[Autologous transplant (AT) with peripheral-blood stem-cell rescue for multiple myeloma. A clinical experience]. / Autotrasplante (AT) de progenitores hematopoyéticos en mieloma múltiple. Experiencia clínica.

BACKGROUND: Multiple myeloma is rarely curable. Advances in high dose chemotherapy and stem cell transplantation have improved overall survival and event-free disease periods, but relapses are inevitable. AIM: To report our experience with AT in multiple myeloma, between 1994 and 2003. MATERIAL AND METHODS: Retrospective analysis of 20 patients (12 women), with a mean age of 51.1 years. VAD (vincristine, doxorubicin and dexamethasone) was used as initial therapy in 19 patients. High dose cyclophosphamide (11 patients) and variations of VAD regimen (7) associated with granulocyte colony stimulating factor were used for peripheral-blood stem cell harvest. The conditioning regimen consisted of melphalan 200 mg/m2 followed by the reinfusion of peripheral-blood stem cells 24 hours later. The median number of CD34 cells infused was 3.3x10(6)/kg. Three patients were subjected to a second auto graft and one to a non-myeloablative transplant. Mean follow up was 35.5 months. RESULTS: Mucositis and febrile neutropenia were common complications. The median number of days for neutrophil engraftment was 9 (range 8-11) and for platelets, 10 (range 7-13). No patient died. Complete remission was obtained in 60% (12/20), progression-free survival was 30 months and overall median survival, 47 months. CONCLUSIONS: The AT with high-dose melphalan is a safe procedure in our hospital, without mortality and engraftment in all the patients. Complete remission and progression free survival were similar to those reported abroad but the overall median survival was lower.

[Free protein S (PS) in normal pregnancy: a comparison between two analytical methods]. / Proteína S libre en embarazadas normales: comparación entre dos métodos.

BACKGROUND: Pregnancy is a physiological hypercoagulable state with an increased incidence of thromboembolic phenomena. There is an increase in the concentrations of most clotting factors, a decrease in concentration of some of the natural anticoagulants and reduced fibrinolytic activity. Changes in PS levels have also been reported. AIM: To establish referral range values of functional PS and free PS antigen, during the second (2nd T) and third trimester (3rd T) of normal gestation. PATIENTS AND METHODS: Forty one normal pregnant women were included in our study, 20 during the 2nd T (22-24 weeks) and 21 during the 3rd T (29-38 weeks). Functional PS was measured by a clot based test and free PS antigen by ELISA. RESULTS: Free PS Antigen was 65.8+/-18.3% during the 2nd T and 62.3+/-16.5% during the 3rd T. The figures for normal controls were 106+/-6.5%. Functional PS was 43.8+/-13.3 and 25.9+/-14.6% during the 2nd T and 3rd T, respectively. The figures for normal controls were 97+/-24% (p <0.001 compared with pregnant women). Free PS antigen did not change from the 2nd to the 3rd T (p=NS), however functional PS fell significantly from the 2nd to the 3rd T (p <0.001) and was significantly lower than free PS antigen in both trimesters (p <0.001). CONCLUSIONS: Pregnancy is associated to a decrease in PS. This abnormality is more pronounced for functional PS than free PS antigen and functional PS falls progressively during pregnancy. These assays should not be used to screen for PS deficiency during pregnancy because they could lead to a misdiagnosis.

La resistencia a aspirina en pacientes cardiovasculares chilenos es frecuente / Aspirin resistance is frecuent in chilean cardiovascular patients

Introducción: La aspirina se usa frecuentemente para la prevención y tratamiento de eventos isquémicos cardiovasculares. Estudios en población anglosajona han mostrado que entre 5-9 por ciento de los pacientes presentan resistencia total a la acción antiplaquetaria de aspirina. Objetivos: Conocer la prevalencia de resistencia a aspirina en enfermos cardiovasculares chilenos. Evaluar factores asociados a la resistencia. Pacientes y Métodos: Se estudian 68 pacientes (21 mujeres, ± 10 años) con enfermedades cardiovasculares estables usuarios de aspirina (100-325 mg/día). Se evalúan variables clínicas y de coagulación básica. Se estudió la agregación plaquetaria con agregómetro óptico en plasma rico en plaquetas con 3 agonista. Se definió Resistencia Total a la aspirina como. 1) agregación (20 por ciento con ácido araquidónico y 2) agregación > 70 por ciento con ADP y/o colágeno. Resultados: Siete pacientes (10,3 por ciento, IC 95 por ciento = 4,2-20,1 por ciento) cumplieron ambos criterios y se consideraron como resistentes totales, 34 (50 por ciento, IC 95 por ciento = 37,6-62,4 por ciento) cumplieron con sólo un criterio y se consideraron como resistentes parciales, y los 27 pacientes restantes (39,7 por ciento, IC 95 por ciento = 28,0-52,3 por ciento) no cumplieron con ninguno de los criterios y se clasificaron como respondedores a AAS. Hubo una mayor frecuencia de fumadores (55,6 vs 23,7 por ciento) en los pacientes con Resistencia Total, pero no alcanzó significación estadística (p = 0,06). Conclusiones: La mayoría de los pacientes cardiovasculares presentan algún grado de resistencia al AAS y un 10,3 por ciento presentan Resistencia Total. No encontramos diferencias significativas entre los los pacientes con y sin resistencia total a aspirina.

[Clinical application of the activated partial thromboplastin time (APTT) with modified incubation time for the diagnosis of lupus anticoagulant (LA)]. / Aplicación del tiempo de tromboplastina parcial activado (TTPA) con tiempo de incubación modificado en el diagnóstico del anticoagulante lúpico (AL).

BACKGROUND: Although several tests are used to screen for the presence of LA, none detects all its types. The shortening of APT observed when the pre-incubation period is prolonged, proved to be a sensitive test for the presence of LA. MATERIAL AND METHODS: We determined the APTT, performed with a 4 or 15 min preincubation period (APETs and APTT15 respectively), in 22 healthy subjects, 3 commercial positive controls for LA, 16 patients with a previous diagnosis of LA and 54 patients with recurrent fetal loss and/or infertility. Evidence of LA was established by a positive Staclot-LA test. RESULTS: APTTs and APTT15 were 31.5 +/- 4.7 and 28.4 +/- 4.5 seconds respectively in samples from 22 normal subjects. The figures in samples with LA, were 71.5 +/- 20.3 s and 58.6 +/- 18 s respectively. The difference between the two APTTs performed on an individual sample was defined as the APTT 4-15 and was 2.6 +/- 2.0 in normal subjects 2.5 +/- 2.8 in 13 patients anticoagulated with warfarin, -10.0 +/- 6.5 in 13 patients receiving heparin, and 13.2 +/- 4.9 in 15 patients with LA. The test values for LA patients were significantly higher than those for normal subjects (p < 0.0001). For values over 5, the APTT 4-15 had 93.3% sensitivity and 100% specificity. In one patient with recurrent fetal loss or infertility, who was LA positive, the APTT 4-15 was positive with a value of 14. CONCLUSIONS: This modified TTPA is easy to perform, and provides a reasonably discriminatory value for the presence of LA. Therefore, we recommend the TTPA 4-15 to screen for LA.

[Catastrophic antiphospholipid syndrome and acute heart failure. Report of a case]. / Síndrome antifosfolípido catastrófico y falla cardíaca aguda. Caso clínico.

A 33 years old woman was admitted to the hospital after four days with cough, dyspnea, orthopnea and hemoptysis. Blood pressure was 170/90 mmHg, pulse was 112 and temperature was normal. She had cyanosis and a left ventricular gallop, without heart murmurs. A chest radiograph revealed pulmonary edema and echocardiogram showed a global left ventricular systolic disfunction. Oxygen and furosemide were started, but cardiopulmonary collapse ensued. The patient was supported with mechanical ventilation and treated with inotropic drugs. A right sided cardiac catheterization showed pulmonary wedge pressure of 18 mmHg and a cardiac index of 3 l/min/m2. The levels of creatinine and urea nitrogen were elevated and a urine protein was 97 mg/dl. Coagulation tests were normal except by a positive lupic anticoagulant. Markers of connective tissue diseases or vasculitis were negatives. The clinical evolution suggested that a catastrophic antiphospholipid syndrome was ongoing. Intravenous corticoids, gammaglobulin and cyclophosphamide were administered with transient improvement. On her fourth day of treatment, the patient presented sudden pulmonary bleeding and embolism. A plasmapheresis was performed with improvement of renal, cardiac and pulmonary function. After this episode, the patient has been treated with prednisone and oral anticoagulants treatment for the last two years, without further clinical events.

Alteración de la estabilización del coágulo de fibrina por la presencia de un inhibidor adquirido del factor XIII. Caso clínico (revisión de la literatura) / Alteration of fibrin clot stabilization due to presence of an acquired factor XIII inhibitor

El factor XIII (FXIII) hace el coágulo de fibrina más estable y más resistente a la fibrinólisis. La deficiencia de FXIII puede ser congénita o adquirida y es causa de hemorragias severas. Se han reportado 24 casos de inhibidores adquiridos de FXIII y existen pocos antecedentes de la evolución y manejo de esta condición. Caso clínico. Mujer 57 años de edad que consulta por presentar en forma espontánea extensos hematomas subcutáneos, sin antecedentes personales ni familiares de tendencia hemorrágica, de ingestión de drogas u otras enfermedades. El examen físico muestra equimosis y hematomas en extremidades y pared abdominal. Radiografia de tórax, función hepática, renal, estudio inmunológico y de coagulación (TTPK, tiempo de protrombina, tiempo de trombina, recuento de plaquetas, fibrinógeno, FDP, dímero D, lisis de euglobulinas, agregación plaquetaria y estudio de von Willebrand) en rangos normales. El test de solubilidad del coágulo con urea fue de 35 min (normal: > 24 h), que no se corrigió con una mezcla 1:1 de plasma normal, demostrando la presencia de un inhibidor. Con mezclas 1:2, 1:4, 1:6 y 1:8 el coágulo se disolvió antes de los 40 min. La terapia con esteroides y ciclofosfamida no fue efectiva. Se encuentra con ácido tranexámico y persiste con hematomas de menor magnitud. Conclusión. Los inhibidores adquiridos de FXIII son una causa poco frecuente de sangrado; deben ser sospechados en pacientes con sangrado grave y test de coagulación de rutina en limites normales. El diagnóstico se confirma con un test de solubilidad del coágulo alterado que no se corrige con una mezcla 1:1 de plasma normal (AU)