ABSTRACT
Se presentan 37 casos de trombosis, en su mayoría jóvenes, con antecedentes trombóticos familiares y con diagnóstico de trombofilia primaria o hereditaria además de cuatro familiares de primer grado de estos pacientes en los cuales se confirmó la portación familiar de trombofilia. La anamnesis reveló que el 82 por ciento presentó la primera trombosis antes de los 45 años; tuvo más de una trombosis en un 59 por ciento y tenía antecedentes familiares en 49 por ciento. Los defectos trombofílicos determinantes encontrados fueron: deficiencia de proteína S (27 por ciento); resistencia a proteína C activada por factor V Leiden (24,3 por ciento); deficiencia proteína C (21,6 por ciento) y antotrombina III (16,2 por ciento); mutación G20210 A del gen protrombina (8,1 por ciento). Entre los defectos adquiridos estudiados simultáneamente, un 27,2 por ciento de los casos presentaron anticoagulante lupico y ninguno hiperhomocisteína. La existencia de mas de un factor de riesgo trombofílico se observó en el 24.3 por ciento de los pacientes. En el estudio de los 4 parientes de primer grado se encontró factor V Leiden en uno; factor V Leiden mas anticoagulante lupico en uno y deficiencia proteína S en dos. El trabajo anterior publicado en 2004 motivó a los pacientes que no se hicieron el estudio a tomar conciencia de su situación y de la necesidad de controlarse, lo que demuestra la importancia de difundir esta patología aún poco conocida.
Subject(s)
Male , Female , Adult , Humans , Blood Coagulation Factors/analysis , Thrombophilia/complications , Thrombophilia/diagnosis , Thrombosis/diagnosis , Thrombosis/etiology , Age Factors , Factor V/analysis , Genetic Predisposition to Disease , Homocysteine/analysis , Lupus Coagulation Inhibitor/analysis , Mutation , C-Reactive Protein/antagonists & inhibitors , Protein C/analysis , Protein S/analysis , Prothrombin/genetics , Risk FactorsABSTRACT
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