Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy

Table 2 The “Three-Hit Hypothesis” for development of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) [7, 15]

Inherent/ non-modifiable risk factors	Transplant-associated risk factors	Post-transplant risk factors
Underlying predispositions: Female sex African American ethnicity Severe aplastic anemia CMV seropositive recipient Prior stem cell transplant Genetic variants	Endothelial injury and procoagulant endothelium: Transplant conditioning Total-body irradiation Unrelated donor transplants HLA mismatch Other factors	Post-HSCT initiators of complement activation: Calcineurin inhibitors mTOR inhibitors aGVHD Infection

Adapted with permission from [7]
Sequential risks facilitate development and progression of HSCT-TMA. The first “hit” comprises inherent or nonmodifiable risk factors, such as underlying predisposition to complement activation via genetic risk factors. The second “hit” involves transplant-associated risk factors such as cytotoxic conditioning regimens that cause endothelial injury. The third “hit” includes post-transplant risk factors that may initiate complement activation, such as medications, aGVHD, infection, and/or circulating antibodies
aGVHD Acute graft-versus-host disease, CMV Cytomegalovirus, HLA Human leukocyte antigen, HSCT Hematopoietic stem cell transplantation, mTOR Mammalian target of rapamycin

ISSN: 2162-3619