Small vessels, big trouble in the kidneys and beyond: Hematopoietic stem cell transplantation-associated thrombotic microangiopathy
ABSTRACT Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenging diagnosis after hematopoietic stem cell transplantation. Although endothelial injury represents the final common pathway of disease, the exact pathophysiology of TA-TMA remains unclear. Potential causes include infections, chemotherapy, radiation, and calcineurin inhibitors. Recent literature addresses the roles of cytokines, graft-versus-host disease, the coagulation cascade, and complement in the pathogenesis of TA-TMA. Current diagnostic criteria are unsatisfactory, because patients who have received a transplant can have multiple other reasons for the laboratory abnormalities currently used to diagnose TA-TMA. Moreover, our lack of understanding of the exact mechanism of disease limits the development and evaluation of potential treatments. Short- and long-term renal complications contribute to TA-TMA's overall poor prognosis. In light of these challenges, future research must validate novel markers of disease to aid in early diagnosis, guide current and future treatments, prevent long-term morbidity, and improve outcomes. We focus on TA-TMA as a distinct complication of hematopoietic stem cell transplantation, emphasizing the central role of the kidney in this disease.
- SourceAvailable from: Omur Gokmen Sevindik
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- "Transplantation-associated thrombotic microangiopathy (TA-TMA) represents a challenge after allogeneic hematopoietic progenitor cell transplantation because of diagnostic uncertainties, lack of established treatment, and an overall poor prognosis . Eculizumab, which is a monoclonal antibody against terminal complement, has been used successfully in atypical hemolytic and uremic syndrome and TA-TMA associated with solid organ transplantation. "
ABSTRACT: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenge after allogeneic hematopoietic progenitor cell transplantation, considering the diagnostic uncertainties and lack of established treatment. We report a 43-year-old male patient who was diagnosed as TA-TMA after allogeneic progenitor cell transplantation for a progressive ALK negative anaplastic large cell lymphoma and responded to eculizumab with dramatically improving neurological status and renal function. Rapid neurological and renal recovery achieved after eculizumab could support a possible relationship between complement activation and TA-TMA. Eculizumab should be a reasonable treatment approach in patients with TA-TMA after allogeneic hematopoietic progenitor cell transplantation.02/2015; 2015. DOI:10.1155/2015/425410
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ABSTRACT: Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.Bone marrow transplantation 12/2011; 47(9):1243-5. DOI:10.1038/bmt.2011.243 · 3.47 Impact Factor
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ABSTRACT: The transplantation of allogeneic or autologous haematopoietic stem cells is an established treatment for many malignant and non-malignant diseases of the bone marrow. Intensive cytoreductive regimens administered before transplantation induce prolonged and severe cytopenia of all haematopoietic lineages. Thrombocytopenia leads to an increased risk of bleeding, which may be further aggravated by consumption of plasmatic factors as a result of tumour lysis or after antibody administration. At the same time, patients after transplantation are also at increased risk of thrombotic complications. Endothelial damage induced by radio- and chemotherapy, indwelling catheters, prolonged immobilization and a high incidence of systemic infection all contribute to the frequent occurrence of thromboembolic events in this population. This review discusses the incidence and risk factors for haemorrhagic and thrombotic complications after stem cell transplantation. Special emphasis is given to complications occurring specifically in the context of transplantation such as diffuse alveolar haemorrhage, haemorrhagic cystitis, veno-occlusive disease, and transplant associated microangiopathy.Hamostaseologie 01/2012; 32(1):56-62. DOI:10.5482/ha-1176 · 1.59 Impact Factor