Our Approach to Treating Concurrent Acute Gastrointestinal Graft Versus Host Disease and Transplant Associated Thrombotic Microangiopathy.

Acute gastrointestinal (GI) graft-versus-host disease (GVHD) and transplant-associated thrombotic microangiopathy (TA-TMA) are complications of allogeneic hematopoietic stem cell transplantation (HSCT) that may coexist and contribute to severe morbidity and mortality. Increasing evidence supports a biologic link between these disorders, with alloimmune inflammation, endothelial injury, and complement activation converging in the gastrointestinal tract. We review the clinical and biologic overlap between acute GI GVHD and intestinal TA-TMA and propose a practical framework for diagnosis and management. Diagnosis requires a high index of suspicion and integration of clinical findings with longitudinal assessment of laboratory markers of endothelial injury and complement activation. Histopathologic evaluation of GI biopsies, when clinically feasible, should include careful assessment for microvascular injury in addition to conventional assessment for GVHD. We propose a multidimensional, five-pillar approach addressing the interconnected mechanisms of disease: (1) hemostasis and supportive care; (2) complement inhibition; (3) management of calcineurin inhibitors and corticosteroids; (4) selection of therapies that target both GVHD and endothelial injury; and (5) nutritional and comprehensive supportive care. Eculizumab should be considered early in patients with high-risk intestinal TA-TMA, with individualized pharmacokinetic/pharmacodynamic-guided dosing and monitoring of eculizumab levels, CH50, and soluble C5b-9. Abrupt withdrawal of calcineurin inhibitors should generally be avoided because uncontrolled GVHD may further amplify endothelial injury. For GVHD-directed therapy, agents such as ruxolitinib or vedolizumab may be combined with therapies that have potential endothelial-protective or mucosal-reparative effects, including alpha-1 antitrypsin, abatacept, and GLP-2 analogues. Acute GI GVHD complicated by intestinal TA-TMA represents a biologically interconnected syndrome requiring simultaneous attention to alloimmune inflammation, complement-mediated endothelial injury, mucosal damage, and nutritional deterioration. Prospective studies are needed to establish early diagnostic biomarkers, optimize complement inhibitor dosing, define treatment duration, and evaluate rational combination strategies.