Talks
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Resident
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Internal medicine
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Resident
Discipline/Specialty (Author 1)
Internal Medicine
Academic Level (Author 2)
Resident
Discipline/Specialty (Author 2)
Internal Medicine
Academic Level (Author 3)
Resident
Discipline/Specialty (Author 3)
Internal Medicine
Academic Level (Author 4)
Resident
Discipline/Specialty (Author 4)
Internal Medicine
Academic Level (Author 5)
Resident
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Internal Medicine
Presentation Type
Oral Presentation
Discipline Track
Clinical Science
Abstract Type
Case Report
Abstract
Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem-cell disorder driven by loss of GPI-anchored complement regulators (CD55, CD59), leading to complement-mediated intravascular hemolysis, cytopenias, and thrombosis. We report a new PNH diagnosis in a young woman with severe pancytopenia who achieved hematologic improvement on oral iptacopan, requiring dose adjustments for mild liver enzyme elevation.
Case Report: On February 27, 2025, a 38-year-old female patient exhibited symptoms of progressive fatigue, dyspnea, and jaundice. Initial laboratory assessments indicated the presence of severe hemolytic anemia accompanied by pancytopenia, hemoglobin level recorded at 4.7 g/dL, white blood cell count at 1.6×10³/µL (absolute neutrophil count at 0.5×10³/µL), and platelet count at 78×10³/µL, alongside a hemolysis profile characterized by elevated lactate dehydrogenase and bilirubin levels, undetectable haptoglobin, and reticulocytosis. Computed tomography of the thoracic, abdominal, and pelvic regions disclosed hepatomegaly. A bone marrow biopsy revealed a normocellular composition (60–70%) featuring trilineage hematopoiesis and erythroid hyperplasia, devoid of any morphologic neoplasm. High-sensitivity flow cytometry employing fluorochrome-labeled aerolysin (FLAER) substantiated the existence of a substantial glycosylphosphatidylinositol (GPI)- deficient paroxysmal nocturnal hemoglobinuria (PNH) clone spanning both red and white blood cell lineages, thereby confirming the diagnosis of paroxysmal nocturnal hemoglobinuria. Following immunization against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b, treatment with iptacopan (Fabhalta) at a dosage of 200 mg twice daily was initiated on March 27, 2025. Throughout the subsequent weeks, the patient reported a notable increase in energy levels; however, a mild transaminitis necessitated a gradual reduction of the dosage to 200 mg once daily, and subsequently to 200 mg every other day on August 5. At that juncture, laboratory results indicated hemoglobin at 13.7 g/dL, white blood cell count at 3.82×10³/µL, platelet count at 122×10³/µL, LDH at 261 U/L, and haptoglobin at < 6 mg/dL. The patient continues to maintain a clinically stable condition with ongoing monitoring of complete blood count, hemolytic indices, and liver function tests . The normocellular nature of the bone marrow, characterized by erythroid hyperplasia and the presence of a large FLAER-defined clone, strongly favored the diagnosis of PNH over marrow-failure syndromes; proximal alternativepathway inhibition via iptacopan effectively rectified anemia and stabilized blood cell counts despite persistent biochemical hemolysis, while titration guided by liver function tests ensured an optimal balance between therapeutic efficacy and safety. Pre-treatment vaccination strategies were implemented to mitigate the risk of infections associated with complement blockade.
Conclusions: This case exemplifies the efficacy of first-in-class oral factor B inhibition with iptacopan in facilitating rapid and sustained hematologic recovery in newly diagnosed paroxysmal nocturnal hemoglobinuria presenting with pancytopenia, whilst simultaneously managing both terminal (intravascular) and C3-mediated (extravascular) hemolysis. Following the commencement of a 200 mg BID regimen, hemoglobin levels normalized and blood counts stabilized; a mild elevation in transaminases was effectively managed through a dose reduction guided by liver function tests, thereby maintaining therapeutic efficacy. These real-world findings are congruent with phase III clinical trial data (e.g., APPLY-PNH: a ≥2 g/dL increase in hemoglobin observed in approximately 82% of patients and hemoglobin levels reaching ≥12 g/dL in around 69% on iptacopan, as opposed to approximately 0% with conventional therapy), thereby highlighting the substantial clinical impact of iptacopan since its FDA approval in December 2023. Looking ahead, future prospective studies should aim to refine dose-adjustment protocols and long-term safety surveillance to maximize therapeutic outcomes associated with proximal complement blockade.
Recommended Citation
Calderon, Aura MC; Loayza, Jose; Arias, Francisco; Matos, Catherine; Peddinani, Bharat; and nguyen, Diane, "Iptacopan-Responsive PNH with Pancytopenia: Hematologic Normalization and Dose Adjustment for Transaminitis" (2026). Research Symposium. 7.
https://scholarworks.utrgv.edu/somrs/2026/talks/7
Included in
Iptacopan-Responsive PNH with Pancytopenia: Hematologic Normalization and Dose Adjustment for Transaminitis
Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem-cell disorder driven by loss of GPI-anchored complement regulators (CD55, CD59), leading to complement-mediated intravascular hemolysis, cytopenias, and thrombosis. We report a new PNH diagnosis in a young woman with severe pancytopenia who achieved hematologic improvement on oral iptacopan, requiring dose adjustments for mild liver enzyme elevation.
Case Report: On February 27, 2025, a 38-year-old female patient exhibited symptoms of progressive fatigue, dyspnea, and jaundice. Initial laboratory assessments indicated the presence of severe hemolytic anemia accompanied by pancytopenia, hemoglobin level recorded at 4.7 g/dL, white blood cell count at 1.6×10³/µL (absolute neutrophil count at 0.5×10³/µL), and platelet count at 78×10³/µL, alongside a hemolysis profile characterized by elevated lactate dehydrogenase and bilirubin levels, undetectable haptoglobin, and reticulocytosis. Computed tomography of the thoracic, abdominal, and pelvic regions disclosed hepatomegaly. A bone marrow biopsy revealed a normocellular composition (60–70%) featuring trilineage hematopoiesis and erythroid hyperplasia, devoid of any morphologic neoplasm. High-sensitivity flow cytometry employing fluorochrome-labeled aerolysin (FLAER) substantiated the existence of a substantial glycosylphosphatidylinositol (GPI)- deficient paroxysmal nocturnal hemoglobinuria (PNH) clone spanning both red and white blood cell lineages, thereby confirming the diagnosis of paroxysmal nocturnal hemoglobinuria. Following immunization against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b, treatment with iptacopan (Fabhalta) at a dosage of 200 mg twice daily was initiated on March 27, 2025. Throughout the subsequent weeks, the patient reported a notable increase in energy levels; however, a mild transaminitis necessitated a gradual reduction of the dosage to 200 mg once daily, and subsequently to 200 mg every other day on August 5. At that juncture, laboratory results indicated hemoglobin at 13.7 g/dL, white blood cell count at 3.82×10³/µL, platelet count at 122×10³/µL, LDH at 261 U/L, and haptoglobin at < 6 mg/dL. The patient continues to maintain a clinically stable condition with ongoing monitoring of complete blood count, hemolytic indices, and liver function tests . The normocellular nature of the bone marrow, characterized by erythroid hyperplasia and the presence of a large FLAER-defined clone, strongly favored the diagnosis of PNH over marrow-failure syndromes; proximal alternativepathway inhibition via iptacopan effectively rectified anemia and stabilized blood cell counts despite persistent biochemical hemolysis, while titration guided by liver function tests ensured an optimal balance between therapeutic efficacy and safety. Pre-treatment vaccination strategies were implemented to mitigate the risk of infections associated with complement blockade.
Conclusions: This case exemplifies the efficacy of first-in-class oral factor B inhibition with iptacopan in facilitating rapid and sustained hematologic recovery in newly diagnosed paroxysmal nocturnal hemoglobinuria presenting with pancytopenia, whilst simultaneously managing both terminal (intravascular) and C3-mediated (extravascular) hemolysis. Following the commencement of a 200 mg BID regimen, hemoglobin levels normalized and blood counts stabilized; a mild elevation in transaminases was effectively managed through a dose reduction guided by liver function tests, thereby maintaining therapeutic efficacy. These real-world findings are congruent with phase III clinical trial data (e.g., APPLY-PNH: a ≥2 g/dL increase in hemoglobin observed in approximately 82% of patients and hemoglobin levels reaching ≥12 g/dL in around 69% on iptacopan, as opposed to approximately 0% with conventional therapy), thereby highlighting the substantial clinical impact of iptacopan since its FDA approval in December 2023. Looking ahead, future prospective studies should aim to refine dose-adjustment protocols and long-term safety surveillance to maximize therapeutic outcomes associated with proximal complement blockade.
