Thrombotic Microangiopathy in Transplantation and Malignancy

Abstract

Thrombotic microangiopathy (TMA) after hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation is a serious complication that may be associated with diverse clinical conditions. The reported incidence varies widely, in part due to different diagnostic criteria. Currently, the diagnosis is based mostly on clinical features and is often uncertain; many disease or therapy-related complications in transplantation and malignancy can manifest clinical features of TMA. Risk factors for TMA post HSCT include the type of conditioning regimen, the presence graft-versus-host disease (GVHD), the use of calcineurin inhibitors (cyclosporine and tacrolimus) for GVHD prophylaxis, and infection. Cyclosporin and tacrolimus are the most commonly reported agents associated with TMA in solid-organ (mainly kidney) transplantations. Cancer-related TMA may be associated with chemotherapy or the malignancy itself. Compared with idiopathic TMA (thrombotic thrombocytopenic purpura), the outcome for patients with TMA post-HSCT or disseminated malignancy is poor. The efficacy of plasma exchange in the treatment of TMA post-HSCT or malignancy is uncertain. In the future, objective criteria integrating laboratory features (including tissue pathology, quantitative hematology, and endothelial cell functionality) with clinical features may assist in the diagnostic accuracy of TMA post HSCT, which would allow better evaluation of treatment modalities and better prediction of prognosis and outcomes.

Synergistic interactions between interferon-γ and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma–associated apoptosis

“…6,8 In other types of thrombotic microangiopathy, including diarrhea/shigatoxin-associated (D ϩ ) hemolytic uremic syndrome (HUS), significant alterations in these cytokines have not been documented. 9,10 However, levels of IL-1 or TNF-␣ required to induce MVEC apoptosis in vitro are 2-to 3-log-fold greater than those present in TTP plasma.TNF-␣, a related cytokine, TNF-related apoptosis-inducing ligand (TRAIL), and another soluble factor up-regulated during the acute phase of TTP, interferon (IFN)-␥, 8 can interact to elicit apoptosis in several cell types. 11,12 Although the levels required still far exceed those present in TTP, such synergy studies offer insight into modulation of cell-specific cytoprotective pathways that might underlie the differential sensitivity of divergent ECs to injury in TTP.…”

“…6,8 In other types of thrombotic microangiopathy, including diarrhea/shigatoxin-associated (D ϩ ) hemolytic uremic syndrome (HUS), significant alterations in these cytokines have not been documented. 9,10 However, levels of IL-1 or TNF-␣ required to induce MVEC apoptosis in vitro are 2-to 3-log-fold greater than those present in TTP plasma.…”

Infection frequently triggers thrombotic microangiopathy in patients with preexisting risk factors: A single‐institution experience

“…In both HUS and TTP, although initial endothelial damage is believed to arise by different mechanisms, the end result is extensive microvascular platelet deposition with resultant thrombocytopenia and occlusion of small vessels. Several rarer TMA syndromes, including HELLP syndrome of pregnancy [10] posttransplant TTP associated with calcineurin inhibitors, and cancer-associated thrombotic microangiopathy can also lead to a similar clinical picture [11].…”

Spectrum of Renal Pathology in Hematopoietic Cell Transplantation

“…Chronic kidney disease occurs in 20 to 60% of HCT patients and has been associated with the use of radiation and/or chemotherapeutic agents, acute and chronic graft-versus-host disease (GVHD), and acute renal failure (1). Many pharmacologic agents, such as cyclosporine and tacrolimus, have been linked to thrombotic microangiopathy (TMA) (2). A range of glomerular injury processes, such as membranous nephropathy (MN) (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and minimal-change disease (MCD) (13)(14)(15)(16)(17)(18)(19)(20), have been observed in the setting of HCT, primarily as individual case reports.…”