In Cureus, Rayas and colleagues presented the case report of a patient with untreated aplastic anemia who was later diagnosed with classical paroxysmal nocturnal hemoglobinuria (PNH). 

Aplastic anemia is characterized by bone marrow failure, leading to pancytopenia (including anemia). It is a rare and life-threatening disease. The most common cause for aplastic anemia is the autoimmune reaction of T lymphocytes against hematopoietic stem cells, during which the disorder can develop with alarming swiftness. 

The main challenge with aplastic anemia is that there is no definite curative treatment that can ameliorate symptoms of the disease. The category of individuals most likely to be affected by this condition are those between 15 and 25 years of age, as well as individuals over the age of 60. Epidemiological studies do not demonstrate significant disparities in age or gender. 

PNH, on the other hand, is an acquired X-linked disease that is characterized by intravascular and extravascular hemolysis, mediated by the complement and reticuloendothelial systems, respectively. The most common triad of signs associated with PNH are hemolytic anemia, pancytopenia, and thrombosis. 

Read more about PNH etiology 

Patients who develop PNH tend to present with vague symptoms such as fatigue, weakness, or chronic dyspnea. As such, efforts to diagnose this condition are often hampered as physicians first seek to rule out more common causes. In addition, many parts of the world lack the proper funding needed for thorough and transparent investigations, meaning that the actual incidence of PNH may be higher than that reported in the medical literature. 

Aplastic anemia is an established risk factor for PNH; studies indicate a strong pathophysiological correlation between both disorders. It is imperative that suspected cases are diagnosed accurately and that supportive care is initiated as early as possible. 

Rayas et al detail the case of a 29-year-old man who presented with a 1-week history of generalized weakness and intermittent nausea on a background of aplastic anemia. Upon physical examination, the patient appeared pale; laboratory investigations revealed low erythrocytes, leukocytes, platelets, hemoglobin, and haptoglobin. He had elevated absolute reticulocyte count, serum creatinine, conjugated bilirubin, creatinine kinase, and lactate dehydrogenase in the absence of chronic kidney disease. 

A peripheral blood smear revealed 1+ schistocytes and 1+ spherocytes. An abdominal ultrasound was unremarkable. A bone marrow biopsy and aspirate revealed a hypercellular bone marrow with around 90% cellularity, probably driven by elevated erythroid precursors with a leftward shifted maturation stage. 

Read more about PNH diagnosis

The patient had an estimated myeloid:erythroid ratio of 1:10—a finding highly suggestive of erythrocyte hyperplasia. Blasts were estimated to be less than 5%, and there were no dysplastic features in any of the 3 lineages. Flow cytometry revealed CD59 deficiency in around 1 in 10 cells. 

The patient’s physicians started him on cyclosporine, which did not result in clinical improvement. He was then put on eculizumab therapy, which improved his generalized weakness and nocturnal hematuria. 

Treating PNH in the Context of Aplastic Anemia 

The treatment of aplastic anemia depends on its underlying cause; the care pathway of patients with acquired aplastic anemia differs from those with congenital forms of the disease. The first-line therapy for very severe aplastic anemia remains allogeneic hematopoietic stem cell transplantation from a matched sibling donor. Symptomatic management, such as the transfusion of red blood cell concentrates, is also encouraged. 

In the case of this patient, he was offered eculizumab after cyclosporine treatment failed. Eculizumab is typically offered for patients diagnosed with classical PNH; it works by countering complement-mediated hemolysis by protecting red blood cells that lack CD55 and CD59. It is highly effective as a form of PNH therapy, with a 70% reduction in the risk of thrombotic events and severe vascular adverse events. 

“While classical PNH patients benefit from anti-complement therapy, there are limited publications to guide treatment in secondary PNH or aplastic anemia/PNH patients,” Rayas and colleagues wrote. 

Read more about PNH treatment 

When both disorders are diagnosed concurrently in the same patient, it is best to treat them as a whole rather than as individual disorders. There is conflicting evidence surrounding the use of immunosuppressants combined with eculizumab; some studies suggest they offer no statistically significant benefit at all. However, other studies suggest that patients with PNH and underlying bone marrow disorders with significant clinical hemolysis may benefit from complement inhibitor therapy, such as in the case of the patient in this report, who achieved clinical recovery with eculizumab treatment. 

Because patients with aplastic anemia are vulnerable to the expansion of PNH clones, physicians should screen for comorbid hematological diseases when a diagnosis of aplastic anemia is established. PNH remains a debilitating and fatal disease, but responds well to timely treatment. The devising of a comprehensive strategy for treating aplastic anemia and PNH in the same individual and providing supportive care when needed are the best guarantee for therapeutic success. 

“Aplastic anemia is a known risk factor of PNH which possesses significant morbidity and mortality,” Rayas et al wrote. “In patients with suspected PNH, rapid diagnosis and concomitant supportive care are critical.” 


Rayas J, Hassan M, Hock RA, et al. Attack of the clones: a patient with untreated aplastic anemia presenting with classical paroxysmal nocturnal hemoglobinuriaCureus. 2023;15(1):e34093. doi:10.7759/cureus.34093

Urbanowicz I, Nahaczewska W, Celuch B. Narrative review of aplastic anemia – the importance of supportive treatmentAnn Palliat Med. 2021;10(1):694-699. doi:10.21037/apm-20-1957