As the Annual Congress of the World Federation of Hemophilia concluded in Orlando, Florida I want to shift your attention to and comment on the significance of the SIPPET study to the developing world.
It is fair to say that a majority of the persons with a bleeding disorder live in the developing world and a majority in this group is yet to be diagnosed. This is a very powerful statement and it is true. The findings of the SIPPET study (SIPPET) have a whole different meaning to the developing world. Let us revisit some of the premise of the SIPPET first, focusing on keywords used. Subjects in SIPPET were 'PUPs' (previously untreated patients) who were 'Toddlers' (<6 years old).
In the developing world PUPs and Toddlers are not mutually exclusive. I mean PUPs are not always Toddlers.
What was the definition of PUPs in SIPPET? PUPs were defined as: "no previous treatment with any factor VIII concentrate, no treatment or minimal treatment (<5 times) with blood components (whole blood, fresh-frozen plasma, packed red cells, platelets, or cryoprecipitate), no treatment with investigational drugs, and a negative test for factor VIII inhibitors at the central laboratory."
By this definition a majority of the diagnosed bleeders in the developing world are PUPs. This is due to the cost and chronic scarcity of purified (plasma or recombinant) factor in the developing world. For example, I was a PUP until 29 years of age (in India) until I received my first dose of monoclonal antibody affinity-purified Factor VIII which I received in the US. There are many PUPs in the developing world. Some younger, some older. These PUPs are not 'toddlers'. Once again this is among the diagnosed bleeders. In the undiagnosed population, ALL ARE PUPS irrespective of age!!
It is important to follow the adult PUP population in the developing world and chart their genetics and inhibitor development- a 'SIPPET' in adult PUPs. Are the findings in this population are similar to those on toddlers?
Personal stories
I have previously written about my life in India with hemophilia. After studying the SIPPET paper and knowing that by definition I was a PUP and on recombinant Factor why I did not develop an inhibitor (thankfully!)? Here are my thoughts. Yes, as a PUP, I started on purified plasma-derived Factor VIII. Recombinant FVIII was not available in the early '90s. After 4-5 years on this I switched to recombinant Factor in the mid-90s. I do not have an inhibitor to FVIII as of today.
In the case of another Indian I know; he was diagnosed at the age of 25 and had received minimal treatment for hemophilia until he came to the US at 27. By SIPPET definition he is a PUP. He started on Recombinant FVIII. A Factor VIII recovery study showed the recovery was poor. Inhibitor analysis led to him being diagnosed with an inhibitor.
I am by no means suggesting any pattern of inhibitor development depending on treatment with plasma-derived or recombinant FVIII. These anecdotes goes to validate that inhibitors can develop in PUPs of any age. The cost of treating and the consequences of not diagnosing and therefore not treating an inhibitor in bleeding disorders is too high to leave SIPPET to toddlers alone. A SIPPET-like study in PUP adults is warranted.
It is fair to say that a majority of the persons with a bleeding disorder live in the developing world and a majority in this group is yet to be diagnosed. This is a very powerful statement and it is true. The findings of the SIPPET study (SIPPET) have a whole different meaning to the developing world. Let us revisit some of the premise of the SIPPET first, focusing on keywords used. Subjects in SIPPET were 'PUPs' (previously untreated patients) who were 'Toddlers' (<6 years old).
In the developing world PUPs and Toddlers are not mutually exclusive. I mean PUPs are not always Toddlers.
What was the definition of PUPs in SIPPET? PUPs were defined as: "no previous treatment with any factor VIII concentrate, no treatment or minimal treatment (<5 times) with blood components (whole blood, fresh-frozen plasma, packed red cells, platelets, or cryoprecipitate), no treatment with investigational drugs, and a negative test for factor VIII inhibitors at the central laboratory."
By this definition a majority of the diagnosed bleeders in the developing world are PUPs. This is due to the cost and chronic scarcity of purified (plasma or recombinant) factor in the developing world. For example, I was a PUP until 29 years of age (in India) until I received my first dose of monoclonal antibody affinity-purified Factor VIII which I received in the US. There are many PUPs in the developing world. Some younger, some older. These PUPs are not 'toddlers'. Once again this is among the diagnosed bleeders. In the undiagnosed population, ALL ARE PUPS irrespective of age!!
It is important to follow the adult PUP population in the developing world and chart their genetics and inhibitor development- a 'SIPPET' in adult PUPs. Are the findings in this population are similar to those on toddlers?
Personal stories
I have previously written about my life in India with hemophilia. After studying the SIPPET paper and knowing that by definition I was a PUP and on recombinant Factor why I did not develop an inhibitor (thankfully!)? Here are my thoughts. Yes, as a PUP, I started on purified plasma-derived Factor VIII. Recombinant FVIII was not available in the early '90s. After 4-5 years on this I switched to recombinant Factor in the mid-90s. I do not have an inhibitor to FVIII as of today.
In the case of another Indian I know; he was diagnosed at the age of 25 and had received minimal treatment for hemophilia until he came to the US at 27. By SIPPET definition he is a PUP. He started on Recombinant FVIII. A Factor VIII recovery study showed the recovery was poor. Inhibitor analysis led to him being diagnosed with an inhibitor.
I am by no means suggesting any pattern of inhibitor development depending on treatment with plasma-derived or recombinant FVIII. These anecdotes goes to validate that inhibitors can develop in PUPs of any age. The cost of treating and the consequences of not diagnosing and therefore not treating an inhibitor in bleeding disorders is too high to leave SIPPET to toddlers alone. A SIPPET-like study in PUP adults is warranted.
No comments:
Post a Comment