scholarly journals Extended half-life clotting factor concentrates: results from published clinical trials

Haemophilia ◽  
2016 ◽  
Vol 22 ◽  
pp. 25-30 ◽  
Author(s):  
G. Young ◽  
J. N. Mahlangu
Keyword(s):  
Clinical Trials ◽  
Half Life ◽  
Clotting Factor ◽  
Clotting Factor Concentrates

scholarly journals Lasting power of new clotting proteins

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 355-363 ◽  
Author(s):  
Jerry S. Powell
Keyword(s):  
United States ◽  
Clinical Trials ◽  
Half Life ◽  
The United States ◽  
Clotting Factor ◽  
Current Therapy ◽  
Activity Levels ◽  
Clinical Use ◽  
Factor Activity ◽  
Bleeding Episodes

Abstract Hemophilia is a genetic disease caused by a deficiency of one of the coagulation proteins. The term usually refers to either hemophilia A, factor VIII (FVIII), with an incidence of ∼1 in 5000 male births, or hemophilia B, factor IX (FIX), with an incidence of ∼1 in 30 000 male births. When severe, the disease leads to spontaneous life-threatening bleeding episodes. Current therapy requires frequent intravenous infusions of therapeutic factor concentrates. Most patients administer the infusions at home every few days and must limit their physical activities to avoid bleeding when the factor activity levels are below normal. In March 2014, a new therapeutic FIX preparation was approved for clinical use in Canada and the United States and, in June 2014, a new FVIII preparation was approved for clinical use in the United States. Over the next couple of years, other new factor products for FIX, FVIIa, and FVIII, which are currently in late stages of clinical trials, will likely also be approved. These new factors have been engineered to extend their half-life in circulation, thus providing major therapeutic advances for patients with hemophilia primarily by allowing treatment with fewer infusions per month. In the clinical trials so far, >500 patients have successfully used these extended half-life products regularly for >1 year to prevent spontaneous bleeding, to treat successfully any bleeding episodes, and to provide effective coagulation for major surgery. Essentially all infusions were well tolerated and effective. These promising new therapies should allow patients to use fewer infusions to maintain appropriate clotting factor activity levels in all clinical settings.

scholarly journals Subcutaneous injection: learning from experience in other specialties

2018 ◽  
Vol 5 (1) ◽  
pp. 35-41
Author(s):  
Debra Pollard ◽  
Steve Chaplin
Keyword(s):  
Clinical Trials ◽  
Subcutaneous Injection ◽  
Clotting Factor ◽  
Injection Technique ◽  
Evidence Based ◽  
Nurse Training ◽  
Learning From Experience ◽  
Training And Education ◽  
Management Plans ◽  
Clotting Factor Concentrates

Abstract Haemophilia treatment is characterised by intravenous infusions of clotting factor concentrates, with nurses frequently taking the lead role in administration, patient training and patient care. In recent years, a number of novel factor and non-factor-based therapies delivered by subcutaneous injection have been developed. These therapies are now undergoing clinical trials and will shortly be available in clinical practice. The coming era of at least some haemophilia treatments being delivered by subcutaneous injection clearly represents a significant change not only for patients (for whom they may be more convenient) but also for haemophilia nurse practice, particularly with respect to bleed and surgical management plans, and hence for nurse training and education. This review describes evidence-based guidance on subcutaneous injection technique and summarises the implications for nurses.

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
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