The Half-life of Infused Factor VIII Is Shorter in Hemophiliac Patients with Blood Group 0 than in those with Blood Group A

2000 ◽  
Vol 83 (01) ◽  
pp. 65-69 ◽  
Author(s):  
Evelien Mauser-Bunschoten ◽  
Antoanette Zarkova ◽  
Els Haan ◽  
Cas Kruitwagen ◽  
Jan Sixma ◽  
...  

SummaryA considerable inter-individual variation in half-life of infused factor VIII is observed among patients with hemophilia A. The factors contributing to this wide range in factor VIII half-life are not known in detail. We analysed the pharmacokinetics of infused factor VIII in 32 patients with hemophilia A, comprising 20 brothers from 10 families, 3 and 4 brothers from 2 families, and 5 patients from 5 single families, respectively. Multiple linear regression analysis was used to asses the effect of several variables on factor VIII half-life. We found that the pre-infusion von Willebrand factor antigen levels (vWF:Ag) were positively correlated with factor VIII half-life (r = 0.52, p = 0.002), i. e., each variable was associated with about 27% of the variance of the other. In fraternal pairs, familial clustering was significant for AB0 blood group (p < 0.001), but could not be detected for factor VIII half-lives or pre-infusion vWF:Ag levels. vWF:Ag level (p = 0.001) and AB0 blood group (p = 0.003) significantly determined factor VIII half-life, whereas age, length, bodyweight, the presence or absence of a factor VIII gene inversion, and Rhesus phenotype did not. Patients with blood group 0 exhibited a statistically significant shorter factor VIII half-life than patients with blood group A (15.3 versus 19.7 h, respectively) (p = 0.003). Patients with blood group A and 0 differ in respect to the presence of anti-A antibodies in the latter. It is possible that these anti-A antibodies interact with endogenous vWF, thus affecting the half-life time of the factor VIII/vWF complex.

1977 ◽  
Author(s):  
G. O. S. de Melo

Factor VIII and factor VIII related antigen were found to change proportionately during normal pregnancy. There was a clear tendency for levels of activity and antigen to increase as the duration of the pregnancy advanced. In the pregnant women studied a significant difference was observed in factor VIII levels between Blood Group A and Blood Group O. A similar difference was found in factor VIII related antigen levels. Age, weight and previous use of contraceptives seems to have no influence on factor VIII and factor VIII related antigen values in pregnancy.


2017 ◽  
Vol 95 (9) ◽  
pp. 847-854
Author(s):  
Elena I. Kukhareva ◽  
P. P. Ogurtsov

Aim. To evaluate the prognostic value of blood group and IL-28B genotype with respect to dynamics of liver fibrosis (LF) in patients with chronic genotype-1 hepatitis C (HCV-1) who did not respond to antiviral therapy (AVT) with pegylated interferon alpha 2 (peg-IFN-α-2) and ribavarin (RBV) Material and methods. The study included 122 primary patients with HCV-1 who underwent paired liver biopsy or elastometry steam. The main group (n=66) consisted of patients who received AVT (peg-IFN-α-2/RBV) but failed to achieve a sustainable virologic response (SVR). Control group (n=56) comprised patients treated without AVT. Results. Negative dynamics of LF in patients of the main group occurred significantly more frequently than in the placebo group (p=0.025, φ2 criterion). LF dynamic patterns in patients of the main group varied depending on the IL-28B genotype and blood group, p=0.001 and p=0.014 respectively. Factorial analysis of negative LP dynamics in the main group revealed the relationship between blood group (fr=0,931) and IL-28B genotype (fr= 0.960) while classification analysis demonstrated the predictive value of combination of gene IL-28B polymorphism and blood group (p<0.0001). The assessment of probability of negative LF dynamics in the main group (logistic analysis) showed that IL-28B gene genotypes ST/TG, TT/TT,TG,GG and blood group A(II) alone or their combination increase the odds ratio of LF negative dynamics in SVR(-) under conditions of interferon therapy. In patients having blood group 0(I) and combination of gene IL-28B genotypes CC/TT, CT/TT with blood group A(II) the odds ratio of negative dynamics in SVR(-) is reduced under the same conditions. Conclusions. Blood group and IL-28B genotype predict dynamics of liver fibrosis in patients with HCV-1 not responding to interferon therapy.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3091-3091
Author(s):  
Karin van Dijk ◽  
Johanna G. van der Bom ◽  
Eveline P. Mauser-Bunschoten ◽  
Goris Roosendaal ◽  
Peter J. Lenting ◽  
...  

Abstract Introduction Patients with severe hemophilia A have considerably different factor VIII half-lives. Whether this is associated with clinical characteristics has not been reported. The aim of this study was to describe the effect of half-life on the clinical characteristics of patients with severe hemophilia. Patients and Methods Patients were selected from a single-centre cohort of 214 patients with severe hemophilia, born between 1944 and 1995. To improve efficiency we measured factor VIII half-life in the patients with the most severe and the mildest clinical phenotypes of severe hemophilia. Patients were selected according to age at first joint bleed, annual joint bleed frequency, clotting factor consumption and radiological Pettersson scores. A first blood sample was taken after a period of 72 hours in which the patient did not use factor VIII. After infusion with 50 IU factor VIII/kg, blood was collected at 15, 30 minutes and 1, 3, 5, 24, 30, 48 and 60 hours. From 1972 onwards, data on joint bleed frequency, clotting factor use and age at first joint bleed were collected from the patients’ files. Pettersson scores were performed at five-year intervals. For calculations of annual clotting factor use (IU/kg/yr) and number of joint bleeds per year, the last 5 years of follow-up were used. Linear regression analysis was used to assess the relation between clinical characteristics and factor VIII half-life. Results Factor VIII half-life was measured in 42 patients and ranged from 7.4–20.4 hours, with a median of 11.8 hours. One hour increase in factor VIII half life was associated with a decrease of 96 (SD 45) IU clotting factor use per kg per year (p&lt;0.05). Joint bleed frequency was similar in patients with a shorter and a longer factor VIII half-life. Median number of joint bleeds was 2.9 per year (interquartile range (IQR) 1.1–4.4) in patients with a factor VIII half-life shorter than 12 hours and 2.6 per year (IQR 1.0–4.8) in patients with a factor VIII half-life longer than 12 hours (p=0.84). Patients with a factor VIII half-life shorter than 12 hours had a median Pettersson score of 52 points (IQR 12–61) and patients with a factor VIII half-life longer than 12 hours had a median Pettersson score of 29 points (IQR 16–52; p=0.90). Conclusion: Patients with a shorter factor VIII half-life need more clotting factor to prevent joint bleeds and subsequent arthropathy than patients with a longer factor VIII half-life.


1979 ◽  
Author(s):  
J.K. Smith ◽  
P.J. Bowell ◽  
H.H. Gunson ◽  
T.J. Snape

Haemolysis may be induced in haemophiliacs of blood group A if they receive very large doses of concentrates containing high levels of anti-A. The anti-A content of factor VIII concentrates made at PFL has been, measured by an automated haemagglutination method. The standard was a pool of 500 sera of random blood groups, assigned a value of 100 units per ml. 23 batches of concentrate prepared from 5 1 packs of FFP, each containing about 24 donations of random blood groups, contained 23.7 ± 4.1 (mean ± S.D.) units anti-A/iu factor VIII.It was predicted that, if 5 l pools were replaced by single donations of FFP which were not mixed until thawing and collection of the cryoprecipitate, there would be less neutralisation of anti-A by group A donations and the anti-A level in the concentrate would be increased. Unexpectedly, the anti-A content of 9 batches prepared from single donations of random blood groups was 5.8 ± 1.5 units/iu factor VIII, significantly lower than for batches made from 5 1 packs. It is postulated that free anti-A is less susceptible to cryoprecipitation than is anti-A completed with A substance during pooling of group O and A plasmas at 20°. After re-solution of the cryoprecipitated complex, equilibrium may be re-established to give free anti-A.


Author(s):  
C MAZURIER ◽  
B SAMOR ◽  
L MANNESSIER ◽  
A PARQUETGERNEZ ◽  
M GOUDEMAND

1974 ◽  
Vol 138 (3) ◽  
pp. 381-386 ◽  
Author(s):  
D. J. Anstee ◽  
M. J. A. Tanner

The distribution of protein and blood-group-antigen activity obtained after butanol extraction of erythrocyte `ghosts' under various conditions is described. Butanol extraction under low-ionic strength conditions results in the recovery of membrane protein in high yield in the aqueous phase. Blood-group-A activity is found in both the aqueous and butanol phases, whereas blood-group-P activity is confined to the butanol phase and blood-group-I and blood-group-MN activity are restricted to the aqueous phase. Much lower yields of protein are obtained in the aqueous phase when high-ionic-strength conditions are used. An appreciable amount of material is precipitated at the interface. Under these conditions blood-group-P activity is found only in the butanol phase, blood group-A activity in the butanol phase and interface material and only blood-group-MN activity in the aqueous phase. In contrast with previous reports no correlation could be demonstrated between the secretor status of the donors and the presence of blood-group-A activity in the aqueous phase after butanol extraction under any of the extraction conditions used. By using butanol extraction under high-ionic-strength conditions it is possible to isolate the blood-group-MN-active sialoglycoprotein in high yield from erythrocyte `ghosts' by a simple procedure.


2020 ◽  
Vol 120 (10) ◽  
pp. 1395-1406 ◽  
Author(s):  
Iris Garcia-Martínez ◽  
Nina Borràs ◽  
Marta Martorell ◽  
Rafael Parra ◽  
Carme Altisent ◽  
...  

AbstractThe pharmacokinetic (PK) response of severe hemophilia A (HA) patients to infused factor VIII (FVIII) shows substantial variability. Several environmental and genetic factors are associated with changes in FVIII plasma levels and infused FVIII PK. Based on the hypothesis that factors influencing endogenous FVIII can affect FVIII PK, the contribution of single-nucleotide variants (SNVs) in candidate genes was investigated in 51 severe HA patients. The effects of blood group, F8 variant type, von Willebrand factor antigen and activity levels, age, and weight were also explored. The myPKFiT device was used to estimate individual PK parameters, and SNVs and clinically reportable F8 variants were simultaneously analyzed in an Illumina MiSeq instrument, using the microfluidics-based Fluidigm Access Array system. The contribution of SNVs to FVIII half-life and clearance was addressed by robust regression modeling, taking into account other modulators. In line with previous studies, we provide robust evidence that age, body weight, and blood group, as well as SNVs in ABO and CLEC4M, participate in the variability of FVIII PK in HA patients. Main results: each copy of the rs7853989 (ABO) allele increases FVIII half-life by 1.4 hours (p = 0.0131) and decreases clearance by 0.5 mL/h/kg (p = 5.57E-03), whereas each additional rs868875 (CLEC4M) allele reduces FVIII half-life by 1.1 hours (p = 2.90E-05) and increases clearance by 0.3 mL/h/kg (p = 1.01E-03). These results contribute to advancing efforts to improve FVIII replacement therapies by adjusting to each patient's PK profile based on pharmacogenomic data. This personalized medicine will decrease the burden of treatment and maximize the benefits obtained.


1987 ◽  
Vol 262 (29) ◽  
pp. 14228-14234
Author(s):  
H Clausen ◽  
S B Levery ◽  
E D Nudelman ◽  
M Stroud ◽  
M E Salyan ◽  
...  

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