Thrombotic Microangiopathy After Hematopoietic Stem Cell and Solid Organ Transplantation: A Review for Intensive Care Physicians

Abstract

Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies.

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

“…The clinical implications of the syndrome are the result of organ injury and include manifestations from the kidneys (hypertension, proteinuria, acute kidney injury), gastrointestinal (GI) tract, central nervous system (headache, confusion, seizures, posterior reversible encephalopathy), and lungs (pulmonary arterial hypertension, pulmonary insufficiency) [37]. Moreover, multiple-organ failure might be established [38]. Various criteria have been proposed for the diagnosis of patients with TA-TMA, while in the most recently published criteria, HSCT-TMA is diagnosed based on clinical and laboratory data, and kidney/GI biopsy can be implemented but is not essential for the diagnosis [37].…”

Hyperbilirubinemia in ABO minor mismatch transplantation

“… 8 Although the patient had intravascular hemolysis, he had no symptoms such as hypertension, fragmented RBC, proteinuria, or worsening renal failure, and therefore did not meet the diagnostic criteria for thrombotic microangiopathy. 9 Viral tests, including hepatitis B virus, hepatitis C virus, cytomegalovirus, and Epstein-Barr virus were all negative, and viral infection was therefore not considered. However, his bilirubin and aminotransferase levels decreased rapidly after treatment with anti-thymocyte immunoglobulin and basiliximab, indicating the possibility of hepatic aGVHD.…”