Introduction:
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder caused by mutations in the PIGA gene, leading to a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins that protect blood cells from complement-mediated destruction. It is classically associated with intravascular hemolysis, thrombosis, and bone marrow dysfunction. Hematuria in PNH is typically linked to hemolysis, but gross painless hematuria is an unusual presentation. Early diagnosis is essential to prevent complications like thrombosis. This case report highlights an atypical presentation of PNH with persistent painless gross hematuria in a young female.
Methods:
A 19-year-old female had a history of intermittent anemia, thrombocytopenia, and gastrointestinal symptoms, including melena, in July 2023. Laboratory tests at that time showed a low hemoglobin (Hb) of 5.5 g/dL and thrombocytopenia. In September and October 2023, her Hb further dropped to 4.7 g/dL, and she was treated with Wysolone (40 mg). A bone marrow biopsy revealed mild dyserythropoiesis. By December 2023, she developed a fever and gross hematuria, which led to discontinuation of steroids. Workups, including a PNH card test, ANA profile, and ENA panel, were negative during this period.
She presented to us with a 7-month history of painless gross hematuria and mild lower abdominal pain. There was no history of oliguria, dark-colored urine, or other systemic symptoms. Laboratory results revealed subnephrotic-range proteinuria with a spot UPCR of 1.3, urine RBC count of 9083/hpf without dysmorphic RBCs, no Hemoglobinuria, and normal renal function. CECT KUB, revealed median arcuate ligament syndrome without any obstructive cause for the hematuria. Renal Artery Doppler showed normal findings.
Results:
A detailed autoimmune workup, including ANA, ENA, ANCA, and anti-GBM antibodies, was negative. A renal biopsy showed normal findings. ENT and Eye workup for Alports syndrome were also negative. Further evaluation for hemolysis revealed mildly elevated lactate dehydrogenase (LDH) levels, normal haptoglobin, and a positive indirect Coombs test (ICT), suggesting an underlying hemolytic process. Given the clinical suspicion for PNH despite the negative PNH card test, further testing was performed using FLAER (Fluorescent Aerolysin) and CD157 expression on neutrophils and monocytes. Flow cytometry identified a small PNH clone, confirming the diagnosis.
Conclusions:
This case underscores the importance of considering PNH in patients presenting with unexplained gross hematuria, particularly when associated with anemia and thrombocytopenia. Although gross hematuria is an uncommon manifestation of PNH, this case highlights the variability in its presentation. The initial negative PNH card test was followed by flow cytometry, which detected a small PNH clone, emphasizing the need for more sensitive diagnostic tests when there is strong clinical suspicion. Early detection of PNH is crucial to prevent complications such as thrombosis and progressive hemolysis. This case illustrates the complexity of diagnosing PNH and the need for thorough investigations in patients with persistent, unexplained hematuria.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.