Factor V Leiden y mutación de la protrombina G20210A en pacientes con trombosis venosa y arterial / Factor V Leiden and prothrombin G20210A among Chilean patients with venous and arterial thrombosis

Background: Factor V Leiden and G20210A mutation of prothrombin gene are two important genetic polymorphisms associated with an increased risk for thrombosis. Aim: To establish the prevalence of factor V Leiden and prothrombin G20210A mutation in the Chilean population and their association to venous and arterial thromboembolism. Material and methods: A case-control study was conducted where 149 patients with thrombosis (87 with arterial and 62 with venous thrombosis) confirmed by CAT-scan, electrocardiogram and cardiac enzymes or Doppler depending on the case, and 160 healthy blood donors were genetically analyzed for the presence of both polymorphisms. Results: Factor V Leiden mutation was found in 5.4% of patients and in 1.3% of healthy controls (p=0.04). Heterozygosity for G20210A prothrombin mutation was found in 5.4% of patients and in 2.5% of the control group (p=NS). When arterial and venous thrombosis were considered as separate entities, 4.6% of patients with arterial thrombosis and 6.5% with venous thrombosis presented factor V Leiden (p=NS). Likewise, 8.1% of patients with venous thrombosis and 3.5% of patients with arterial thrombosis had G20210A prothrombin mutation (p=NS). Conclusions: In non selected consecutive Chilean patients with arterial and venous thrombosis the frequency of factor V Leiden and prothrombin G20210A is less than we could expect from their prevalence in the general population.

Aloinmunización transplacentaria por antígenos plaquetarios específicos: prevalencia y características en una población chilena / Transplacental alloimmunization against platelet antigens: prevalence and features in a chilean population

Backgrour: Neonatal alloimmune thrombocytopenia (NAIT) is a result of fetomaternal incompatibility. Platelet destruction is caused by a maternal alntibody directed against a fetal platelet antigen inherited from the father and lacking on the mother's platelets. The incidence and features of transplacental alloimmunization depend on the frequency of expression of platelet specific antigens, which are highly variable among different populations. Aim: To determine the prevalence and characteristics of transplacental alloimmunization in a large, group of pregnant women in Chile. Material and methods: We, studied 3,041 samples obtained during the third trimester of gestation. In all samples, anti platelet antibodies were screened by ELISA with platelet membranes fixed to a microtiter plate. Positive samples were further studied for antigenic specificity with the monoclonal antibody specific immobilization of platelet antigens (MAIPA) test. Results: Anti platelet antibodies were found in 261 samples (8.5 percent). The MAIPA test identified 6 samples with antibodies directed against major platelet membrane glycoproteins, 2 anti GPIb, 2 anti GPIIb/IIIa and 2 anti GPIa/IIIa. In four cases, anti HLA antibodies coexisted. Two cases corresponded to well defined platelet antigen systems: one anti HPA-1a and one anti HPA-5b. No clinical evidence of thrombocytopenia of the newborn was detected in all these cases with anti GP antibodies. Conclusions: A prevalence of platelet specific antibodies of 0.2 por ciento with only one anti HPA-1a was detected. These findings are in contrast with those of other populations but in accordance with the low frequency of the HPA-1b/b phenotype in the Chilean population. The very low incidence of platelet specific antibodies and the lack of association with clinical thrombocytopenia in the newborn, do not support the recommendation of routine antenatal screening to all women in Chile

Aloinmunización plaquetaria en pacientes onco-hematológicos politransfundidos: estudio prospectivo en adultos y niños / Platelet alloimmunization in patients with multiple transfusions. Prospective study in adults and children

Background: Refractoriness continues to he a major complication of platelet transfusion therapy in patients with multiple transfusions: Despite most cases are secondary to non-immune causes, the most serious is that associated to alloimmunization. The incidence and consequences of HLA and non-HLA (platelet specific) antibodies are unknown in our country. Aim: To prospectively determinate the frequency and characteristic of post transfusion alloimmunization and the incidence of platelet specific antibodies. Patients and methods: Forty one adults and 24 children with a recently diagnosed malignancy and undergoing chemotherapy that required multiple transfusions were studied. Screening for antiplatelet antibodies (platelet membrane ELISA) was performed before the first transfusion, every four weeks or whenever the 1 hour corrected count increment for platelet transfusions was lower that 5000. Platelet specific antibodies werw identified with a monoclonal antibody-specific immobilization of platelet antigens (MAIPA), with anti-GPIIb, GPIIb/IIIa, GPIa/lia and anti-HLA class I. Results: Adult patients received an averafge of 10.2 ñ 5.5 units of red blood cells and 58.6 ñ 35.4 units of platelets. Children received 4.8 ñ 3.7 units of red blood cells and 9.6 ñ 6.7 units of platelets. HLA antibodies appeared in 7 of 41 adult patients (17 percent), platelet specific alloantibodies were found in two patients (one anti GP Ia/IIa and one anti GP ib). Platelet refractoriness appeared in three alloimmunized patients. No Child had detectable serum antibodies during follow up. Conclusions: Platel transfusion refractoriness of immune origin occurs infrequently in our population and the presence of platelet antibodies does not mean that it will appear. The use of leukocyte depleted blood components to prevent refractoriness cannot be justified at this time

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