I Alberca

Hospital Universitario de Salamanca, Helmantica, Castille and León, Spain

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Publications (97)344.81 Total impact

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    ABSTRACT: Bleeding is a frequent complication after allogeneic haematopoietic stem cell transplantation (HSCT) and may affect survival. The purpose of this study was to determine the incidence and risk factors for life-threatening bleeding after HSCT by retrospective evaluation of 491 allogeneic HSCT recipients. With a median follow-up of 33 months, 126 out of 491 allogeneic HSCT recipients experienced a haemorrhagic event (25·7%) and 46 patients developed a life-threatening bleeding episode (9·4%). Pulmonary and gastrointestinal bleeding were the most common sites for life-threatening bleeding, followed by central nervous system. In multivariate analyses, the presence of severe thrombocytopenia after day +28 and the development of grade III-IV acute graft-versus-host disease (GVHD) or thrombotic microangiopathy (TMA) retained their association with life-threatening bleeding events. The overall survival at 3 years among patients without bleeding was 67·1% for only 17·1% for patients with life-threatening bleeding (P < 0·001). In conclusion, life-threatening bleeding is a common complication after allogeneic HSCT. Prolonged severe thrombocytopenia, acute grade III-IV GVHD and TMA were associated with its development. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 03/2015; 169(5). DOI:10.1111/bjh.13344 · 4.71 Impact Factor
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    ABSTRACT: Prosthetic material (mesh) is commonly used to repair inguinal hernias. Its implantation close to the common femoral vein (CFV) can induce slow flow and favor the appearance of venous thromboembolism (VTE) events. To investigate the speed of flow, diameter and area of the CFV after inguinal hernioplasty. Two hundred and fifty patients receiving open hernioplasty with a non-resorbable mesh for the repair of a unilateral, primary, simple inguinal hernia were prospectively investigated. Patients were stratified, by consensus, into a low or a moderate risk of VTE group. The moderate-risk group (n = 163) received low molecular weight heparin. On day 10 post-operation a blinded Echo-Doppler was carried out, and repeated 7 days later in patients with a venous flow of <15 cm/s. The speed of flow (cm/s), diameter (cm), and area (cm(2)) of the ipsilateral and contralateral CFV of the groin operated upon were measured. No event symptomatic of VTE was documented. One case of asymptomatic deep vein thrombosis (1/163, 0.6 %) was found in the moderate-risk group. In 29 patients (2 and 27 in the low- and moderate-risk groups, respectively; p < 0.001) a maximum blood flow velocity of <15 cm/s was found in the ipsilateral CFV; these flows were close to normal in the second measurement. Taking the entire sample into account, the maximum venous blood flow found in the ipsilateral CFV of the operated groin was less than that measured in the contralateral CFV (20.88 vs. 24.01 cm/s; p < 0.001); this difference was significant in both VTE risk groups. The diameter and area of the CFV were both greater in the ipsilateral than the contralateral CFV (p < 0.01); this finding proved to be significant only in hernias of the left groin (p < 0.001). In the immediate postoperative period, inguinal hernioplasty with mesh induces a temporarily slow venous flow in the ipsilateral CFV. However, this does not lead to an increase in the incidence of VTE.
    Hernia 02/2015; DOI:10.1007/s10029-015-1353-x · 2.05 Impact Factor
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    ABSTRACT: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.Bone Marrow Transplantation advance online publication, 24 February 2014; doi:10.1038/bmt.2014.17.
    Bone marrow transplantation 02/2014; 49(5). DOI:10.1038/bmt.2014.17 · 3.57 Impact Factor
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    ABSTRACT: Few studies specifically focus on elderly splenectomized immune thrombocytopenia (ITP) patients. Older patients with ITP and excellent health are often excluded from surgery splenectomy. We aimed to compare the safety and efficacy of splenectomy in elderly and non-elderly ITP patients and to examine the effect of age on therapeutic response. We carried out a retrospective analysis of a series of 218 patients who had undergone splenectomy for ITP. We compared the data from the elderly group (≥65 yrs, 57 patients) with the young group (<65 yrs, 162 patients). Surgical technique (laparoscopy or open laparotomy splenectomy) was comparable between the two age groups. The adjusted risk of major bleeding following splenectomy for elderly patients was three times that for young patients (OR 3.05, 95% CI: 1.44–6.52). The median duration of postoperative hospital stay was longer for elderly than for young patients (8 d vs. 4 d, P < 0.001). However, we identified a subgroup of elderly ITP patients, those aged between 65 and 70 yrs who had undergone laparoscopic splenectomy, with a low risk of postoperative complications. Of the 218 patients, 89% achieved a favorable response to splenectomy. A favorable response was significantly less common in elderly than in young people (79% vs. 92%, P = 0.005). However, we observed an acceptable long-term control of ITP in the elderly group, in which the probability of maintaining response for 14 yrs after splenectomy was 56%. Patients aged ≥65 yrs experienced negative effects on safety and efficacy outcomes of splenectomy for ITP, but further studies are needed to identify predictors of postsplenectomy outcomes in this group.
    European Journal Of Haematology 09/2013; 91(3). DOI:10.1111/ejh.12146 · 2.07 Impact Factor
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    ABSTRACT: Objective: To investigate the association of the THBD c.1418C>T polymorphism, which encodes for the replacement of Ala455 by Val in thrombomodulin (TM), with venous thromboembolism (VTE), plasma soluble TM, and activated protein C levels. In addition, human umbilical vein endothelial cells (HUVEC) isolated from 100 umbilical cords were used to analyze the relation between this polymorphism and THBD mRNA and TM protein expression. Approach and results: The THBD c.1418C>T polymorphism was genotyped in 1173 patients with VTE and 1262 control subjects. Levels of soluble TM and activated protein C were measured in 414 patients with VTE (not on oral anticoagulants) and 451 controls. HUVECs were genotyped for the polymorphism and analyzed for THBD mRNA and TM protein expression and for the ability to enhance protein C activation by thrombin. The 1418T allele frequency was lower in patients than in controls (P<0.001), and its presence was associated with a reduced VTE risk, reduced soluble TM levels, and increased circulating activated protein C levels (P<0.001). In cultured HUVEC, the 1418T allele did not influence THBD expression but was associated with increased TM in cell lysates, increased rate of protein C activation, and reduced soluble TM levels in conditioned medium. Conclusions: The THBD 1418T allele is associated with lower soluble TM, both in plasma and in HUVEC-conditioned medium, and with an increase in functional membrane-bound TM in HUVEC, which could explain the increased activated protein C levels and the reduced VTE risk observed in individuals carrying this allele.
    Arteriosclerosis Thrombosis and Vascular Biology 03/2013; 33(6). DOI:10.1161/ATVBAHA.113.301360 · 6.00 Impact Factor
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    Thrombosis Research 10/2012; 130:S110–S111. DOI:10.1016/j.thromres.2012.08.029 · 2.45 Impact Factor
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    ABSTRACT: Background. Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two these life-threatening complications in these complex patients are currently not well defined. Design and Methods. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Results. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft versus host disease to be the only independent prognostic risk factor. By contrast, eight factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III - IV graft versus host disease and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (p = 0.856). However, significant clinical bleeding was associated with inferior survival (p < 0.001). Conclusions. In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.
    Haematologica 08/2012; 98(3). DOI:10.3324/haematol.2012.069559 · 5.81 Impact Factor
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    ABSTRACT: Few studies have evaluated the risk of pregnancy-related adverse events in asymptomatic relatives of probands for VTE and factor V Leiden or the G20210A variant. The antepartum management of this population ranges from antepartum anticoagulation therapy to clinical surveillance. To evaluate the risk of placenta-mediated pregnancy complications and pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and who are heterozygous carriers of either factor V Leiden or PT-G20210A mutation. One hundred and fifty-eight relatives, who had 415 pregnancies, were retrospectively evaluated. Odds ratios and 95% confidence intervals were calculated to compare pregnancy outcomes between women with and without thrombophilia. In the factor V Leiden group, 22 placenta-mediated pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25 adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13 adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of factor V Leiden or G20210A prothrombin were not associated with a higher risk of pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40-2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy-associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in the G20210A group, one in the factor V Leiden group, and one episode in the non-carrier group were noted. In VTE-asymptomatic relatives of probands with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in heterozygosis should not lead to a decision to instigate antepartum prophylaxis.
    European Journal Of Haematology 05/2012; 89(3):250-5. DOI:10.1111/j.1600-0609.2012.01809.x · 2.07 Impact Factor

  • World Congress of Cardiology Scientific Sessions; 05/2012
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    ABSTRACT: Venous thromboembolism (VTE) is a multifactorial disease in which both environmental and genetic factors are involved. The presence of mutations in genes coding for haemostatic, fibrinolytic and, also, inflammatory proteins is associated with an increased risk of first episode and recurrence of venous thrombosis. So, in the last years, several polymorphisms associated with thrombosis have been reported. Recently, the 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (a C > T substitution at base pair 677 leading to the exchange of alanine to valine) has been proposed by some studies to be a thrombophilic risk factor. This mutation causes moderate hyper-Hcy, and Hyper-Hcy is well known to cause VTE. We analysed the role of C677T MTHFR in VTE, as well as its clinical applicability.
    Angiología 11/2010; 62(6):225-231. DOI:10.1016/S0003-3170(10)70053-5
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    ABSTRACT: There is currently intense debate as to whether pharmacogenetic algorithms for estimating the initial dose of coumarins provide a more accurate dose than the fixed-dose approach. Recently, it has been suggested that the greatest benefit of pharmacogenetic algorithms is observed in patients with extreme dose requirements. To identify clinical and genetic factors that better characterize patients who need extreme acenocoumarol doses for steady anticoagulation state. We reviewed 9538 patients with a steady acenocoumarol dose from three Spanish hospitals, selecting 83 who took <or= 5.00 mg week(-1) (percentile 5, p5) and 203 taking >or= 30.00 mg week(-1) (p95). We also selected patients matched by gender and age taking 13.50-14.00 mg week(-1) (p50). We genotyped VKORC1 (rs9923231), CALU (rs1043550), GGCX (rs699664), CYP2C9 (rs1799853; rs1057910), CYP4F2 (rs2108622) and F7 (rs5742910) single-nucleotide polymorphisms (SNPs). Comparison between p5 and p95 revealed five parameters with significant differences: body surface area (BSA) (P = 0.006), age, VKORC1, CYP2C9 and CYP4F2 genotypes (all P < 0.001). First VKORC1, and second, CYP2C9 SNPs played a strong effect by determining extreme doses, particularly in p95. Only one out of 203 p95 had the VKORC1 A-1639A genotype, but this subject was CYP2C9*1/*1. In contrast, nine out of 83 p5 carried the VKORC1 G-1639G genotype, although six of them were CYP2C9*3 homozygotes and another two were heterozygotes. Surprisingly, CYP4F2 V433M SNP displayed prevalences that suggest that its influence might only be evident when patients are treated with high doses. Two clinical data, age and BSA, and three SNPs in the VKORC1, CYP2C9 and CYP4F2 genes strongly predict outlier patients treated with acenocoumarol.
    Journal of Thrombosis and Haemostasis 02/2010; 8(5):1012-7. DOI:10.1111/j.1538-7836.2010.03800.x · 5.72 Impact Factor

  • Thrombosis and Haemostasis 01/2010; 103(1):247-9. DOI:10.1160/TH09-02-0124 · 4.98 Impact Factor
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    ABSTRACT: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count and bleeding, whose incidence is approximately 6.2 for each 100,000 adults per year. Intravenous immunoglobulins (IVIG) can be useful in patients with ITP to prevent bleeding or prior to surgery. In this study, the efficacy and safety of Flebogammadif, a new high-purity IVIG, were assessed by an open, multicentre, non-controlled, prospective study in adult patients with chronic ITP. A total of 20 patients (enrolled if experiencing chronic ITP since at least 6 months before recruitment and if platelet count <20 x 10(9)L(-1) before treatment) received 0.4 g kg(-1)-bw of Flebogammadif for 5 consecutive days and were followed-up for 3 months. Efficacy endpoints were three: proportion of patients who reached a platelet count > or = 50 x 10(9)L(-1), time for the platelet count to reach that level and duration of response. Safety parameters [adverse events (AE), laboratory determinations and vital signs] and viral markers were regularly monitored. A total of 14 patients achieved a platelet count of > or = 50 x 10(9)L(-1). The median time to platelet response was </=2.5 days, and the median number of days in which the platelet count remained > or = 50 x 10(9)L(-1) was > or = 7 days. A regression of haemorrhages was reported for 17 patients on day 14. Eight patients presented 21 AEs (mostly mild) potentially related to the study drug. Neither abnormalities in laboratory values nor in viral markers were registered during the follow-up period. Flebogammadif was well tolerated and succeeded in providing a haemostatic platelet count in patients with ITP.
    Transfusion Medicine 10/2009; 19(5):260-8. DOI:10.1111/j.1365-3148.2009.00945.x · 1.65 Impact Factor
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    ABSTRACT: Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by an accelerated destruction of platelets as a result of the presence of autoreactive antibodies. Patients with ITP also display activated platelet-autoreactive T cells. Mesenchymal stem cells (MSC) inhibit both T- and B-cell activation and may have functional impairments in autoimmune disorders. We analyzed the potential role of MSC in the pathogenesis of ITP. MSC from ITP showed an impaired proliferative capacity and a lower capability of inhibiting activated T-cell proliferation compared with healthy donors. While MSC from controls showed a decreased expression of p27 after stimulation with platelet-derived growth factor, this effect was not observed in MSC from patients. Furthermore, MSC from healthy donors down-regulated p16 upon exposure to platelet-released supernatant, while this effect was not observed for ITP. Interestingly, caspase 9 expression was higher in MSC from ITP. These abnormalities suggest a role of MSC malfunction in the physiopathology of the disease and may have therapeutic implications.
    Cytotherapy 01/2009; 11(6):698-705. DOI:10.3109/14653240903051558 · 3.29 Impact Factor
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    ABSTRACT: Routine analyses for thrombophilia include determination of the presence of factor V Leiden and prothrombin 20210A polymorphisms. However, the usefulness of these determinations is controversial and the clinical benefit remains questioned because of the moderate risk of associated thrombosis in carriers. In the search for clusters of thrombotic risk factors to estimate individual risk better, we studied the effect of AB0 blood group, a highly prevalent factor with mild prothrombotic features, on the risk and severity of venous and arterial thromboses in carriers of these polymorphisms. We genotyped the AB0 blood group in 981 carriers of factor V Leiden or prothrombin 20210A polymorphisms. In order to avoid the over-representation of a particular genotype and to suppress confounding factors, we included only non-related heterozygous carriers without additional genetic risk factors. We studied 609 patients with venous thromboembolism (287 with factor V Leiden, and 322 with prothrombin 20210A), 174 patients with myocardial infarction (78 with factor V Leiden, and 96 with prothrombin 20210A), and 198 controls (96 with factor V Leiden, and 102 with prothrombin 20210A). Non-OO blood group did not increase the risk of myocardial infarction in carriers of factor V Leiden or prothrombin 20210A. However, non-OO blood group contributed significantly to the expression of venous thrombosis associated with both factor V Leiden (OR: 1.76; 95%CI: 1.06-2.91) and prothrombin 20210A (OR: 2.17; 95%CI: 1.33-3.53). Exclusion of A(2)A(2) and A(2)O from the non-00 blood group (because factor VIII-von Willebrand factor levels are similar in these and the 00 blood group) increased the thrombotic risk. Finally, non-OO blood group was associated with an earlier onset in symptomatic carriers of these polymorphisms. Our study suggests that non-OO blood group increases the risk and severity of venous thrombosis in carriers of prothrombotic polymorphisms. Thus, AB0 phenotyping or genotyping analyses may be valuable components in assessing future thrombophilic risk profiles and might have implications for the policy of thrombosis prophylaxis and treatment.
    Haematologica 06/2008; 93(5):729-34. DOI:10.3324/haematol.12271 · 5.81 Impact Factor
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    ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a deficient expression of glycosylphosphatidylinositol-anchored proteins (GPI-APs), due to somatic mutations of the phosphatidylinositolglycan complementation Class A (PIG-A) gene. In this study, the expression of a high number of GPI-APs on different subsets of peripheral blood (PB) cells from 14 PNH patients and their potential association with underlying genetic abnormalities has been analyzed. This study confirms the existence of variable patterns of expression of different GPI-APs on both major and minor PB-cell subsets from PNH patients. The size of the PNH clone within PB neutrophils and monocytes was systematically higher than that of other cell populations. Genetic changes were detected in the PIG-A gene in 5 of 13 cases analyzed. Interestingly, the reactivity for many GPI-APs was significantly higher on different subsets of normal PB cells from PNH patients than those observed on healthy volunteers. The best combination of markers for the diagnostic screening of PNH would include evaluation of CD14 on monocytes and of CD16 on neutrophils, although further analysis of CD55 and CD59 expression may contain additional clinically useful information. Clear association between the genetic changes detected in the PIG-A gene in 5 of 13 cases analyzed, and the phenotypic profile of PNH cells has not been found. Additionally, an abnormally higher expression of several GPI-APs among normal residual cells from PNH patients in comparison to healthy donors was observed, suggesting that factors other than the PIG-A mutation could determine the phenotypic profile of PB cells in PNH.
    Transfusion 05/2008; 48(7):1403-14. DOI:10.1111/j.1537-2995.2008.01686.x · 3.23 Impact Factor
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    ABSTRACT: Introducción. La trombosis venosa profunda (TVP) postoperatoria es una entidad frecuente y potencialmente grave, cuya actuación diagnóstica, profiláctica y terapéutica posee excelentes niveles de evidencia. No obstante, existen circunstancias patogénicas especiales, como el síndrome antifosfolípido (SAF), que pueden complicar la evolución de la trombosis con una hemorragia suprarrenal bilateral motivando incertidumbre en la toma de decisiones. Caso clínico. Varón de 75 años, con antecedentes de TVP de repetición en el contexto de un SAF primario (tratado indefinidamente con acenocumarol), que se somete a cirugía por cáncer de colon. En el postoperatorio presenta una TVP en la extremidad inferior izquierda, a pesar de una correcta profilaxis antitrombótica. Durante el tratamiento de la TVP presenta un cuadro abdominal compatible con una hemorragia suprarrenal bilateral. Se suspende el tratamiento, se inserta un filtro en vena cava inferior (TrapEase) y, días más tarde, confirmada la estabilización de la hemorragia, se reinicia la anticoagulación al observarse progresión de la trombosis. Evolución satisfactoria del paciente. Conclusión. El SAF es una conocida causa de TVP de repetición, que también origina hemorragia suprarrenal bilateral, máxime si se asocia a postoperatorio y fármacos anticoagulantes/antitrombóticos. El complejo equilibrio de tratar una TVP y evitar la progresión de una hemorragia suprarrenal bilateral forma parte del arte médico.
    Angiología 01/2008; 60(4). DOI:10.1016/S0003-3170(08)04008-X
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    ABSTRACT: Introducción. La influencia genética en la trombosis venosa profunda es muy importante. Por tanto, la búsqueda de cualquier factor de riesgo genético que incremente el riesgo de aparición o recurrencia de una trombosis venosa profunda (TVP) es de gran relevancia. Ciertas investigaciones sugieren el papel anticoagulante del inhibidor dependiente de la proteína Z. Recientemente, nuestro grupo ha identificado un nuevo marcador genético que incrementa el riesgo de TVP, la mutación puntual en la posición 1277 de la región aminoterminal del inhibidor dependiente de la proteína Z (G1277A). Caso clínico. Varón de 36 años con antecedentes de TVP del miembro inferior izquierdo, que bajo tratamiento anticoagulante desarrolló a los cinco meses un nuevo episodio de TVP del miembro inferior derecho con embolismo pulmonar bilateral. A pesar de recibir un correcto tratamiento antitrombótico, la asociación de dos factores genéticos trombogénicos en nuestro paciente, el factor V de Leiden y la mutación G1277A del inhibidor dependiente de la proteína Z, originó una recidiva precoz de la TVP. Conclusión. La mutación G1277A del gen del inhibidor dependiente de la proteína Z puede constituir un marcador genético de riesgo de aparición o recurrencia de TVP. Su búsqueda, junto con la identificación del factor V de Leiden y la mutación G20210A del gen de la protrombina, puede estar justificada.
    Angiología 01/2008; 60(4). DOI:10.1016/S0003-3170(08)04007-8
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    ABSTRACT: The antithrombin A384S mutation has a relatively high frequency in the British population but has not been identified in other populations. This variant has been associated with cases of thrombotic disease, but its clinical relevance in venous thrombosis remained unclear. We have conducted a secondary analysis of the prevalence of the mutation in a large case-control study, including 1018 consecutive Spanish patients with venous thromboembolism. In addition, we evaluated its functional consequences in 20 carriers (4 homozygous). This mutation, even in the homozygous state, did not affect anti-Xa activity or antigen levels, and it only slightly impaired anti-IIa activity. Thus, routine clinical methods cannot detect this anomaly, and, accordingly, this alteration could have been underestimated. We identified this mutation in 0.2% of Spanish controls. Among patients, this variant represented the first cause of antithrombin anomalies. Indeed, 1.7% patients carried the A384S mutation, but 0.6% had any other antithrombin deficiency. The mutated allele was associated with an increased risk of venous thrombosis with an adjusted OR of 9.75 (95% CI, 2.2-42.5). This is the first study supporting that antithrombin A384S mutation is a prevalent genetic risk factor for venous thrombosis and is the most frequent cause of antithrombin deficiency in white populations.
    Blood 06/2007; 109(10):4258-63. DOI:10.1182/blood-2006-08-040774 · 10.45 Impact Factor
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    ABSTRACT: Despite the well-known pro-thrombotic and pro-inflammatory plasma homocysteine effects, it remains uncertain whether these effects can be associated with an adverse cardiac outcome in young patients admitted with acute coronary syndromes. Homocysteine levels were determined within 24 h after admission in 244 consecutive patients aged less than 56 years who presented with an acute coronary syndrome. We evaluated the relationship between homocysteine and both short-term (death, myocardial [re]infarction), and long-term prognosis (death, recurrent acute coronary syndrome and/or ischemic stroke), after 3.4+/-1.7 years of follow-up. Homocysteine levels were similar in patients both with and without in-hospital event: 8.65 (5.36-10.48) vs. 8.98 (7.38-11.13) micromol/l, p=NS. However, patients who presented with the combined event during follow-up had higher homocysteine levels than those free of the event: 10.54 (7.90-11.76) micromol/l vs. 8.52 (7.11-10.23) micromol/l, p=0.001. Patients who either died (13.78 vs. 8.87 micromol/l, p=0.012) or had a myocardial infarction (10.75 vs. 8.76 micromol/l, p=0.006) or unstable angina (10.46 vs. 8.76, p=0.006) during follow-up had higher homocysteine levels. According to the Cox regression analysis: age [hazard ratio 1.05, CI 95%, 0.99-1.10], left ventricular ejection fraction < or =40% [hazard ratio 1.93, CI 95%, 0.98-3.79], and homocysteine tertile 3 [hazard ratio 2.05, CI 95%, 1.13-3.71] were the significant determinants of the combined adverse event during follow-up. Although 41 (18%) of patients presented the TT genotype of the methylen-tetrahydrofolate-reductase thermolabile variant mutation, its occurrence had a neutral effect on morbid-mortality. High homocysteine levels at admission strongly predict late cardiac events in young patients with acute coronary syndromes.
    International journal of cardiology 05/2007; 118(2):183-8. DOI:10.1016/j.ijcard.2006.06.046 · 4.04 Impact Factor

Publication Stats

1k Citations
344.81 Total Impact Points


  • 1985-2014
    • Hospital Universitario de Salamanca
      Helmantica, Castille and León, Spain
  • 1983-2008
    • Universidad de Salamanca
      • Department of Medicine
      Helmantica, Castille and León, Spain
  • 2002
    • University of Murcia
      • Faculty of Medicine
      Murcia, Murcia, Spain
  • 1988
    • University of Milan
      • Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
      Milano, Lombardy, Italy