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What Are Inhibitors ?
Inhibitors are antibodies that the immune system develops when it reacts to the proteins in factor concentrates ( hemophilia treatment ) as if they were harmful substances . Inhibitors fight against the proteins , as if they are foreign substances , thereby preventing the treatment from effectively managing a patient ’ s bleeding risk .
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( strength ) of the inhibitor , either high titer (> 5 BU ) or low titer (< 5 BU ). Generally , high-titer inhibitors quickly counteract infused factor concentrates , whereas low-titer inhibitors act more slowly .
Inhibitors are also classified by response , according to how strongly a patient ’ s immune system reacts to factor concentrates :
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Who Is Affected by Inhibitors ?
Inhibitors occur more often in individuals with hemophilia A ( factor VIII deficiency ) and severe hemophilia ( those with < 1 % of normal clotting factor activity that is associated with bleeding into the muscles or joints , bleeding that occurs one to two times per week , or bleeding for no clear reason ).
Most patients develop inhibitors within the first 75 exposures to factor concentrates , with the greatest risk occurring within the first 10 to 20 rounds of treatment .
Children and adults with newly diagnosed hemophilia should be tested regularly for inhibitors , as well as before any major surgery .
Other factors linked to an increased risk of developing inhibitors include :
• a family history of inhibitor development
• severe defects in the factor gene
• African ancestry
• early intensive treatment with high doses of factor concentrates ( particularly in the first 50 doses )
What Are the Symptoms of Inhibitors ?
A person with hemophilia who develops inhibitors does not get better after standard treatment with factor concentrates . Signs and symptoms of inhibitors include :
• bleeding that is not promptly controlled with the usual dose of factor concentrates
• treatment becoming less effective
• bleeding becoming more difficult to control
How Are Inhibitors Diagnosed ?
Inhibitors are often discovered during a routine laboratory test for activated partial thromboplastin time , which measures how long it takes for blood to clot . When inhibitors are present , the blood takes longer to clot and does not coagulate fully .
To confirm the diagnosis , a Bethesda assay is performed ( measured in Bethesda units [ BU ]); it determines the titer
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• Low-responding inhibitors have stayed below 5 BU , and the patient has a weaker inhibitor response to factor concentrates .
• High-responding inhibitors have exceeded 5 BU at least once , and repeated exposure to factor concentrates will quickly trigger the formation of new inhibitors .
What Are the Treatment Options ?
Decisions regarding treatment of hemophilia with inhibitors should take into account the person ’ s inhibitor titer and anamnestic response , the site and severity of the bleed , and whether the patient has started or is planning to start immune tolerance induction therapy . Treatment options include :
• High-dose factor concentrates : administering factor concentrates at higher doses and / or at more frequent intervals
• Bypassing agents : activated prothrombin complex concentrates and recombinant factor VIIa ( These agents carry a risk for blood clot formation , are expensive , and are not always available in every country .)
• Tranexamic acid : an antifibrinolytic drug given as an additional therapy to help stop blood clots from breaking down
• Epsilon aminocaproic acid : an antifibrinolytic drug given as an additional therapy to help hold clots in place in certain parts of the body , such as the mouth , bladder , and uterus
• Plasmapheresis : a procedure that removes inhibitors from the patient ’ s bloodstream , usually performed when the inhibitor titer needs to be brought down quickly
• Immune tolerance induction therapy : administering frequent doses of factor concentrates over several months to train the body to recognize the treatment without adversely reacting to it ( This type of treatment requires specialized medical expertise , is expensive , and requires a lengthy process .) ●
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Resources From the World Federation of Hemophilia
For over 50 years , the World Federation of Hemophilia ( WFH ) has provided global leadership to improve and sustain care for people with inherited bleeding disorders , including hemophilia , von Willebrand disease , rare factor deficiencies , and inherited platelet disorders . Their vision of “ Treatment For All ” is that one day , all people with a bleeding disorder will have proper care , no matter where they live . The WFH is a global network of patient organizations in 134 countries and has official recognition from the World Health Organization .
For more Patient Information tools , visit elearning . wfh . org .
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