ALBERT

Description: Introduction: Anaemia is a common finding in general practice, with a prevalence rising from about 5% in the age group 50-64 years to over 20% in the age group 85+ years. Anaemia has been associated with increased all-cause mortality in a general practice population. However, only the influence of the four main causes of anaemia (anaemia of chronic disease, nutrient deficiency, renal anaemia and unknown anaemia) on mortality has been analysed. We prospectively studied the influence of a wide range of causes of anaemia on mortality, including less prevalent causes such as folic acid deficiency and haemolysis. In addition, we calculated the standardized mortality ratio for men and women per five-year age group to determine up to which age anaemia continues to exert a negative influence on mortality. Methods: Between the 1st of February 2007 and the 1st of February 2014, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia (i.e. no anaemia the preceding two years) were included in the study. Anaemia was defined as a haemoglobin level below 13.7 g/dL (8.5 mmol/L, men) and below 12.1 g/dL (7.5 mmol/L, women). A wide range of laboratory parameters was established for each patient. Based on the laboratory results, two independent experts determined the cause or causes of anaemia. Patients were followed until either their deaths or until the 1st of September 2014, at which moment they were censored at the last date they were documented as alive in the hospital or laboratory information system. Mortality risk of the overall Dutch population in the year 2010 was extracted from Statistics Netherlands, which collects all population statistics in the Netherlands, and compared to the mortality risk of the anaemic cohort. Results: A total of 2929 patients were included in the study, 1428 men (median age 72 years, range 50-101) and 1501 women (median age 77 years, range 50-103). Among the patients presenting with a single cause of anaemia, anaemia of chronic disease was found 848 times (29.0%), haemoglobinopathy 18 times (0.6%), haemolysis 10 times (0.3%), possible bone marrow disease 42 times (1.4%), other causes 64 times (2.2%) and renal anaemia 290 times (9.9%). Iron deficiency was found 499 times (17.0%), vitamin B12 deficiency 61 times (2.1%) and folic acid deficiency 11 times (0.4%). A total of 260 patients (8.9%) presented with multiple causes while the cause remained unknown in 826 patients (28.2%). A Cox proportional hazards model was used to assess the influence of the different causes of anaemia on mortality, correcting for age, gender and severity of anaemia. Patients presenting with an unknown cause were used as the reference group. We found significant hazard ratios for the following causes: anaemia of chronic disease (HR = 2.1 95% CI 1.64-2.70, P 〈 0.001), possible bone marrow disease (HR = 3.08 95% CI 1.72-5.52, P 〈 0.001), folic acid deficiency (HR = 6.89 95% CI 2.79-17.04, P 〈 0.001), renal anaemia (HR = 2.15 95% CI 1.61-2.87, P 〈 0.001) and multiple causes (HR = 2.31 95% CI 1.69-3.16, P 〈 0.001). The mortality risk of the anaemic general practice population was compared to the mortality risk of the overall Dutch population. Statistically significant standardized mortality ratios were observed for both men (M) and women (W) in the age groups 50-54 years (M:5.01, and W:5.30), 60-64 years (M:4.32, and W:3.57), 70-74 years (M:1.96, and W:2.04), 75-79 years (M:1.69, and W:2.09) and 80-84 years (M:1.34, and W:1.50). In addition, significant ratios were observed for men in the age groups 55-59 years (4.40) and 65-69 years (2.91). From age group 85-89 years and up, no significant effect of all-cause anaemia on mortality was found. Conclusion: Anaemia of chronic disease, possible bone marrow disease, folic acid deficiency, renal anaemia and presenting with multiple causes of anaemia are associated with a higher mortality. An increased standardized mortality ratio was demonstrated until the age of 85 years. The ratio showed a linear decrease with age. Above 85 years no increased mortality risk for patients with all-cause anaemia was found. Disclosures Sonneveld: Janssen-Cilag, Celgene, Onyx, Karyopharm: Honoraria, Research Funding; novartis: Honoraria.

Description: Introduction: Anaemia is a common finding in the elderly population and for many years it was assumed to be a normal consequence of aging. Recently, anaemia has been shown to be associated with increased mortality and morbidity and decreased quality of life. The prevalence of anaemia increases with age, starting with a prevalence of 4.4% in men and 6.8% in women in the age group 50-64 years and rising to a prevalence of 26.1% in men and 20.1% in women in the age group 85 years and older. Despite this high prevalence and the significance of anaemia, information on the causes of anaemia in general practice is limited. A large prospective cohort study with general practice patients newly diagnosed with anaemia was set up to increase knowledge regarding the causes of anaemia and improve quality of care for anaemia patients. Methods: Between the 1st of February 2007 and the 1st of February 2013 patients presenting to one of the 63 participating general practitioners with a newly diagnosed anaemia (i.e. no anaemia in the preceding two years) were included in the study, resulting in a population-based registry. Anaemia was defined as haemoglobin level below 13.7 g/dL (men) and below 12.1 g/dL (women). Men were included from age 18 and women were included when 50 years or older to prevent an overabundance of iron deficiency due to hypermenorrhea as a cause of the anaemia. The follow-up period ended on the 1st of September 2013. A wide range of parameters was analysed for each patient to aid diagnosis. Two experts independently reviewed the laboratory results of all patients and established the underlying cause of anaemia. In case of discordance, the experts deliberated until a consensus was reached. The survival in months after entry into the study was determined per gender and per class of anaemia (microcytic, normocytic or macrocytic). Results: A total number of 2738 patients were included in the study, 1463 men (average age at entry 66.8 years) and 1275 women (average age at entry 75.1 years). Of these 2738 patients, 242 presented with two or more causes for their anaemia. Anaemia of chronic disease was established in 910 patients (30.3%), haemoglobinopathy in 23 patients (0.8%), renal anaemia in 342 patients (11.4%), haemolysis in 18 patients (0.6%) and possible bone marrow disease in 117 patients (3.9%). Iron deficiency was established in 563 patients (18.7%), vitamin B12 deficiency in 123 patients (4.1%) and folic acid deficiency in 24 patients (0.8%). Other causes were established in 117 patients (3.9%). If no cause could be established it was classified as unknown, which was found in 768 patients (25.6%). The distribution of these causes in the microcytic, normocytic and macrocytic cohort is presented in Table 1. Overall survival of the cohort was 66.2 months (95% CI 65.2-67.3) after entry into the study. Men demonstrated an overall survival of 66.5 months (95% CI 65.1-67.9) and women a survival of 65.2 months (95% CI 63.6-66.7) (p = 0.637). The survival of patients with microcytic, normocytic and macrocytic anaemia was 65.5 (95% CI 62.6-68.4), 66.9 (95% CI 65.7-68.0) and 57.9 (95% CI 53.4-62.5) months respectively. The survival of both microcytic and normocytic patients was significantly longer than the survival of patients with a macrocytic anaemia (p = 0.005 and p 〈 0.001 respectively). Analysis of the different causes and their influence on survival will be presented. Conclusion: An extensive cohort of 2738 general practice patients newly diagnosed with anaemia was set up, resulting in a detailed study of the prevalence of a broad range of causes of anaemia and of the factors influencing survival of this group of patients. Table 1 Distribution of causes in the microcytic, normocytic and macrocytic cohorts Cause Microcytic anaemia Normocytic anaemia Macrocytic anaemia Total Anaemia of chronic disease 30 (9.0%) 839 (33.9%) 41 (20.7%) 910 (30.3%) Haemoglobinopathy 22 (6.6%) 1 (0.0%) 0 (0.0%) 23 (0.8%) Haemolysis 1 (0.3%) 10 (0.4%) 7 (3.5%) 18 (0.6%) Possible bone marrow disease 9 (2.7%) 90 (3.6%) 18 (9.1%) 117 (3.9%) Iron deficiency 215 (64.8%) 344 (13.9%) 4 (2.0%) 563 (18.7%) Vitamin B12 deficiency 11 (3.3%) 85 (3.4%) 27 (13.6%) 123 (4.1%) Folic acid deficiency 3 (0.9%) 11 (0.4%) 10 (5.1%) 24 (0.8%) Renal anaemia 14 (4.2%) 298 (12.0%) 30 (15.2%) 342 (11.4%) Other 6 (1.8%) 79 (3.2%) 32 (16.2%) 117 (3.9%) Unknown 21 (6.3%) 718 (29.0%) 29 (14.6%) 768 (25.6%) Total 332 (100%) 2475 (100%) 198 (100%) 3005 (100%) Disclosures Sonneveld: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Millenium: Honoraria, Research Funding.

Description: Introduction Macrocytic anaemia (MCV ≥ 100 fl) is regularly encountered in general practice and in hospital settings. However, the incidence of macrocytic anaemia in newly diagnosed patients remains elusive. In addition, factors influencing laboratory diagnosis and prognosis are unclear. PAGAS (Project of Anaemia from the General practitioner to the Albert Schweitzer hospital) is a collaboration of 63 general practitioners and the Albert Schweitzer hospital (Dordrecht, the Netherlands), which aims at improving quality of care for anaemic patients. We set out to clarify the incidence of newly discovered macrocytic anaemia in the PAGAS cohort and to determine the underlying causes of macrocytic anaemia. Methods Anaemia was defined as a haemoglobin level below 13.7 g/dL for men and below 12.1 g/dL for women. These values were used for persons older than 16 years. Patients who were included in the PAGAS study had to present to their general practitioner with a newly diagnosed anaemia i.e. no known anaemia in the preceding two years. Women were included when aged 50 years or older, in order to prevent an overabundance of iron deficiency anaemia (IDA) due to hypermenorrhea. Men were included when aged 17 or older. Patients were included between the 1st of February 2007 and the 1st of February 2013. For each patient an extensive laboratory work-up was performed, considering a broad range of causes of anaemia. Furthermore all additional hospital work-up was analyzed as well, including bone marrow examinations and a report of alcohol abuse when present. A classification system was developed that included the following causes: 1) anaemia of chronic disease (ACD 2) haemolysis 3) bone marrow disease 4) vitamin B12 deficiency 5) folic acid deficiency 6) iron deficiency 7) reported alcohol abuse 8) renal anaemia and 9) other. If no cause could be established, it was classified as unknown. The cause of each anaemia was established by 2 independent observers. In case of a discrepancy, the observers deliberated until a consensus was reached. Results Over the span of 6 years a total of 2738 patients were included in the PAGAS study. 190 (6,9%) of these 2738 patients presented with a macrocytic anaemia; 108 men (56,8%) and 82 (43,2%) women. Men were aged 70,7 years on average at the time of inclusion while women had an average age of 79 years when included. In 83,7% of patients (N=159), the underlying cause of the anaemia could be established. Seven patients displayed a double underlying cause. Bone marrow disease was found 18 times (9,1%), vitamin B12 deficiency 27 times (13,7%), folic acid deficiency 10 times (5,1%), haemolysis 7 times (3,6%) and alcohol abuse 27 times (13,7%). In addition, we found 39 patients (19,8%) with ACD, 4 patients (2,0%) with IDA and 29 patients (14,7%) with renal anaemia. Five cases of anaemia (2,5%) were classified as other. Overall survival was 57 months (95% CI 52,6-61,4) after entry into the study. The survival of patients with a nutrient deficiency, vitamin B12 or folic acid, was significantly shorter (41,8 months, 95% CI 33,2-50,3) when compared to the survival of the other patients in the cohort (58,3 months, 95% CI 53,7-63) (p-value = 0,024). See figure 1. Significantly more alcohol abuse was found as a cause in the age group of 50-64 years (20 of 27 cases) compared to the other four age groups (17-49, 65-74, 75-84 and 85+ years) combined (p-value = 0,000). In addition, the number of cases of renal anaemia found in the combined 75-84 and 85+ age groups (27 of 29 cases) differed significantly when compared to the other three age groups combined (p-value = 0,000). Nutrient deficiency was observed more often in the two highest age groups combined (24 of 37 cases) when compared to the lower three combined but this difference was not significant (p-value = 0,165). Discussion In our cohort study the well known causes of macrocytic anaemia – bone marrow disease, alcohol abuse, haemolysis and vitamin B12 and folic acid deficiency – were found in 45,2% of patients. However, ACD, IDA and renal anaemia, typically reported in normocytic and microcytic anaemic patients, were leading causes of anaemia in 36,5% of patients. As shown in our population the causes of macrocytic anaemia are diverse. Therefore we consider a broad diagnostic work-up warranted to completely elucidate the underlying cause. Disclosures: No relevant conflicts of interest to declare.