scholarly journals Updating the Canadian Hemophilia Outcomes–Kids’ Life Assessment Tool (CHO‐KLAT) in the era of extended half‐life clotting factor concentrates

2021 ◽  
Author(s):  
Victoria E. Price ◽  
Saunya Dover ◽  
Victor S. Blanchette ◽  
Robert J. Klaassen ◽  
Mark Belletrutti ◽  
...  
Keyword(s):  
Half Life ◽  
Assessment Tool ◽  
Life Assessment ◽  
Clotting Factor ◽  
Clotting Factor Concentrates

scholarly journals Pharmacokinetic-based prediction of real-life dosing of extended half-life clotting factor concentrates on hemophilia

2018 ◽  
Vol 9 (6) ◽  
pp. 149-162 ◽  
Author(s):  
Massimo Morfini ◽  
Stefano Gherardini
Keyword(s):  
Half Life ◽  
Real Life ◽  
Dose Interval ◽  
Time Profile ◽  
Phase Iii ◽  
Clotting Factor ◽  
Time Interval ◽  
Bolus Administration ◽  
The One ◽  
Clotting Factor Concentrates

The improvement of clotting factor concentrates (CFCs) has undergone an impressive boost during the last six years. Since 2010, several new recombinant factor (rF)VIII/IX concentrates entered phase I/II/III clinical trials. The improvements are related to the culture of human embryonic kidney (HEK) cells, post-translational glycosylation, PEGylation, and co-expression of the fragment crystallizable (Fc) region of immunoglobulin (Ig)G1 or albumin genes in the manufacturing procedures. The extended half-life (EHL) CFCs allow an increase of the interval between bolus administrations during prophylaxis, a very important advantage for patients with difficulties in venous access. Although the inhibitor risk has not been fully established, phase III studies have provided standard prophylaxis protocols, which, compared with on-demand treatment, have achieved very low annualized bleeding rates (ABRs). The key pharmacokinetics (PK) parameter to tailor patient therapy is clearance, which is more reliable than the half-life of CFCs; the clearance considers the decay rate of the drug concentration–time profile, while the half-life considers only the half concentration of the drug at a given time. To tailor the prophylaxis of hemophilia patients in real-life, we propose two formulae (expressed in terms of the clearance, trough and dose interval between prophylaxis), respectively based on the one- and two-compartmental models (CMs), for the prediction of the optimal single dose of EHL CFCs. Once the data from the time decay of the CFCs are fitted by the one- or two-CMs after an individual PK analysis, such formulae provide to the treater the optimal trade-off among trough and time-intervals between boluses. In this way, a sufficiently long time-interval between bolus administration could be guaranteed for a wider class of patients, with a preassigned level of the trough. Finally, a PK approach using repeated dosing is discussed, and some examples with new EHL CFCs are shown.

The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing

The Lancet ◽  
2021 ◽  
Vol 397 (10274) ◽  
pp. 630-640
Author(s):  
Maria Elisa Mancuso ◽  
Johnny N Mahlangu ◽  
Steven W Pipe
Keyword(s):  
Half Life ◽  
Gene Editing ◽  
Clotting Factor ◽  
Clotting Factor Concentrates

Antibody to Hepatitis G Mrus after a Vapour-Heated Factor Vlll Goncentrate

1990 ◽  
Vol 64 (02) ◽  
pp. 232-234 ◽  
Author(s):  
P M Mannucci ◽  
A R Zanetti ◽  
M Colombo ◽  
A Chistolini ◽  
R De Biasi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Factor Viii ◽  
Alanine Aminotransferase ◽  
Household Contact ◽  
Clotting Factor ◽  
Double Infection ◽  
Marked Elevation ◽  
Clotting Factor Concentrates

SummaryTo evaluate whether or not clotting factor concentrates exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984–1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti- HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.

Azidothymidine (AZT) in the Treatment of Symptomatic HIV-1-Infected Hemophiliacs

1990 ◽  
Vol 64 (01) ◽  
pp. 108-112 ◽  
Author(s):  
S Eichinger ◽  
I Pabinger ◽  
H Hartl ◽  
C Stain ◽  
S Mayerhofer ◽  
...  
Keyword(s):  
Risk Groups ◽  
Clotting Factor ◽  
Bleeding Tendency ◽  
Probability Of Survival ◽  
Immunodeficiency Virus ◽  
Progression Of Disease ◽  
Bleeding Episodes ◽  
Clotting Factor Concentrates ◽  
Dose Dependent ◽  
Hiv 1

SummaryTwenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months.At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with intermption of treatment. Three patients developed severe leukopenia and 3 patients severe anemii during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was intermpted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of noncompliance.No signiticant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted.We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patientr ur. comparable to those seen in other risk groups . AzT does not increase the bleeding tendency in this patient group.

Acute Hepatitis C in Haemophiliacs Due to “Virus-Inactivated” Clotting Factor Concentrates

1992 ◽  
Vol 68 (06) ◽  
pp. 781-781 ◽  
Author(s):  
A Gerritzen ◽  
B Scholt ◽  
R Kaiser ◽  
K E Schneweis ◽  
H-H Brackmann ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Acute Hepatitis ◽  
Clotting Factor ◽  
Acute Hepatitis C ◽  
Clotting Factor Concentrates

Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

1994 ◽  
Vol 72 (01) ◽  
pp. 033-038 ◽  
Author(s):  
N Schinaia ◽  
A M G Ghirardini ◽  
M G Mazzucconi ◽  
G Tagariello ◽  
M Morfini ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
National Registry ◽  
Factor Ix ◽  
Clotting Factor ◽  
Coagulation Disorders ◽  
Factors Associated ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Congenital Coagulation Disorders ◽  
Clotting Factor Concentrates

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

Hepatitis-Free Interval After Clotting Factor Therapy in First Infused Haemophiliacs

1986 ◽  
Vol 56 (03) ◽  
pp. 268-270 ◽  
Author(s):  
M Morfini ◽  
D Rafanelli ◽  
G Longo ◽  
A Messori ◽  
P Rossi Ferrini
Keyword(s):  
Life Table ◽  
Lower Risk ◽  
Clotting Factor ◽  
Rank Test ◽  
Life Table Method ◽  
Table Method ◽  
Log Rank Test ◽  
Free Interval ◽  
Post Infusion ◽  
Clotting Factor Concentrates

SummaryPost-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis.To evaluate this hypothesis, we retrospectively reviewed the medical records of 25 first infused haemophiliacs (from 1981 to 1984) treated with unheated commercial clotting factor concentrates (n = 19) or cryoprecipitate (n = 6).The hepatitis-free interval after the beginning of therapy was expressed as exposure days. The end point of each patient, i.e. the hepatitis occurrence, was defined as an increase of aminotransferases (ALT and AST) and/or the seroconversion of HBV-markers, which were checked every three months.The life-table method and log-rank test showed that cryo-precipitates had a significantly longer hepatitis-free interval (p = 0.0131, log-rank test) and a lower risk of transmitting hepatitis (p = 0.01-0.05, life-table method) than the commercial concentrates. However, the safety of cryoprecipitate therapy was shown to cover only a few exposure days, and so the real advantage of this product depends on the bleeding frequency of the patient concerned.We believe that these methods and our findings may be useful to assess and compare the safety of the new “heat-treated” clotting factor concentrates.

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