Does the Use of Different Factor VIII Products Influence Inhibitor Formation in Patients with Haemaphilia A.
Authors: Howarth David E. , Kennedy Jayne L. , Will Andrew M. , Carr Trevor F. , Robert Wynn 
Published: October 2019

This retrospective study looked at all patients with Haemophilia A who attended Manchester Pendlebury Childrens Hospital for their first and subsequent Factor replacement therapy between January 1980 and May 2005. The aim was to determine :-

Does an increased number of different products used influence inhibitor formation. Does using a B domain deleted factor (Refacto) concentrate influence inhibitor formation. Does changing from plasma derived to recombinant factor influence inhibitor formation.

A total of 107 patients who received a cumulative total of 65,102 trearment days were identified and the following information was recorded for each patient :-severity of haemophilia (mild, moderate or severe) and baseline factor VIII level, date and age of first product, all types of products used, number of treatment days used of each product, detection of inhibitor and if present date of ocurrence and age of patient. The policy of the unit was to test for inhibitors every six months, pre operatively or when clinically indicated. Thirteen different products were in use during the period of the study :- AHFC(anti haemophilic factor concentrate), Cryoprecipitate, 8Y, 8SM, Alphanate, Replenate, Monoclate P, Helixate, Refacto, Recombinate, Hemophil M, Advate and Haemate P.

Only 4 patients out of 107 developed inhibitors and all were exposed to less than 4 products.

Inhibitor patient demographics Haemophilia type and baseline factor VIII Number of treatment days before inhibitor Products used with respective treatment days Severe (<1%) 249 Cryoprecipitate (128) 8Y(121) Severe (1%) 75 Alphanate(34) 8SM(34) Replinate(7) Moderate (2%) 39 Alphanate(30) Helixate(9) Moderate (2%) 18 Refacto(2) Helixate(16)

A total of 37 patients received 6 or greater factor products. The mean number of treatment days was 1224 (median 1285, SDV 863) and the mean number of factor products used was 6.8 (median 7, SDV 0.81).

In severe patients (baseline factor VIII of 2% or less) a total of 31 patients received 4 or greater factor products. The mean number of treatment days was 1512 (median 1501, SDV 776) and the mean number of factor products used was 6.45 (median 6, SDV 1.31). A total of 23 patients received 6 or greater factor products. The mean number of treatment days was 1664 (median 1525, SDV 776) and the mean number of products used was 7.04 (median 7, SDV 0.93).

There were 10443 exposure days of Refacto in those patients that did not develop an inhibitor. 69 out of 103 patients were exposed to the product with a mean number of treatment days of 151 (median 43, SDV 237). In the same population 29 out of 43 severe patients (baseline factor VIII of 2% or less) were exposed to the product with a total number of exposure days of 6464 with a mean number of treatment days of 222 (median 241, SDV 241). There were only 2 exposure days of ReFacto in just one of the inhibitor patients.

64 patient changed from using plasma to recombinant products. Only one of these patients developed an inhibitor. In this study the number of different factors used, use of a B deleted domain factor and change from plasma derived to recombinant factors did not appear to be factors in the formation of inhibitors.