Maurizio Margaglione

Publications (99)415.2 Total impact

• Source

  Available from: Andrea Patriarca

  Article: TET2 mutations in Ph-negative-Myeloproliferative Neoplasms: identification of three novel mutations and relationship with clinical and laboratory findings.

  Andrea Patriarca, Donatella Colaizzo, Gianluca Tiscia, Raffaele Spadano, Silvia Di Zacomo, Antonio Spadano, Ida Villanova, Maurizio Margaglione, Elvira Grandone, Alfredo Dragani
  [show abstract] [hide abstract]
  ABSTRACT: High-throughput DNA sequence analysis was used to screen for TET2 mutations in peripheral blood derived DNA from 97 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Overall six mutations in the coding region of the gene were identified in 7 patients with an overall mutational frequency of 7.2%. In polycythemia vera patients (n=25) were identified 2 mutations (8%); in those with essential thrombocythemia (n=55) 2 mutations (3.6%); in those with unclassifiable MPN (n=8) 3 mutations (37.5%). No primary myelofibrosis patiens (n=6) harboured TET2 mutations. Three unreported mutations were identified (p.P177fs, p.C1298del, p.P411del,) the first two in patients with unclassifiable MPN, the last in a patient with essential thrombocythemia. On multivariate analysis the diagnosis of an unclassifiable MPN was significantly related to the presence of TET2 mutations (p=0.02; OR: 2.81; 95%CI 1.11- 7.06). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN and are more frequent in MPN-U patients. This could represent the biological link between the different classes of myeloid malignancies.
  Biomedical Research 05/2013; · 1.15 Impact Factor
• Source

  Available from: Andrea Patriarca

  Article: TET2 mutations in Ph-negative-Myeloproliferative Neoplasms

  Andrea Patriarca, Donatella Colaizzo, Gianluca Tiscia, Raffaele Spadano, Silvia Di Zacomo, Antonio Spadano, Ida Villanova, Maurizio Margaglione, Elvira Grandone, Alfredo Dragani
  [show abstract] [hide abstract]
  ABSTRACT: High-throughput DNA sequence analysis was used to screen for TET2 mutations in peripheral blood derived DNA from 97 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Overall six mutations in the coding region of the gene were identified in 7 patients with an overall mutational frequency of 7.2%. In polycythemia vera patients (n=25) were identified 2 mutations (8%); in those with essential thrombocythemia (n=55) 2 mutations (3.6%); in those with unclassifiable MPN (n=8) 3 mutations (37.5%). No primary myelofibrosis patiens (n=6) harboured TET2 mutations. Three unreported mutations were identified (p.P177fs, p.C1298del, p.P411del,) the first two in patients with unclassifiable MPN, the last in a patient with essential thrombocythemia. On multivariate analysis the diagnosis of an unclassifiable MPN was significantly related to the presence of TET2 mutations (p=0.02; OR: 2.81; 95%CI 1.11-7.06). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN and are more frequent in MPN-U patients. This could represent the biological link between the different classes of myeloid malignancies.
  05/2013;
• Article: Influence of the Gly1057Asp variant of the insulin receptor substrate 2 (IRS2) on insulin resistance and relationship with epicardial fat thickness in the elderly.

  Gianluigi Mazzoccoli, Mariangela Pia Dagostino, Andrea Fontana, Elvira Grandone, Giovanni Favuzzi, Giovanni Tiscia, Maurizio Margaglione, Angela de Matthaeis, Antonio Greco, Gianluigi Vendemiale
  [show abstract] [hide abstract]
  ABSTRACT: Insulin receptor substrate 2 (IRS2) plays a crucial role in the regulation of insulin signaling. Several polymorphisms of the gene encoding IRS2 have been identified. The variant causing Gly1057Asp substitution is relatively frequent in humans and its impact on insulin sensitivity seems to be dependent on age and body weight. The aim of our study was to evaluate the relationships between Gly1057Asp variant and insulin sensitivity assessed by HOMA, and adiposity evaluated by measurement of epicardial fat (EpiF) thickness in the elderly. We studied 87 subjects, 42 men and 45 women, mean age±SD: 74.23±7.24years. In the subjects carrying the Gly1057Asp variant of the IRS2 gene we found higher HOMA index values (3.40±1.14 vs. 2.21±1.25, p<0.001) and increased epicardial adipose tissue (11.77±1.65 vs. 10.43±1.93mm, p<0.001) compared to wild type subjects. Univariate linear regression analyses evidenced that HOMA index was correlated with BMI (beta=0.152, p<0.001), fasting plasma glucose (beta=0.018, p=0.002), LDL cholesterol (beta=0.008, p=0.024), total cholesterol (beta=0.007, p=0.039), weight (beta=0.054, p<0.001), presence of Gly1057Asp variant (beta=1.185, p<0.001) and EpiF thickness (beta=0.540, p<0.001). In multivariate analysis HOMA index was still associated with the presence of the Gly1057Asp variant of the IRS-2 gene (beta=0.568, p=0.002) and with EpiF thickness (beta=0.414, p<0.001). Furthermore, a statistically significant positive correlation between EpiF thickness and HOMA was found (r=0.773, p<0.001) and this was not different between wild type control subjects and carriers of Gly1057Asp variant of the IRS2 gene (p=0.718). Similar results were obtained in comparing subjects with normal fasting glucose levels. In conclusion, in our elderly subjects the presence of the allelic variant Gly1057Asp of IRS2 gene was associated to the degree of insulin resistance assessed by HOMA index and with EpiF thickness, independently from the extent of obesity, suggesting its contribution to global cardiometabolic risk.
  Experimental gerontology 09/2012; · 3.34 Impact Factor
• Article: A reliable and rapid tool for plasma quantification of 18 psychotropic drugs by ESI tandem mass spectrometry.

  Gennaro Vecchione, Bruno Casetta, Antonella Chiapparino, Alessandro Bertolino, Michela Tomaiuolo, Filomena Cappucci, Raffaella Gatta, Maurizio Margaglione, Elvira Grandone
  [show abstract] [hide abstract]
  ABSTRACT: A simple liquid chromatographic tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous analysis of 17 basic and one acid psychotropic drugs in human plasma. The method relies on a protein precipitation step for sample preparation and offers high sensitivity, wide linearity without interferences from endogenous matrix components. Chromatography was run on a reversed-phase column with an acetonitrile-H₂O mixture. The quantification of target compounds was performed in multiple reaction monitoring (MRM) and by switching the ionization polarity within the analytical run. A further sensitivity increase was obtained by implementing the functionality "scheduled multiple reaction monitoring" (sMRM) offered by the recent version of the software package managing the instrument. The overall injection interval was less than 5.5 min. Regression coefficients of the calibration curves and limits of quantification (LOQ) showed a good coverage of over-therapeutic, therapeutic and sub-therapeutic ranges. Recovery rates, measured as percentage of recovery of spiked plasma samples, were ≥ 94%. Precision and accuracy data have been satisfactory for a therapeutic drug monitoring (TDM) service as for managing plasma samples from patients receiving psycho-pharmacological treatment.
  Journal of pharmaceutical and biomedical analysis 04/2012; 67-68:104-13. · 2.45 Impact Factor
• Article: Hereditary protein C deficiency and thrombosis risk: genotype and phenotype relation in a large Italian family.

  Arturo Cafolla, Giovanna D'Andrea, Erminia Baldacci, Maurizio Margaglione, Maria Gabriella Mazzucconi, Robin Foà
  [show abstract] [hide abstract]
  ABSTRACT: Protein C (PC) deficiency is an autosomal dominant inherited disorder associated with spontaneous and recurrent thrombotic events. Factor V Leiden (FVL) increases the risk of thrombosis in PC-deficient type I families. We have investigated the relationship between PC deficiency genotype and clinical phenotype in a large four-degree Italian family followed since 1988. Methods: PC activity and antigen levels were quantified; sequencing of PC DNA was performed to identify polymorphism. FVL and factor II (G20210A) polymorphism were screened. Results: PC activity ranged from 5% to 9%, and PC antigen levels were 5,3% in two homozygous for PROC missense mutation Arg32Cys; PC activity ranged from 18% to 60% and antigen levels from 21% to 64%, respectively, in 11 heterozygous for Arg32Cys; PC activity was 99% and 120% in two wild type. Of 15, eight were heterozygous for FVL. The two subjects with PC < 6%, homozygous for Arg32Cys and heterozygous for FVL, suffered from thrombosis during childhood. Of 11, six subjects with PC deficiency and heterozygous for FVL showed the first thrombosis at an age between 21 and 54. None of the five PC-deficient subjects, who were wild type for FVL, showed thrombosis. Two subjects with PC > 70%, both heterozygous for FVL developed thrombosis in the presence of another risk factor. This study suggests that FVL and PROC mutations increase the risk of thrombosis in subjects with PC deficiency, which could be considered as a 'variable' risk factor. The thrombosis-prone PC-deficient families carry additional risk factors for thrombosis.
  European Journal Of Haematology 12/2011; 88(4):336-9. · 2.61 Impact Factor
• Article: The risk of occurrence of venous thrombosis: focus on protein Z.

  Valeria Bafunno, Rosa Santacroce, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984 characterized by an homology with other vitamin K-dependent factors. PZ acts as the cofactor of the PZ dependent inhibitor (ZPI), in the inhibition of activated factor X bound on phospholipid surface. In humans, PZ is characterized by an unusual wide distribution in plasma partly explained by a genetic control. Several PZ gene polymorphisms influencing plasma concentration have been described. In mice, the disruption of PZ gene is asymptomatic, but in association with homozygous FV Leiden produced a severe prothrombotic phenotype. This review analyzes the results obtained from different studies so far published in order to understand whether PZ deficiency could be considered as a risk factor for venous thrombosis. The roles of PZ plasma level and PZ gene polymorphisms remain debated with conflicting results. Many of these studies reported low PZ levels in association with an increased risk of venous thrombosis. On the other side, some studies did not observe an association between low levels of PZ and thrombotic events. A relationship between PZ deficiency and pregnancy complications was also described but not confirmed by all studies. These discrepancies can be explained by the heterogeneity of populations chosen as control, by the PZ interindividual variability and by the small size of the cohorts in mainly retrospective studies. Large prospective studies remain to be done to investigate its possible role in thrombosis.
  Thrombosis Research 08/2011; 128(6):508-15. · 2.44 Impact Factor
• Article: Fatal pulmonary thromboembolism. A retrospective autopsy study: searching for genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus.

  Vittorio Fineschi, Valeria Bafunno, Stefania Bello, Francesco De Stefano, Maurizio Margaglione, Margherita Neri, Irene Riezzo, Emanuela Turillazzi, Alessandro Bonsignore, Gennaro Vecchione, Francesco Ventura, Elvira Grandone
  [show abstract] [hide abstract]
  ABSTRACT: The accuracy of antemortem diagnosis of pulmonary embolism is within the range of just 10-30%, so representing one of the most frequent missed diagnosis in sudden, unexpected death. We describe 43 fatal cases of pulmonary embolism as confirmed by post-mortem examination. The aim of our study was to verify the systematic search for the most common genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus. As a whole, 41 patients (95.3%) had at least one risk factor. Pre-existing symptoms are described just before fatal embolism in 18 (41.9%) out 43 patients. In 18 out of 43 (41.9%) it was not possible to find the thrombotic site. In 24 out of the remaining 25 cases the involvement of the deep veins of one leg was shown; in 1 case the thrombus was localised in the inferior caval vein. 10 (41.7%) were iliac vein thromboses, 7 (29.1%) femoral, 2 (8.3%) popliteal, 3 (12.6%) posterior-tibial, 1 (4.1%) anterior-tibial and 1 (4.1%) peroneal vein thromboses. In our cohort of patients, 4 (10%) out of 40 cases carried the 20210A prothrombin gene variant in heterozygosis. One (2.5%) out of 40 carried the Factor V Leiden (G1691A) gene variant in heterozygosis. Patients carrying these gene variants in homozygosis or carrying both were not present in our case-series. We strongly underline the relevance of a complete methodological approach, integrating clinical data by means of autopsy findings and histological study. On the contrary, investigating common inherited thrombophilia is not warranted.
  Forensic science international 08/2011; 214(1-3):152-8. · 2.10 Impact Factor
• Article: Sex modulation of the occurrence of jak2 v617f mutation in patients with splanchnic venous thrombosis.

  Donatella Colaizzo, Giovanni Luca Tiscia, Valeria Bafunno, Lucio Amitrano, Patrizia Vergura, Maria Rosaria Lupone, Elvira Grandone, Maria Anna Guardascione, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: The JAK2 V617F mutation is an independent risk factor for MPN and SVT. Gender-related differences in MPN distribution have been reported and, recently, variability in the JAK2 V617F allele burden between sexes has been suggested. We wondered whether gender would modulate the role of the JAK2 V617F mutation as susceptibility risk factor for SVT. In 180 patients presenting with SVT, medical history was collected. The presence of the JAK2 V617F mutation and 46/1 haplotype was determined by polymerase chain reaction followed by TaqMan SNP genotyping assays. Among patients with SVT, 43 (23.9%; 95%-CI: 18.2-30.7) carried the JAK2 V617F mutation. The JAK2 V617F mutation was found more frequently in women (29/95: 30.5%; 95%-CI: 22.1-40.4) than in men (14/85: 16.5%; 95%-CI: 10.0-25.9; OR: 2.2; 95%-CI: 1.1-4.5). The distribution of 46/1 haplotype frequencies did not differ significantly between men and women. In women carrying the rs12343867 CC genotype, the frequency observed for the occurrence of the V617F mutation was significantly higher than that observed in those not carrying (60.0% [95% CI: 31.2-83.3] vs. 26.8% [95% CI: 18.4-37.4]; OR: 4.1; 95%-CI: 1.1-14.9). In men, a similar prevalence was found among carriers of the rs12343867 CC genotype (16.7% [95% CI: 3.5-46.0]) and in non carriers (16.4% [95% CI: 9.3-27.2]). The V617F allele burden was unrelated to clinical characteristics and significantly higher in carriers of the rs12343867 CC genotype. Present findings suggest that, in patients presenting with SVT, the JAK2 V617F mutation is frequently found in women and, possibly by interacting with the 46/1 haplotype, may represent a gender-related susceptibility allele for SVT.
  Thrombosis Research 04/2011; 128(3):233-6. · 2.44 Impact Factor
• Article: Increased warfarin consumption and residual fibrin turnover in thrombotic patients with primary antiphospholipid syndrome.

  Paul R J Ames, Maurizio Margaglione, Antonio Ciampa, Donatella Colaizzo, Felicetto Ferrara, Luigi Iannaccone, Vincenzobrancaccio
  [show abstract] [hide abstract]
  ABSTRACT: Anedoctal reports suggest that some thrombotic primary antiphospholipid antibody syndrome (PAPS) patients on oral anticoagulation require higher than average doses to achieve given targets international normalized ratios (INR). To test the hypothesis of relative warfarin resistance in thrombotic PAPS and the effect of baseline IgG anticardiolipin antibodies, the cytochrome CYP2C9 and the vitamin K epoxide reductase (VKORC1) haplotypes we compared weekly warfarin consumption of 40 TPAPS (mean age 44 ± 16years) with that of 65 thrombotic patients with inherited thrombophilia (IT) (mean age 52 ± 18) at similar target INR 2.0-3.0 followed up between January-1994 and January 2003. To investigate an involvement of the epoxidation pathway in this difference and to assess enhanced residual fibrin turnover decarboxylated prothrombin (PIVKA-II) and D-dimers (DD) were cross-sectionally investigated in the same patients between March and May 2008. CEX7 and VKORC1 polymorphisms explained 45.1% of the variability in warfarin consumption, whose age-adjusted mean weekly consumption was greater in PAPS than IT (27.62 vs 21.24 mg, p = 0.03). In PAPS baseline IgG aCL and VKORC1 predicted weekly warfarin consumption (p = 0.028 and p = 0.024). IgG β(2)GPI and warfarin dose independently predicted plasma PIVKA-II (p = 0.01 and p = 0.02). Age and sex adjusted DD was greater in PAPS than IT (132 ± 34 vs 83 ± 37 mg/dl, p = 0.03). Thrombotic PAPS exhibit a degree of warfarin resistance partly accounted by antiphospholipid antibodies and are in a state of enhanced fibrin turnover despite oral anticoagulation that might have implications for re-thrombosis and atherosclerosis.
  Thrombosis Research 03/2011; 127(6):595-9. · 2.44 Impact Factor
• Article: The spectrum of subclinical Best vitelliform macular dystrophy in subjects with mutations in BEST1 gene.

  Giuseppe Querques, Jennyfer Zerbib, Rossana Santacroce, Maurizio Margaglione, Nathalie Delphin, Lea Querques, Jean-Michel Rozet, Josseline Kaplan, Eric H Souied
  [show abstract] [hide abstract]
  ABSTRACT: To describe the morphologic and functional characteristics of subclinical Best vitelliform macular dystrophy (VMD) in subjects with mutation in the BEST1 gene. Best-corrected visual acuity (BCVA), funduscopic appearance, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), and electro-oculography (EOG) were assessed in 23 consecutive subjects from nine unrelated families with known mutations in the BEST1 gene (eight distinct BEST1 mutations). Six subjects were identified with BEST1 mutations (three male, three female; aged 8 to 30 years) without clinically detectable (subclinical) Best VMD (absence of both symptoms and funduscopic lesions). All six subjects showed 20/20 BCVA and normal FAF findings. In these 6 of 26 subjects from five different families, we found five distinct mutations in the BEST1 gene. In three (six eyes) out of these six subjects with BEST1 gene mutations (two families: p.G15D; p.A243V), SD-OCT showed overall normal findings. In the other three subjects (six eyes) with BEST1 gene mutations (three families: p.V9A; p.R92C; p.I230T), we found, on SD-OCT, a thicker and more reflective appearance of the layer between the retinal pigment epithelium and the interface of inner segments and outer segments of the photoreceptor (the Verhoeff's membrane). EOG showed a reduced light-peak:dark-trough ratio in 5 of 12 eyes. Changes on SD-OCT were present in the absence of EOG abnormalities (two of six eyes), and vice versa (one of six eyes). Subclinical Best VMD (absence of both symptoms and funduscopic lesions) in subjects with BEST1 mutation may vary from the absence of any morphologic and functional abnormalities to the presence of specific SD-OCT and EOG changes.
  Investigative ophthalmology & visual science 03/2011; 52(7):4678-84. · 3.43 Impact Factor
• Article: Gene polymorphisms and sport attitude in Italian athletes.

  Francesco Sessa, Massimiliano Chetta, Annamaria Petito, Mauro Franzetti, Valeria Bafunno, Daniela Pisanelli, Michelina Sarno, Salvatore Iuso, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: The aim of this study was to evaluate whether the distribution of polymorphisms in the ACE, ACTN3, NOS3, UCP2, and UCP3 genes, which has been reported to be correlated with different physiological parameters, played a role in sport performance. We focused on a cohort of 82 Italian athletes: first of all, athletes were divided according to type of sport: team (n=72) versus individual (n=10), and subsequently, according to the performance, into "power" sports (n=29; sprinters, short distance swimmers, and volleyball players) and "intermittent" sports (n=53; football, basketball, and hockey players). All the populations studied were in Hardy-Weinberg equilibrium for the following polymorphisms: ACE (I/D), ACTN3 (R577X), NOS3 (-786 T/C), UCP2 (A55V), and UCP3 (-55 C/T). We observed that the frequency of NOS3-786 T and UCP2 C alleles was higher among power athletes compared with controls (p=0.011 and p=0.012, respectively); these alleles were also overrepresented in individual athletes (p=0.02 and p=0.045, respectively), although a small sample was analyzed. The frequency of NOS3 298G allele was higher among power athletes compared with controls (p=0.015); these data remained suggestive after correction for multiple testing. We found a suggestive association between NOS3 (-786 T/C; G298A) and UCP2 (A55V) polymorphisms and power athletes, whereas no significant correlation was found with UCP3 (-55C/T), ACE (I/D), and ACTN3 (R577X) polymorphisms, in contrast to previous studies. Analysis of multiple performance-associated genetic polymorphisms needs further examination to explain the relationship between genetic background and potential success in sport performance.
  Genetic Testing and Molecular Biomarkers 01/2011; 15(4):285-90. · 1.11 Impact Factor
• Article: McKusick-Kaufman or Bardet-Biedl syndrome? A new borderline case in an Italian nonconsanguineous healthy family.

  Massimiliano Chetta, Nenad Bukvic, Valeria Bafunno, Michelina Sarno, Rosario Magaldi, Gianpaolo Grilli, Vincenzo Bertozzi, Francesco Perfetto, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: McKusick-Kaufman syndrome (MKS, OMIM #236700) is a rare syndrome inherited in an autosomal recessive pattern with a phenotypic triad comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP), and congenital cardiac disease (CHD). The syndrome is caused by mutations in the MKKS gene mapped onto chromosome 20p12 between D20S162 and D20S894 markers. Mutations in the same gene causes Bardet-Biedl-6 syndrome (BBS-6, OMIM #209900) inherited in an autosomal recessive pattern. BBS-6 comprises retinitis pigmentosa, polydactyly, obesity, mental retardation, renal and genital anomalies. HMC, CHD, and PAP defects can also occur in BBS-6, and there is a significant clinical overlap between MKS and BBS-6 in childhood. We describe a new borderline case of MKS and BBS syndrome and suggest insights for understanding correlation between MKKS gene mutations and clinical phenotype. Here, we report the results of molecular analysis of MKKS in a female proband born in an Italian nonconsanguineous healthy family that presents HMC and PAP. The mutational screening revealed the presence of two different heterozygous missense variants (p.242A>S in exon 3, p.339 I>V in exon 4) in the MKKS gene, and a nucleotide variation in 5'UTR region in exon 2 (-417 A>C).
  Indian Journal of Human Genetics 01/2011; 17(2):94-6.
• Article: Role of the M2 haplotype within the annexin A5 gene in the occurrence of pregnancy-related venous thromboembolism.

  Elvira Grandone, Giovanni Tiscia, Donatella Colaizzo, Elena Chinni, Daniela Pisanelli, Valeria Bafunno, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: Knowledge about risk factors for venous thromboembolism (VTE) is still limited. A recently found haplotype within the natural anticoagulant protein annexin A5 (ANXA5) exerts an important modulating effect on gene expression. Eighty-three nonanticoagulated patients with a documented pregnancy-related VTE and 195 controls were investigated. The presence of the ANXA5 haplotypes was determined. Twenty-seven patients (32.5%) carried the M2 haplotype. Among them, 17 (63.0%) had a history of VTE in puerperium and 10 (37.0%) during pregnancy. The prevalence of the M2 haplotype was different as compared with that recorded among controls (odds ratio, 2.7; 95% confidence interval, 1.5-4.9, P < .001). A logistic regression analysis, correcting for potential confounders (age at which the thrombotic event occurred, factor V Leiden, and factor IIA20210 variants) showed a significant increase (odds ratio, 3.4; 95% confidence interval, 1.7-6.7) of the occurrence of VTE in carriers of the M2 haplotype as compared with noncarriers. The M2 haplotype within the ANXA5 gene may represent a new thrombophilic risk factor for pregnancy-related VTE.
  American journal of obstetrics and gynecology 11/2010; 203(5):461.e1-5. · 3.28 Impact Factor
• Article: Genetic basis of thrombosis.

  Valeria Bafunno, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: Venous thrombosis (VT) represents a common and serious disorder that occurs as the result of clotting of the blood in the venous system and venous obstruction. Environmental risk factors and genetic predisposition play an important role in the development of thrombosis. It is therefore seen as a classic example of a complex common disease. We have focused on the role of genetic risk factors, primarily related to the hemostatic system, in triggering thrombotic events. Since the identification of antithrombin deficiency in 1965, major efforts have been made during the past 15 years to identify other genetic entities that lead to increased thrombotic risk. Results of early genetic studies demonstrated that two types of genetic defects cause VT: loss of function mutations in the natural anticoagulants antithrombin, protein C and protein S and gain of function mutations in procoagulant factors V (FV Leiden) and II (prothrombin G20210A). The high incidence of these mutations in Caucasians induced a shift from family studies to case-control association studies. Several investigations have been performed on the role of other candidate genetic risk factors predisposing to VT, including such variants in FXIII, FIX and fibrinogen genes. Moreover, the contribution of genetic variation in genes encoding less-well studied proteins that are part of the anticoagulant pathways has been evaluated. Recently, different genome-wide association studies have been performed in which several single nucleotide polymorphisms were investigated and related to the risk of VT. However, further studies are needed to identify additional genetic causes of thrombosis and to assess functional molecular mechanisms.
  Clinical Chemistry and Laboratory Medicine 10/2010; 48 Suppl 1:S41-51. · 2.15 Impact Factor
• Article: New TET2 gene mutations in patients with myeloproliferative neoplasms and splanchnic vein thrombosis.

  D Colaizzo, G L Tiscia, D Pisanelli, V Bafunno, L Amitrano, E Grandone, M A Guardascione, M Margaglione
  Journal of Thrombosis and Haemostasis 02/2010; 8(5):1142-4. · 5.73 Impact Factor
• Article: A platelet defect modulates bleeding in mild hemophilia: the tale of 2 brothers.

  Mario Lapecorella, Rosa Santacroce, Mariasanta Napolitano, Valeria Bafunno, Giovanni Favuzzi, Vittoria Longo, Elvira Grandone, Guglielmo Mariani, Maurizio Margaglione
  Clinical and Applied Thrombosis/Hemostasis 12/2009; 15(6):715-6. · 1.33 Impact Factor
• Article: Markers of haemostasis and angiogenesis in placentae from gestational vascular complications: impairment of mechanisms involved in maintaining intervillous blood flow.

  Elena Chinni, Donatella Colaizzo, Giovanni L Tiscia, Pasquale Martinelli, Giuseppe M Maruotti, Maria Matteo, Maurizio Margaglione, Elvira Grandone
  [show abstract] [hide abstract]
  ABSTRACT: Preeclampsia (PE) and fetal growth restriction (FGR) are multifactorial diseases, whose pathogenesis is largely unknown. A significant relationship between haemostasis and angiogenesis in placentae from uneventful pregnancies was previously shown. RNA expression of haemostasis (TF, TFPI, TFPI-2, PAI-2, Anx V, TM) and angiogenesis (Ang-1, Ang-2, PlGF, VEGF) markers in placentae from PE (n=12), PE+FGR (n=17) and FGR (n=20) in respect of placentae from uncomplicated pregnancies (n=21) were investigated. Placentae from complicated pregnancies showed a significant lower expression (p<or=0.05 Mann-Whitney U test) of TF, TFPI, TFPI-2, Anx V, PAI-2 than those from in uncomplicated ones. VEGF and PlGF were not different in the considered groups; Ang-1 and Ang-2 were significantly higher (p<or=0.05 Mann-Whitney U test) in the PE group. Correlations between factors involved in haemostasis and those involved in angiogenesis, observed in placentae from uneventful pregnancies are lacking in those from complicated ones. Haemostasis factors are reduced in placentae from complicated pregnancies. The relationship between haemostasis and angiogenesis observed in uncomplicated pregnancies is impaired in PE and FGR.
  Thrombosis Research 11/2009; 125(3):267-71. · 2.44 Impact Factor
• Article: Inherited platelet disorders: thrombocytopenias and thrombocytopathies.

  Giovanna D'Andrea, Massimiliano Chetta, Maurizio Margaglione
  Blood transfusion = Trasfusione del sangue 10/2009; 7(4):278-92. · 2.10 Impact Factor
• Article: Role of thrombophilia in adverse obstetric outcomes and their prevention using antithrombotic therapy.

  Elvira Grandone, Michela Tomaiuolo, Donatella Colaizzo, Paul R J Ames, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: A series of case-control studies in the last decade have shown the role of inherited thrombophilia in the occurrence of adverse obstetric outcomes. In small series of cases, it has been proven that rare inherited causes of thrombophilia such as natural anticoagulant deficiencies can be associated with fetal losses. The confirmed presence of antiphospholipid antibodies in plasma, representing an acquired thrombophilic condition, is also an established cause of fetal losses, although other studies with a smaller sample size have found an association with other obstetric complications, namely preeclampsia, fetal growth restriction, and abruption placentae. Case-control studies have been performed regarding the potential association between unexplained fetal losses and mild hyperhomocysteinemia. Although case-control and prospective studies are also available regarding hyperhomocysteinemia and other gestational vascular complications, published data are conflicting. Intervention studies have been performed to prevent adverse obstetric outcomes in women with inherited or acquired thrombophilia and previous adverse outcomes. There is much debate in the literature regarding the need for treatment of women with thrombophilia during pregnancy. Although in most cases these are not randomized controlled trials, all studies found significantly better outcomes in treated pregnancies compared with those of untreated pregnancies.
  Seminars in Thrombosis and Hemostasis 10/2009; 35(7):630-43. · 4.52 Impact Factor
• Article: Detection of new deletions in a group of Italian patients with Hemophilia A by multiplex ligation-dependent probe amplification.

  Rosa Santacroce, Vittoria Longo, Valeria Bafunno, Francesco Sessa, Massimiliano Chetta, Michelina Sarno, Nenad Bukvic, Giovanna D'Andrea, Michela Tomaiuolo, Maurizio Margaglione
  [show abstract] [hide abstract]
  ABSTRACT: Hemophilia A is an X-linked bleeding disorder caused by mutations widespread in the human coagulation F8 gene. Apart from common intrachromosomal translocations, most of the mutations in the F8 gene are detectable using genomic sequencing analysis. However, deletions of one or more exons or deletion encompassing the entire gene can go undetected, especially in heterozygous females. The multiplex ligation-dependent probe amplification is an efficient tool, new and fast, for discovering these rearrangements. In this study different deletions, which were detected using multiplex ligation-dependent probe amplification assay on 25 patients affected by severe hemophilia A, were classified as "mutation negative" by sequencing analysis. These data suggest that this screening could be systematically included in genetic screening of patients with Hemophilia A.
  Genetic Testing and Molecular Biomarkers 09/2009; 13(5):573-6. · 1.11 Impact Factor