Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors.

In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies in response to replacement therapy with factor VIII (FVIII), requiring bypass therapy such as activated prothrombin complex concentrate (APCC). Because bypass therapy has not been broadly available in Mexico even in recent years, this study aimed to evaluate the thrombin generation assay (TGA) in assessing the response to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We studied 189 patients with severe HA. Clinical severity was verified by one-stage APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen-Bethesda (N-B) method, and type of inhibition was assessed through serial plasma dilutions. Thrombin generation was measured with the calibrated automated thrombogram in inhibitor-positive plasmas previously spiked and incubated with FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests. We detected 47 (24.9%) subjects with high-titre (5-1700 N-B U mL(-1)) and 25 (13.2%) subjects with low-titre inhibitor antibodies (0.6-4.7 N-B U mL(-1)). We found an association between kinetic behaviour and clinical response to FVIII (P = 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global concordance between clinical and in vitro response was 70%. By evaluating the capacity of thrombin formation in a plasma sample, TGA predicts the response to FVIII or APCC therapy and allows individual optimization of resources in patients with severe HA and high-titre inhibitors. The inhibition pattern of the antibodies to FVIII:C correlated with the TGA parameters and showed an association with the clinical response to FVIII.

Haemophilic arthropathy: the usefulness of intra-articular oxytetracycline (synoviorthesis) in the treatment of chronic synovitis in children.

Synoviorthesis is already widely used in the treatment of chronic haemophilic synovitis. The aim of this study was evaluate the effectiveness of oxytetracicline synoviorthesis on the frequency of haemarthrosis in haemophilic children with chronic synovitis and its impact on joint function. Between January 2001 and October 2006, we performed 34 synoviorthesis in 28 paediatric patients (6-16 years old) with diagnosis of haemophilic arthropathy stage I-II. At each joint were administered five doses of oxytetracycline for five consecutive weeks at doses of 100 mg in elbow and ankle and 250 mg in the knee. The frequency of haemarthrosis and range of joint mobility were evaluated before and after of treatment. The results were analysed with Student t-test and descriptive statistics. Thirty-four joints were treated, including 20 knees (58.8%), eight elbows (23.5%) and six ankles (17.6%). Median follow-up was 46.3 months (range 12-71 months). The frequency of haemarthrosis was recorded before treatment 47.3 year(-1) (range 12-96, P < 0.0001) and decreased to 3.5 year(-1) (range 0-15, P = 0.0119) after treatment. The range of joint motion in flexion-extension before treatment was 84.9°, while after this was 97.5° (P = 0.0119). The synoviorthesis with oxytetracycline has shown a favourable effect in the treatment of chronic haemophilic synovitis in reducing the frequency of haemarthrosis and improvement was observed consistently in the range of motion.

[Peripheral pancytopenia]. / Pancitopenia periférica.

Peripheral pancytopenia is a syndrome which allows for an early diagnosis, and although is may cover a large number of pathological entities, it can be clearly defined into three groups of illnesses which evolve with this syndromal manifestations. The first group includes non-neoplastic illnesses which include aplastic anemia, hemophagocytic syndrome associated to infection, immunological diseases and the deficiency of folates or vitamin B12. The second group includes neoplastic diseases as acute leukemia, non-Hodgkin lymphoma, and Hodgkin's lymphoma with myelofibrosis, malignant histiocytosis and non-hematological neoplasms, like the neuroblastoma and the embryonal rhabdomyosarcoma. The third group is formed by illnesses which have some similarity with neoplasms.

Hemoglobina E (26 GLU-LIS) y talasemia beta en una familia mexicana. / Hemoglobin E (26 GLU-LIS) and beta thalassemia in a Mexican family

Se informa del hallazgo en una familia mexicana de tres hermanos dobles heterocigotos para la hemoglobina E y la talasemia beta que padecen anemia hemolitica. Son originarios del centro del pais y no tienen ancestros asiaticos, africanos ni mediterraneos. Se estudiaron tres generaciones de la familia identificando varios heterocigotos para la hemoglobina E y la talasemia beta. La hemoglobina E no habia sido encontrada antes en Mexico y asociada a talasemia beta no tiene antecedentes en America Latina