[Treatment of chronic refractory idiopathic thrombocytopenia purpura. 10 years experience at the Salvador Zubiran National Institute of Nutrition]. / Tratamiento de la púrpura trombocitopénica idiopática crónica refractaria. Experiencia de diez años en el Instituto Nacional de la Nutrición Salvador Zubirán.

A total of 126 patients with chronic idiopathic thrombocytopenic purpura were diagnosed from January 1980 to January 1990 in our institute. In this group of patients, 21 were refractory to prednisone therapy, splenectomy or both, or had had a relapse after a good response with these treatments. They were given other therapies. There was enough information for evaluation in 16 of the 21 patients. The treatment responses were classified according to the post-therapy platelet counts: complete response (CR) = > 150 x 10(9)/L for more than three months; partial response (PR) = 50-150 x 10(9)/L for more than three months; any response (AR) = CR + PR; no response (NR) = < 50 x 10(9)/L. There were 15 women and one male. The median age was 41 years (range 11 to 65). 6-mercaptopurine was given in all patients with CR = 31.2%, PR = 18.8%, AR = 50% and NR = 50%. Seven patients received cyclophosphamide with CR = 28.6%, PR = 14.3%, AR = 42.9% and NR = 57%. Vincristine was given in four patients with only one PR. Interferon alpha 2B was given in four patients with two transitory PR. One patient received colchicine and vitamin C without response. It is concluded that 6-mercaptopurine and cyclophosphamide are useful drugs in refractory thrombocytopenic purpura.

Long-term results of high-dose methylprednisolone in aplastic anemia.

Four males and two females, aged 13 to 57 years (median 22 years), with acquired severe aplastic anemia (AA) were treated with intravenous bolus of high doses of 6-methylprednisolone (MPL). Patients received MPL within a 30-day period at a dose of 20 mg/kg/day (3 days), 10 mg/kg/day (4 days), 5 mg/kg/day (4 days), 2 mg/kg/day (9 days), and 1 mg/kg/day (10 days). Within the first 3 months following MPL therapy, a response rate of 83%, assessed by means of increase in reticulocytes, neutrophils or platelets, was recorded in the group: two cases showed partial response and three improvement. The 3-month, and 1-, 2- and 3-year survival of the group was 67%, 50%, 33% and 33%, respectively. Neither the presence of reticulocytopenia or thrombocytopenia prior MPL therapy, nor age, gender, etiology of AA or time between diagnosis and initiation of MPL influenced survival. In contrast, neutrophil counts before MPL treatment had a strong prognostic value. Patients with less than 0.5 x 10(9)/L neutrophils had a median survival of 4.2 months (range 1.2 to 5.2 months) as compared to the 36.1 months median survival (range 12.1 to 36.8 months) of patients whose neutrophil counts were greater than 0.5 x 10(9)/L. Follow-up data suggest that the administration of androgens two months after MPL therapy did not modify survival. It is concluded that high-dose MPL is useful in the treatment of some patients with acquired severe AA, particularly in those with greater than 0.5 x 10(9)/L neutrophils who are not candidates for bone marrow transplantation.

[Control of oral anticoagulation. Current concepts]. / El control de la anticoagulación oral. Conceptos actuales.

The main objective of this short review is to bring into focus the most relevant of the recent advances in prothrombin time standardization and analyze the recommendations of the World Health Organization (WHO) for monitoring patients with thrombotic disorders under treatment with oral anticoagulant drugs. The prothrombin time (PT) is indicative of the proper therapeutic range in patients receiving oral anticoagulant drugs; however the reliability of the results will depend on the source and nature of the thromboplastin used. Different normal and therapeutic rangers are frequently observed when different brands of thromboplastin reagents and/or methods are used. The WHO, in conjunction with the International Committee of Thrombosis and Hemostasis and the International Committee of Standardization in Hematology, has recommended a calibration scheme for thromboplastin standardization with special reference for anticoagulant monitoring. Instead of reporting patient values, either in seconds or percent activity, WHO recommends the PT results in terms of an international normalized ratio (INR). This is obtained by formula: INR = RC in which R is the patient's PT and C is the international sensitivity index (ISI) of the thromboblastine employed. The INR represents the PT that would be obtained if it were performed with the WHO thromboplastin reference preparation. We suggest that these new concepts should be implemented by both laboratory and clinical professionals with the purpose of improving the effectiveness and safety of oral anticoagulation.

[Non-Hodgkin's lymphoma secondary to Hodgkin's disease treated with chemo- and radiotherapy. Report of a case]. / Linfoma no Hodgkin secundario a enfermedad de Hodgkin tratada con quimio- y radioterapias. Informe de un caso.

In 18 years of experience in the use of combined chemotherapy in Hodgkin's disease at the Instituto Nacional de la Nutrición Salvador Zubirán, the first case of non-Hodgkin's lymphoma secondary to Hodgkin's disease was identified. The patient was a 23 year old male who initially developed a nodular sclerosis type of Hodgkin's disease. Three years later, the biopsies showed lymphocyte predominance type of Hodgkin's disease. Finally, one year later, the patient developed a diffuse small cleaved cell lymphoma. Non-Hodgkin's lymphoma occurring in patients treated with combined chemotherapy and radiotherapy after Hodgkin's disease is a rare complication. We believe that the genesis of a second neoplasm in these cases may be due to both disturbances in the cellular immunity intrinsic to Hodgkin's disease and the treatment with combined chemotherapy and radiotherapy.

Treatment of methimazole-induced severe aplastic anemia with recombinant human granulocyte-monocyte colony-stimulating factor and glucocorticosteroids.

The in vivo response to recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF) in facilitating the reconstitution of granulomonopoiesis was evaluated in a patient with Graves' disease who developed severe aplastic anemia during methimazole therapy. After 10 days of treatment with rHu GM-CSF, the neutrophil and monocyte counts rose to 1.65 x 10(9)/l and 0.41 x 10(9)/l, respectively. However, the patient was still dependent on erythrocyte and platelet transfusions. Two days after rHu GM-CSF withdrawal, the neutrophil count dropped off to 0.41 x 10(9)/l.rHu GM-CSF was reinitiated for 2 days along with glucocorticosteroids. With this combined therapeutic approach, the neutrophil count returned to normal and remained stable, and both Hb and platelet values began to improve. It is concluded that the combination of rHu GM-CSF and glucocorticosteroids can be used as a therapeutic option that may lead to beneficial results in drug-induced aplastic anemia.

The incidence of protein C deficiency in thrombosis-related portal hypertension.

OBJECTIVE: To know the incidence of protein C deficiency associated with noncirrhotic, thrombosis-related portal hypertension. METHODS: Thirty-six patients were studied who had thrombosis-related portal hypertension diagnosed by means of hepatic venography or abdominal echocardiography or during abdominal surgery. Liver disease was excluded in 20 patients based on normal liver function tests and normal histology on liver biopsy. At the time of protein C assays, these patients were not receiving oral anticoagulation, and, in those recently diagnosed, the assays were performed more than 14 days after the last thrombotic event. Antigenic and functional assays for protein C were performed by ELISA and chromogenic assay, respectively. RESULTS: We found 11 patients with protein C deficiency who had a median age of 28 yr (range 19-55 yr) at time of diagnosis. Five patients had a history of systemic thromboembolism, and upper GI bleeding was the most frequent symptom related to portal hypertension (six cases). Antigenic protein C levels were measured in nine of the 11 patients (mean 31.88%, range 10-49%). Functional protein C level was assayed for all 11 patients (mean 40.90%, range 15-58%). After diagnosis, all patients received oral anticoagulants (ideally International Normalized Ratio: 2-3). CONCLUSION: We suggest that protein C screening should be performed in patients with thrombosis-related portal hypertension.

[Hemophagocytic syndrome associated with histoplasmosis in the acquired immunodeficiency syndrome: description of 3 cases and review of the literature]. / Síndrome hemofagocítico asociado a histoplasmosis en el síndrome de inmunodeficiencia adquirida: descripción de tres casos y revisión de la literatura.

Three cases of haemophagocytic syndrome (HPS) due to histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS) are described. At admission all had pancytopenia and the bone marrow aspirate showed typical haemophagocytosis and the presence of intracellular inclusions compatible with Histoplasma capsulatum. One patient had also cerebral toxoplasmosis. One patient died shortly after admission from multiple organ failure. Two patients survived, one treated with fluconazole and another with amphotericin-B with good response and progressive increase in their blood cell counts. We suggest that haemophagocytic syndrome due to disseminated histoplasmosis should be included in the causes of pancytopenia in patients with AIDS. Bone marrow aspirate is the best method for diagnosis.

Comparison of colony-stimulating activities for evaluating in vitro granulomonopoiesis in normal subjects and in patients with myeloid leukemias

El crecimiento in vitro de unidades formadoras de colonias granulomonocíticas (UFC-GM) en sangre periférica (SP) y médula ósea (MO) humana requiere de fractores estimuladores denominados actividad estimuladora de colonias (AEC). El ensayo de Pike & Robinson emplea como fuente de AEC capa alimentadora (CA) compuesta por leucocitos de SP inmovilizados en agar. No obstante que este ensayo de bicapa presenta desventajas técnicas es ampliamente utilizado. Los sobrenadantes tisulares y celulares con actividad biológica para la UFC-GM, también conocidos como medios condicionados (MC), eliminan lsos incovenientes teécnicos de la estimulación con CA. En el presente trabajo se prepararon dos MC, uno de CA (MC-CA) y otro de leucocitos estimulados con fitohemaglutinina (MC-LEF). La AEC de ambos MC se comparó con la producida por la CA. Las tres AEC, evaluadas por el número de racimos (agregados celulares con 3 a 39 células) y de colonias (agregados celulares con -> 40 células) presentes en el cultivo, se probaron en células obtenidas de SP de 17 individuos sanos, y en células de SP (17 muestras) y MO (12 muestras) de enfermos con leucemias mieloides. Se encontró que el MC-CA indujo un número significativamente menor de agregados celulares tanto en muestras de sujetos normales como de enfermos leucémicos al compararlo con el ensayo de CA. En muestras de pacientes con leucemia, el crecimiento clonal mediado por el MC-LEF fue similar al encontrado con CA. En cambio, la adición de MC-LEF a muestras de sujetos sanos dio como resultado un número promedio de colonias significativamente menor al observado con CA. Estos resultados indican que el MC-CA es una fuente inapropiada de AEC para muestras provenientes de sujetos normales y de pacientes leucémicos, mientras que la AEC derivada del MC-LEF mantiene adecuadamente el crecimiento de UFC-GM en muestras de enfermos con leucemia, pero no en muestras de personas normales. Basados en estos hallazgos y en los incovenientes técnicos del ensayo de Pike & Robinson, se concluye que el MC-LEF permite una mejor evaluación de la granulomonopoyesis in vitro en pacientes con leucemias mieloides