Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis.Key words: ABO blood group, Factor V Leiden, venous thrombosis. Deep vein thrombosis (DVT) is one of the main clinical manifestations of venous thromboembolism (VTE). DVT is a multi-factorial disorder caused by genetic and/or acquired abnormalities of the hemostatic mechanism, resulting in hypercoagulation (Dahlbäck, 2003;Dahlbäck and Villoutrex, 2003). Hereditary thrombophilia is responsible for most cases of predisposition to VTE and the greatest prevalence is of a resistance to activated protein C (Svensson and Dahlbäck, 1994), caused in most cases by a point mutation in the gene of the coagulation factor V (FV), known as Factor V Leiden (FVL), FV: R506Q or FV: G1691A. (Bertina et al., 1994). FV is a plasma glycoprotein of 330 kDa, formed by 2196 amino acids and coded by a gene with 25 exons located in chromosome region 1q21-25 (Wang et al., 1988;Cripe et al., 1992). In its activated form (FVa), it participates in the prothrombinase complex of the coagulation cascade as an essential cofactor to factor Xa in thrombin genesis. FV is also a proteolytic target for activated protein C (APC), which exercises its anti-coagulant function by deactivating it. The deactivated FV and protein S act as co-factors of APC, deactivating the factor VIII (FVIII) molecule (Dahlbäck and Villoutrex, 2003). The R506Q mutation occurs in exon 10 of the FV gene and is characterized by a G ® A transition at nucleotide 1691, which results in a change from Arginine to Glutamine (Arg ® Gln) at position 506 in the amino acid sequence (Bertina et al., 1994). The main consequence of this mutation is the loss of one of the cleavage sites, which makes FVa partially resistant to the proteolytic degradation of APC. This flaw in the anticoagulation mechanism mainly results in high FVIII and trombin levels, thereby increasing the risk of VTE due to the installation of a state of hypercoagulability (Franco and Reitsma, 2001).The AB alleles of the ABO blood group, high FVIII levels and von Willebrand factor (vWF) have been associated to a risk of venous thrombosis (Jic...

ABSTRACT. In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.

As tromboses são eventos de etiopatogênese multifatorial resultantes da interação de fatores genéticos e ambientais, constituindo na atualidade uma das causas mais comuns de morbimortalidade. Uma mutação de ponto no fator V da coagulação, o fator V Leiden (FVL), constitui o defeito genético mais comum associado com trombofilia. No Brasil, o estudo deste fator de risco é relativamente recente e se dispõe de poucos dados na literatura especializada. Este trabalho teve como objetivo determinar a freqüência da mutação do fator V Leiden em 292 indivíduos sob investigação de trombofilia no Hemocentro de Pernambuco. A técnica molecular utilizada foi a RE/PCR (Enzima de Restrição/Reação em Cadeia da Polimerase), usando primers específicos e a enzima MnlI. A freqüência do FVL encontrada foi de 13,3%, sendo 36 heterozigotos e 3 homozigotos. A presença da mutação foi semelhante em indivíduos com idade tanto inferior quanto superior a 45 anos. Os resultados da pesquisa mostraram que a freqüência do FVL na população estudada é semelhante à descrita na literatura científica para indivíduos selecionados com tromboembolismo e confirmam a importância do estudo molecular nas diferentes faixas etárias.

Background The establishment of regional development poles in the State of Pernambuco, Brazil was characterized by industrial expansion and consequent concerns about the increase in the occurrence of diseases, specifically those having long latency periods, as is the case of Chronic Myeloid Leukemia. Methods The study included 367 patients diagnosed with Chronic Myeloid Leukemia over a ten-year period at a reference treatment center. Records of patient charts and the TerraView software were used, respectively, for data collection and geographic mapping of the cases from the twelve established State development regions. Results A total incidence of 3.4 cases per 100,000 inhabitants was found, with a predominance of the disease among males, a median age of 47 years, a mestizo ethnicity, with elementary schooling and residence in urban area. Microregional incidence varied, but there was no significant variation in numbers over the years, and no relevant socio-environmental determinants were identified. Conclusion The present study determined the incidence and characterized the spatial distribution of Chronic Myeloid Leukemia cases over a decade in a northeastern Brazilian state. The variation in the incidence rate by region of development is compatible with a homogeneous distribution of the cases. The work is a baseline study to be used for present and future analyses of the impact of the state economic development poles and the occurrence of this chronic malignant disease.

Introdução: A doença tromboembólica é bastante freqüente, com incidência anual na população de 1 caso por mil indivíduos. Os fatores de risco para trombose incluem condições hereditárias e adquiridas. Uma mutação de ponto no fator II da coagulação, a protrombina G20210A (PTCR), constitui o segundo defeito genético mais comum associado à predisposição para trombose ou trombofilia. No Brasil, o estudo desse fator de risco é relativamente recente e se dispõe de poucos dados na literatura especializada. Objetivo: Este trabalho teve como objetivo determinar a freqüência da PTCR em 285 indivíduos sob investigação de trombofilia na Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE/ PE). Material e método: A técnica molecular utilizada foi a enzima de restrição/reação em cadeia da polimerase (RE/PCR), com primers específicos e a enzima Hind III. Resultados: A freqüência encontrada da PTCR foi de 6% em heterozigose. A presença da mutação foi semelhante em indivíduos com idades tanto inferiores quanto superiores a 45 anos. Discussão: A presença da PTCR pode ter sido determinante para o surgimento dos quadros trombóticos, e a baixa mediana de idade do grupo estudado sugere que outras causas genéticas de trombofilia devem ser investigadas, pois a maioria dos trabalhos associa a presença de fator de risco genético a eventos trombóticos em indivíduos com idade inferior a 45 anos. Conclusões: Os resultados da pesquisa mostraram que a freqüência da PTCR na população estudada é semelhante à descrita na literatura científica para indivíduos selecionados com tromboembolismo e confirmam a importância do estudo molecular em diferentes faixas etárias. II, prothrombin G20210A (PTCR) abstract resumo Background: Thromboembolic disease is very common, with a yearly incidence in the general population of approximately 1 case per a thousand individuals. The risk factors for thrombosis include both hereditary and acquired conditions. A point mutation in coagulation factor

ObjectiveThis study investigated the occurrence of the p190 and p210 breakpoint cluster region-Abelson (BCR-ABL) rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival.MethodsForty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was employed to identify molecular rearrangements.ResultsAt diagnosis, the median age was 33 years, and there was a predominance of males (61%). The most common immunophenotype was B lineage (76%). BCR-ABL rearrangements was detected in 14 (34%) patients with the following distribution: p190 (28%), p210 (50%) and double positive (22%). Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44%) and positive BCR-ABL (28%).ConclusionThese results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

Dentre as doenças cardiovasculares, a trombose venosa (TV) destaca-se pela associação entre fatores de riscos adquiridos e fatores genéticos. A resistência hereditá-ria à proteína C ativada tem sido identificada como a principal causa dos casos de Artigo / Article REVISTA BRASILEIRA DE HEMATOLOGIA E H E M O T E R A P I A IntroduçãoMundialmente, as doenças trombóticas constituem um problema de saúde de origem multifatorial e multigênica. As tromboses são caracterizadas pela formação aguda de trombos em veias e artérias. Dentre as doenças cardiovasculares, a trombose venosa (TV) destaca-se pela associação entre fatores de riscos adquiridos, como imobilização prolongada, cirurgias, fraturas, gestação, etc, e fatores genéticos, mutações nos genes da proteína C, proteína S e antitrombina III. 1,2,3 A resistência hereditária à proteína C ativada (RPCA) tem sido identificada como a principal causa da maioria dos casos de trombose venosa, 95% dos casos de RPCA estão

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