scholarly journals Treatment of Joint-Bleedings in Hemophiliacs with Antibodies to Factor VIII with High doses of Fraction Feiba.

1977 ◽  
Author(s):  
Kl. Schimpf ◽  
K. Zimmermann ◽  
P. Zeltsch
Keyword(s):  
Knee Joint ◽  
Factor Viii ◽  
Half Life ◽  
Clinical Effect ◽  
Single Injection ◽  
Life Time ◽  
Joint Effusion ◽  
The Third ◽  
Inhibitor Level ◽  
High Doses

Observations in 3 patients demonstrated, that joint-bleedings can be controlled with high doses of fraction FEIBA alone or in combination with factor (f) VIII on out-patient basis. First patient, inhibitor 5-10 units (u) per ml, suffered from 24 joint-bleedings within 392 days. 2o of them could be stopped by a single injection of 150-200 u of fraction FEIBA per kg bodyweight (bw). A combination of 90 u of FEIBA and 36 u of f VIII per kg bw had the same effect. But after 5 injections of this combination within 6 weeks, the inhibitor level had risen from 10 to 240 u per ml. During further treatment with 180 u of fraction FEIBA without addition of f VIII, the inhibitor fell down with a half life time of 50 days. The clinical effect of fraction FEIBA was not influenced by the elevated antibody level. Two further patients, inhibitors 2-4 and 32 u respectively, obtained combined injections of 50-100 u of FEIBA plus 36-42 u of f VIII. One patient was on a prophylaxis of 3 injections weekly for 193 days. After 57 injections the inhibitor had fallen from 2-4 u to unmeasurable values. The third patient obtained the above mentioned dosis twice a day for treatment of a knee joint effusion. After 1 week the inhibitor was diminished from 32 to 13 u.

Effect of Treatment with Activated Prothrombin Complex Concentrate (FEIBA) on Factor VIII-Antibody Level

1978 ◽  
Vol 40 (02) ◽  
pp. 478-485 ◽  
Author(s):  
K Lechner ◽  
Ch Nowotny ◽  
B Krinninger ◽  
M Zegner ◽  
E Deutsch
Keyword(s):  
Factor Viii ◽  
Antibody Level ◽  
Prothrombin Complex Concentrate ◽  
Anamnestic Response ◽  
Activated Prothrombin Complex Concentrate ◽  
Inhibitor Level ◽  
Complex Preparation ◽  
Effect Of Treatment ◽  
High Doses ◽  
Stimulation Of

SummaryThe influence of treatment with an activated prothrombin complex preparation (FEIBA) on the antibody level was studied in 10 haemophiliacs with an antibody to factor VIII. The antibody level was observed to rise at least once in five patients, while in the remaining five patients no rise occurred. In all, 6 out of 31 treatments were followed by an anamnestic rise of the antibody level, corresponding to 19.4%. A rise of the inhibitor level following FEIBA treatment is likely to occur in patients who show a marked antibody rise after factor VIII treatment (good responders), but have a low antibody level at the time of treatment. High doses of FEIBA and simultaneous transfusion of red cells may also enhance the likelihood of an anamnestic response. Stimulation of antibody production is probably due to the presence of small amounts of factor VIII in this preparation.

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 ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Group ◽  
Half Life ◽  
Hemophilia A ◽  
Linear Regression Analysis ◽  
Life Time ◽  
Blood Group A ◽  
Wide Range ◽  
Group A ◽  
Blood Group P

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.

Development of inhibitors in haemophilia

2011 ◽  
Vol 31 (S 01) ◽  
pp. S20-S23
Author(s):  
D. Mihailov ◽  
L. Pop ◽  
H. Ionita ◽  
E. Ursu ◽  
S. Talpos-Niculescu ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Life Time ◽  
Haemophilia A ◽  
Surgical Interventions ◽  
Recovery Index ◽  
Frequent Switching ◽  
Reliable Interpretation ◽  
Time Assessment ◽  
Relevant Factors

SummaryA number of 513 consecutive patients (494-haemophilia A and 19-haemophilia B) from eight haemophilia treatment centers have been investigated with Bethesda assay for the presence of factor VIII or IX inhibitors. The overall prevalence of inhibitors was 15.20%, 18.48% in severe, 5.60% in moderate and 12.24% in mild forms. The prevalence was higher than reported in most of the western countries. The age at start of substitution (p = 0.9775), the frequent switching of factor concentrates (p = 0.8931) were not relevant factors for the development of inhibitors. It is worth to be mentioned the unexpectedly occurrence of inhibitors in prior inhibitor negative (6/72) patients (during surgical interventions) probably due to their previous scarce substitution, occurrence which seems not being connected with the continuous infusion modality of factor VIII administration (p = 0.8341). In controversial situations, in the field of low titer (≤1 BU/ml) inhibitors for a reliable interpretation of the results the performance of recovery index and half-life time assessment of FVIII/IX was undertaken.

Comparative in Vitro and in Vivo Study of Various Factor VIII Preparations

1979 ◽  
Author(s):  
J.P. Allain ◽  
F. Verroust ◽  
J.P. Soulier
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Half Life ◽  
Hemophilia A ◽  
Post Injection ◽  
High Doses ◽  
Antibody Levels ◽  
Similar Risk

A comparison of nine commercial and non-commercial Factor VIII preparations was made. They consisted of llyophilized cryoprecipitate, 4 intermediate and 4 high purity concentrates. Protein, Fibrinogen, Factor VIII complex, IgG, anti-A and anti-B antibody levels were measured. Factor VIII:C content varied from 4-7 u/ml in cryoprecipitate, 12-31 u/ml in intermediate and 21-40 u/ml in high purity concentrates. These three categories of Factor VIII preparations can be better defined by 2 ratios: u FVIII/mg proteins and u F VIII/mg fibrinogen. They were respectively < 0.5 and < 1 in cryo, 0.5-1 and 1-3 in intermediate purity concentrates, > 1 and > 3 in high purity concentrates. The F VIII :C/F VIII : AG ratio ranged from 0.3 to 0.6 in any preparation. The F VIII:C/F VIII :VWF ratio was always lower than 1.Each preparation was injected to several classic hemophilia A patients for treatment of minor hemorrhages. The peak of activity was always found 1 hour post-injection and the recovery ranged from 80 to 105%. The Factor VIII half-life ranged from 10 to 12.5 hours. No significant differences in half-life or recovery was found, and the clinical efficacy was similar. With the exception of fibrinogen load, all products carry similar risk for hepatitis, anti-IgG immunization and hemolysis. The differences lie in the ease of injection, the price and the yield of Factor VIII from starting plasma. Nevertheless, high purity concentrates should be used when high doses are reauired for surgery or treatment of patients with inhibitor.

Effects of Vancomycin on Platelets, Plasma Proteins and Hepatitis B Surface Antigen

1975 ◽  
Vol 34 (01) ◽  
pp. 083-093 ◽  
Author(s):  
Barry S Coller ◽  
W. B Lundberg ◽  
Harvey R Gralnick
Keyword(s):  
Hepatitis B ◽  
Factor Viii ◽  
Surface Antigen ◽  
Plasma Proteins ◽  
Hepatitis B Surface Antigen ◽  
Infusion Site ◽  
Vancomycin Therapy ◽  
Intravenous Injections ◽  
Low Concentrations ◽  
High Doses

SummaryThe antibiotic vancomycin shares many similarities with ristocetin, an agent noted for its effects on platelets and plasma fibrinogen. Vancomycin did not aggregate platelets as ristocetin, but platelets were incorporated into precipitates induced by vancomycin. Fibrinogen and factor VIII were precipitated from plasma at low concentrations of vancomycin. The precipitated fibrinogen remained clottable. Hepatitis B surface antigen was selectively precipitated from serum and could be recovered from the precipitate. Rabbits receiving bolus intravenous injections of high doses of vancomycin developed hypofibrinogenemia and thrombocytopenia within minutes and often went on to die. Studies with 125I-vancomycin revealed little stable binding of the antibiotic to platelets or fibrinogen. A relationship is suggested between the potent protein precipitating effects and phlebitis at the infusion site commonly associated with vancomycin therapy.

A Higher than Expected Incidence of Factor VIII Inhibitors in Multitransfused Haemophilia A Patients Treated with an Intermediate Purity Pasteurized Factor VIII Concentrate

1993 ◽  
Vol 69 (02) ◽  
pp. 115-118 ◽  
Author(s):  
Kathelijne Peerlinck ◽  
Jef Arnout ◽  
Jean Guy Gilles ◽  
Jean-Marie Saint-Remy ◽  
Jos Vermylen
Keyword(s):  
Factor Viii ◽  
Randomized Trials ◽  
Specific Factor ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Viral Inactivation ◽  
Gradual Decline ◽  
Inhibitor Level ◽  
Factor Viii Concentrates ◽  
Viii Inhibitor

SummaryIn May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation.Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII.This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials.

The Spectrum of von Willebrand’s Disease

1967 ◽  
Vol 18 (01/02) ◽  
pp. 040-056 ◽  
Author(s):  
E. J Walter Bowie ◽  
P Didisheim ◽  
J. H Thompson ◽  
C. A Owen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Platelet Adhesiveness ◽  
Platelet Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Generation Test

SummaryPatients (from 5 kindreds) with variants of von Willebrand’s disease are described. In one kindred the depression of factor VIII was moderate (20 to 40% of normal) and transfusion of 500 ml of normal plasma led to an increase higher than anticipated and to an almost normal level of factor VIII 17 to 24 hrs later. This represents the usual type of von Willebrand’s disease.In the second kindred the concentration of factor VIII was less than 2 % of normal in the son and daughter, who had severe bleeding and hemarthroses.The third kindred was characterized by reduction of factor VIII and a long bleeding time as well as by a serum defect in the thromboplastin-generation test comparable to that seen in patients with hemophilia B, yet with normal levels of factors IX, X, and VII. The severity of the serum defect, the positive result with the Rumpel-Leede test, and the reduced platelet activity in the thromboplastin-generation test are all compatible with the diagnosis of thrombopathy or ‘‘thrombopathic hemophilia.” In two other kindreds, one patient had a long bleeding time and normal levels of factor VIII and another had a normal bleeding time and decrease of factor VIII. The last patient had the type of response to transfusion usually seen in von Willebrand’s disease.In four kindreds, platelet adhesiveness in vivo was found to be strikingly abnormal (virtually absent).It would appear, therefore, that von Willebrand’s disease forms a spectrum, and whether the kindreds reported simply reflect variations of a single genetic disease state or represent separate entities will be answered only by clarification of the underlying etiology of that disease.

Covalent Complexes Between Low Molecular Weight Heparin Fragments and Antithrombin III – Inhibition Kinetics and Turnover Parameters

1983 ◽  
Vol 49 (02) ◽  
pp. 109-115 ◽  
Author(s):  
M Hoylaerts ◽  
E Holmer ◽  
M de Mol ◽  
D Collen
Keyword(s):  
Molecular Weight ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Life Time ◽  
Low Molecular Weight ◽  
High Affinity ◽  
Plasma Half Life ◽  
Covalent Complex

SummaryTwo high affinity heparin fragments (A/r 4,300 and M, 3,200) were covalently coupled to antithrombin III (J. Biol. Chem. 1982; 257: 3401-3408) with an apparent 1:1 stoichiometry and a 30-35% yield.The purified covalent complexes inhibited factor Xa with second order rate constants very similar to those obtained for antithrombin III saturated with these heparin fragments and to that obtained for the covalent complex between antithrombin III and native high affinity heparin.The disappearance rates from plasma in rabbits of both low molecular weight heparin fragments and their complexes could adequately be represented by two-compartment mammillary models. The plasma half-life (t'/j) of both low Afr-heparin fragments was approximately 2.4 hr. Covalent coupling of the fragments to antithrombin III increased this half-life about 3.5 fold (t1/2 ≃ 7.7 hr), approaching that of free antithrombin III (t1/2 ≃ 11 ± 0.4 hr) and resulting in a 30fold longer life time of factor Xa inhibitory activity in plasma as compared to that of free intact heparin (t1/2 ≃ 0.25 ± 0.04 hr).

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