Abstract 

The Reticulocyt-hemoglobin-equivalent (RetHe) is an established laboratory value to diagnose iron deficiency anemia (IDA). Thus, it might be a potential marker for latent or hidden bleeding, in particular in patients on antithrombotic and anticoagulant medication. The PRISCA Study (Predictive value of immature blood cells for risk stratification in cardiovascular patients) investigates the clinical association of RetHe with the incidence of bleeding events in patients with cardiovascular disease. 

The retrospective study analyzed all hospitalized patients from the University Heart Center Freiburg – Bad Krozingen between 07/2020 and 12/2021. At time of admission, routine laboratory was tested including RetHe, which were determined automatically using the Sysmex XN1000-Cytometer. In total, 17.836 patients could be included. This is the first proof of concept analysis of 9147 patients. The associations of RetHe with clinical events were adjusted for age, sex and treatment. Intrahospital bleeding complications were classified using the BARC classification. 

Patient’s demographics show a typical cardiovascular risk profile (64.7% male, 74.5% arterial hypertension, 38.0% smoker or former smoker, 64.9% hypercholesterinemia, 24.0% diabetes mellitus). In total there were 678 bleeding complications defined as BARC ≥ 2 (7.4%).

In our cohort, 3.3% of patients showed an RetHe < 28 pg and only 3.0% of the patients had a history of IDA.

RetHe values were significantly associated with in-hospital bleeding complications BARC ≥ 2 (figure 1; RR=0.972, p=0.001, 95%CI: 0.954-0.989). Additionally, RetHe values were significantly associated with the 30-day mortality (figure 2; RR=0.881, p<0.001, 95%CI: 0.844-0.919). 

In summary, RetHe is a reliable and affordable laboratory value to diagnose IDA. Thus, IDA seems to be a slightly underdiagnosed disease in cardiovascular patients. Even though IDA is significantly asssociated with bleeding complications and mortality. How to use RetHe in daily practice to identify cardiovascular patients at risk for bleeding and increased mortality needs to be part of further investigation.