Would you treat this case of PNH as PNH with hemolysis or PNH with bone marrow failure? A 55-year-old man was initially referred to hematology for low platelet count in 2023, at that time, it was isolated, and platelet count of 70k. He was again evaluated in 2023 with platelet count of 3, Hgb 6.4 and WBC 1.9, ANC 0.7. Haptoglobin was undetectable, LDH mildly elevated at 300, and corrected retic was low. Coombs and super coombs were negative. PNH flow from peripheral blood showed PNH clone in 10.85% clone in granulocytes and 19% in monocytes and 3.12 in RBC with complete loss. He is getting weekly RBC and or platelet transfusion. Bone marrow biopsy results are pending but prelim shows "erythroid hyperplasia" unlikely aplastic. I was thinking of giving a trial of Eculizumab/Ravulizumab in PNH with BMF while waiting for transplant, however, it is not expected to work. Would you agree that this is PNH with bone marrow failure to that? And how strongly you think of offering Eculizumab/Ravulizumab? Would you prefer one vs other?
Some patients can have an overlap syndrome of PNH and aplastic anemia. This patient has both aplastic anemia as well as hemolysis in my opinion, since there is erythroid hyperplasia with severe anemia. In cases of AA, definitive therapy is directed at the aplastic anemia, but sometimes PNH clone also needs to be addressed if there are symptoms or thrombosis, or in this case hemolysis if it is severe or transufsion dependent. This patient meets criteria for severe aplastic anemia; allo BMT is indicated and has the potential to eradicate both the aplastic anemia and the PNH clone. Eculizumab may be useful as a “bridge” therapy to control the hemolysis. Because long-term complement inhibition is not needed after successful transplantation, eculizumab can be considered. C5 inhibition does not adversely affect outcomes of BMT.
