Diagnosis of Anaemia in Patients Presenting to the General Practitioner: Causes and Survival
Authors: Stouten Karlijn , Riedl Jurgen A , Sonneveld Pieter , Levin Mark-David 
Published: October 2019

Abstract
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.