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Background: Aplastic anaemia (AA) is known to progress to paroxysmal nocturnal haemoglobinuria (PNH) during treatment, and thrombosis is a characteristic symptom of PNH. This case report investigates a case of repeated and rapidly progressive multiple arterial thrombosis due to PNH. Case Summary: This case is a 24-year-old woman undergoing treatment for AA. She presented with chest pain and underwent emergency coronary angiography. Thrombus occlusion was found in the distal portion of the right coronary artery, acute myocardial infarction was diagnosed and percutaneous coronary intervention was performed. Thrombus aspiration and balloon dilation were performed. Anticoagulants were administered, but chest pain flared up again on Day 9; coronary angiography was performed, indicating that the proximal portion of the right coronary artery had caused occlusion. On Days 9 and 24, she experienced back pain and was diagnosed with renal infarction. Considering that AA had evolved into PNH and intravascular haemolysis and thrombosis appeared, the diagnosis of PNH was made via flow cytometry. Multiple arterial thrombosis due to PNH was diagnosed, and ravulizumab treatment was started, resulting in the improvement of thrombus progression, chest pain, and back pain. Discussion: Thrombosis due to PNH can recur even after the administration of anticoagulants and antiplatelet agents and has been associated with a high fatality rate. The treatment with ravulizumab, a humanized monoclonal antibody against complement C5, helps with the prevention of thrombosis. Furthermore, anti-complement component C5 therapy is very effective in improving rapidly progressive multiple arterial thrombosis resistant to anticoagulants and antiplatelet agents due to PNH.
RESUMO
OBJECTIVE: Antibody-mediated rejection (AMR) could induce acute or chronic graft failure during organ transplantation. Several reports have shown that anti-C5 antibodies are effective against AMR after kidney transplantation. However, few reports have assessed the efficacy of anti-C5 antibodies against AMR after lung transplantation. Therefore, this study aimed to evaluate the efficacy of this novel therapy against AMR after lung transplantation. METHODS: BALB/c and C57BL/6 mice were used as donors and recipients. One group was pre-sensitized (PS) by skin transplantation 14 days before lung transplantation. The other group was non-sensitized (NS). Orthotopic left-lung transplantation was performed in both groups. Animals were killed at 2 or 7 days after lung transplantation and evaluated for histopathology, C4d immunostaining, and serum donor-specific antibodies (DSAs) (n = 5 per group). Isograft (IS) models with C57BL/6 mice were used as controls. To evaluate the efficacy of C5 inhibition, other animals, which received similar treatments to those in the PS group, were treated with anti-C5 antibodies, cyclosporine/methylprednisolone, anti-C5 antibodies/cyclosporine/methylprednisolone, or isotype-matched irrelevant control monoclonal antibodies (n = 5 per group). RESULTS: Two days after lung transplantation, the NS group exhibited mild, localized graft-rejection features (rejection score: 0.45 ± 0.08, p = 0.107). The PS group exhibited AMR features with a significantly higher rejection score (2.29 ± 0.42, p = 0.001), C4d vascular-endothelium deposition, and substantial presence of serum DSA. On day 7 after lung transplantation, both groups showed extensive graft alveolar wall destruction, and high acute-rejection scores. Mice receiving anti-C5 antibodies or anti-C5/antibodies/cyclosporine/methylprednisolone demonstrated significantly lower acute-rejection scores (0.63 ± 0.23, p = 0.002; 0.59 ± 0.22, p = 0.001, respectively) than those receiving isotype control antibodies. CONCLUSIONS: Murine orthotopic allograft lung transplant models met the clinical diagnosis and pathogenesis classification criteria of AMR. In these models, anti-C5 antibodies suppressed AMR. Therefore, anti-C5 therapy may be effective against AMR after lung transplantation.