Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the introduction of a new pasteurised factor VIII concentrate (Factor VIII CPS-P) in The Netherlands in June 1990, an increase in the occurrence of inhibitors in hemophilia A patients was reported. The clinical course of this group of inhibitors (n = 12) was compared with hemophilia patients in whom an inhibitor developed before June 1990 (classic inhibitors) (n = 32). Striking differences were found between both groups not only in patient age (median 22 years versus 8 years) and number of exposure days (< 50 - > 1000 versus < 50), as described in previous reports, but also in clinical course and response to treatment. In the recent group of inhibitors antibody titers showed a rapid decline when product was changed which was not the case in the group with classic inhibitors. In the group of classic inhibitors immune tolerance therapy with low dose factor VIII succeeded in 83%. Success was to a high degree dependent on the inhibitor level. In the group of recent inhibitors immune tolerance with the same concentrate was only successful in a single patient. However, once the patients were switched to another concentrate, antibody levels dropped to less than 2 BU/ml within 8 months in all patients. It seems likely that in this group of product associated inhibitors, treatment success was due to elimination of antigen stimulation rather than induction of immune tolerance.
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PMID:Clinical course of factor VIII inhibitors developed after exposure to a pasteurised Dutch concentrate compared to classic inhibitors in hemophilia A. 797 35

The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient-years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group. 847 77