Clinical, economical and safety impact of ferric carboxymaltose use in Patient Blood Management programme in Portuguese National Health Service hospitals.

Ferric carboxymaltose (FCM) can be used in Patient Blood Management (PBM) to promote the optimization of preoperative haemoglobin (Hb), which aims to minimise the use of allogeneic blood components and improve clinical outcomes, with better cost-effectiveness. This was an observational study conducted in a retrospective and multicentre cohort with adults from elective orthopaedic, cardiac and colorectal surgeries, treated according to local standards of PBM with allogeneic blood product transfusions (ABTs) on demand and with FCM to correct iron deficiency with or without anaemia. In this work, only the first pillar of the PBM model issue by Directorate-General for Health (DGS) was evaluated, which involves optimising Hb in the preoperative period with iron treatment if it's necessary/indicated. Before the implementation of PBM in Portugal, most patients did not undergo preoperative laboratory evaluation with blood count and iron kinetics. Therefore, the existence of Iron Deficiency Anaemia (IDA) or Iron Deficiency (ID) without anaemia was not early detected, and there was no possibility of treating these patients with iron in order to optimise their Hb and/or iron stores. Those patients ended up being treated with ABTs on demand. A total of 405 patients from seven hospitals were included; 108 (26.7%) underwent FCM preoperatively and 197 (48.6%) were transfused with ABTs on demand. In the FCM preoperative cohort, there was an increase in patients with normal preoperative Hb, from 14.4 to 45.7%, before and after FCM, respectively, a decrease from 31.7 to 9.6% in moderate anaemia and no cases of severe anaemia after FCM administration, while 7.7% of patients were severely anaemic before FCM treatment. There were significant differences (p < 0.001) before and after correction of preoperative anaemia and/or iron deficiency with FCM in Hb, serum ferritin and transferrin saturation rate (TS). In the ABT group, there were significant differences between pre- and postoperative Hb levels (p < 0.001). Hb values tended to decrease, with 44.1% of patients moving from mild anaemia before transfusion to moderate anaemia in the postoperative period. Concerning the length of hospital stay, the group administered with ABTs had a longer hospital stay (p < 0.001). Regarding the clinical outcomes of nosocomial infection and mortality, there was no evidence that the rate of infection or mortality differed in each group (p = 0.075 and p = 0.243, respectively). However, there were fewer nosocomial infections in the FCM group (11.9% versus 21.2%) and mortality was higher in the transfusion group (21.2% versus 4.2%). Economic analysis showed that FCM could reduce allogenic blood products consumption and the associated costs. The economic impact of using FCM was around 19%. The preoperative Hb value improved when FMC was used. Patients who received ABTs appeared to have a longer hospital stay. The FCM group reported fewer infections during hospitalisation. The economic results showed savings of around €1000 for each patient with FCM administration. The use of FCM as part of the PBM program had a positive impact on patients' outcomes and on economic results. However, it will be essential to perform studies with a larger sample to obtain more robust and specific results.

[Dabigatran Reversal: A Practical Approach]. / Reversão do Dabigatrano: Abordagem Prática.

Dabigatran is a direct oral anticoagulant used to prevent stroke and systemic embolism in patients with atrial fibrillation. In situations that require the urgent reversal of its anticoagulant activity, such as in the case of severe bleeding that is life-threatening; urgent/ emergent surgery or invasive procedures with significant bleeding risk; and the need for thrombolysis in a patient with ischemic stroke, several measures can be taken, including the use of its specific reversal agent, idarucizumab. Based on the guidelines for the use of reversal agents for oral anticoagulants, and on the clinical experience of reversal of dabigatran, a practical guide is presented for use in clinical situations where reversal of dabigatran anticoagulation is required, including the use of idarucizumab. The adoption of this type of guideline contributes to therapeutic optimization and, consequently, greater reversal efficiency and a better resource management.

O dabigatrano é um anticoagulante oral direto utilizado na prevenção do acidente vascular cerebral (AVC) e embolia sistémica em doentes com fibrilhação auricular. Em situações que implicam a reversão urgente da sua atividade anticoagulante, como em caso de hemorragia grave com risco de vida; cirurgia ou manobra invasiva urgente/ emergente com risco hemorrágico significativo; e necessidade de trombólise em doente com AVC isquémico, podem ser adotadas diversas medidas, nomeadamente o recurso ao seu agente de reversão específico, o idarucizumab. Com base nas orientações de utilização dos agentes de reversão dos anticoagulantes orais e na experiência clínica de reversão do dabigatrano, apresenta-se um guia prático de atuação em situações urgentes de necessidade de reversão da anticoagulação do dabigatrano, incluindo a utilização de idarucizumab. A adoção deste tipo de protocolos contribui para a otimização terapêutica e, consequentemente, uma reversão mais eficaz e uma melhor gestão dos recursos.

[Anemia in Chronic Kidney Disease: The State of the Art]. / Anemia da Doença Renal Crónica: O Estado da Arte.

The aging of the population has led to an increased prevalence of chronic diseases such as chronic kidney disease. Anemia is one of the most frequent complications of chronic kidney disease, with an impact not only on the quality of life but also on the patient's prognosis and associated costs. Knowledge in this therapeutic area has increased significantly: from the appearance of recombinant erythropoietin in 1989, through the use of increasing doses of parenteral iron and, more recently, to new molecules such as hypoxia-inducible factor inhibitors. The aim of this article is to present a pragmatic review of the state of the art in the epidemiology, pathophysiology, diagnosis and treatment of anemia associated with chronic kidney disease.

O envelhecimento populacional tem-se traduzido no aumento de prevalência de doenças crónicas como a doença renal crónica. A anemia é uma das complicações mais frequentes da doença renal crónica, com impacto não só na qualidade de vida como no prognóstico do doente e nos custos associados. O conhecimento nesta área terapêutica tem aumentado de forma significativa: desde o aparecimento da eritropoietina recombinante em 1989, passando pelo uso de doses crescentes de ferro parentérico e, mais recentemente, a novas moléculas como os inibidores do hypoxia-inducible factor. Os autores pretendem rever, de uma forma pragmática, o estado da arte da anemia associada à doença renal crónica, desde a epidemiologia, à fisiopatologia, ao diagnóstico e ao tratamento.

Improving Awareness about Patient Blood Management in Portugal: A Call for Action Arising from a Delphi Panel.

INTRODUCTION: Anaemia and iron deficiency are associated with increased mortality and poor surgical outcomes. Consensus in their definitions is expected to optimize their management, which is encompassed by patient blood management, providing patient-centred care while improving patient safety and clinical outcomes. Patient blood management implementation is even more relevant in contingency times and faces barriers due to lack of standardization, among others. The aim is to establish a consensus on these diagnoses and implement patient blood management principles in clinical practice in Portugal. MATERIAL AND METHODS: Eight experts in Transfusion Medicine, Haematology, Anaesthesiology, Internal Medicine, and Obstetrics/Gynaecology were assembled; a focus group was conducted, defining 33 statements. A Delphi panel was conducted, with experts from the clinical specialities named above as well as from General Surgery, Urology, and Orthopaedics. RESULTS: The Delphi panel's rounds had 70 (Round 1) and 46 (Round 2) respondents. Specialists were consensual in only two statements, on the existence of a preoperative patient blood management consultation for candidates to elective surgeries in which the use of blood derivatives is anticipated and, on the importance of the correction of postoperative anaemia and iron deficiency. Of the remaining 31 statements, 27 reached high agreement or disagreement by the respondents. CONCLUSION: Consensus was reached in only two (6%) of the 33 statements. There was a consensual agreement on the relevance of establishing patient blood management as the standard of care and of valuing preoperative and postoperative patient blood management interventions. Nevertheless, our results point to the lack of awareness regarding patient blood management principles - which could result in better postoperative outcomes, shorter hospitalizations, reduced costs and increased availability of beds. Training and literacy initiatives could help further implement patient blood management standards in Portuguese hospitals.

Introdução: A anemia e ferropenia estão associadas a um aumento da mortalidade e a piores resultados no período pós-operatório. Consensualizar as suas definições permitirá otimizar a sua gestão. O patient blood management engloba essa gestão, com relevo acrescido em situações de contingência, focado nos cuidados centrados no doente e na melhoria da segurança e dos outcomes. As barreiras à implementação de princípios patient blood management prendem-se, entre outras, com falta de padronização. Pretende--se estabelecer um consenso sobre estes diagnósticos e implementação de patient blood management na prática clínica em Portugal. Material e Métodos: Foram reunidos oito especialistas em Imuno-hemoterapia, Hematologia Clínica, Anestesiologia, Medicina Interna e Obstetrícia/ Ginecologia. Foi realizado um focus group, onde foram definidas 33 afirmações. Além disso, foi realizado um painel Delphi, com especialistas das áreas mencionadas acima, assim como de Cirurgia Geral, Urologia e Ortopedia. Resultados: As duas rondas do painel Delphi tiveram, respetivamente, 70 e 46 respondedores. Estes foram consensuais em apenas duas afirmações, na existência de consulta pré-operatória de patient blood management para os candidatos a cirurgias eletivas em que se antecipa o uso de hemoderivados e, na importância da correção da anemia e ferropenia pós-operatórias. Das 31 afirmações restantes, 27 atingiram alta concordância ou discordância pelos respondentes. Conclusão: Foi alcançado consenso em apenas duas (6%) das 33 afirmações. Houve consenso sobre a relevância de estabelecer o patient blood management como standard of care e a valorização das intervenções de patient blood management pré e pós-operatórias. No entanto, os resultados indiciam falta de consciencialização sobre os princípios de patient blood management ­ que poderiam levar a melhores resultados pós-operatórios, com redução do tempo de hospitalização e dos custos e maior disponibilidade de camas. Iniciativas de formação e literacia poderiam ajudar a uma melhor implementação dos princípios de patient blood management nos hospitais portugueses.

Correction to the article "Viscoelastic Tests in the Evaluation of Haemostatic Disorders in SARS-CoV-2 Infection", Published on Acta Med Port 2021 Jan;34(1):35-46.

On page 36, in the fifth sentence of right-side column, where it reads: "Direct thrombin inhibitors (DTI) (argatroban, bivalirrubin) are used in COVID-19 infected patients with significantly lower antithrombin levels,24 or if heparin induced thrombocytopenia (HIT) occurs."It should read: "Direct thrombin inhibitors (DTI) (argatroban, bivalirudin) are used in COVID-19 infected patients with significantly lower antithrombin levels,24 or if heparin induced thrombocytopenia (HIT) occurs."Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/14784.

Viscoelastic Tests in the Evaluation of Haemostasis Disturbances in SARS-CoV2 Infection.

COVID-19 associated coagulopathy is a dysfunction of severe SARS-CoV-2 infection, characterized by significantly increased fibrinogen, D-dimer and C reactive protein and normal to near-normal prothrombin time, activated partial thromboplastin time and platelet count. Hypercoagulopathy and hypofibrinolysis coexist and are detected by viscoelastic tests. These features, when associated with immobilization and intrinsic risk factors (age, obesity, comorbidities, drugs) of the patient, can trigger thromboembolic events, despite thromboprophylaxis. The lungs are the first and most severely damaged organ. To date, most patients have exhibited hypercoagulability on viscoelastic tests not detected by standard coagulation tests. A high rate of thrombotic events was reported, suggesting that it should be considered as a cause of clinical deterioration in intensive care and potentially other clinical settings. In advanced stage, COVID-19 associated coagulopathy, fibrinogen and platelet count can decrease significantly, depending on the severity of clinical status resembling consumptive coagulopathy. In this stage, bleeding events can occur, especially if the patient is under extracorporeal membrane oxygenation (ECMO). Viscoelastic tests are very useful tools to assess hypercoagulability and hypofibrinolysis (not detectable by standard coagulation tests) in critically ill SARS-CoV-2 patients with COVID-19 associated coagulopathy and look like very promising tools for anticoagulation management. However, further research needs to be carried out to determine whether abnormal viscoelastic tests alone or in combination with other clinical or laboratory findings can identify patients at increased thrombotic risk. Clinical trials to evaluate hypercoagulability using viscoelastic tests and the need for personalized dosage of anticoagulation in SARS-CoV-2 patientsare quickly emerging.

A coagulopatia associada à COVID-19 é uma disfunção associada à infeção SARS-CoV-2 grave, caraterizada por aumento significativo do fibrinogénio, D-dímeros e Proteína C reativa, e por valores normais/muito pouco alterados do tempo de protrombina, tempo de tromboplastina parcial ativado, e número de plaquetas. A hipercoagulabilidade e a hipofibrinólise coexistem e são detetadas por testes viscoelásticos. Quando associadas à imobilização e aos fatores de risco intrínsecos do doente (idade, obesidade, comorbilidades, drogas) potenciam eventos tromboembólicos, apesar da tromboprofilaxia. Os pulmões são o órgão inicialmente e mais gravemente afetado. Até à data, a maioria dos doentes apresentou hipercoagulabilidade nos testes viscoelásticos, não detetada pelos testes de coagulação de rotina, e foi reportada uma elevada taxa de eventos trombóticos, sugerindo que esta deveria ser considerada uma das causas de deterioração clínica, não só em cuidados intensivos. Na coagulopatia associada à COVID-19 avançada, o número de plaquetas e o fibrinogénio podem diminuir significativamente, dependendo da gravidade clínica da infeção, assemelhando-se o quadro a uma coagulopatia de consumo. Nesta fase pode haver hemorragia, especialmente se o doente estiver sob extracorporeal membrane oxygenation. Os testes viscoelásticos afiguram-se muito úteis para avaliar a hipercoagulabilidade e a hipofibrinólise em doentes críticos SARS-CoV-2 com coagulopatia associada à COVID-19, parecendo também promissores para a gestão da anticoagulação. No entanto, é necessária mais investigação para determinar se testes viscoelásticos alterados, individualmente ou quando combinadoscom outros resultados clínicos/laboratoriais, podem identificar os doentes com risco trombótico acrescido. Estão a emergir rapidamente ensaios clínicos para avaliação da hipercoagulabilidade por testes viscoelásticos e da necessidade de personalização da anticoagulação em doentes SARS-CoV-2.

Screening for Anemia and Iron Deficiency in the Adult Portuguese Population.

Anemia and iron deficiency (ID) can impair quality of life and socioeconomic development. We evaluated the prevalence of anemia and ID in the adult Portuguese population in real-life contexts by gender, age, and pregnancy status. We performed a cross-sectional screening in adult individuals in mainland Portugal from 2013 to 2017. Participants completed a survey about demographics and signs or symptoms compatible with anemia, and ID and hemoglobin and ferritin concentrations were determined by point-of-care tests. We estimated and compared prevalence ratios (PR) of anemia and ID using Poisson regression with robust variance and the Wald chi-square test. We collected data from 11,030 individuals (26% men, 64% nonpregnant women, and 10% pregnant women). We found anemia in 51.8% (95% CI 50.1-53.4%) of nonpregnant women in fertile age, 46.6% (95% CI 44.7-48.6%) of nonpregnant women >51 years, 38.2% (95% CI 35.4-41.1%) of pregnant women, and 33.3% (95% CI 31.6-35.1%) of men. The prevalence of ID was 72.9% (95% CI 71.4-74.4%) in nonpregnant women in fertile age, 50.5% (95% CI 48.5-52.4%) in nonpregnant women >51 years, 94.8% (95% CI 93.3-96.0%) in pregnant women, and 28.9% (95% CI 27.3-30.6%) in men. We found significant associations between the prevalence of anemia or ID and nonpregnant women (PR: 1.50, 95% CI 1.42-1.59 or PR: 2.21, 95% CI 2.09-2.35, respectively), manifestation of signs or symptoms (PR: 1.19, 95% CI 1.53-1.23 or PR: 1.22, 95% CI 1.18-1.26), pregnant women (PR: 0.74, 95% CI 0.68-0.80 or PR: 1.30, 95% CI 1.27-1.33), and nonpregnant women ≤51 years (PR: 1.11, 95% CI 1.06-1.17 or PR: 1.42, 95% CI 1.36-1.48). In conclusion, anemia and ID represent moderate to severe public health problems, particularly among women in fertile age and in 3rd trimester, of pregnancy emphasizing the need to raise the public and health professionals' awareness of these problems and their prevention, diagnosis, and treatment.

Portal Vein Thrombosis Secondary to Occult Polycythemia Vera.

Portal vein thrombosis (PVT) is an uncommon finding in patients without cirrhosis. The underlying x\aetiology is challenging and the condition has a wide differential diagnosis. We present a case of PVT in an anaemic patient with chronic iron and folic acid deficiency masking underlying polycythemia vera (PV). Only a careful review of the patient's clinical history allowed the identification of a short period of laboratory erythrocytosis, 6 months before the clinical onset of PVT, while the patient was on iron and folic acid supplementation. The finding raised clinical suspicion of PV previously masked by iron deficiency anaemia. Subsequent investigation confirmed the presence of the JAK2 V617F mutation and, ultimately, showed that the patient met all diagnostic criteria for PV. Myeloproliferative disorders (MPD) are associated with systemic prothrombotic states. PV is distinguished clinically from other MPD by the presence of increased red blood cell mass. Moreover, patients with abnormal haematocrit values in the pre-JAK2 V617F era may have had occult or latent PV. Diagnosis confirmation requires a combination of major and minor criteria to capture occasional cases of occult PV. This case emphasizes the importance of always considering MPD in the aetiological investigation of PVT, even in patients who apparently do not fulfil the diagnostic criteria. LEARNING POINTS: We describe a rare gastroenterological presentation of a haematological condition, which provided an unexpected diagnosis.Myeloproliferative disorders should always be considered in the investigation of portal vein thrombosis.

Corrigendum to "Efficacy and Tolerability of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency at a Hospital Outpatient Clinic: A Retrospective Cohort Study of Real-World Clinical Practice".

[This corrects the article DOI: 10.1155/2017/3106890.].

Efficacy and Tolerability of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency at a Hospital Outpatient Clinic: A Retrospective Cohort Study of Real-World Clinical Practice.

Ferric carboxymaltose (FCM) is an intravenous iron formulation to correct iron deficiency. Although its use has been extensively studied in clinical trials, real-world evidence regarding FCM treatment is scarce. Our aim was to evaluate the efficacy and tolerability of FCM treatment in patients with iron deficiency, with or without anemia, at a hospital outpatient clinic. Data was collected retrospectively from medical records. During this 2-year study, 459 patients were included. Mean age was 58.6 ± 17.5 years and most patients received cumulative FCM doses of 501-1000 mg (63.2%). Six weeks after administration of FCM, efficacy endpoints hemoglobin increase ≥2 g/dL, hemoglobin increase ≥3 g/dL, and transferrin saturation > 20% were attained by 41%, 20%, and 63% of patients, respectively. Patients who received higher FCM doses showed significant reduced odds of not achieving hemoglobin increase ≥2 g/dL (501-1000 mg, adjusted odds ratio [OR]: 0.34, 95% confidence interval [CI] 0.18-0.62; 1001-3000 mg, OR: 0.19, 95% CI 0.07-0.49), compared to 500 mg doses. Treatment-emergent adverse events were documented in <4% of patients. In conclusion, FCM treatment was effective and well-tolerated by outpatients with iron deficiency at a hospital clinic, and its dosage should be adjusted to improve iron deficiency management in clinical practice.

Prevalence of anemia and iron deficiency in older Portuguese adults: An EMPIRE substudy.

AIM: The present study aimed to characterize the prevalence of anemia and iron deficiency in older Portuguese adults, and to compare it with the prevalence in younger individuals. METHODS: A population-based, cross-sectional study (EMPIRE study) enrolling a representative sample of 6267 adults aged <65 years and 1617 adults aged ≥65 years was carried out. Hemoglobin, ferritin, creatinine and C-reactive protein levels were measured by Point-of-Care tests. RESULTS: Anemia was more prevalent (P < 0.001) in participants aged ≥80 years (31.4%) compared with participants aged <65 years (19.6%) and 65-79 years (17.3%). At a 30-ng/mL ferritin cut-off, iron deficiency was more prevalent in participants aged ≥80 years (42.8%) compared with participants aged <65 years (31.5%) and 65-79 years (30.2%). Alternative ferritin cut-offs showed overall similar patterns. Anemia and iron deficiency were significantly more prevalent in older individuals who self-reported heart failure, coronary heart disease and gastritis. Anemia was more prevalent in participants aged <65 years in the north of Portugal and participants aged ≥65 years in central Portugal, following the prevalence of iron deficiency in the regions. In all regions, anemia was more prevalent in participants aged ≥80 years (reaching 39.0% in Lisbon and Tagus Valley, and 51.0% in the south). CONCLUSIONS: Anemia and iron deficiency are highly prevalent in older Portuguese adults, particularly among those aged ≥80 years. Better diagnosis, prevention and treatment strategies should be implemented taking into account the outstanding role of iron deficiency in older Portuguese adults, the differences between regions and the intrinsic characteristics of this population. Geriatr Gerontol Int 2017; 17: 1814-1822.