Microvascular stasis and hemolysis: coincidence or causality?

Abstract

Katharina Effenberger-Neidnicht,1 Simon Bornmann,1 Johannes Jägers,2 Vivien Patyk,1 Michael Kirsch11Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany; 2Institute of Physiology, University Hospital Essen, Essen, GermanyMicrovascular stasis in course of sepsis might be a consequence of hemolysisThere are various studies demonstrating that hemolysis or the presence of cell-free hemoglobin and heme causes microvascular stasis (Figure 1). Buurman and his team of researchers already showed that acute hemolysis (with plasma levels of cfHb ~20–30 μmol/L) – induced by infusion of water or pre-lysed red blood cells – was associated with an impaired renal, hepatic and intestinal microvasculature.2 They further showed that intraoperative hemolysis (with plasma levels of cfHb ~20 μmol/L) during major aortic surgery was associated with postoperative acute kidney injury.3 The offset times between occurring hemolysis and intestinal microvascular changes or renal microvascular changes were approximately 15–30 mins2 respective 120 mins3. Moreover, Vinchi and co-workers could reduce liver damage in a mouse model of heme overload in wild-type mice compared to hemopexin-null mice.4 They concluded that hemopexin prevents from hemolysis-induced hepatic microvascular stasis.4 Belcher et al compared different treatments to induce hemolysis and heme overload (eg, infusion of water, hemoglobin or heme) in transgenic sickle mice and found a relationship between microvascular stasis and total plasma heme concentrations (with plasma levels of heme ~25–80 μmol/L).5 They further proved that intravascular hemolysis during sickle cell disease elicits microvascular stasis via Toll-like receptor 4 signaling.5 Further studies of the researchers around Belcher and Vercellotti showed inhibition of hemoglobin-induced microvascular stasis in transgenic sickle mice by hemopexin and haptoglobin supplementation,6 overexpression of hemopexin7 or overexpression of ferritin heavy chain ferrioxidase.8

Keywords

• Lipopolysaccharide – capillary congestion – blood accumulation – cell-free hemoglobin – microcirculation – intestine