# Subclinical Cardiac Diseases and the Role of Extracellular Vesicles in Patients with Hemophilia A Treated on-Demand

## TL;DR

This study explores subclinical heart disease in hemophilia A patients using electrocardiography and extracellular vesicles, finding no differences in heart disease likelihood but altered blood clotting and vesicle levels.

## Contribution

The study introduces the use of extracellular vesicles and advanced electrocardiography to assess subclinical cardiac disease in hemophilia A patients.

## Key findings

- No difference in subclinical CAD likelihood between hemophilia A patients and controls via A-ECG.
- Impaired fibrin formation and clot stability observed in hemophilia A patients.
- Higher platelet-derived and CD62P+ extracellular vesicles in patients, inversely correlated with clot stability metrics.

## Abstract

Patients with hemophilia A (HA) can reach normal life expectancy and suffer from coronary artery disease (CAD). The study evaluates the likelihood of subclinical CAD evaluated by advanced electrocardiography (A-ECG), global hemostasis and extracellular vesicles (EVs) in Chinese patients with HA treated on-demand.

Patients with HA (n = 42) and age-matched male controls (n = 37) were included. The likelihood of having CAD was evaluated by A-ECG. Fibrin formation and fibrinolysis were assessed by the overall hemostatic potential (OHP) assay. EVs derived from platelets (PEVs), endothelial cells (EEVs) and leukocytes (LEVs), and expressing phosphatidylserine (PS + EVs), tissue factor (TF + EVs) or P-selectin (CD62P + EVs) were measured by flow cytometry.

The likelihood of CAD evaluated by A-ECG did not differ between patients and controls. Fibrin formation and clot stability were significantly impaired in patients. Patients had higher PEVs and CD62P + EVs. CD62P + EVs counts were inversely correlated with OHP, velocity and clot lysis time. Subclinical CAD did not correlate with OHP or EVs.

Controls and patients with HA treated on-demand exhibited no differences in A-ECG, but varied in fibrin formation and clot stability. Larger studies are required to explore the significance of this finding in the context of CAD risk in this population.