Trombofilia primaria: detección y manifestación clínica en 105 casos / Primary thombophilia: Report of 93 cases and 12 asymptomatic relatives

Background: Thrombophilia is defined as an altered hemostasis that predisposes to thrombosis. It can be primary when there is a family clustering of the disease or secondary, when it is associated to an acquired risk factor. Aim: To report clinical features in a series of patients with primary thrombophilia. Material and methods: Review of clinical records of patients with thrombotic episodes that lead to the suspicios of primary thrombophilia. Analysis of asymptomatic adult close relatives of these patients. Results: We report 93 subjects (56 females, age range 14-77 years) with repeated episodes of thrombosis and a family history of thrombosis and 12 asymptomatic close relatives. Seventy one percent had the first thrombotic episode before the age of 40 years, 62% had more than one thrombotic episode and 37% had a family history of thrombosis. Twenty four percent had protein C deficiency, 24% had antithrombin III deficiency, 18% had resistance to activated C protein by factor V Leiden, 10% had protein S deficiency, and 10% had the G20210 mutation of prothrombin gene. Among acquired defects studied simultaneously, 30% had lupus anticoagulant and 11% had hyperhomocysteinemia. Twenty four percent of cases had more than one thrombophilic risk factor. Among asymptomatic relatives, five had factor V Leiden, four had protein C deficiency and three had the G20210 mutation of prothrombin gene. Conclusions: Thrombophilia must be suspected in young subjects with thrombotic episodes and a family history. The type of coagulation defect will determine prognosis, and the type of treatment.

Hemorragias mucocutáneas: evaluación clínica, secuencia de estudio y frecuencia relativa de enfermedades hereditarias de la hemostasia en población chilena / Mucocutaneous hemorrhages: clinical evaluation, study sequency and related frequency of hemostatic hereditary disases in Chilean population

Patients and methods: Five hundred eighty nine patients whose main symptom was the presence of mucocutaneous hemorrhages were studied. Bleeding time, platelet count, coagulant activity of factor VIII (FVIII:C), FvW: Ag and FvW:CoRis and ABO blood group were measured in all patients in a first stage. According to the results of these tests, further studies were decided. Results: In patients younger than 13 years old, males predominated and, in older patients, females consulted with higher frequency. There was a higher proportion of individuals with O blood type than in the normal population. Bleeding time was abnormal in 330 patients (56 percent). One hundred ten patients (19 percent) had von Willebrand disease and, among them, one third had a normal bleeding time. Isolated reduction of factor VIII activity was found in 66 patients (11 percent, 51 males) and 32 of these had normal bleeding time. Eighty one patients (14 percent) were considered to have an hereditary platelet function defect. A precise diagnosis was not achieved in 332 patients (56 percent). Conclusions: Among patients consulting for mucocutaneous hemorrhages, 19 percent had von Willebrand disease, 11 had an isolated reduction of factor VIII activity, 14 percent had platelet function defects and in 56 percent, a precise diagnosis was not reached

Hemofilia A: análisis de intron 18 e intron 7 del gen del factor VIII y su rol en una estrategia de diagnóstico de portadoras en una población chilena / Hemophilia A: analysis of intron 18 and intron 7 of factor VIII gene and its role in a strategy of carrier diagnosis in a chilean population

Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. A large number of different mutations in the VIII gene have been identified. Thus, the detection of female carriers, depends upon the analysis of DNA polymorphism in and near the factor VIII gene. Our aim was to develop a strategy, earlier reported, for carrier testing in families at risk of hemophilia A. In this study, we analyzed the DNA polymorphisms in 26 affected families, with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes Bcll and AlwNI and by differential hybridization with sequence-specific oligonuclaotide probes recognizing Bcll and AlwNI polymorphisms. While the DNA polymorphism detected by Bcll site in intron 18 of the factor VIII gene was informative for 30 percent families studied, the AlwNI/intron 7 polymorphism provided aditional information (4 percent). The carrier status of the remaining 58 percent could be determined utilizing the other polymorphisms suggested the strategy. The 2 polymorphic sites used combined with the other polymorphisms, intragenic and extragenic, can generate levels of informativeness greater than 98 percent. We concluded that the strategy for carrier testing would be a good alternative in genetic counselling for hemophilia A., but its limitations must be carefully taken into account

Resistencia a la proteína C activada: estudio de laboratorio y prevalencia del defecto en la población chilena / Activated protein C resistance: laboratory study and prevalence of the defect in chilean population

Activated protein C resistance (APCR) or factor V leiden has been recently described as the most prevalent hemostatic abnormality associated with venous thrombosis. In patients with familial thrombophilia, the prevalence of APCR is 19-60 percent and around 20 percent in sporadic venous thrombosis. APCR is usually measured by the degree of prolongation of activated Partial Thromboplastin Time (APTT) on patient's plasma, induced by addition of APC in comparison to normal plasma. At the molecular level the defect is caused by a single-point mutation in the gene for factor V (FV) (G1.691-A), that predict the replacement of Arg506 by Glutamine. This mutation makes activated factor V resistant to inactivation by APC. Since the prevalence of the defect is highly variable among different populations, the objective of this work was to study its frequency in our population and in patients with thrombophilia. We defined the normal range for APTT ratio (APTT+APC/APTT-APC) in a group of 73 healthy volunteers in whom the presence of FV Q506 mutation was searched using Mnll enzyme digestion of PCR amplified genomic fragment containing the nucleotide 1.691. The lower limit of APTT ratio stablished in this group was 2.13. APCR was found in 6 out of 159 control subjects (3.8 percent) and in 14/50 (28 percent) of patients with thrombosis. In 13 cases as a single defect and in 1 associated to type I protein C deficiency. All the APCR patients and control subjects were heterozygotes by gene analysis. The results demonstrate that in our population APCR is also the most common defect associated with thrombosis, in accordance with a high prevalence in the population. The ability to screen for this defect will permit the identification of carriers that would benefit preventive therapy at risk situations