Immunotherapy helps suppress inhibitors in acquired hemophilia A
17 patients out of 20 achieved full or partial remission with treatment strategy
Immunotherapy is an effective treatment strategy to suppress the production of autoantibodies and induce remission in people with acquired hemophilia A, a small study in China suggests.
In some cases, however, multiple cycles of immunosuppressive treatment may be required for patients to achieve a good treatment response.The results were published in the Journal of International Medical Research, in a study titled “Retrospective study of the clinical manifestations and efficacy of immunotherapy for patients with acquired hemophilia A.”
Acquired hemophilia A is a bleeding disorder caused by the production of autoantibodies, which are also called inhibitors, usually directed against factor VIII (FVIII), a protein that’s crucial for blood to clot correctly. People with the disorder are prone to episodes of spontaneous or excessive bleeding.
“Raising awareness of acquired hemophilia A … and early diagnosis is critical to reduce the associated mortality rate. We aimed to characterize acquired hemophilia in Chinese patients and evaluate the effectiveness of immunotherapy,” wrote the researchers, who analyzed data from people with a diagnosis of acquired hemophilia A admitted between January 2012 to December 2020 to Xi’an Central Hospital in China.
Data from 20 patients (six men, 14 women) with a median age of 57.5 that ranged between ages 19-82 were assessed. The median time between the onset of symptoms and diagnosis was 4.5 weeks. None of the patients had any record of having used anticoagulants or other treatments that may affect coagulation function before disease onset.
A positive response to immunotherapy
Half the patients showed bleeding under the skin (bruises), with the most extensive involving the arms, legs, and the back of the body. Other bleeding was in the gums, joints and muscles, the abdomen, and gastrointestinal tract, among others. Patients with muscular, joint, intra-abdominal, or gastrointestinal bleeding developed more severe hemorrhage symptoms. Those who mainly showed cutaneous hemorrhages had relatively mild bleeding.
All were treated first with bypass hemostasis treatments using prothrombin complex concentrate (PCC), combined with human FVIII administration, fresh frozen plasma, cryoprecipitate, and antifibrinolytics. Those with severe hemorrhage were treated with activated recombinant human FVIIa.
Bleeding was fully controlled in all patients, including those with severe hemorrhage.
Treatment was followed by starting immunosuppressive therapy, or immunotherapy, to eliminate FVIII inhibitors, as per regular practice. The immunosuppressants used varied depending on the severity of the hemorrhage and each patient’s response to initial therapy.
According to international guidelines, “the principal means of immunosuppression that are used to eliminate FVIII inhibitors include the administration of glucocorticoids, [cyclophosphamide], rituximab, or a combination of these,” the researchers wrote.
Single glucocorticoid administration was used in nine patients (45%). Four others received a combination of rituximab with cyclophosphamide and glucocorticoid or rituximab with cyclophosphamide, vincristine, and a glucocorticoid. Three received cyclophosphamide combined with a glucocorticoid, three were treated with human immunoglobulin in combination with glucocorticoids, and one received cyclophosphamide monotherapy.
Six patients (30%) achieved complete remission, demonstrating full control of their hemorrhage symptoms and no new manifestations. Eleven patients (55%) showed partial remission, with some still presenting new minor hemorrhages, including skin bruises. Three patients (15%) showed no remission.
The data showed most patients (85%) had a positive response to the therapeutic strategy of immunotherapy combined with coagulation factors.
The fact that 55% “of patients only achieved [partial response] … suggest that the complete elimination of inhibitors requires prolonged immunosuppression therapy,” wrote the researchers, who emphasized that “further, multicenter studies with larger sample sizes” are needed to confirm the results, given the limited number of patients analyzed.
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