Rituximab effective in rare dual autoimmune blood disorder case
Therapy improved anemia and clotting in patient with CAD and AHA
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Rituximab helped improve signs and symptoms of cold agglutinin disease (CAD) occurring alongside acquired hemophilia A, another autoimmune blood disorder, in a 53-year-old man in China, a case report describes.
In CAD, the immune system mistakenly attacks red blood cells, while in acquired hemophilia A, it targets factor VIII (FVIII), a protein needed for blood clotting.
“This report describes the first documented case of concurrent cold agglutinin disease (CAD) and acquired hemophilia A (AHA),” the researchers wrote. “This unique presentation advances our understanding of shared autoimmune mechanisms in [blood disease] and supports the use of early B-cell-directed therapy [like rituximab] in complex autoimmune [blood] conditions.”
Rare overlap highlights shared autoimmune disease mechanisms
B-cells are immune cells that produce antibodies, including the self-reactive antibodies that drive CAD and AHA.
The study, “Case Report: Coexisting cold agglutinin disease and acquired hemophilia A: a rituximab-responsive dual autoimmune disorder,” was published in Frontiers in Medicine by researchers in China.
CAD is caused by self-reactive antibodies, called cold agglutinins, that bind to red blood cells at cold temperatures, causing the cells to clump together. This activates the complement system, part of the immune system, leading to destruction of red blood cells, known as hemolysis, and resulting anemia.
Acquired hemophilia A is a rare bleeding disorder caused by antibodies that mistakenly target factor VIII (FVIII). It is often associated with other autoimmune diseases, cancers, or pregnancy.
“The co-occurrence of CAD and AHA in a single patient is exceedingly rare,” the researchers wrote. “This case report describes a patient who simultaneously presented with both autoimmune disorders, a scenario with significant diagnostic and therapeutic implications.”
Patient diagnosed with both CAD and acquired hemophilia A
The 53-year-old man was admitted to the hospital with a four-year history of recurrent tea-colored urine, suggestive of hemoglobinuria, and nose bleeding that had started one day earlier.
He had previously experienced episodes of blood in the urine, as well as acrocyanosis — painless blue discoloration of the fingers and ears — triggered by cold exposure and resolved with warming.
One month before admission, he experienced vomiting of blood, dark brown urine, chest tightness, and fatigue.
Blood tests at another clinic showed severe anemia and prolonged activated partial thromboplastin time, indicating impaired blood clotting. He also had elevated bilirubin levels, a marker of hemolysis, and very low factor VIII (FVIII) activity, along with a factor VIII inhibitor, confirming a diagnosis of acquired hemophilia A.
At that point, he began treatment with intravenous immunoglobulin (IVIG) to help suppress the abnormal immune response, and tranexamic acid (sold as Cyklokapron and Lysteda, with generics available) to help stabilize blood clots and reduce bleeding. However, his anemia and blood clotting issues persisted.
At the researchers’ hospital, further testing confirmed ongoing hemolysis, abnormal clotting parameters, and persistently low FVIII activity levels. He also showed several signs of CAD, including red blood cells clumping at room temperature, a positive direct antiglobulin test indicating complement proteins bound to red blood cells, and detectable cold agglutinins. These findings confirmed a diagnosis of CAD.
Rituximab treatment leads to remission and clinical improvement
Initial immunosuppressant therapy included prednisone, a corticosteroid, and cyclophosphamide, but this approach led to minimal improvement. He was then given a short course of high-dose methylprednisolone, another corticosteroid, along with prothrombin complex concentrate and blood transfusions to help improve clotting and treat anemia.
During treatment, he developed a severe lung infection that progressed to septic shock, a life-threatening complication. His anemia and clotting abnormalities worsened during this time.
Because initial therapies were ineffective, the man was treated with rituximab, “reflecting a targeted B-cell depletion strategy supported by evidence in both CAD and AHA,” the team wrote. Following treatment, his clotting function improved and his anemia lessened.
After treatment, the patient was discharged and monitored closely. His factor VIII inhibitor became undetectable, indicating complete remission of AHA, and his hemoglobin levels increased, reflecting improvement in anemia.
He also reported less fatigue and no further episodes of bleeding or blood in the urine. He continued receiving low-dose cyclophosphamide to help reduce the risk of recurrence.
“This is the first reported case of CAD and AHA occurring simultaneously … [highlighting] the importance of recognizing overlapping autoimmune disorders, particularly in patients exhibiting atypical clinical presentations,” the researchers wrote. “Integrating rituximab earlier in the treatment algorithm for patients with concurrent autoimmune [blood diseases] could mitigate the risks associated with ineffective immunosuppressive therapies and improve overall outcomes.”
