Case Series: Plasma Exchange Can Help Reduce Bleeding in AHA
Therapeutic plasma exchange (TPE) was found to reduce bleeding and ease disease symptoms in six people with acquired hemophilia A (AHA), a case series reported.
These findings support TPE — in which the liquid part of blood is replaced with substitute plasma — as an alternative treatment option in geographic areas, including western China, without access to bypassing agent therapies.
“We advocate that a more intensive first-line treatment, including TPE may potentially achieve faster remission, without bypassing agent therapy, especially in several poor countries where that medical treatment is unaffordable,” the researchers wrote.
The study, “Feasibility of therapeutic plasma exchange-based combination therapy in the treatment of acquired hemophilia A,” was published in the journal Medicine.
Acquired hemophilia A, known as AHA, is an autoimmune bleeding disorder caused by the abnormal production of antibodies that target clotting factor VIII (FVIII). As a result, FVIII is functionally blocked (inhibited), which can lead to excessive bleeding.
The first-line treatment for AHA is to control immediate bleeding episodes by injecting blood clotting factors directly into the bloodstream. Because people with AHA carry antibodies against FVIII, patients usually are given a combination of clotting factors without FVIII, known as bypassing agents. Additionally, to limit the autoimmune response and reduce anti-FVIII antibody levels, immunosuppressive therapies also are recommended.
However, in many poorer countries, such as western China, bypassing agents are not readily available or are unaffordable to most patients. That means that healthcare providers need to consider cost-effective alternative therapies.
Therapeutic plasma exchange or TPE, also known as plasmapheresis, is a treatment strategy in which plasma ━ the liquid part of blood that contains antibodies ━ is replaced with substitute plasma. The therapy, which also is used in other autoimmune disorders, including multiple sclerosis and myasthenia gravis, has been proven to rapidly remove disease-causing antibodies.
Early studies have evaluated such plasma exchange in people with AHA — but in combination with various other medications. More recently, in 2020, a case report described how TPE successfully treated an AHA patient with life-threatening bleeding who did not respond to immunosuppressant therapy.
Now, a team of investigators at the Second Affiliated Hospital, Chongqing Medical University, in west China, described six AHA cases treated by TPE plus corticosteroid immunosuppressive medications and rituximab. Rituximab is an approved cancer therapy that has been used in autoimmune diseases to deplete immune B-cells to lower antibody production.
“To the best of our knowledge, our study is the first-of-its-kind to report treatment of 6 cases who underwent TPE and received adjunctive immunosuppressants as an alternative to [bypassing agent] administration,” the team wrote.
The six patients included one man and five women, ranging in age from 18 to 66, with a median age of 51. Three had other autoimmune diseases, including Sjögren’s syndrome, lupus, and undifferentiated connective tissue disease.
Overall, in all of the patients, FVIII levels were severely low, anti-FVIII antibodies were high, and the activated partial thromboplastin time, or aPTT, were markedly extended ━ a sign of impaired blood clotting.
Four of the six patients showed bleeding below the skin surface of the legs and feet, one had vaginal bleeding, and another had bleeding in the digestive tract.
Along with TPE — two to eight cycles per person — all patients were treated individually with different combinations of corticosteroids and rituximab. The team used dexamethasone, methylprednisolone, and prednisone as the corticosteroids.
Following treatment, aPPT decreased in all patients, and all six saw their bleeding symptoms ease. Three months later, anti-FVIII antibodies were undetectable in all participants.
These effects were sustained for up to 104 months, or almost nine years, with no further bleeding or increase in antibodies levels. All but two patients experienced at least partial remission after maintenance therapy was discontinued.
Moreover, no adverse events associated with therapeutic plasma exchange were reported in any of the six cases.
The first patient, a woman who had bruising (hematoma) in the legs and feet, received two cycles of TPE on days 11 and 12 of admission plus a combination of corticosteroids. The therapy in this case resulted in no bleeding symptoms and lower aPTT. Maintenance therapy included low-dose rituximab for five months, but the woman only achieved partial remission after it was stopped.
The second case also featured hematoma or bruising of the lower limbs as well as bleeding in the gums. This patient, also female, was given TPE on days two and three plus a combination of corticosteroids. After three months, no anti-FVIII antibodies were detected, and she started rituximab maintenance therapy, which resulted in complete remission.
In the third case, a woman with a past medical history of under-the-skin hematoma in both lower limbs was initially treated for a sudden onset of severe pain in her left ankle and hand. Following examination, she was diagnosed with AHA and underwent two cycles of TPE plus corticosteroid treatment. She temporarily achieved partial remission but was later readmitted to the hospital and given two additional TPE cycles and rituximab. However, the patient died after 11 months due to a lung infection and acute respiratory distress syndrome.
A 33-year-old woman who had abnormal vaginal bleeding following the birth of a child was the fourth case of this series. Blood tests confirmed AHA and she received two initial cycles of therapeutic plasma exchange. In response to ongoing vaginal bleeding, the woman was given three additional cycles of TPE, followed by rituximab. That led to her antibody levels decreasing and no bleeding complications occurred. By day 25, her blood coagulation profiles significantly improved, and she achieved complete disease remission.
The fifth case described a male patient who had hematomas in both lower limbs and a history of Sjögren’s syndrome. Upon AHA diagnosis, he was first treated with corticosteroids for six days, then underwent three TPE cycles, followed by rituximab treatment. After discontinuing maintenance therapy, he experienced partial remission.
Finally, an 18-year-old female with bleeding in the digestive tract over 24 hours was treated as the sixth case. She had persistent dizziness, weakness, and fatigue, and her medicinal history showed lower back pain and intermittent fever of unknown origin for the previous three months. This patient was first diagnosed with hemolytic anemia, a disorder characterized by the premature destruction of red blood cells. Due to the unknown cause of anemia and her persistent symptoms, she underwent a bone marrow biopsy that confirmed pre-existing lupus. Blood tests were consistent with AHA, and she was treated with six cycles of therapeutic plasma exchange. While TPE improved her symptoms temporarily, no remission was seen. Following sudden abdominal infection and multiple organ failure, the patient died.
“Our results from this study indicate that TPE in combination with corticosteroids and rituximab may be an effective and promising therapy for AHA in the absence of alternatives,” the researchers wrote, noting that this is especially relevant in countries in which certain medical treatments, such as bypassing agents, are unaffordable or not readily available.
“Our experience suggests that plasma exchange should be initiated early in AHA patients with severe bleeding and high titers [levels] of FVIII inhibitor,” they added.
The researchers noted that the case series was small, and done retrospectively, but concluded that a TPE-based combination therapy “may be an effective and reliable treatment for AHA.”