Drawing First Blood
We invite two experts to debate controversial topics in hematology and health care .
FEATURE
Choosing Between Treatment Strategies for Patients With Acquired Hemophilia A
Alice Ma , MD
Rebecca Kruse-Jarres , MD , MPH
Disclaimer : The following positions were assigned to the participants and do not necessarily reflect ASH ’ s opinion , the participants ’ opinions , or what they do in daily practice .
Agree ? Disagree ? We want to hear from you ! Send your thoughts and opinions on this controversial issue to ashclinicalnews @ hematology . org .
Acquired hemophilia A ( AHA ) is a rare bleeding disorder in which patients develop inhibitors against clotting factors – most often factor VIII ( FVIII ). For nearly 10 years , the standard of care for the treatment of AHA was either recombinant factor VIIa ( rFVIIa ) or FVIII inhibitor bypass activity ( FEIBA ), known as a “ bypassing agent ” because it causes coagulation without the need for FVIII . In October 2014 , the U . S . Food and Drug Administration ( FDA ) approved antihemophilic factor [ recombinant ], porcine sequence ( rpFVIII ) for the treatment of AHA , which replaces FVIII , rather than bypassing it . rpFVIII has been effective in clinical trials , however , pricing concerns put this treatment out of reach for some patients .
ASH Clinical News invited Alice Ma , MD , and Rebecca Kruse- Jarres , MD , MPH , to debate the question : “ In AHA treatment , should we use rpFVIII or standard bypassing agents ?” Dr . Ma will be arguing on the “ standard bypassing agents ” side , and Dr . Kruse- Jarres will be arguing on the “ rpFVIII ” side .
Dr . Ma is an associate editor of ASH Clinical News and a professor of medicine in the Department of Medicine in the Division of Hematology and Oncology at the University of North Carolina ( UNC ) School of Medicine in Chapel Hill . Dr . Kruse-Jarres is director of the Washington Center for Bleeding Disorders at Bloodworks NW and associate professor of medicine in the division of hematology at the University of Washington School of Medicine in Seattle , Washington .
Dr . Ma : In general , hematologists have used either rFVIIa or FEIBA for patients with AHA for a number of years and have a lot of experience with them . They are effective in controlling bleeding without substantially increasing thrombotic risk – except for in high-risk patients , like older people with underlying vascular disease . The introduction of rpFVIII has provided us with a new therapeutic option but , in the current economic climate , our hospital administration mandates bypassing agents as first-line therapy for these patients .
Dr . Kruse-Jarres : rpFVIII works differently than bypassing agents such as rFVIIa or FEIBA . It is a replacement product – essentially , it “ plugs the hole ” and fixes the defect in the coagulation cascade , rather than bypassing the defect . rpFVIII contains a recombinant analogue of porcine FVIII , which is similar enough to human FVIII , but is less likely to be affected by FVIII inhibitors that are present in patients with AHA .
The FDA ’ s approval was based on results of a multicenter , open-label , controlled phase II / III trial . All 28 patients with AHA treated with rpFVIII had a good response – bleeding stopped or was reduced at 24 hours after the initial infusion . rpFVIII also results in measurable factor VIII activity ; being able to check those levels lets us know if the patient is getting enough , but not too much , of the product .
It is thus difficult to compare these products physiologically . They do different things , so how would we determine which one is the “ better product ?” In my opinion , rpFVIII simply offers more advantages ; it replaces what ’ s missing , and it can be measured .
Dr . Ma : True , that is a concern with the bypassing agents ; we cannot monitor their efficacy in a standard , reliable way . Monitoring efficacy is possible , but it requires sophisticated equipment ; not all healthcare centers have that available , and , even in some hands , the sophisticated monitoring is not reliable .
Most centers will only be able to use crude measures of efficacy . Because we ’ re not able to monitor its efficacy , we don ’ t know how much of the bypassing agent to give , when to give it , or if it is effective . I like to say , ‘ To measure the efficacy of these drugs , you need a Sharpie marker , a complete blood count , and a tape measure to measure limb girth or the size of a hematoma .’
Again , these agents also can be fairly pro-thrombotic in certain patients with circulating activated platelets and significant vascular disease . These are the patients for whom I worry the most about a potential thrombosis .
Dr . Kruse-Jarres : I agree – considering the thrombogenicity in individual patients is important when we are deciding on a treatment approach . AHA is a rare disease that typically affects older people who do not have a bleeding disorder to begin with . Because of their age and the possibility of an underlying disorder , such as a hematologic malignancy , these patients are at an increased thrombotic risk before treatment begins . When we start these patients on a hemostatic agent , we need to keep in mind that they are also being treated with immunosuppressive therapy that will eventually get rid of the inhibitor . During that time , there is definitely an elevated risk for thrombosis .
We have good hemostatic treatment options available , in the form of FEIBA and rFVIIa – which are both about 90 percent effective when used as a first-line agent for hemostasis – but neither one offers measurable efficacy and both of them have thrombogenic potential .
Dr . Ma : Still , I would say standard bypassing agents are preferable to rpFVIII in a couple of circumstances . The first occurs when you are at a center where FVIII levels cannot be measured in real time ; using rpFVIII in this case would completely negate the one great benefit of the agent . In clinical trials , rpFVIII
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