Recognizing risk factors of thrombosis and carefully monitoring medication doses are crucial for minimizing thrombotic complications in older patients with acquired hemophilia and serious illnesses like cardiovascular disease, a report describing four cases says.
The study, “Acquired Haemophilia A. Which is the best therapeutic choice in older adults? Single center study of 4 cases,” was published in Reumatismo.
Acquired hemophilia (AHA) is a non-hereditary, autoimmune disorder in which the patients’ immune system starts attacking and destroying a clotting protein, called factor VIII (FVIII). As a result, their blood progressively loses the ability to clot, leading to spontaneous bleeding episodes similar to those in people with inheritable forms of hemophilia, in which patients have little or no clotting factor.
“[B]ypassing agents, i.e. recombinant activated factor VII (rFVIIa) [NovoSevenRT] and activated prothrombin complex concentrate (aPCC) are considered the first choice of treatment in combination with immune-modulating agents in AHA. However, in the bypassing agents treatment, severe thrombotic complications have been reported,” the researchers said. (In thrombosis, blood clots block veins or arteries.)
Bypassing agents are a combination of different blood clotting factors that go around, or bypass, the missing clotting factor to control bleeding; immune-modulating agents are used to prevent the patients’ immune system from producing antibodies, or blood proteins, against FVIII.
To evaluate the risk of thrombotic complications, clinicians from the Pordenone General Hospital in Italy reviewed the clinical case reports of four older patients with AHA and other disorders, who were treated to prevent such complications.
The patient received a transfusion of two units of red blood cells and doctors confirmed there were no more bleeding sites. After that, he started treatment with vitamin K and fresh frozen plasma, but was forced to discontinue therapy due to an allergic reaction that caused skin rashes, angioedema (tissue swelling), and shortness of breath.
Physicians decided to treat his hemophilia using only immunosuppressive therapy (prednisone 1 mg/kg and cyclophosphamide 1.4 mg/kg), without bypassing agents. The patient’s FVIII levels returned to normal within 20 days. Treatment was well-tolerated until the antibodies against FVIII were completely eliminated, which took two months, the study reported.
The second patient was an 84-year-old man admitted with spontaneous skin bleeding, hematoma to the back of the throat, and abdominal pain spreading to the lower left leg. He had a medical history of high blood pressure and a rare heart deformity (intraseptal atrial aneurism), for which he had been prescribed anti-platelet therapy, namely aspirin, to prevent blood clots from forming.
Computed tomography (CT) scans revealed a large hematoma on the left side of his abdomen. He stopped anti-platelet therapy, received two units of red blood cells, and was started on NovoSevenRT (at 90 μg/kg every six hours for six days, then every eight hours for one day, then every 12 hours for four days, and finally once daily for two days) together with immunosuppressants (prednisone 1.3 mg/kg and cyclophosphamide 1.3 mg/kg) to manage his AHA.
FVIII levels returned to normal within 24 days and anti-FVIII antibodies were eliminated within a month of treatment. No thrombotic complications were reported.
The third patient was a 69-year-old man admitted with extensive bruising in the skin of the arms and legs, a neck hematoma, and joint pain. He had a medical history of diabetes and was on anti-platelet therapy due to pericarditis, which is inflammation of the sac that surrounds and protects the heart.
He stopped anti-platelet therapy, received four units of red blood cells, and was started on the bypassing agent aPCC Feiba (70 U/kg every 12 hours for four days, then 66 U/kg every other day for nine days, then 44 U/kg every other day for 18 days), together with immunosuppressants (6-metilprednisolone 1.2 mg/kg and cyclophosphamide 1.1 mg/kg).
The anti-FVIII antibodies were eliminated within 30 days of treatment, with no thrombotic complications.
The fourth patient was a 78-year-old woman admitted with a large hematoma in her right arm. She had a medical history of COPD, hepatitis C not associated with chronic liver disease, and Lewy body dementia. She was bedridden and was on anticoagulant medication (low molecular weight heparin, or LMWH) to prevent blood clots.
Doctors immediately stopped treatment with LMWH, infused two units of red blood cells, and started her on Feiba (100 U/kg every six hours for five days) together with immunosuppressants (prednisone 1 mg/kg and cyclophosphamide 2 mg/kg).
Her hematoma receded gradually within the first three weeks of treatment. FVIII levels returned to normal within four weeks, and immunosuppressive therapy was stopped after six weeks.
“All these together highlight the complex management of AHA in older adults with cardiovascular comorbidities. Although the cases are few, we have highlighted the efficacy and the safety of aPCC (Feiba) and recombinant activated FVII (rFVIIa) standard dose in older adults with cardiovascular diseases in anti-thrombotic therapy,” the investigators said.
“In conclusion, recognition of thrombotic risk factors and attention to drug dose play a key role in avoiding thrombotic AEs [adverse events] in particular settings of older adult patients with comorbidities and multi-drug intake. However, considering the different experiences in the field of AHA treatment, prospective studies involving a large number of patients are required,” they added.