tetano
Editor, Senior Moderator
Clin Nephrol Case Stud
. 2025 Mar 14:13:28-36.
doi: 10.5414/CNCS111525 . eCollection 2025. Atypical presentation of H1N1-induced thrombotic microangiopathy with CD46 gene mutation
Aman Pal[SUP] 1 [/SUP], Emmanuel Aydin-Ghormoz[SUP] 2 [/SUP], Swati Mehta[SUP] 2 [/SUP], M J Hajianpour[SUP] 3 [/SUP], Emily Gaine[SUP] 4 [/SUP], Muhammad Ali Zia[SUP] 1 [/SUP], Elie Tannous[SUP] 5 [/SUP], Andrea Lightle[SUP] 5 [/SUP], Krishnakumar Hongalgi[SUP] 2 [/SUP]
Affiliations
Introduction: Thrombotic microangiopathy (TMA) is a pathological description which clinically presents with thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and organ dysfunction. The etiology of TMA is broadly classified into four categories: primary hereditary, primary acquired, secondary, and infection associated. H1N1 influenza is a rare etiology of complement-mediated TMA (CM-TMA) with there being under 30 cases reported to date, and its odd presentation with hemoptysis making it a challenge to diagnose.
Case presentation: We present a case of a Caucasian female in her 20s presenting to the hospital with a viral prodrome in setting of a new acute kidney injury (creatinine 8.2 mg/dL), thrombocytopenia (platelet count 14,000/mm[SUP]3[/SUP]), and H1N1 influenza positive. She developed hemoptysis the next day, with no respiratory distress. Rheumatology work-up for antineutrophilic cytoplasmic antibodies (ANCA), anti-glomerular basement membrane (anti-GBM), and antiphospholipid syndrome (APS) antibodies was negative. CT chest was also negative for pulmonary hemorrhage. Plasma exchange was started empirically until ADAMTS13 activity returned normal (120%), and she was further commenced on eculizumab after an atypical hemolytic uremic syndrome (aHUS)/TMA/Complement 3 Glomerulopathy (C3G) gene panel was sent. Molecular studies revealed a splice site variant of MCP/CD46 gene, which was reiterated on a renal biopsy. The patient was counselled on the genetic results, including predisposition to future events and the importance of long-term eculizumab treatment.
Discussion: CM-TMA is a consequence of alternative pathway dysregulation, commonly associated with genetic mutations which could phenotypically be unmasked by infections, such as influenza virus.
Conclusion: Our case highlights the importance of keeping a broad differential beyond classic pulmonary-renal syndromes in patients presenting with hemoptysis and TMA, while understanding the pathophysiology of infections unmasking genetic mutations in CM-TMA. .
Keywords: TMA; aHUS; complement-mediated TMA; eculizumab; genotype-phenotype correlation; hemoptysis; influenza virus; plasmapheresis.
. 2025 Mar 14:13:28-36.
doi: 10.5414/CNCS111525 . eCollection 2025. Atypical presentation of H1N1-induced thrombotic microangiopathy with CD46 gene mutation
Aman Pal[SUP] 1 [/SUP], Emmanuel Aydin-Ghormoz[SUP] 2 [/SUP], Swati Mehta[SUP] 2 [/SUP], M J Hajianpour[SUP] 3 [/SUP], Emily Gaine[SUP] 4 [/SUP], Muhammad Ali Zia[SUP] 1 [/SUP], Elie Tannous[SUP] 5 [/SUP], Andrea Lightle[SUP] 5 [/SUP], Krishnakumar Hongalgi[SUP] 2 [/SUP]
Affiliations
- PMID: 40115863
- PMCID: PMC11924108
- DOI: 10.5414/CNCS111525
Introduction: Thrombotic microangiopathy (TMA) is a pathological description which clinically presents with thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and organ dysfunction. The etiology of TMA is broadly classified into four categories: primary hereditary, primary acquired, secondary, and infection associated. H1N1 influenza is a rare etiology of complement-mediated TMA (CM-TMA) with there being under 30 cases reported to date, and its odd presentation with hemoptysis making it a challenge to diagnose.
Case presentation: We present a case of a Caucasian female in her 20s presenting to the hospital with a viral prodrome in setting of a new acute kidney injury (creatinine 8.2 mg/dL), thrombocytopenia (platelet count 14,000/mm[SUP]3[/SUP]), and H1N1 influenza positive. She developed hemoptysis the next day, with no respiratory distress. Rheumatology work-up for antineutrophilic cytoplasmic antibodies (ANCA), anti-glomerular basement membrane (anti-GBM), and antiphospholipid syndrome (APS) antibodies was negative. CT chest was also negative for pulmonary hemorrhage. Plasma exchange was started empirically until ADAMTS13 activity returned normal (120%), and she was further commenced on eculizumab after an atypical hemolytic uremic syndrome (aHUS)/TMA/Complement 3 Glomerulopathy (C3G) gene panel was sent. Molecular studies revealed a splice site variant of MCP/CD46 gene, which was reiterated on a renal biopsy. The patient was counselled on the genetic results, including predisposition to future events and the importance of long-term eculizumab treatment.
Discussion: CM-TMA is a consequence of alternative pathway dysregulation, commonly associated with genetic mutations which could phenotypically be unmasked by infections, such as influenza virus.
Conclusion: Our case highlights the importance of keeping a broad differential beyond classic pulmonary-renal syndromes in patients presenting with hemoptysis and TMA, while understanding the pathophysiology of infections unmasking genetic mutations in CM-TMA. .
Keywords: TMA; aHUS; complement-mediated TMA; eculizumab; genotype-phenotype correlation; hemoptysis; influenza virus; plasmapheresis.