Thrombotic microangiopathy following haematopoietic stem cell transplant

Abstract

Thrombotic microangiopathy is a potentially lethal complication of haematopoietic stem cell (bone marrow) transplantation. The pathophysiology is incompletely understood, although endothelial damage appears to be central. Platelet activation, neutrophil extracellular traps and complement activation appear to play key roles. Diagnosis may be difficult and universally accepted diagnostic criteria are not available. Treatment remains controversial. In some cases, withdrawal of calcineurin inhibitors is adequate. Rituximab and defibrotide also appear to have been used successfully. In severe cases, complement inhibitors such as eculizumab may play a valuable role. Further research is required to define the pathophysiology and determine both robust diagnostic criteria and the optimal treatment.

Complement inhibitors are useful in secondary hemolytic uremic syndromes

“…Plasma exchange is usually initiated in these patients, but the evidence of its favorable effect on secondary HUS is even poorer than in primary aHUS (see S65 in Supplementary References). 9,14 Complement blockade in secondary HUS Over the last few years, many case reports as well as several series of patients have reported the favorable effect of complement inhibition with eculizumab in different types of secondary HUS. A rapid improvement of renal function with disappearance of hematologic abnormalities and resolution of extrarenal complications (e.g., seizures, coma, and heart failure) has been reported in many patients after the onset of eculizumab.…”

Case Report: Management Approach and Use of Extracorporeal Membrane Oxygenation for Diffuse Alveolar Hemorrhage After Pediatric Hematopoietic Cell Transplant

“…In the setting of TA-TMA, DAH has a reported mortality rate of up to 100% ( 15 ). Eculizumab is a complement inhibitor that is promising in the treatment of TA-TMA ( 17 ). Therefore, if there is suspicion of TA-TMA as in our second case, the addition of eculizumab is considered in collaboration with the transplant team.…”

Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation

“…We attribute it to the fact that all NPA samples were collected in the morning, and almost all patients receiving non-manipulated grafts (60% of our cohort) had finished their infusions prior to NPA collection. Pre-transplant conditioning, such as high-dose chemotherapy is toxic to many cells and render the endothelium vulnerable 40 which could lead to increased T cells in NPA of many patients.…”