Amsterdam Cardiovascular Sciences

Life-saving support, hidden risks

Extracorporeal circulation techniques, including extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB), are crucial for patients with severe cardiac and/or respiratory failure. “ECMO and CPB can mean the difference between life and death,” says Carolien Volleman. “But we are increasingly aware that these techniques come with their own set of complications, especially at the microvascular level.”

Focus on hemolysis

Volleman’s thesis centers on hemolysis, the breakdown of red blood cells, and particularly on cell‑free hemoglobin (CFHb), which is released into the bloodstream during this process. “We wanted to understand whether hemolysis is just inevitable consequence, or whether it actively drives microvascular damage during extracorporeal circulation,” Volleman explains. Her clinical studies show that microvascular dysfunction may persist throughout ECMO support and is accompanied by ongoing endothelial injury, while hemolysis levels change dynamically over time.

Kidney injury is multifactorial

Acute kidney injury (AKI) is a frequent and serious complication in patients on extracorporeal circulation. Volleman’s work demonstrates that, although patients with higher levels of hemolysis tend to have worse outcomes, hemolysis alone does not independently predict AKI. “Kidney injury in these patients is clearly multifactorial,” says Volleman. “Hemolysis is an important piece of the puzzle, but not the only one. This means we need to look at the whole pathophysiological picture when trying to prevent organ damage.”

Experimental models reveal mechanisms

To disentangle these mechanisms, Volleman combined clinical observations with experimental animal and in vitro models. These studies show that ECMO itself induces hemolysis, endothelial injury, and impaired microcirculatory perfusion. “In our models, we saw that extracorporeal circulation doesn’t just support the patient; it also actively stresses the vascular system,” she notes. “This dual effect is exactly what we need to better understand.” Importantly, CFHb was found to directly disrupt the endothelial barrier and reduce microvascular perfusion, supporting its role as a mediator of vascular dysfunction.

Towards better patient outcomes

By linking hemolysis, endothelial injury, microvascular dysfunction, and renal damage, Volleman’s thesis provides a coherent framework for future research and potential interventions. “Our findings highlight that protecting the microvasculature should be a key goal in patients on ECMO or cardiopulmonary bypass,” Volleman concludes. “If we can better prevent microvascular and endothelial injury, we may significantly improve outcomes for these critically ill patients.”