Approved Research

Risk of death, cause-specific death, hematologic cancer, non-hematologic cancer and other adverse outcomes in individuals with incidentally discovered paraclinical tests indicating hematologic disease

Lay summary

New scope:

Historically, most individuals diagnosed with hematologic conditions (including hematologic cancer) has been diagnosed due to having symptoms. This has changed in recent years, as many asymptomatic individuals are now referred to hematologists for evaluation of possible hematologic conditions due to incidental findings of abnormal results on routine blood tests or incidentally discovered splenomegaly on CT, ultrasound or MR scans. However, very little is known about the prognosis in such individuals with incidentally discovered abnormal paraclinical tests.

Therefore, we will examine risk of death from any cause and cause-specific death as well as risk of hematologic disease, non-hematologic cancer and other adverse outcomes in individuals with incidentally discovered abnormal blood parameters or incidentally discovered splenomegaly. Specifically, we will study individuals with incidentally discovered abnormal blood cell parameters (hemoglobin, hematocrit, leukocyte/differential count, platelets, etc), abnormal hemolysis parameters, signs of hereditary hemochromatosis and/or incidentally discovered splenomegaly on MR scans.

By studying prognosis in subgroups according to categories of other standard blood tests, spleen size, and genetic tests, we will seek to identify low-risk and high-risk groups, laying ground for evidence-based diagnostic algorithms guiding clinicians on when to refer individuals with incidentally discovered abnormal paraclinical tests to further evaluation for possible hematologic disease.

In addition to the above mentioned research questions, we will also study how to best identify individuals with congenital or aquired haematologic conditions. Specifically, we will study the prevalence of congenital and aquired haematologic conditions (including malignant and non-malignant haematologic conditions, hereditary disorders of iron regulation, hereditary metabolic disorders that may affect haematologic blood parameters, and potential non-affected carriers in case of congenital conditions) and we will study how individuals with these conditions (including potential non-affected carriers in case of congenital conditions) can be identified based on blood sample measurements, MR scans and other information that is available from the UK Biobank. This includes studying whether screening for the above mentioned conditions and carrier-states can be improved. We will use both conventional statistical analysis and machine learning approaches.

Furthermore, we will study prognosis, including risk of all-cause death and cause-specific death as well as risk of hematologic disease, non-hematologic cancer, cardiovascular disease, other conditions and adverse outcomes in individuals with congenital or aquired haematologic conditions (including malignant and non-malignant haematologic conditions, hereditary disorders of iron regulation, hereditary metabolic disorders that may affect haematologic blood parameters, and potential non-affected carriers in case of congenital conditions).

Finally, we will include the UK Biobank data in our clinical decision-making to examine whether our current clinical decision-making when diagnosing individual patients with possible congenital or aquired haematologic conditions can be improved by also using information from the UK Biobank (e.g. genetic data including WES/WGS, blood sample measurements, clinical outcome data) to interpret whether specific genetic variants encountered in our current individual patients are likely pathogenic.