Complement-mediated thrombotic microangiopathy as a link between endothelial damage and steroid-refractory GVHD

Complement activation in thrombotic microangiopathy.

The endothelium lining the vascular lumen is continuously exposed to complement from the circulation. When erroneously activated on host cells, complement may generate a deleterious effect on the vascular wall leading to endothelial injury, exposure of the subendothelial matrix and platelet activation. In this review the contribution of complement activation to formation and maintenance of the ...

Complement, thrombotic microangiopathy and disseminated intravascular coagulation

In the blurring boundaries between clinical practice and scientific observations, it is increasingly attractive to propose shared disease mechanisms that could explain clinical experience. With the advent of available therapeutic options for complement inhibition, there is a push for more widespread application in patients, despite a lack of clinically relevant research. Patients with dissemina...

Steroid-Refractory Acute GVHD: Predictors and Outcomes

Patients with steroid-resistant acute graft versus host disease (aGVHD) have a dismal prognosis, with mortality rates in excess of 90%. We sought to identify a subgroup of patients less likely to benefit from initial therapy with corticosteroids as well as the impact of response on day 14 on outcome. Retrospective evaluation was performed of patients with biopsy-proven aGVHD treated with cortic...

The malignant hypertension-thrombotic microangiopathy link.

Therapeutic Complement Targeting in ANCA-Associated Vasculitides and Thrombotic Microangiopathy

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of systemic autoimmune disorders characterized by necrotizing inflammation of medium-tosmall vessels, a relative paucity of immune deposits, and an association with detectable circulating ANCAs. AAVs include granulomatosis with polyangiitis (renamed from Wegener’s granulomatosis), microscopic polyangiitis, an...