Manuel Campos

Clínicas de anticoagulação, situação actual e perspectivas futuras

Resumo Existem varias modalidades de monitorizacao da terapeutica anticoagulante oral, nomeadamente: monitorizacao a nivel hospitalar efectuada por medico especialista, monitorizacao a nivel de cuidados de saude primarios efectuada por medico de medicina geral e familiar, monitorizacao a nivel de laboratorios de analises privados, monitorizacao efectuada pelo proprio doente em aparelhos de point-of-care. Em Portugal, a modalidade mais frequente continua a ser a monitorizacao a nivel hospitalar/clinicas de anticoagulacao, embora a monitorizacao a nivel de cuidados de saude primarios/cuidados medicos de rotina, tenha comecado a ser implementada em algumas zonas do pais desde ha cerca de 5 anos. As clinicas de anticoagulacao constituem ainda na actualidade uma das organizacoes que melhor optimizam o seguimento clinico e laboratorial dos doentes anticoagulados com varfarina. A avaliacao da qualidade do controlo anticoagulante foi avaliada, em 2011, atraves da determinacao da proporcao de RNIs dentro do intervalo terapeutico. Nesta avaliacao procedeu-se a analise de doentes em regime de ambulatorio, durante 2 meses, o que correspondeu a 1.067 controlos de 687 doentes (media de idades dos doentes: 69xa0±xa013 anos, 54%, nxa0=xa0576 do sexo feminino). 71% (nxa0=xa0756) dos controlos estavam dentro do intervalo terapeutico. Fora do intervalo terapeutico encontraram-se 27% (nxa0=xa0287) controlos, apos exclusao dos doentes com cirurgia ou procedimentos invasivos programados. Abaixo do intervalo terapeutico encontravam-se 13,8% (nxa0=xa0148), sendo que 8,6% (nxa0=xa092) apresentavam RNI ≤ 1,5. Acima do intervalo terapeutico encontravam-se 13,2% (nxa0=xa0139) e destes 4,4% (nxa0=xa046) apresentavam RNI entre 5 e 8 e 0,3% (nxa0=xa04) RNI ≥ 8. O ACES do Baixo Tâmega procedeu, igualmente em 2011, a avaliacao da qualidade do controlo anticoagulante atraves da determinacao da proporcao de RNIs dentro do intervalo terapeutico. Os resultados dessa avaliacao sao semelhantes aos encontrados na clinica de anticoagulacao do Hospital de Santo Antonio - CHP, o que mostra que a monitorizacao a nivel de cuidados de saude de rotina pode ter igual qualidade a da das clinicas de anticoagulacao. O aparecimento de novos anticoagulantes orais, dispensando a monitorizacao laboratorial constitui um desafio, nao havendo ainda em Portugal experiencia para responder a questao se as clinicas de anticoagulacao serao fundamentais para o registo dos doentes, avaliacao de risco hemorragico, seguimento clinico ou avaliacao da adesao a terapeutica.

Circulating endothelial cells in patients with venous thromboembolism and myeloproliferative neoplasms.

Background Circulating endothelial cells (CEC) may be a biomarker of vascular injury and pro-thrombotic tendency, while circulating endothelial progenitor cells (CEP) may be an indicator for angiogenesis and vascular remodelling. However, there is not a universally accepted standardized protocol to identify and quantify these cells and its clinical relevancy remains to be established. Objectives To quantify CEC and CEP in patients with venous thromboembolism (VTE) and with myeloproliferative neoplasms (MPN), to characterize the CEC for the expression of activation (CD54, CD62E) and procoagulant (CD142) markers and to investigate whether they correlate with other clinical and laboratory data. Patients and Methods Sixteen patients with VTE, 17 patients with MPN and 20 healthy individuals were studied. The CEC and CEP were quantified and characterized in the blood using flow cytometry, and the demographic, clinical and laboratory data were obtained from hospital records. Results We found the CEC counts were higher in both patient groups as compared to controls, whereas increased numbers of CEP were found only in patients with MPN. In addition, all disease groups had higher numbers of CD62E+ CEC as compared to controls, whereas only patients with VTE had increased numbers of CD142+ and CD54+ CEC. Moreover, the numbers of total and CD62+ CEC correlated positively with the white blood cells (WBC) counts in both groups of patients, while the numbers of CEP correlated positively with the WBC counts only in patients with MPN. In addition, in patients with VTE a positive correlation was found between the numbers of CD54+ CEC and the antithrombin levels, as well as between the CD142+ CEC counts and the number of thrombotic events. Conclusions Our study suggests that CEC counts may reveal endothelial injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes depending on the disease status.

Soluble endothelial cell molecules and circulating endothelial cells in patients with venous thromboembolism

&NA; To evaluate the plasma levels of soluble endothelial cell molecules in patients with venous thromboembolism (VTE) out of the acute phase as compared with healthy individuals. We also investigated the possible associations of the soluble endothelial cell molecules among them, as well as with other clinical and laboratory data, including the numbers of circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP), and CEC expressing activation-related [cluster of differentiation (CD)54 and CD62E] and procoagulant (CD142) markers. In total, 15 patients with VTE and 20 normal individuals were studied. The CEC and CEP were quantified and characterized by flow cytometry. The soluble molecules studied included P-selectin, E-selectin, intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1 and tissue factor (ELISA), and von Willebrand factor antigen (immunoturbidimetry). VTE patients had significantly higher levels of vascular cell adhesion molecule 1 and von Willebrand factor antigen and lower levels of soluble E-selectin than controls. They also showed significantly higher numbers of CEC, as of activated/procoagulant CEC and lower numbers of CEP, compared with controls. We did not find any correlation between the levels of soluble molecules and the numbers of endothelial cell in circulation, but there was with several clinical and laboratory data in VTE patients. Our results would suggest that in VTE patients, the endothelium remains activated and in some hypercoagulable state. The levels of soluble endothelial cell molecules did not seem to be directly related to the numbers of CEC and CEP neither reflected the number of activated CEC, which may be because of the different function that surface and soluble molecules may have.

Advances in the genotyping of thrombosis genetic risk factors: clinical and laboratory implications

Since FV-Leiden polymorphism was first described in 1994, a growing number of polymorphic loci have been identified in association with increased genetic risk for thrombophilia. Often however, these risk factors have been studied in isolation of the remaining known phenotype linked polymorphisms. This fact has, at least in part, been justified by the laborious techniques traditionally used in the genotyping studies, as well as its relatively high costs. Another major problem concerning these studies has been the non-negligible incidence of dubious genotypes, resulting from the manual, labour intensive techniques applied, and their sometimes difficult to read outputs. These difficulties have also hampered the widespread use of genotyping data in the clinical assessment of the genetic risk levels both in patients and their relatives, leaving some clinicians less than convinced about its clinical usefulness. Recently however, the introduction of new genetic techniques in the clinical genetics laboratory has started to change this picture. Most notably, the advent of Real-time-PCR has brought the possibility of genotyping patients and controls at a large scale, with increased specificity, automation and speed. Moreover, the use of these techniques in the clinical genetics setting has not only increased the quality of the results, but most importantly has also increased our capability of answering questions at a deeper level. Among the new questions that can now be answered without increased costs and uncertainty is the study of the association of genetic risk factors in thrombophilia. Our results show that indeed even common polymorphic loci may increase our ability to further discriminate the genetic thrombosis risk of individual patients and relatives. It must however be noted that the innovation level in the clinical genetics lab is just starting to grow. In fact we havent even started to experience the advantages brought about by the genome program, and its massive identification of SNPs. The technology to test these is also presently being refined, and is expected to go from research to the clinical lab in the near future. Only then, can we expect to define with high certainty the combined genetic risks for such complex pathologies as the thrombophilias.