBJECTIVE: The aim of this study was to investigate the effect of postmenopausal hormone therapy on coagulation and whether this effect differs according to ABO blood groups. METHODS: This was a prospective observational study to evaluate factor VIII (FVIII) activity, factor von Willebrand (vWF), and D-dimer (D-Di) levels and ABO blood groups in 61 postmenopausal women using oral estrogen plus progestogen therapy (EPT; 2 mg estradiol + 1 mg norethisterone acetate) for 3 months and in 101 women not using EPT. After 3 months, all eligible women who had completed the treatment scheme proposed for the EPT group or those who opted to participate but had not undergone EPT had a blood sample collected for analysis. RESULTS: Significant differences were observed in FVIII activity and vWF levels in the control group between those carrying group O and non-group O blood. For EPT users, significant differences were observed for FVIII activity, vWF, and D-Di levels. After a multivariate regression analysis, FVIII activity and ABO blood groups were independently associated with vWF levels, whereas interaction between ABO blood groups and EPT were independently associated with FVIII activity. Besides diabetes, the ABO × EPT interaction was also noted to be independently associated with D-Di levels. CONCLUSIONS: These findings suggest an interactive effect between oral EPT and non-O blood groups, contributing to the mechanism by which estrogen triggers the hypercoagulability state and increased risk for venous thrombosis in women undergoing oral EPT.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/fisiología , Coagulación Sanguínea/efectos de los fármacos , Estrógenos/efectos adversos , Terapia de Reemplazo de Hormonas/efectos adversos , Progestinas/efectos adversos , Trombofilia/inducido químicamente , Estrógenos/uso terapéutico , Factor VIII/análisis , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Persona de Mediana Edad , Progestinas/uso terapéutico , Estudios Prospectivos , Factor de von Willebrand/análisisRESUMEN
A 28 year-old female without history of previous disease. In the seventh month of her first pregnancy she developed hemorrhagic tendency that worsened in the early postpartum period. Activated partial thromboplastin time was 110 sec (control=35.8 sec) with negative tests for lupus anticoagulant. Factor VIII was <1% and a factor VIII inhibitor titer was 84 Bethesda Units/mL (BU). Initial therapy included methylprednisolone, prednisone, and cyclophosphamide. After two weeks of treatment, clinical conditions of the patient improved slightly and she was discharged. Outpatient therapy included azathioprine, and prednisone for a period of 22 months but in-hospital management was several times required. We initiated rituximab 375 mg/m2/week/4 weeks. A clinical improvement and increased levels of factors VIII and XI were observed 10 weeks later and factor VIII inhibitor decreased to undetectable levels. After a 82-month follow-up period (since the first rituximab infusion), she is asymptomatic and factor VIII and factor XI plasma levels are 70% and 94%, respectively FVIII inhibitor level is still undetectable. Rituximab seems an alternative for the treatment of acquired hemophilia refractory to standard treatment.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , Factor VIII/inmunología , Deficiencia del Factor XI/tratamiento farmacológico , Trastornos Puerperales/tratamiento farmacológico , Hemorragia Uterina/etiología , Adulto , Formación de Anticuerpos/efectos de los fármacos , Antígenos CD20/inmunología , Autoanticuerpos/sangre , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Cesárea , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Quimioterapia Combinada , Factor VIII/análisis , Factor XI/análisis , Factor XI/inmunología , Deficiencia del Factor XI/inmunología , Femenino , Hematoma/etiología , Hematoma/inmunología , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Penfigoide Gestacional/inmunología , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Embarazo , Trastornos Puerperales/etiología , Trastornos Puerperales/inmunología , Rituximab , Hemorragia Uterina/inmunologíaAsunto(s)
Carcinoma Hepatocelular/cirugía , Factor VIIa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Inhibidores de Factor de Coagulación Sanguínea/sangre , Carcinoma Hepatocelular/complicaciones , Factor VIII/análisis , Factor VIII/antagonistas & inhibidores , Hemofilia A/complicaciones , Humanos , Neoplasias Hepáticas/complicaciones , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
In this work, we evaluated the frequency of prothrombotic defects associated with deep venous thrombosis (DVT) in southern Chilean subjects. A total of 261 individuals, 87 patients with DVT confirmed by Doppler ultrasonography and 174 controls, were included in this study. Factor V and factor VIII levels, activated protein C (APC) resistance, and lupus anticoagulant detection were assayed by clotting methods. Basal homocysteine was quantified by immunoassay, and the polymorphisms in factor V (F5), methylenetetrahydrofolate reductase (MTHFR), and cystathionine ß-synthase (CBS) genes were genotyped by molecular methods. The most frequent defects were APC resistance, hyperhomocysteinemia, and increased levels of factor VIII. We observed a complete absence of the F5 G1691A variant in the studied population, and the frequency of MTHFR C677T polymorphism was significantly different between patients and controls (odds ratio = 3.2; 95% confidence interval, 1.513-6.735; p = 0.016). In addition, subjects carrying the homozygous MTHFR 677TT genotype exhibited higher levels of plasma homocysteine. Our data suggest that the APC resistance is the most important defect in Chilean patients with DVT. However, this phenotype is not associated with the presence of the F5 G1691A variant. In addition, only MTHFR C677T polymorphism constituted a molecular biomarker of DVT in Chilean population.
Asunto(s)
Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Protrombina/genética , Trombofilia/genética , Trombosis de la Vena/epidemiología , Resistencia a la Proteína C Activada/epidemiología , Resistencia a la Proteína C Activada/genética , Adolescente , Adulto , Anciano , Chile/epidemiología , Cistationina betasintasa/genética , Factor V/genética , Factor VIII/análisis , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hiperhomocisteinemia/epidemiología , Hiperhomocisteinemia/genética , Inhibidor de Coagulación del Lupus/análisis , Masculino , Persona de Mediana Edad , Mutación Missense , Fenotipo , Factores de Riesgo , Trombofilia/diagnóstico , Trombofilia/epidemiología , Ultrasonografía , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/genética , Adulto JovenRESUMEN
Conocer la frecuencia de defectos hemostáticos en mujeres con sangrado uterino anormal. Se estudiaron 55 mujeres de edades comprendidas entre 17 y 55 años, que presentaban sangrado uterino anormal. En cada paciente se realizó un estudio que comprendió: Historia clínica, examen físico (incluido examen ginecológico), biopsia endometrial, ultrasonograma transvaginal y pélvico y estudio hemostático a través de la determinación de los tiempos de protrombina y de tromboplastina parcial, concentraciones de factor VIII (FVIII), factor von Willebrand (FvW) y IX y agregación plaquetaria con epinefrina, ADP, colágeno y ristocetina. Hospital Nuestra Señora de Chiquinquirá, e Instituto de Investigaciones Clínicas Dr. Américo Negrette, Facultad de Medicina. Universidad del Zulia, Maracaibo, Venezuela. En todas las mujeres se halló una alteración orgánica, funcional o mixta en el área genital. Los tiempos de coagulación y las concentraciones de los factores estudiados fueron normales con excepción de una paciente cuya concentración de FVIII fue de 0,47U/μL. La agregación plaquetaria mostró alteraciones en el 51,1 por ciento de los casos. La frecuencia de alteraciones de la coagulación en mujeres con sangrado uterino anormal, fue similar a la de la población general, por esta razón no se justifica que todas las pacientes con sangrado uterino anormal, se sometan a un estudio de coagulación; sin embargo, la alta frecuencia de agregación plaquetaria anormal, se debe tomar en cuenta antes de decidir una conducta quirúrgica.
Asunto(s)
Humanos , Adolescente , Adulto , Femenino , Persona de Mediana Edad , Agregación Plaquetaria , Factor VIII/análisis , Factor de von Willebrand/análisis , Menorragia/diagnóstico , Metrorragia/diagnóstico , GinecologíaRESUMEN
OBJECTIVE: To study maternal complication associated to delivery and the puerperium period in pregnancies affected by von Willebrand's disease. METHODS: Chart data of all the pregnant women with diagnosis of von Willebrand disease were retrospectively reviewed. All cases with von Willebrand's disease that had given birth at this institution, between March 2001 and August 2007, were analyzed. The following variables were investigated: mode of delivery, hemorrhage complications during delivery and postpartum, maternal blood exams and perinatal results. Variables were studied descriptively, using absolute and relative frequencies, means, medians and standard deviations. RESULTS: 13 pregnancies of eight women with the disease were reviewed. During this sane period, there were 13,037 deliveries in the institution, resulting in an incidence of 0.1%. Six women (75%) were type 1 disease and, two (25%) were type 2. The last Factor VIIIc activity presented a mean value of 98.5%. A Cesarean section was performed in nine pregnancies, with epidural anesthesia in seven. Delivery complication occurred in two cases: one presented placental abruption and a Cesarean was performed. The other, presented postpartum hemorrhage in the first day and required reposition with factor VIII. Two cases received factor VIII before Cesarean section. Fetal growth restriction was detected in five pregnancies (38.5%). Mean birth weight was of 2676 grams and one case presented 1st minute Apgar score below seven. CONCLUSION: Delivery in patients with von Willebrand disease has a favorable evolution when specific assistance is provided. In these pregnancies,fetal growth should be monitored.