[Thrombogenic and endothelial damage markers in patients with ischemic systolic impairment]. / Marcadores de hipercoagulabilidad y daño endotelial en pacientes con disfunción sistólica de origen isquémico.

INTRODUCTION: Anticoagulation is rarely indicated in patients with left ventricular dysfunction who show an increased risk for thromboembolism. In theory, the three arms of the Virchow' triad may be present: abnormal blood flow, endothelial damage and prothrombotic markers. The aim of this study was to identify the last two arms. PATIENTS AND METHOD: We studied 82 consecutive patients with demonstrated ischaemic heart disease and sinus rhythm, and compared them with a control group comprised of 32 healthy subjects matched for age and sex. None or the patients had had an acute coronary event or hemodynamic decompensation within the 3 months prior to inclusion in the study. The plasma concentration or von Willebrand factor and fibrin d-dimer and fibrinogen were determined as endothelial damage and prothrombotic markers, respectively. A fractional shortening less than 29% by echography was defined as ventricular systolic dysfunction. RESULTS: The patients showed significantly higher levels of von Willebrand factor with respect to the control group (109.2 31.9 vs 85.5 32.6%, p < 0.01), with no differences in fibrinogen and fibrin d-dimer values. Twenty-six patients fulfilled criteria of left ventricular systolic dysfunction. Patients with left ventricular dysfunction showed higher fibrinogen (386 118 vs 322 102 mg/dl, p = 0.03) and fibrin d-dimer (0.36 0.22 vs 0.26 0.10 g/ml; p = 0.04) levels, with no differences in von Willebrand factor levels. CONCLUSIONS: After acute coronary events, patients with ischaemic heart disease show markers of endothelial damage. However, patients with left ventricular dysfunction show a hypercoagulable state.

[Improvement in fibrinolytic function following anticoagulant treatment in chronic rheumatic atrial fibrillation]. / Mejoría de la función fibrinolítica tras el tratamiento anticoagulante en la fibrilación auricular reumática crónica.

INTRODUCTION AND OBJECTIVES: Patients with rheumatic atrial fibrillation are considered at high risk of systemic embolism and require oral anticoagulation. Fibrinolytic function has been little studied. We evaluated fibrinolytic activation markers before starting anticoagulation, at 1 and 6 months following the introduction of oral anticoagulation therapy. We analyzed the relationship with left atrial diameter and mitral area. METHODS: Tissue plasminogen activator (tPA), its inhibitor (PAI-1), plasmin-antiplasmin complexes (PAP) and D-dimer were measured in 13 patients with rheumatic atrial fibrillation. Basal levels were compared with those found in plasma of 20 healthy subjects matched by sex and age. Transthoracic echocardiography was made. RESULTS: A significant increase for PAI-1 and D-dimer levels were detected in patients with atrial fibrillation group (p < 0.05), with no differences in tPA and PAP concentrations. Significant correlation between left atrial diameter and basal t-PA levels was found. Levels of t-PA, PAI-1 and D-dimer decreased significantly under anticoagulation therapy, whereas PAP levels were significantly increased. CONCLUSIONS: Patients with rheumatic atrial fibrillation show a relative hypofibrinolytic state due to elevated PAI-1 levels with no increase in PAP concentration. At six months of anticoagulation therapy, an improvement of fibrinolytic function markers was observed. This is consistent with the prophylactic effect of oral anticoagulants therapy against thromboembolic risk.

[Replacement therapy with protein C for meningococcal sepsis and fulminant purpura in pediatric patients]. / Tratamiento sustitutivo con proteína C en sepsis meningocócica y púrpura fulminante en pacientes pediátricos.

Disseminated intravascular coagulation as associated to sepsis contributes to the development of clinical multiple organ failure by extensive thrombosis in microcirculation vessels. This condition commonly manifests itself in severe meningococcal sepsis. On the skin, its clinical manifestation is extensive purpura with necrotic lesions that usually progress to serious distal ischemia and may call for amputation. A common denominator in these events regarding hemostasis is a depletion of so-called natural anticoagulant proteins, particularly protein C. According to clinical observations replacement therapy with human plasma-derived protein C concentrates has been associated with significantly improved clinical outcome in patients with meningococcal sepsis and fulminant purpura. This paper reports a case of acquired protein C deficiency in a girl with meningococcal sepsis, fulminant purpura, disseminated intravascular coagulation, and septic shock. Fresh plasma therapy was intended to increase consumption coagulopathy-depleted coagulation factors and to provide small amounts of protein C. The inability to restore protein C concentrations above 30%, and the presence of severe thrombopenia in the setting of disseminated intravascular coagulation led to the onset of replacement therapy using a human protein C concentrate (Ceprotin), which increased plasma protein C concentrations and contributed to revert the existing hypercoagulability status. Finally, evidence available in the literature regarding fulminant meningococcal sepsis management using human protein C concentrates and recombinant activated protein C is discussed.

[Clinical comments on genetic marker prevalence (factor V Leiden, prothrombin 20210A and homozygous methylenetetrahydrofolate reductase form [Ho-MTHFR]): based on a study conducted in Health Department No. 19 of the Valencian Community]. / Prevalencia de factor V Leiden, protrombina 20210 A y homozigosis de la MTHFR: a propósito de un estudio en el Departamento de Salud n.o 19 de la Comunidad Valenciana.

The prevalence of genetic markers in ETV disease patients in the 19th Health Department of Valencian Community were: FVL: 9.2%; PT20210 A: 10.5% and Ho-MTHFR: 23.7%. The FVL and PT20210 A prevalence results are lower respect to the literature, while Ho-MTHFR patients, have a higher prevalence with statistical significance difference respect the control group. We considered FVL, PT20210 A and Ho-MTHFR as ETV risk markers. The prevalence of genetic markers in healthy population of the same Health Department were: FVL: 5.8%; PT20210 A: 7.1%, and Ho-MTHFR: 7.7%. We must considered the specific study of these genetic risk markers (FVL, PT20210 A, Ho-MTHFR) in ETV disease affected subjects. The study of first degree relatives of the analyzed patients, should be of great utility to planified genetic advice and practice ETV prophylaxis.

[Levels of antithrombin III and proteins C in the newborn infant]. / Niveles de antitrombina III y proteína C en el recién nacido.

Antithrombin III and protein C levels were studied in cord blood from 91 babies born at term with weight adequate to their gestation age. No history of drug ingestion or any other cause of impaired blood coagulation in newborns was present in any of the mothers, and none of these had had thromboembolic diseases. Basic coagulation study and clinical status were normal in all the newborns. Antithrombin III was measured as antigen concentration and functional heparin cofactor, both values being similar (ratio: 0.97) and significantly lower than those of adults (p less than 0.001). Antigenic protein C was assayed by enzyme immunoassay, the value attained being also significantly lower than that of normal adults (p less than 0.001). Factor VII: C rates were assayed in order to establish the protein C/factor VII: C relationship, since this might be useful in detecting protein C deficiency due to the similar biological characteristics of both proteins. It was concluded that health normal newborns show decreased antithrombin III and protein C rates, probably due to lack of liver maturity.

[Diabetes mellitus and changes in hemostasis: study of the fibrinolytic response of insulin-dependent patients without vascular disease]. / Diabetes mellitus y alteraciones de la hemostasia: estudio de la respuesta fibrinolítica en pacientes insulinodependientes sin vasculopatía.

Diabetes mellitus (DM) is characterized by a hypercoagulability state and many of these disorders are corrected with adequate metabolic control. The goal of this study was to assess diverse hemostatic and fibrinolytic parameters in 12 insulin-dependent (IDDM) metabolically controlled patients without vascular lesions and in a group of 12 healthy volunteers. A significant difference was observed in the euglobulin lysis time (ELT), after a stress test, since only 3 patients had an adequate fibrinolytic response. These results suggest that the fibrinolytic alterations found in DM are not secondary to metabolic disorders caused by the disease and we can consider that the existence of subclinical alterations of the vascular endothelium would be responsible for these alterations.

[Tissue plasminogen activator as a prognostic factor in myocardial infarct patients]. / Activador tisular del plasminógeno como factor pronóstico en pacientes con infarto de miocardio.

Changes in hemostasis inducing hypercoagulability are pathogenic factors for the development of ischemic heart disease and myocardial infarction. Nevertheless, their role is unknown in the emergence of new coronary events in patients with infarction. A group of 58 patients who had survived to a first infarction episode were studied; the cardiovascular risk factors were determined and blood concentrations of fibrinogen, t-PA, PAI and FRW measured. These patients were followed for two years to observe the development of new ischemic problems. In the study only the t-PA concentration was found to be a factor for poor prognosis.

[Abnormalities in coagulation and fibrinolysis in septic shock with purpura]. / Alteraciones del sistema de la coagulación y la fibrinólisis en el shock séptico asociado a púrpura.

OBJECTIVE: To describe abnormalities in coagulation and fibrinolysis in septic shock with purpura and to assess the relationship between plasma plasminogen activator inhibitor-1 (PAI-1) concentrations and multiple organ system failure (MOSF). METHODS: Observational study in the pediatric intensive care unit of a tertiary care hospital. The presence of early MOSF was assessed at admission in 15 children with septic shock and purpura consecutively admitted to the pediatric intensive care unit. Blood samples were taken to determine coagulation and fibrinolysis parameters. RESULTS: At admission, MOSF was diagnosed in 7 patients (46.7 %), acute respiratory distress syndrome (ARDS) in 6 (40 %), consumption coagulopathy in 7 (46.7 %) and acute renal failure in 1 (6.7 %). The overall mortality rate was 40 %. Coagulation parameters were generally affected but statistically significant differences were found only in concentrations of fibrinogen and antithrombin III, which were lower in patients with MOSF than in those without organ dysfunction. Fibrinolysis parameters were increased in all patients but plasma PAI-1 concentrations were significantly elevated only in patients with MOSF and in those with ARDS. CONCLUSION: These data indicate that impaired fibrinolysis could play a major role in the development of MOSF in children with septic shock and purpura.

[Safety of oral anticoagulation in aged patients with heart diseases]. / Seguridad en la anticoagulación oral en ancianos con cardiopatía.

BACKGROUND: Anticoagulation therapy in the elderly poses some doubts on the possible increase in hemorrhagic risk. The hemorrhagic complications in a population of patients over 70 years of age anticoagulated with acenocoumarol by heart disease were studied. MATERIALS AND METHODS: A study was made of seventy-two patients (43 females and 29 males; mean age: 73 years) anticoagulated for one year and controlled on an outpatient basis by means of INR (international normalized ratio) measurement with a maximal interval of four weeks. INR values above 4.5 or below 2.0 were considered out of range. RESULTS: Nineteen patients had an INR above the recommended value on one occasion and eleven patients on two or more occasions. Sixteen patients had hemorrhagic complications, five were admitted on account of hemorrhages although none of them required transfusional therapy. No cases of brain hemorrhage or peripheral embolism occurred. CONCLUSIONS: Most anticoagulated elderly patients were within their therapeutic range. The percentage of severe hemorrhagic complications was low. Advanced age had did not prove to be a factor against therapy with oral anticoagulants.

Indicaciones para el uso de heparinas de bajo peso molecular en pacientes con diabetes mellitus / Indications for the use of low molecular weight heparins in patients with diabetes

La diabetes mellitus es reconocida como una situación clínica que favorece laaparición de enfermedad tromboembólica tanto en el territorio arterial comoen el venoso. Las heparinas de bajo peso molecular son un grupo de fármacosbioequivalentes de amplio uso en la profilaxis y tratamiento de la enfermedadtrombótica, especialmente en el tromboembolismo venoso. Sin embargo,en la bibliografía y las guías de práctica clínica no se encuentran referenciasque permitan obtener un grado de recomendación alto para protocolizar suuso en pacientes con diabetes. En este artículo de revisión se analizan los datospublicados sobre uso de las heparinas de bajo peso molecular en la diabetesmellitus, considerando los factores de riesgo tromboembólico asociadosque suelen presentar estos pacientes y el manejo especial en caso de insuficienciarenal, así como el beneficio que aportan en el manejo de las úlcerasdistales isquémicas cuando estas heparinas se asocian al tratamiento(AU)

Diabetes mellitus is recognized as a clinical situation that favors the occurrenceof thromboembolic disease, in the arterial as well as in the venous territory.Low-molecular-weight heparins are a bioequivalent group of drugs used in theprophylaxis and treatment of thrombotic disease, especially in the venousthromboembolism. However, searching in the literature and in the guides ofclinical practice no references can be found to obtain a high grade of recommendationto implement their use in patients with diabetes. In this review article,published date on the use of low-molecular-weight heparins in diabetesare analyzed, considering the associated thromboembolic risk factors thatthese patients have and especial management in case of renal insufficiency, aswell as their benefits in ischemic distal ulcers when these heparins are includedin the treatment(AU)

Hipercoagulabilidad y cardiopatía isquémica: potencial interacción entre los anticuerpos antifosfolípidos y elementos celulares implicados en la hemostasia / Hipercoagulability and ischemic cardiopathy: potential interaction between antiphospholipid antibodies and cellular elements related with haemosthasis

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Prevalencia de factor V Leiden, protombina 20210 A y homozigosis de la MTHFR: a propósito de un estudio en el Departamento de Salud n. º 19 de la Comunidad Valenciana / Clinical comments on genetic marker prevalence (factor V Leiden, prothrombin 20210A and homozygous methylenetetrahydrofolate reductase form [Ho-MTHFR]): based on a study conducted in Health Department nº 19 of the Valencian Community

La prevalencia de marcadores genéticos en los pacientes con ETV en el Departamento 19 de Salud de la Comunidad Valenciana es: factor V Leiden (FVL): 9,2%; protombina (PT) 20210 A: 10,5%, y forma homozigota de MTHFR (Ho-MTHFR): 23,7%. Los resultados tanto del FVL como de la PT20210 A son algo inferiores a los encontrados en la literatura, mientras que los pacientes Ho-MTHFR tienen una prevalencia superior, con una diferencia significativa respecto a los controles, considerando, en nuestro estudio, estos factores genéticos como marcadores de riesgo de ETV. La prevalencia en la población sana del mismo Departamento de Salud es: FVL: 5,8%; PT 20210 A: 7,1%, y Ho-MTHFR: 7,7%. concluimos que en sujetos afectos de ETV se deben estudiar específicamente estos marcadores. El estudio de familiares de primer grado de estos pacientes puede ser de gran utilidad a la hora de planificar un consejo genético y práctica de profilaxis de la ETV

The prevalence of genetic markers in ETV disease patients in the 19th Health Department of Valencian Community were: FVL: 9.2%; PT20210 A: 10.5% and Ho-MTHFR: 23.7%. The FVL and PT20210 A prevalence results are lower respect to the literature, while Ho-MTHFR patients, have a higher prevalence with statistical significance difference respect the control group. We considered FVL, PT20210 A and Ho-MTHFR as ETV risk markers. The prevalence of genetic markers in healthy population of the same Health Department were: FVL: 5.8%; PT20210 A: 7.1%, and Ho-MTHFR: 7.7%. We must considered the specific study of these genetic risk markers (FVL, PT20210 A, Ho-MTHFR) in ETV disease affected subjects. The study of first degree relatives of the analyzed patients, should be of great utility to planified genetic advice and practice ETV prophylaxis

Alteraciones del sistema de la coagulación y la fibrinólisis en el shock séptico asociado a púrpura / Abnormalities in coagulation and fibrinolysis in septic shock with purpura

Objetivos: Describir las alteraciones en el sistema de la coagulación y la fibrinólisis en el shock séptico asociado a púrpura y analizar la relación entre concentración plasmática de inhibidor del activador del plasminógeno tipo 1 (PAI-1) y la presencia de fracaso multiorgánico (FMO). Métodos: Estudio observacional en la Unidad de Cuidados Intensivos Pediátricos (UCIP) de un hospital universitario de tercer nivel. Se analizó en 15 niños ingresados de forma consecutiva con shock séptico y púrpura la presencia de FMO en el momento del ingreso. Se obtuvieron muestras sanguíneas para estudiar los parámetros del sistema de coagulación y la fibrinólisis. Resultados: En el momento del ingreso 7 pacientes (46,7%) presentaban FMO; 6 pacientes (40%), síndrome de distrés respiratorio agudo (SDRA); 7 pacientes (46,7%), coagulopatía de consumo, y 1 paciente (6,7%), fracaso renal agudo. La mortalidad observada fue de 40%. Los parámetros del sistema de la coagulación analizados estaban en general alterados, aunque sólo se observaron diferencias estadísticamente significativas en las concentraciones plasmáticas de fibrinógeno y antitrombina III que fueron menores en el grupo con FMO que en los pacientes sin disfunción de órganos. Los parámetros de la fibrinólisis estaban aumentados en todos los pacientes pero sólo se observaron concentraciones plasmáticas de PAI-1 significativamente elevadas en el grupo con FMO y en aquellos con SDRA. Conclusiones: Los resultados sugieren que las alteraciones del sistema fibrinolítico pueden tener un papel importante en el desarrollo de FMO en niños con shock séptico y púrpura (AU)