RESUMEN
The tools for diagnosis of epidermolysis bullosa have advanced greatly since Hintner's group introduced antigen mapping as a diagnostic test for this family of genodermatoses. Monoclonal or polyclonal antibodies raised against some of the specific proteins found in the epidermis and basement membrane of the epidermis have allowed 4 types of epidermolysis bullosa de be identified and all variants to be classified. When a newborn baby presents with blisters, many conditions are implicated in the differential diagnosis. Examination under an optical microscope can suggest epidermolysis bullosa, but immunofluorescence mapping and electron microscopy are required for confirmation of the diagnosis and further classification of congenital epidermolysis bullosa. This article explains the importance of immunofluorescence antigen mapping and describes the methods employed for classification and subclassification of epidermolysis bullosa.
Asunto(s)
Epidermólisis Ampollosa/diagnóstico , Técnica del Anticuerpo Fluorescente Directa , Membrana Basal/inmunología , Biopsia , Diagnóstico Diferencial , Epidermis/inmunología , Epidermis/ultraestructura , Epidermólisis Ampollosa/clasificación , Epidermólisis Ampollosa/inmunología , Epidermólisis Ampollosa/patología , Epidermólisis Ampollosa Distrófica/diagnóstico , Epidermólisis Ampollosa Distrófica/inmunología , Epidermólisis Ampollosa Distrófica/patología , Epidermólisis Ampollosa Simple/diagnóstico , Epidermólisis Ampollosa Simple/inmunología , Epidermólisis Ampollosa Simple/patología , Epidermólisis Ampollosa de la Unión/diagnóstico , Epidermólisis Ampollosa de la Unión/inmunología , Epidermólisis Ampollosa de la Unión/patología , Humanos , Recién Nacido , Microscopía Fluorescente , Manejo de EspecímenesRESUMEN
Las herramientas para el diagnóstico en las epidermólisis ampollosas (EA) han tenido un gran avance desde que Hintner et al, introdujeron el mapeo antigénico como prueba diagnóstica en este grupo de genodermatosis. La utilización de anticuerpos monoclonales/policlonales dirigidos contra algunas de las proteínas específicas que conforman la epidermis y la membrana basal epidérmica, han servido para clasificar los 4 tipos de epidermólisis ampollosa y subclasificar todas sus variantes. Ante la presencia de un recién nacido con ampollas surgen diagnósticos diferenciales múltiples, en donde la microscopia de luz orienta el diagnostico de epidermólisis ampollosa. Sin embargo, el mapeo por inmunofluorescencia y la microscopia electrónica permiten confirmar y clasificar a las epidermólisis ampollosas congénitas. En este artículo, se explica la importancia y metodología para desarrollar la técnica de mapeo antigénico por inmunofluorescencia, con el propósito de clasificar y subclasificar las epidermólisis ampollosas (AU)
The tools for diagnosis of epidermolysis bullosa have advanced greatly since Hintner's group introduced antigen mapping as a diagnostic test for this family of genodermatoses. Monoclonal or polyclonal antibodies raised against some of the specific proteins found in the epidermis and basement membrane of the epidermis have allowed 4 types of epidermolysis bullosa de be identified and all variants to be classified. When a newborn baby presents with blisters, many conditions are implicated in the differential diagnosis. Examination under an optical microscope can suggest epidermolysis bullosa, but immunofluorescence mapping and electron microscopy are required for confirmation of the diagnosis and further classification of congenital epidermolysis bullosa. This article explains the importance of immunofluorescence antigen mapping and describes the methods employed for classification and subclassification of epidermolysis bullosa (AU)
Asunto(s)
Humanos , Masculino , Femenino , Técnica del Anticuerpo Fluorescente Directa/instrumentación , Técnica del Anticuerpo Fluorescente Directa/métodos , Técnica del Anticuerpo Fluorescente Directa , Epidermólisis Ampollosa/diagnóstico , Epidermólisis Ampollosa/patología , Epidermólisis Ampollosa/terapia , Biopsia/instrumentación , Biopsia/métodos , Anticuerpos/análisis , Anticuerpos/inmunología , Colágeno/análisis , Epidermólisis Ampollosa Simple/diagnóstico , Epidermólisis Ampollosa Simple/patología , Epidermólisis Ampollosa Distrófica/diagnóstico , Epidermólisis Ampollosa Distrófica/patologíaRESUMEN
Between June 2003 and November 2004, we collected mobilized peripheral blood units from 29 patients with non-Hodgkin's lymphoma and multiple myeloma for autologous peripheral blood stem cell transplantation. They received granulocyte colony-stimulating factor (G-CSF) (16 micro g/kg/day) for a total of 5 days. Immediately before and 3 h after the fourth and fifth dose of G-CSF, we performed flow cytometry analysis to quantify: T cells (CD3+CD4+, CD3+CD8+), B cells (CD19+), NK cells (CD3-CD16+CD56+), NKT cells (CD3+CD16+CD56+), type 1 dendritic cells (DC1) (lin-HLA-DR+CD11c+), type 2 dendritic cells (DC2) (lin-HLA-DR+CD123+), regulatory T cells (Tregs) (CD4+CD25+), and activated T cells (CD3+HLA-DR+). All cell subsets were mobilized after G-CSF treatment with the exception of B, NK, and NKT lymphocytes. The median number of Treg cells before and after G-CSF was statistically different (29+/-14.9x10(6)/l vs 70.1+/-46.1x10(6)/l, P<0.02). DCs were mobilized significantly with a 5.9-fold increase in DC2 (15.1+/-30.3x10(6)/l vs 89.8+/-81.0x10(6)/l, P<0.02) and a 2.6-fold increase for DC1 (41+/-42.5x10(6)/l vs 109.5+/-58.0x10(6)/l, P<0.04). Patients received a mean of 3.1+/-1.2x10(7)/kg NK cells, 1.3+/-0.9x10(7)/kg NKT cells, 0.41+/-0.29x10(7)/kg DC1, 0.2+/-0.22x10(7)/kg DC2, and 1.8+/-1.9x10(7)/kg Tregs. In conclusion, intermediate doses of G-CSF induce mobilization of different lymphocyte subsets, with the exception of B, NK, and NKT cells. The mobilization of certain suppressive populations (DC2 and Treg) could be in theory deleterious, at least in patients with cancer.
Asunto(s)
Células Dendríticas , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Linfocitos , Linfoma no Hodgkin , Mieloma Múltiple , Adulto , Anciano , Antígenos de Diferenciación/metabolismo , Fraccionamiento Celular/métodos , Células Dendríticas/patología , Femenino , Filgrastim , Humanos , Linfocitos/patología , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Proteínas Recombinantes , Trasplante AutólogoRESUMEN
To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) +/- VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6x10(6)/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5x10(7)/kg NKT cells and less than 1.7x10(6)/kg DC2 for disease-free survival (DFS), and a dose of less than 3x10(7)/kg NK cells, less than 1.5x10(7)/kg NKT cells, less than 3x10(6)/kg DC1, and less than 1.7x10(6)/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8x10(6)/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT.
Asunto(s)
Células Dendríticas/metabolismo , Factor Estimulante de Colonias de Granulocitos/metabolismo , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Células Asesinas Naturales/citología , Adolescente , Adulto , Antígenos CD19/biosíntesis , Antígenos CD34/biosíntesis , Complejo CD3/biosíntesis , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Niño , Femenino , Enfermedad Injerto contra Huésped/terapia , Humanos , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Linfocitos T Reguladores/metabolismo , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoRESUMEN
We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Trasplante de Células/métodos , Células Dendríticas/inmunología , Factor Estimulante de Colonias de Granulocitos/farmacología , Activación de Linfocitos , Linfocitos/inmunología , Receptores de Interleucina-2/análisis , Células Madre/citología , Adulto , Antígenos CD/análisis , Eliminación de Componentes Sanguíneos/métodos , Femenino , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , HermanosRESUMEN
OBJECTIVE: Compare the speed of neutrophil recovery and the unwanted secondary effects in two groups of acute leukemia patients treated with intensive chemotherapy and G or GM-CSF. PATIENTS AND METHODS: Patients were randomly assigned to receive subcutaneous G-CSF at a daily dose of 300 micrograms for adults and 150 micrograms for children or GM-CSF at 400 and 200 micrograms respectively, starting With chemotherapy and stopping when the absolute neutrophil count (ANC) reached 500/microL. Secondary effects were attributed to growth factors only when not coincidental with infection, chemotherapy or hemoderivative transfusion. RESULTS: 34 patients were included in the G-CSF arm and 37 in the GM-CSF arm. Distribution by sex, age, type of acute leukemia, induction or post-induction therapy, as well as initial neutrophil count were comparable among the two groups. Mean time for ANC > 500/microL was 19 days for G-CSF group and 16 days for GM-CSF group (p = 0.08). There were no statistically significant differences in secondary unwanted side effects between the two groups. There were two cases of growth factor-related-fever in the G-CSF group and five in the GM-CSF group (p = 0.25). There was a case of systemic reaction in the G-CSF group. Twenty-nine patients in each group presented febrile neutropenia episodes (p = 0.45). The only factor that showed significance on neutrophil recovery speed was type of leukemia (p = 0.04). CONCLUSIONS: We found no clear advantage of one growth factor over the other for this indication.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Leucemia/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Enfermedad Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Fiebre/inducido químicamente , Filgrastim , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Idarrubicina/administración & dosificación , Leucemia/sangre , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Neutrófilos/fisiología , Dolor/inducido químicamente , Prednisona/administración & dosificación , Estudios Prospectivos , Proteínas Recombinantes , Inducción de Remisión , Factores de Tiempo , Resultado del Tratamiento , Vómitos/inducido químicamenteRESUMEN
This paper reports the long-term, disease-free survival of children with high-risk (HR) acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. HR was defined in children with ALL, younger than 2 or older than 10 years, with or without initial extrahematopoietic disease, with a leukocyte count higher than 25 x 10(9)L, or with L3 FAB type. The first group, LAL1, included 67 patients; they received induction with vincristine (VCR) and prednisone (PDN), early consolidation with 3 cycles of 6-mercaptopurine (6MP), citarabine (ARA) and VCR: central nervous system (CNS) prophylaxis (PFX) consisted of both chemotherapy in induction, consolidation and maintenance, radiotherapy (RT) in consolidation. Maintenance was given with 6MP, methotrexate (MTX), VCR adriamycin (ADR), ARA, cyclophosphamide (CFA) and PDN. The second group, LAL2, with 45 patients, received induction with VCR, PDN, CFA, epirrubicin (EPI), L-Asparaginase (L-ASP); early and late consolidation with 6MP, ARA, VCR, carmustine (BCNU), CFA, EPI, MTX and teniposide 8VM26): CNS PFX consisted of both chemotherapy in induction, consolidation and maintenance, RT in consolidation, maintenance with 6MP, MTX, EPI, CFA, ARA VM26 and BCNU. At the time of diagnosis, both groups were comparable. Disease-free survival probability, for LAL1 group was 0.41 at 14 years and for LAL2 group 0.34 at 8 years (p = 0.45). In the LAL1 group there were three failures and 20 relapses, and in the LAL2 group, there were two failures and 22 relapses. CNS relapses were one and seven in LAL1 and LAL2 groups respectively (p = 0.04). In the LAL2, group relapses were more frequent in patients with dose reduction or difered dose due to marrow toxicity (p = 0.02). We believe that the increase in CNS relapse in the LAL2 group was caused by the late administration of CNS PFX. We also believe that although intensive chemotherapy can increase long-term survival, dose adjustments due to marrow toxicity have a negative effect on long-term, relapse-free survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , RecurrenciaRESUMEN
OBJECTIVE: To compare the effectiveness of two chemotherapy regimens for the treatment of relapsed and refractory acute leukemias. METHODS: We randomly assigned 24 patients in two groups: the LARR1 group received induction with 4 days of etoposide and 4 days of high-dose ara-C; the LARR2 group received induction therapy with 4 days of etoposide plus 3 days of mitoxantrone. Consolidation was given using the same drugs at the same dosage. Maintenance therapy was the same for both groups alternating methotrexate, vincristine, L-asparaginase, carmustine, cyclophosphamide and Ara-C. Every 15 weeks both groups repeated consolidation according to their group. Granulocyte-colony stimulating factor was used in both groups. RESULTS: Median survival for both groups was 5 months (range 1-17). Ten months after starting therapy three patients were disease free in the LARR1 group and two in the LARR2 group. There were no statistically significant differences in complete remission rate (p = 0.62), refractoriness (p = 0.58), deaths in induction (0.14) and other parameters. CONCLUSIONS: Our results were comparable with those of others. The only advantage we found was the possibility of using the LARR1 treatment in patients who have reached or are about to reach cardiotoxic-anthracycline doses.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Asparaginasa/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Ácido Fólico/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Pronóstico , Recurrencia , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
The purpose of this study is to know the disease-free survival in children with acute lymphoblastic leukemia (ALL), submitted to two therapeutic programs. Habitual risk was defined as age older than 2 and younger than 10 years, without neurological, mediastinal or testicular infiltrations, leukocytes < 25 x 10(9)/l and morphologic cell type distinct of L-3. The first group (LAL81) included 30 patients, from 1981 to 1986, and they received: induction with vincristine (VCR) and prednisone (PDN); consolidation with mercaptopurine (MP), cytosine arabinoside (ARA) and doxorubicin (DOX); prophylaxis to the central nervous system (CNS) with radiotherapy and methotrexate (MTX)-ARA-hydrocortisone (HDR) intrathecal, and maintenance with MP and MTX. In the second group (LAL87), 28 patients were included from 1987 to 1993. They received: induction with VCR, PDN and lasparaginase (ASP); consolidation with MP, ARA, DOX, carmustine (BCNU) and cyclophosphamide (CFA); prophylaxis to the (CNS) with intrathecal MTX-ARA-HDR, and maintenance with MP and MTX. There was just one therapeutic failure. In the LAL81, protocol 11 relapses and 9 in LAL87 (p = 0.71) were observed. Of these, two in each group went to the CNS. The disease-free survival in LAL81 was 0.39 at 14 years; in LAL87, was 0.53 at 8 years (p = 0.62).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Factores de Edad , Antiinflamatorios/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Asparaginasa/uso terapéutico , Carmustina/uso terapéutico , Niño , Preescolar , Ciclofosfamida/uso terapéutico , Citarabina/uso terapéutico , Interpretación Estadística de Datos , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Humanos , Hidrocortisona/uso terapéutico , Masculino , Mercaptopurina/uso terapéutico , Metotrexato/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Prednisona/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Vincristina/uso terapéuticoRESUMEN
We describe the case of a patient with myelodysplastic syndrome (MDS) classified as Refractory Anemia with our Excess blasts, who suffered from high transfusional requirements and who did not respond to the administrations of B12 vitamin, folates, danazol, low dose cytarabine or recombinant human erythropoietin (rHuEPO). The patient was administered two cytokines: granulocyte colony stimulating factor (G-CSF) followed by rHuEPO. The patient remained transfusion free for more than 4 months until his death from causes not related to MDS or the therapy he received. It is the opinion of the authors that the initial G-CSF administration stimulated the early erythroid precursors, making them capable of finishing their maturation when rHuEPO was administered. We believe that this could be a useful therapeutic measure in the treatment of patients with MDS and high transfusional requirements.
Asunto(s)
Anemia Refractaria/terapia , Transfusión de Eritrocitos , Eritropoyetina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Proteínas RecombinantesRESUMEN
OBJECTIVE: To evaluate the safety and effectiveness of a single subcutaneous perilesional administration of 300 micrograms of recombinant human granulocyte-macrophage colony stimulating factor (rHGM-CSF) for the treatment of chronic leg ulcers. DESIGN: Prospective, descriptive evaluation in an outpatient group. SETTING: The Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City. PATIENTS: 10 patients with chronic leg ulcers. MEASUREMENTS: Ulcer diameter and side effects. RESULTS: After 4 weeks observation, 8 of the 10 ulcers had healed; the other two had a mean diameter decrease of 21%. The only side effect was found in a 58 year old female who complained of moderate perilesional pain two days after having received treatment: it was successfully treated with paracetamol. CONCLUSION: We believe that a single perilesional subcutaneous administration of rhGM-CSF is safe and effective for the treatment of chronic leg ulcers.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Úlcera Varicosa/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
We studied 30 patients in order to evaluate the therapeutic efficacy and toxicity of alfa interferon associated with busulfan as maintenance treatment in de novo chronic granulocytic leukemia. Patients received 0.2 mg/kg of busulfan and reached complete hematological remission (CHR). Patients were then randomized in two groups: one to receive busulfan to be administered when the leukocyte count was above 15 x 10(9)/L, and another to receive subcutaneously 5 million IU of alpha-interferon three times per week (plus busulfan if the leukocyte count went above 15 x 10(9)/L). The duration of CHR was longer in the alfa-interferon group: 31 vs 16 months (p = 0.03) but no cytogenetic remissions were observed. Alfa interferon was well tolerated: no patient was excluded from the study due to toxicity.
Asunto(s)
Antineoplásicos/uso terapéutico , Busulfano/uso terapéutico , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de RemisiónRESUMEN
Primary pulmonary hypertension (PPH) is a rare disorder, usually fatal. Although the cause of the disease is unknown, the vascular endothelium seems to play a key role. It has been proposed that a vascular endothelial dysfunction would provoke pulmonary vasoconstriction, platelet activation and thrombin formation; some of these events have already been proven. The presence of thrombosis in PPH patients has been demonstrated, and it seems to have a relationship with a vascular endothelium-dependent coagulation abnormality. Substances of endothelial cell origin capable of modifying the coagulation mechanisms are: heparan-sulfate, thrombomodulin, protein S, tissue factor pathway inhibitor (TFPI), tissue factor, von Willebrand factor, prostacyclin and endothelial-derived relaxing factor; functional and multimeric-pattern alterations in von Willebrand factor have already been reported in PPH patients.