Evans syndrome is defined by autoimmune haemolytic anaemia and immune thrombocytopenia occurring in the same patient. Although known to be rare the frequency and prognosis of Evans syndrome in ...children is unknown, and only few registry-based studies are available. The epidemiology and prognosis of Evans syndrome in patients above 13 years of age has recently been investigated. In this age group both incidence and prevalence of Evans syndrome increased during the study period and median survival was just 7.2 years. Using Danish health registries and the same approach, we identified 21 children below 13 years of age with Evans syndrome during 1981-2015. Patients with Evans syndrome were age-and sex matched with children both from the general population, and with patients with either autoimmune haemolytic anaemia or immune thrombocytopenia. The incidence of Evans syndrome ranged between 0.5 and 1.2/1,000,000 person-years. Prevalence was 6.7 and 19.3/1,000,000 in 1990 and 2015 respectively. Hazard ratio for death was 22 fold higher for children with ES compared to matched children from general population, and was also elevated compared to children with autoimmune haemolytic anaemia or immune thrombocytopenia. We conclude that pediatric ES is very rare and associated with elevated mortality. However, despite the nationwide study and a long and complete follow-up, results are imprecise due to the rarity of this disorder.
Patients with Evans syndrome have both immune thrombocytopenia and autoimmune hemolytic anemia, but little is known about the epidemiology of this rare syndrome. Evans syndrome can be primary or ...secondary. This nationwide retrospective study linked health registries to identify 242 patients with Evans syndrome in Denmark in 1977‐2017. For comparison, we identified three age‐matched and sex‐matched cohorts of patients with only immune thrombocytopenia or only autoimmune hemolytic anemia, and a general population cohort. The Evans syndrome cohort had a mean age of 58.5 years at diagnosis, 51.2% were women, and 27.3% were classified as secondary Evans syndrome. The annual Evans syndrome incidence and prevalence rose significantly during the study period, to 1.8 per million person‐years and 21.3 per million persons, respectively, in 2016. The median survival with Evans syndrome was 7.2 years (primary Evans syndrome: 10.9 years; secondary Evans syndrome: 1.7 years). Secondary Evans syndrome was associated with higher mortality rates than any of the other cohorts, with a 5‐year survival of 38%. Among patients with Evans syndrome, the prevailing causes of death were bleeding, infections, and hematological cancer. In conclusion, we found that both primary and secondary Evans syndrome conferred a poor prognosis. Lethal complications probably derive primarily from manifestations of underlying autoimmune hemolytic anemia and immune thrombocytopenia. Our findings suggested that suspicion of Evans syndrome should prompt vigilant clinical follow‐up. International collaborations are warranted to advance our knowledge of optimal management of this rare disease.
Background
Few studies have investigated long‐term survival in patients with primary immune thrombocytopenia (pITP). Further, changes in prognosis over the past decades and prognosis of secondary ...immune thrombocytopenia (sITP) are largely unstudied. Our objectives were to study comorbidity‐adjusted prognostic changes and causes of death in chronic pITP and sITP patients.
Study Design/Methods
Using nationwide Danish health registries 1980–2016, we identified 1762 patients with chronic pITP (median age 58 (IQR, 37–73) years) and 128 with chronic sITP (median age 59 (IQR, 40–73) years). Patients were age‐sex‐matched to 74,781 general population comparators.
Comorbidity was assessed using Charlson Comorbidity Index (CCI).
Results
Overall median survival was reduced by 5.1 years (95% CI, 0.7–9.4) (p < .001) for pITP and 11.1 years (95% CI, 5.8–16.4) (p < .001) for sITP. 5‐year survival increased from 69% (95% CI, 59–78) in 1980–89 to 80% (95% CI, 75–83) in 2010–16 for pITP, and decreased from 100% (95% CI, 89–98) to 64% (95% CI, 87–91) for sITP. However, numbers were small for sITP. 5‐year survival for pITP with high CCI was 41% (95% CI, 32–49), and 85% (95% CI, 83–87) for low CCI.
Bleeding, infection and hematological cancer were relatively frequent causes of death with adjusted subhazard ratios of 3.25 (95% CI, 2.33–4.52), 1.53 (95% CI, 1.08–2.16) and 2.16 (95% CI, 1.12–4.16) in pITP respectively, and 10.52 (95% CI, 1.43–77.36) for hematological cancer in sITP.
Conclusions
Long‐term survival is reduced in chronic ITP but seems to be improving. Comorbidity and sITP are associated with a poor prognosis.
Summary
Corticosteroids remain the first‐line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of ...osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry‐based cohort study. We identified 4030 patients with pITP (median age 60 years IQR, 40–74), 550 with sITP (median age 59 years IQR, 43–74) and 182 939 age–sex‐matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar‐years and in temporal relation to the ITP diagnosis. Adjusted cause‐specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval CI 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first‐year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar‐years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population.
hemolysis is associated with thromboembolism. Although an increased Hemolysis Index (HI) can be due to
as well as
hemolysis, both reflects a more fragile erythrocyte population. We therefore ...hypothesized that HI above upper reference limit would be associated with an increased risk of cardiovascular disease (CVD).
We identified persons with two elevated HI (HI
) from blood samples analyzed at a university hospital laboratory from 2012 to 2017. We compared their risk of CVD with the risk in matched comparators with normal HI and from the general population. HI
persons and comparators were followed from start date (date of the second elevated HI) until the first of the main outcome: CVD, emigration, death, or end of observation time on December 31, 2018.
In 43,102 unique HI
persons, the risk of developing CVD was 40% higher compared with the general population and 13% higher compared with the matched blood sample cohort. HI
was associated with a significantly increased cumulative incidence of both arterial and venous CVD compared with the matched blood sample cohort and the general population (respectively 47 and 14% for arterial CVD; 78 and 24% for venous CVD). Moreover, overall mortality risk was significantly higher in patients with HI
than in the two comparator groups.
Elevated HI is associated with increased risk of arterial and venous CVD and with increased mortality. Our findings imply that HI may contribute as a CVD risk biomarker.
Introduction
Autoimmune hemolytic anemia (AIHA) is considered a chronic disease, with an overall good prognosis. However, recent reports indicate pre‐mature mortality. Causes of death have not been ...evaluated previously.
Methods
In a nationwide setting, we identified all patients with warm type AIHA or cold agglutinin disease (CAD), and age–sex‐matched comparators from Denmark, 1980–2016. We estimated overall survival and cause‐specific mortality from anemia, infection, cardiovascular causes, hematological or solid cancer, bleeding, or other causes, using cumulative incidence proportions.
Results
We identified 1460 patients with primary AIHA, 1078 with secondary AIHA, 112 with CAD, and 130 801 comparators. One‐year survival and median survival were, 82.7% and 9.8 years for primary AIHA, 69.1% and 3.3 years for secondary AIHA, and 85.5% and 8.8 years for CAD. Prognosis was comparable to the general population only in patients with primary AIHA below 30 years. In all other age and subgroups, the difference was considerable. Cumulated cause‐specific mortality at 1 year was increased among patients versus comparators.
Discussion
All groups of autoimmune hemolytic anemia are associated with increased overall and cause‐specific mortality compared to the general population. This probably reflects unmet needs in both treatment and follow‐up programs.
Our aim was to assess the validity of the ICD-10 code for splenomegaly in the Danish National Registry of Patients (DNRP), as well as to investigate which underlying diseases explained the observed ...splenomegaly.
Splenomegaly is a common finding in patients referred to an internal medical department and can be caused by a large spectrum of diseases, including haematological diseases and liver cirrhosis. However, some patients remain without a causal diagnosis, despite extensive medical work-up.
We identified 129 patients through the DNRP, that had been given the ICD-10 splenomegaly diagnosis code in 1994-2013 at Odense University Hospital, Denmark, excluding patients with prior splenomegaly, malignant haematological neoplasia or liver cirrhosis. Medical records were reviewed for validity of the splenomegaly diagnosis, diagnostic work-up, and the underlying disease was determined. The positive predictive value (PPV) with 95% confidence interval (CI) was calculated for the splenomegaly diagnosis code. Patients with idiopathic splenomegaly in on-going follow-up were also invited to be investigated for Gaucher disease.
The overall PPV was 92% (95% CI: 85, 96). Haematological diseases were the underlying causal diagnosis in 39%; hepatic diseases in 18%, infectious disease in 10% and other diseases in 8%. 25% of patients with splenomegaly remained without a causal diagnosis. Lymphoma was the most common haematological causal diagnosis and liver cirrhosis the most common hepatic causal diagnosis. None of the investigated patients with idiopathic splenomegaly had Gaucher disease.
Our findings show that the splenomegaly diagnosis in the DNRP is valid and can be used in registry-based studies. However, because of suspected significant under-coding, it should be considered if supplementary data sources should be used in addition, in order to attain a more representative population. Haematological diseases were the most common cause, however in a large fraction of patients no causal diagnosis was found.
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