High Frequency of Low Plasma Haptoglobin Values Found in Hemophilia A Patients on Prophylactic Treatment with Factor VIII Concentrates - A Sign of Hemolysis?

1981 ◽  
Vol 46 (02) ◽  
pp. 554-557 ◽  
Author(s):  
Nils Egberg ◽  
Margareta Blombäck
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
High Frequency ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Factor Viii Concentrates ◽  
Fraction I ◽  
Elevated Lactate ◽  
Elevated Lactate Dehydrogenase ◽  
Plasma Haptoglobin

SummaryLow plasma haptoglobin values have been observed in hemophilia A patients on regular prophylactic treatment with factor VIII concentrates. Two of 3 patients treated with fraction I-0 (Kabi) and 7 of 11 patients treated with high-purity concentrates (Hyland) had low haptoglobin values. Four of 8 patients who were treated with high-purity concentrates prescreened for a low content of anti-A and anti-B immunoglobulins still showed low haptoglobin levels. Unexpectedly, 2 patients of blood group 0 showed low haptoglobin values. The presence of irregular erythrocyte alloantibodies and/or other contaminants of the concentrates might thus also be a cause of hemolysis resulting in an increased consumption of haptoglobin.Elevated lactate dehydrogenase levels were also frequent. No correlations were found between albumin, aspartate or alanine aminotransferase levels and haptoglobin levels.

Incidence of Factor VIII Inhibitor Development in Hemophilia A Patients Treated with Less Pure Plasma Derived Concentrates

1994 ◽  
Vol 71 (05) ◽  
pp. 544-547 ◽  
Author(s):  
R de Biasi ◽  
A Rocino ◽  
M L Papa ◽  
E Salerno ◽  
L Mastrullo ◽  
...  
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Hemophilia A ◽  
Cumulative Risk ◽  
Factor Viii Inhibitor ◽  
Anamnestic Response ◽  
Inhibitor Development ◽  
Increased Risk ◽  
Factor Viii Concentrates ◽  
Very High

SummaryVery-high-purity Factor VIII concentrates produced by monoclonal or recombinant technology have been postulated to be more antigenic resulting in an increased risk of inhibitor development in hemophilia A patients. However, previous reports, mainly based on prevalence figures, may have understimated the “true” risk of this complication in patients treated with less pure Factor VIII concentrates. The present study, started in 1975, has been designed to calculate the risk of inhibitor development in patients with severe or moderate hemophilia A, followed since their first exposure to intermediate or high-purity Factor VIII concentrates, produced by conventional technologies. Sixty-four hemophiliacs fulfilled the enrollment criteria. Inhibitors developed in 20.3% (13/64) of all patients and in 23% (11/48) of those with severe Factor VIII deficiency. Eleven patients manifested a strong anamnestic response after exposure to Factor VIII (high responders) and 2 had low inhibitor concenlialions despite repeated Factor Vlll infusions (low responders). The incidence of inhibitor development was 24.6 per 1000 patient yeuis of observalion. The, cumulative! risk of inhibitor formation was 19,9% at age of 6 years, and 20.3% at 5 years after the first exposure. The risk was 19.3% at 70 days of exposure to Factor VIII concentrates, and 17.2% after a total of 50,000 units of Factor VIII given.Further stuides are needed to confirm the above risk of acquiring an inhibitor, which indicates and under-estimations by previous studies. In addition, more data is needed to demonstrate whether very high purity Factor VIII concentrates may be more antigenie than conventional preparations.

A Survey of the Effectiveness of Prothrombin Complex Concentrates in Controlling Hemorrhage in Patients with Hemophilia and Anti-Factor VIII Antibodies

1980 ◽  
Vol 44 (01) ◽  
pp. 039-042 ◽  
Author(s):  
Philip M Blatt ◽  
Doris Ménaché ◽  
Harold R Roberts
Keyword(s):  
Factor Viii ◽  
Ad Hoc ◽  
Hemophilia A ◽  
Working Party ◽  
International Committee ◽  
Factor Ix ◽  
Prothrombin Complex Concentrates ◽  
Factor Viii Concentrates

SummaryThe treatment of patients with hemophilia A and anti-Factor VIII antibodies is difficult. Between July 1977 and June 1978, a survey was carried out by an ad hoc working party of the subcommittee on Factor IX concentrates of the International Committee on Thrombosis and Hemostasis to assess the effectiveness of Prothrombin Complex Concentrates in controlling hemorrhage in these patients. The results are presented in this paper and, although subjective, support the view that these concentrates are not as effective in patients with inhibitors as Factor VIII concentrates are in patients without inhibitors.

Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Final Results from Extension Studies

2021 ◽  
Author(s):  
Matteo Nicola Dario Di Minno ◽  
Alessandro Di Minno ◽  
Ilenia Calcaterra ◽  
Ernesto Cimino ◽  
Francesco Dell'Aquila ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Factor Viii Concentrates

Comparative Investigations on Factor VIII Assays

1975 ◽  
Author(s):  
R. Pflugshaupt ◽  
S. Moser ◽  
K. Züger ◽  
R. Bütler
Keyword(s):  
Factor Viii ◽  
High Activity ◽  
Hemophilia A ◽  
Statistical Evaluation ◽  
Two Stage ◽  
One Stage ◽  
Normal Plasma ◽  
Calibration Curves ◽  
Factor Viii Concentrates

Six one stage methods and one two stage method were tested for precision and reproducibility. With each method twenty calibration curves of normal plasma and two lots of Factor VIII concentrates were established. Statistical evaluation revealed only minor differences. Neither one of the methods was optimal for both the physiological-pathological region and the region of high activity preparations.Three selected methods were tested in vivo for accuracy: nine patients with hemophilia A were treated with equal amounts of Factor VIII concentrates or kryoprecipitates respectively. The methods showed different activities for preparations as well as for patient’s plasma. The discrepancy between measured and expected recovery differed for each method.

Source and Purity of Factor VIII Products As Risk Factors for Inhibitor Development In Previously Untreated Patients with Severe Hemophilia A

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 25-25
Author(s):  
Maria Elisa Mancuso ◽  
Pier Mannuccio Mannucci ◽  
Angiola Rocino ◽  
Isabella Garagiola ◽  
Annarita Tagliaferri ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor Viii ◽  
High Purity ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Specific Activity ◽  
Sensitivity Analyses ◽  
Severe Hemophilia ◽  
Inhibitor Development ◽  
Treatment Data

Abstract Abstract 25 Background: Inhibitor development is influenced by several genetic and environmental factors and the type of factor VIII (FVIII) products may play a role. Methods: We designed a cohort study whose novelty resides in the classification of products not only according to the plasmatic (pdFVIII) or recombinant (rFVIII) source of FVIII but also to the degree of purity expressed as FVIII specific activity per mg of protein. The role of FVIII product as risk factor for inhibitor development was evaluated in a multivariate model adjusting for potential confounders (i.e. age at first FVIII exposure, intensive treatment and prophylaxis). Cumulative incidences of all and high-responding inhibitors were calculated for the whole cohort of 721 patients with severe and moderate hemophilia A followed-up in 3 Italian Hemophilia Centers. Detailed treatment data from the first FVIII infusion up to inhibitor development or 150 exposure days were available for 377 patients and in this group of patients risk factors for inhibitor development including the type of FVIII product and its degree of purity (i.e. low/intermediate-, high-purity pdFVIII and rFVIII) were analysed. Results: The overall cumulative incidence of inhibitors was 22% (n=160; 130 high-responders, 18%) and it was lower in patients first treated with pdFVIII (107/586, 18%) than in those treated with rFVIII (53/135, 39%). Similar results were obtained by evaluating only high-responding inhibitors and patients with severe hemophilia. The adjusted hazard ratio of inhibitor development was 4.9 with rFVIII and 2.0 with high-purity pdFVIII (95%CI: 2.9–8.3 and 1.1–4.0), taking as reference low/intermediate-purity pdFVIII. There was no difference in the frequency of inhibitor testing between treatment groups. Sensitivity analyses - in patients who never switched product type, previously untreated patients, those treated on-demand and those with high-risk F8 mutations - confirmed an increased inhibitor risk in patients first treated with rFVIII or high-purity pdFVIII than in those treated with low/intermediate-purity pdFVIII. In fact, in all the aforementioned subgroups by multivariate analysis the risk of inhibitor development was invariably 3- to 6-fold higher in patients first treated with rFVIII than in those first treated with pdFVIII, and similar results were obtained for both all inhibitors and high-responding inhibitors. Conclusions: This study shows that the degree of purity of FVIII products influences inhibitor development independently from other risk factors, and emphasizes that differences exist also within pdFVIII products. Disclosures: No relevant conflicts of interest to declare.

METHODS OF PREPARING INTERMEDIATE- AND HIGH-PURITY FACTOR-VIII CONCENTRATES

1972 ◽  
Vol 22 (5) ◽  
pp. 631-631
Author(s):  
Alan J. Johnson ◽  
Jack Newman ◽  
Joseph G. Montalto
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Factor Viii Concentrates
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