Hemolytic Anemia

Morgan, Megan; Hackner, Susan G.

doi:10.1002/9781119028994.ch66

Cited by 2 publications

(3 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the mechanism of echinocyte formation in other systems [8,9]. Erythrocyte shape changes, such as echinocyte formation, are associated with increased RBC clearance via extravascular hemolysis [10][11][12]. This is driven by large groups of macrophages and phagocytic cells present in reticular connective tissue of the liver and spleen which remove the altered RBCs [10].…”

Section: Introductionsupporting

confidence: 80%

“…Erythrocyte shape changes, such as echinocyte formation, are associated with increased RBC clearance via extravascular hemolysis [10][11][12]. This is driven by large groups of macrophages and phagocytic cells present in reticular connective tissue of the liver and spleen which remove the altered RBCs [10]. Within the spleen, RBCs must pass through the Cords of Billroth to enter into the sinusoids.…”

Section: Introductionmentioning

confidence: 99%

“…Within the spleen, RBCs must pass through the Cords of Billroth to enter into the sinusoids. Changes to RBC morphology, such as echinocyte formation, hinders the passage into the sinusoids leading to the phagocytic removal of such cells [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Storage Primes Erythrocytes for Necroptosis and Clearance

2019

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Like nucleated cells, erythrocytes (red blood cells, RBCs) are capable of executing programmed cell death pathways. RBCs undergo necroptosis in response to CD59specific pore-forming toxins (PFTs). The relationship between blood bank storage and RBC necroptosis was explored in this study. Methods: Human RBCs were stored in standard blood bank additive solutions (AS-1, AS-3, or AS-5) for 1 week and hemolysis was evaluated in the context of necroptosis inhibitors and reactive oxygen species (ROS) scavengers. Activation of key factors including RIP1, RIP3, and MLKL was determined using immunoprecipitations and western blot. RBC vesiculation and formation of echinocytes was determined using phasecontrast microscopy. The effect of necroptosis and storage on RBC clearance was determined using a murine transfusion model. Results: Necroptosis is associated with increased RBC clearance post-transfusion. Moreover, storage in AS-1, AS-3, or AS-5 sensitizes RBCs for necroptosis. Importantly, storage-sensitized RBCs undergo necroptosis in response to multiple PFTs, regardless of specificity for CD59. Storage-sensitized RBCs undergo necroptosis via NADPH oxidase-generated ROS. RBC storage led to RIP1 phosphorylation and necrosome formation in an NADPH oxidase-dependent manner suggesting the basis for this sensitization. In addition, storage led to increased RBC clearance post-transfusion. Clearance of these RBCs was due to Syk-dependent echinocyte formation. Conclusion: Storage-induced sensitization to RBC necroptosis and clearance is important as it may be relevant to hemolytic transfusion reactions.

show abstract